Cancer Therapy Advisor Fall 2014 Issue by Haymarket Media

CancerTherapyAdvisor.com

FALL 2014 | VOL 1, ISSUE 1

CancerTherapyAdvisor

A10 CME ACTIVITY

Quality Improvement with Current and Emerging Therapies for Patients with Glioblastoma Reports from the Society for Neuro-Oncology (SNO) Annual Meeting

FEATURING Cancer Therapy Regimens and Oncology Drug Monographs from



1 Bone Cancer 7 Brain Cancer

 10 Breast Cancer 27 Endocrine Cancer 31 Gastrointestinal Cancer

A8 IN THE PIPELINE

Elotuzumab Granted Breakthrough Therapy for Multiple Myeloma

 37 Genitourinary Cancer 53 Gynecologic Cancer

 57 Head and Neck Cancer

A22 FEATURE

63 Hematologic Cancer

Palliative Care Integration and Expertise Are Pressing Goals for Oncologists

85 Lung Cancer 90 Sarcoma

 91 Skin Cancer

A24 IN THE CLINIC

Everolimus Use in Sorafenib-Refractory Hepatocellular Carcinoma FALL 2014 | VOL 1, ISSUE 1

A5 FEATURED PRODUCT

Zykadia Approved for Metastatic ALKPositive NSCLC

96 Associated Hematological

Disorders



Regimen included

A5 FEATURED PRODUCT

A26

Zykadia Approved for Metastatic ALK-Positive NSCLC

New Weapon Against Advanced Gastric/ Gastroesophageal Junction. STEVEN J. COHEN, MD

A6 LATEST NEWS Headlines in Oncology Research and Practice

A8 IN THE PIPELINE The Latest on Newly Approved Oncology Drugs

A10 CME ACTIVITY Quality Improvement with Current and Emerging Therapies for Patients with Glioblastoma

A22

FEATURE Palliative Care Integration and Expertise Are Pressing Goals for Oncologists BRYANT FURLOW

A24 IN THE CLINIC Everolimus Use in Sorafenib-Refractory Hepatocellular Carcinoma

A25

EXPERT PERSPECTIVE

A28 REGIMEN & MONOGRAPH INDEX -118 CANCER THERAPY REGIMENS & 1 DRUG MONOGRAPHS Highlighted topics () contain both treatment regimens and drug monographs.

 1 Bone Cancer

7 Brain Cancer

 10 Breast Cancer

27 Endocrine Cancer

31 Gastrointestinal Cancer

 37 Genitourinary Cancer

53 Gynecologic Cancer

 57 Head and Neck Cancer

63 Hematologic Cancer 85 Lung Cancer

C. ANDREW KISTLER, MD, PharmD, RPh

90 Sarcoma

VIEWPOINT

 91 Skin Cancer

Topical Gel May Be as Effective as Oral Tamoxifen in DCIS

96 Associated Hematological Disorders

GREG OTIS

119 ALPHABETICAL INDEX

Cancer Therapy Advisor (ISSN pending), Fall 2014, Volume 1, Number 1. Published quarterly by Haymarket Media, Inc., 114 West 26th Street, 4th Floor, New York, NY 10001. For Advertising Sales, Editorial and Subscription information call (646) 638-6000 (M–F, 9am–5pm, ET). Standard Postage paid at Orem, UT. Postmaster: Send changes of address to Cancer Therapy Advisor, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher.

A2 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

CTA_TOC_Fall14_F.indd 2

8/29/14 10:28 AM

EDITOR’S LETTER

Dear Oncology Professional, isor.com

CancerTherapyAdv FALL 2014

| VOL 1, ISSUE 1

dvisor CancerTherapyA

Welcome to the premiere print issue of Cancer Therapy Advisor! If you are familiar with CancerTherapyAdvisor.com—formerly ChemotherapyAdvisor.com—you may already know that we strive to deliver relevant, up-to-date oncology information. You may also be familiar with our sister publication, Monthly Prescribing Reference (MPR), and its quarterly Hematology/Oncology edition featuring cancer treatment regimens, drug monographs, and other important oncology news. What you are now holding in your hands combines all of these elements into one comprehensive, user-friendly publication with one goal: to provide the best and latest clinical information to oncology health professionals.

FEATURING

VITY A10 CME ACTI

ent with Quality Improvem rging Current and Eme nts with Therapies for Patie Glioblastoma

y Regimens Cancer Therap and Oncology from Drug Monographs



1 Bone Cancer 7 Brain Cancer

Society for Reports from the Annual Meeting Neuro-Oncology (SNO)

Cancer  10 Breast 27 Endocrine Cancer 31 Gastrointestinal

A8 IN THE PIPEL

INE

gh ted Breakthrou Elotuzumab Gran oma for Multiple Myel

Neck Cancer  57 Head and Cancer 63 Hematologic

DUCT FEATURED PRO Cancer

A22 FEATURE

85 Lung

Expertise Integration and Palliative Care for Oncologists Are Pressing Goals Rx

90 Sarcoma

Zykadia

 91 Skin Cancer Hematological 96 Associated Disorders

s Company: Novarti

C A24 IN THE CLINI

Cancer

inary Cancer  37 Genitour Cancer 53 Gynecologic

Therapy

FALL 2014 | VOL

ctory kinase inhibitor. enib-Refra class: Tyrosine Regimen included in Soraf  caps. Pharmacologic Everolimus Use 150mg; hard gelatin ents: Ceritinib Carcinoma a kinase (ALK)Active ingredi Hepatocellular anaplast ic lymphom progressed of patients with

nt ) who have Indication: Treatme lung cancer (NSCLC in survival or ic non-small cell for improvement positive metastat b. Not established A5 t to crizotini on or are intoleran s. REDsymptom disease-related FEATU

PRODUCT

1, ISSUE 1

y: Ceritinib inhibits Pharm acolog tion of ALK, ALKautophosphoryla rylation of the downmediated phospho and protein STAT3, stream signaling pendent cancer proliferation of ALK-de in vivo assays. and vitro in in cells

Zykadia with a median DOR a partial response CI: 5.6, NE). Approved for of 7.1 months (95% Metastatic ALK(at Positive NSCLC an empty stomach Adults: Take on or after a meal). 750 least 2 hours before disease progression mg once daily until inue toxicity. Discont table unaccep or d. daily not tolerate if 300 mg once impairvere hepatic Moderate-to-se ed. Dose modifica ment: not establish . tions: see full labeling

We recognize that the oncology practitioner is possibly the most specialized professional in medicine; your approach to patient care is vastly different than that of other specialties. Therefore, we want to provide you with an all-encompassing resource that will better address your professional needs. In the pages of Cancer Therapy Advisor (CTA), the drug information that you are accustomed to receiving from the MPR Hematology & Oncology Edition will be organized by cancer type, and some sections of each issue will begin with a detailed treatment regimen from the CTA Website. Our new journal-sized format also allows for the use of larger type, making the content easier to fi nd and read. This new “desk-journal” can be placed in your examining room, on your office desk, or in your home. A pocket-size format will still be available through the CTA app on your mobile device.

y Pregnancy (Categor bradycardia occur. ctive potential D). Females of reprodu ption during contrace should use effective at least 2 weeks after treatment and for mothers: not Nursing ion. complet recommended.

concomitant strong Interactions: Avoid s (eg, ritonavir, macroCYP3A4 inhibitor nefazodone), grapeefficacy of Zykadia lides, ketoconazole, Clinical trials: The sinble, reduce ceritinib in a multicenter, fruit juice; if unavoida was established concomitant strong el clinical trial (Study dose by 1/3. Avoid gle-arm, open-lab ic metastat carbamazepine, with (eg, CYP3A4 inducers 1) involving 163 patients ed. who progressed , St. John’s Wort). phenytoin, rifampin Children: Not establish ALK-positive NSCLC (eg, t to CYP3A substrates or were intoleran Avoid concomitant while receiving Monitor Zykadia s: ergots, fentanyl, received rine, caution alfentanil, cyclospo Warnin gs/Pre crizotinib. All patients , tacrolimus) t GI toxicity; if The major efficacy , quinidine, sirolimus severe or persisten pimozide for 750 mg once daily. s (eg, phenytoin, until improved; resume was objective response or CYP2C9 substrate occurs, withhold outcome measure ALT/AST and therapeutic indices; g to RECIST v1.0 warfarin) with narrow at reduced dose. Monitor rate (ORR) accordin these drugs. , and more both investig ators ble, reduce doses of bilirubin once monthly unavoida if total as evaluate d by cause dent Central transaminases develagents known to Avoid concomitant frequently if elevated and a Blinded Indepen kers, non-dihyreduce dose, or permatee (BIRC). Duration bradycardia (eg, beta-bloc op; withhold then Review Commit . al clonidine, digoxin). was an addition as clinically indicated dropyridine CCBs, nently discontinue of response (DOR) QT syndrome; avoid. . Congenital long outcome measure as, electroly te s: Diarrhea, nausea, that the overall Adverse reaction Results showed CHF, bradyar rhythmi ECG, electrolytes al pain, constipa patients with ALKvomiting, abdomin abnormalities; monitor response rate in if ue prior inases, fatigue, ntly discontin who received tion, elevated transam periodically. Permane positive NSCLC 47, ; bradycardia, hepin combination with 54.6% (95% CI: decreased appetite QTc prolongation crizotin ib was eumonitis, QTc CI: 36, 52) in the or polymorphic venatotoxic ity, ILD/pn Torsade de pointes 62) and 43.6% (95% ia cemia. and BIRC assessia or serious arrhythm prolongation, hypergly tricular tachycard investigator (n=163) ; ely. Also, in the HR and BP regularly respectiv Monitor (n=163), develop. ment s a nt, 1.2% achieved Caps—70 pulmonary symptom How supplied: serum glucose and investigator assessme . Permanently diswhile 53.4% achieved as clinically indicated complete response al 669-6682 (888)comcancer t-related interstiti ondcall with a median DOR advance informati with For more continue if treatmen a partial response Patients weak. eumonitis, unconCI: 5.4, 10.1). In fatigue and markedadia.com visit www.Zyk orsuffer lung disease (ILD)/pn of 7.4 months (95% a or life-threateningmonly and energy, pain, Wnt, 2.5% achieved assessme T FURLO trolled hyperglycemia, the BIRC ness, loss of appetite BY BRYAN while 41.1% achieved which can prostress, al complete response emotion 6 A5 and ADVISOR interof life. THERAPY their quality arly palliative care affect| CANCER | FALL 2014 foundly isor.com g ially erapyAdv initiatin that substant s CancerTh ventions can Researc h indicate upon and cancer earlier, such as improve cancer support ive care ted effects ic disease, can treatment–associa diagnosis with metastat of life, pain, gical psycholo quality life and improve patients’ to the quality of 4,6,7 is even evidence and family memmobility. There and well-being of patients pain, mobility with terminal lung that, among patients bers, including patient pallias of breath, nausea te initiation of pallia cancer, immedia impairment, shortnes median survival and depression. tive care can prolong4,7 and vomiting, anxiety, of early palliative times by 2.7 months. But implementation a ASCO to issue y has been slow. Such findings led care in clinical oncolog opinion recproposed by the provisional clinical 2012 New payment reforms y Oncolog integrat ion of palliaof ClinicalN ommending the American Society ENT REGIME one important into standard cancer CANCER TREATM tive care services (ASCO) would remove tis with metasta ntation by allowing care upon diagnos 1 barrier to impleme ng Accordi to sements. ic or advanced cancer. bundled reimbur y ns should regularl patients with cancer ASCO, physicia The majority of is last nt. their prognos for treatme care only in their standardabout gold patients update receive palliative of trials as the about their quality all. Attitudes among ation in clinical and ask bythem healthcare team. pain, days of life, if at patient particip s an experienced ends cancer fatigue,. family member like be handled symptom s accordingly d andrecomm should that NCCN administere patients, be The s, process life and s should Trials: clinician to supClinical provided diagnoly equate t of related adverse events can be a complex are onlytely upon supportive care intervention regimens immedia ly and mistaken modifications and indications/regimens. the managemen anxiety and These still common patient; drug dose the administration, and unapproved individual hospice and dosing, the d explain on ife also end-of-l options based with Administration-approve Cancer therapy selection, treatment care verify sis. Physicians should of its authors regard-away.1 palliative and U.S. Food and Drug include both be underright Clinicians must chooseregimens below may in the are a consensus statement e care judgment t medical r—something to of palliativ treatment The NCCN Guidelines® purpose independen surrende The canceror is expected to use warranties of any kind whatsoever ASCO’s treatment strategies.efforts to prolong as new significant data becomes available. any NCCN Guidelines® Network makes nomore plement the latest than 2 years later, after all that may be refined as often to apply or consult Now, sive Cancer takenareonly ion Any clinician seeking rhetoric a work in progress National Comprehen 1,2 Politica to ltreatment. for early integrat or treatment. The These Guidelines have failed. any patient’s care their application or use in any way. recommendation life,of currently accepted approaches es to determine ing their views e reform circumstanc responsibility for has yet to be comprehealth insuranc individual clinical and disclaims any ding context of surroun of palliative care use, or application nted, and referrals regarding their content, some people’s concerns about hensively impleme indicated. has fueled otherwise plany near the unless care 2A d primaril advance are category care and edations 3 recommen continue to be made 8,9 Note: Allpalliativ 1 with terminal disease. e Disease patients’ lives. of egativ end ning for patientsens for HER2-n refers care requires Regim edreality, palliative care simply r sam rerit PreferrIn Truly patient-centered Et laborum quametu of patients with at alleviating the occulparum Aped the empowe rment to interventions aimed DOSING the rest dolorum, sit, REGIMEN a role in clinical and treatment on 2 day 1 est inum information and effect of disease in 60mg/m IV aborepel 2 of patients • Doxorubic IV day 1 g andbyquality of life phamide 600mg/m Followed by: e AC followed well-bein •s.Cyclophos 4,5 Dose-dens 4 cycles. 2 memberCycled every 14 days for paclitaxel IV infusion day 1 2 and their family 175mg/m via 3-hour with filgrastim support)

FEATURE

Integration Palliative Care e Pressing Ar se rti pe Ex and logists co On for als Go Palliative care is underutilized by oncologists and misunderstood by many patients and their families.

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THERAPY A22 CANCER

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AM 8/29/14 10:35

REVISED

2 IV day 1 • Docetaxel 75mg/m 600mg/m2 IV day 1 support) • Cyclophosphamide for 4 cycles. (All cycles are with filgrastim Cycled every 21 days

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DRUG MONOG

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AC4

The other departments you’ve seen in MPR, such as Newsline, New Products, and Pipeline, will appear in the front of each issue of Cancer Therapy Advisor and will also include sections you might recognize from CancerTherapyAdvisor.com, such as Viewpoints, In the Clinic, and a CME-accredited activity (don’t miss this issue’s report on current and emerging therapies for glioblastoma).

2 IV day 1 • Docetaxel 75mg/m 2 IV day 2 1 head • Doxorubicin 50mg/m TAC5 support) 500mg/m IV day cell carcinoma of the • Cyclophosphamide for 6 cycles. (All cycles are with filgrastimadvanced squamous with 5-FU). Monitor Cycled every 21 days and neck. every platinum-based therapy , infusion over 1hr once , potassium days 1 and 4 Adults: Give by IV2 s (eg, magnesium oral 2 1 and 8 or ℞ electrolyte IV days therapy. . Premedicate with cetuximab acil 500mg/m continuous infusion) after 3 weeks. 75mg/m cin (various) during and • 5-fluorour via 72-hour 2 calcium) IV day 1 (or Bleomy not dose based on tolerability 6,7 in 50mg/m 2 mothers: Nursing 1 corticosteroid. Adjust (Cat.C). FACglycopepti de antibiotic. Bleomycin • Doxorubic Pregnancy 500mg/m IV day labeling); allow neutrophils for • Cyclophosphamide Cytotoxic t and effect (see full ded. al; lyophilized pwd recommen before subsequen 21 days for 6 cycles.mucositis (Grade 15units/vial, 30units/vi administration after Cycled every and platelets to recover ns: Increased l rash, Interactio intrapleura or acneiform IM, IV, SC, cycles. recall syndrome, 2 1–14 PO days d. 3–4), radiation100mg/m disturbances with reconstitution. electrolyte for squamous• Cyclophosphamide Children: Not establishe 2 events, and 1 and 8 cardiac Neutrophil count <1500 s: Palliative treatment in 30mg/m IV2days 1 and 8 Indication Contraindications: e 80. • Doxorubic CAF8 IV days and neck). radiation and cisplatin. itivity to polysorbat 3 cell carcinoma (head SC weekly • 5-fluorouracil 500mg/m : Cutaneous reactions n; cells/mm . Hypersens reactions for 6 cycles. units/kg IV, IM, or Adverse ons: Hepatic dysfunctio 28 days rash, every Adults: 0.25–0.5 Warnings/Precauti impairment: see literature.Cycled (pruritus, nail changes), acneform and/or SGPT >1.5×ULN asthenia, or twice weekly. Renal infection, bilirubin >ULN, SGOT 2 1–14 se diarrhea, increased risk of days PO n, units: phosphata headache, >400 75mg/m alkaline dehydratio , Total doses phamide loss, xerostomia concomitant with • Cyclophos weight 2 1 and 8 reactions ded. Obtain bilirubin, mucositis, toxicity. 60mg/m IV days pulmonary infusion 2 ies; prior >2.5×ULN: not recommen • Epirubicin CEF9 ded. abnormalit IV days 1 and 8dyspnea),for 6 cycles. electrolyte phosphatase values acil 500mg/m asm, 28 days Children: Not recommen Renal impairment. • 5-fluorour AST/ALT, and alkaline eg, bronchosp Cycled every severe: ons: support. (may bezole peripheral blood counts onary arrest, renalWith cotrimoxa Warnings/Precauti to each cycle. Monitor Monitor function. Monitor lung disease, cardiopulm failure, platelets). , pulmonary interstitial sed neutrophils kidney Compromi fever, sepsis, 2 frequently (esp. 1–14 (Cat.D); avoid use. esemia, PO days hypomagn reactions (esp. during 100mg/m function. Elderly. Pregnancy phamide (see full labeling). ded. for hypersensitivity • Cyclophos 2 others embolus; days 1 and 8 pulmonary Pre-existing effusions. nd mothers: not recommen by nephrotoxic Methotrex ate 40mg/m IV Nursing 2 • 1st and 2 infusions). 1 and 8 CMF10 IV daysvials–1 be potentiated How supplied: Single-use neurosensory symptoms Interactions: May • 5-fluorouracil 600mg/m Adjust dose if severe for 6 cycles. a, pain) occur; ℞ drugs. Cycled every 28 days eye (eg, paresthesia, dysesthesi rs Squibb : Erythema, rash, striae, of persist. Monitor for HYDREA Bristol-Mye Adverse reactions discontinue if symptomscystoid macular edema caps. entation, tenderness e if 1 Hydroxyurea 500mg; vesiculation, hyperpigm nail changes, alopecia, in disorders; discontinu Substituted urea. non-taxaneADVISOR osis, alternativeTHERAPY with irradiation therapy s 201X | CANCER the skin, hyperkerat | XXXX(consider use is diagnosed Indications: Adjunct isor.com pneumonitis, pulmonary id) carcinoma Pregnancy (Cat.D; erapyAdv (epidermo stomatitis; Elderly. cell isor.com CancerTh pruritus, on, squamous erapyAdv not chemotherapy). primary | CancerTh ic reaction (hypotensi | XXXX 201X ion); nursing mothers: excluding the lip. fibrosis, idiosyncrat ADVISOR adequate contracept of the head and neck, chills, wheezing). THERAPY fever, as single dose CANCER 80mg/kg 1 confusion, mental recommended. by, other Adults: See literature. supplier. dose. affect, or be affected impairment: reduce rd How supplied: Contact Interactions: May every 3 day. Renal or substrates (eg, ded. inducers, ℞ CYP3A4 inhibitors, Children: Not recommen bone marrow rs Squibb Marked a, ketoconazole, ritonavir). ERBITUX Bristol-Mye Contraindications: : Infections, neutropeni factor receptor blocker. IV Adverse reactions depression. Epidermal growth for a, hypersensitivity/ ons: Previous irradiation l, 200mg/vial; soln anemia, febrile neutropeni before Warnings/Precauti Cetuximab 100mg/via thrombocytopenia, apy. Correct anemia e-free. n, infusion site reactions, therapy or chemother infusion; preservativ dyspnea, constipatio ic, renal, hepatic n with radiation neuropathy, dysgeusia, starting. Monitor hematologtreatment. Marked Indications: In combinatioor regionally advanced fluid retention, asthenia, during locally anorexia, nail disorders, function before and disorders; therapy for treating vomiting, mucositis, of the head and neck Myeloproliferative pain, nausea, diarrhea, renal dysfunction. reactions (eg, ulcerations squamous cell carcinoma with platinum-based vasculitic cutaneous n alopecia, myalgia; myeloid discontinue if cutaneous agents. Elderly. (SCCHN). In combinatio cil (5-FU) for first-line desquamation), acute erythema, edema, develop and use alternative mothers: or therapy with 5-fluoroura and nonseptic), cystoid avoid use. Nursing locoregional disease leukemia, death (septic Pregnancy (Cat.D); treatment of recurrent single agent for recurrent As a macular edema. not recommended. metastatic SCCHN. e vials (1mL, 4mL, didanosine, nt prior of Single-dos failure concomita after How supplied: als Interactions: Avoid or metastatic SCCHN supplies) or other antiretrovir 8mL)–1 (w. diluent, with or without stavudine,[monitor], fatal platinum-based therapy. blocker. Give by IV s H ℞ (may cause pancreatiti neuropathy). Adults: Pretreat with 1 rate: 10mg/min. Initial max hepatotoxicity, peripheral stic TREXALL Teva infusion (use filter); 5mg, 2 once over 2 hours; then potentiate antineopla . Methotrexate sodium n Myelosuppressives dose: 400mg/m Folic acid antagonist antigout agents. Increased over 1 hour. Combinatio 2 scored tabs. effect. May antagonize with interferon therapy. 250mg/m once weekly 1 week prior to initiation ℞ 7.5mg, 10mg, 15mg; dose injection Bedford risk of vasculitic toxicities urease, uricase, lactate therapy: Give initial tion Also: Methotrexate elevated Complete administra for IV, IM, intraMay cause falsely of radiation therapy. te 25mg/mL; soln with therapy Methotrexa ased administration after dehydrogenase. 1 hour prior to platinum-b arterial, or intrathecal : Leukopenia, anemia, t weekly dose for duration Adverse reactions 5-FU. Give subsequen weeks) or until topenia, preservative-free. ℞ thrombocy dilution; ies, Bedford (6–7 for injection erythrocytic abnormalit fever, CNS effects, of radiation therapy toxicity. Also: Methotrexate n or unacceptable IV, IM, intra-arterial, GI upset, rash, erythema, t, acute pulmonary if Grade disease progressio te 1g/vial; pwd for 50% by rate Methotrexa infusion tion after dilution; temporary renal impairmen Permanently reduce reaction or intrathecal administra leukemias, skin cancer. s Grade 3 infusion caps reactions, secondary 3 or 4 1 or 2 and non-seriou preservative-free. gloves when handling ly discontinue if Grade cancers of the head Note: Wear disposable occurs; permanent Indications: Epidermoid Monitor patient during or bottle. serious reaction occurs. Skin toxicity: see full neck. and on. How supplied: Caps–100 and for 1 hr post-infusi Adults: See literature. . labeling. ℞ Children: Not established Nursing ded. Sanofi Aventis Pregnancy (Cat.X). Children: Not recommen Discontinue if TAXOTERE Contraindications: ons: soln Warnings/Precauti Docetaxel 20mg/mL; e with mothers. or interstitial lung Antimicrotubule agent. polysorbat ons: Be fully familiar severe infusion reactions infusion reactions, dilution; contains Warnings/Precauti e if for for IV infusion after before use. Discontinu disease occur. Monitor pulmonary toxicity, alcohol. this drug’s toxicity arrest, 80; diluent contains s occur. Obtain baseline n with cisplatin cardiopulmonary malignant lymphoma n; avoid sun, UV light. Indications: In combinatiotreatment of locally skin inflammation/infectio with irradiation. induction l: reactions and fluorouraci Additive cutaneous 61 (w. irradiation or THERAPY ADVISOR Cardiovascular diseases 2014 | CANCER

I hope you enjoy this new publication—it will be coming to you every other month— and fi nd it useful and relevant in day-to-day clinical decision making. Let me know what you think! You can reach me at nora.ray@haymarketmedia.com. Sincerely,

isor.com | FALL

CancerTherapyAdv

8/27/14 8:47 AM

dd 61

CTA_Premier2014_MB.in

Nora Ray Editorial Director, Haymarket Oncology

CancerTherapyAdvisor.com | FALL 2014 | CANCER THERAPY ADVISOR A3

CTA_EditorsLetter_Fall14_F.indd 3

8/29/14 11:32 AM

EDITORIAL & BUSINESS STAFF

EDITORIAL ADVISORY BOARD

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Nora Ray

Yale Cancer Center  New Haven, CT

Managing Editor Lauren Burke

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E. David Crawford, MD

Editorial Coordinator

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A4 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

LATEST NEWS

The FDA announced the approval of expanded use of Imbruvica (ibrutinib; Pharmacyclics and Janssen Biotech) to treat patients with chronic lymphocytic leukemia (CLL) who carry a deletion in chromosome 17 (17p deletion), for which it was granted Breakthrough Therapy designation. The FDA also approved new labeling to reflect that Imbruvicaâ&#x20AC;&#x2122;s clinical benefit in treating CLL has been verified. The approval was based on a clinical study in 391 previously treated participants, 127 of whom had CLL with 17p deletion. Participants were randomly assigned to receive Imbruvica or Arzerra until disease progression or side effects became intolerable. The trial was stopped early for efficacy after a preplanned interim analysis showed Imbruvica-treated participants experienced a 78% reduction in risk of disease progression or death (progression-free survival). Results also showed a 57% reduction in risk of death (overall survival) in participants treated with Imbruvica. Of the 127 participants who had CLL with 17p deletion, those treated with Imbruvica experienced a 75% reduction in risk of disease progression or death.

Updated Jakafi Labeling Approved by FDA Incyte has announced that the FDA has approved supplemental labeling for Jakafi (ruxolitinib) to include new Kaplan-Meier overall survival curves as well as additional safety and dosing information. The new survival information is based on 3-year data from two pivotal phase 3 trials, COMFORT-I and â&#x20AC;&#x201C;II. This information shows that at 3 years, the probability of survival for patients treated with Jakafi in COMFORT-I was 70% and was 61% for those patients originally randomly assigned to receive placebo. In COMFORT-II, at 3 years the probability of survival for patients treated with Jakafi was 79% and 59% for patients originally randomized to best available therapy.

Zydelig Approved for Three B-Cell Blood Cancers Gilead Sciences has announced that the FDA has approved Zydelig (idelalisib) in combination with rituximab for patients with relapsed chronic lymphocytic leukemia for whom rituximab

alone would be considered appropriate therapy, as monotherapy for patients with relapsed follicular B-cell non-Hodgkin lymphoma and small lymphocytic lymphoma who have received at least two prior systemic therapies. Zydelig is a first-in-class oral inhibitor of PI3K delta, a protein which plays a role in the activation, proliferation, and viability of B cells.

Antiemetic Drug Gains Pediatric Indication Eisai and the Helsinn Group announced that the FDA has approved Aloxi (palonosetron HCl) injection for the prevention of acute nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including highly emetogenic cancer chemotherapy, in children aged 1 month to 17 years. This marks the first approved drug for acute chemotherapy-induced nausea and vomiting (CINV) prevention in patients aged 1 to 6 months. Four pediatric clinical trials were conducted to assess Aloxi as requested by the FDA. The approval was based on a randomized, double-blind, non-inferiority trial comparing single-dose Aloxi 20 mcg/kg IV given 30 minutes prior to chemotherapy vs. ondansetron 0.15 mg/kg IV (standard of care) given 30 minutes prior to chemotherapy followed by infusions 4 and 8 hours after the first dose of ondansetron. Within the first 24 hours after chemotherapy, complete response (defined as no vomiting, no retching, and no antiemetic rescue medication) was achieved in 59.4% of patients who received Aloxi vs. 58.6% of those who received the ondansetron regimen.

Chemotherapy Drug May Cause Alcohol Intoxication The FDA has issued a warning that the intravenous chemotherapy drug docetaxel may cause patients to feel or experience intoxication during and after treatment due to the presence of ethanol in the drug. A revision to the labels of all docetaxel drug products to warn about this risk has been ordered by the FDA. Docetaxel is indicated for the treatment of locally advanced or metastatic breast cancer, advanced gastric adenocarcinoma, locally advanced squamous cell carcinoma of the head and neck, hormone-refractory metastatic prostate cancer, and locally advanced or metastatic non-small cell lung cancer).

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8/28/14 12:35 PM

IN THE PIPELINE Glioblastoma Multiforme Therapy Designated Orphan Drug AbbVie announced that the FDA has granted orphan drug designation to ABT-414, an anti-epidermal growth factor receptor monoclonal antibody drug conjugate, being evaluated for patients with glioblastoma multiforme. ABT-414 is designed to be stable in the bloodstream and only release the potent cytotoxic agent once inside targeted cancer cells. For more information call (800) 633-9110 or visit AbbVie.com.

Acute Myelogenous Leukemia Treatment Designated Orphan Drug Agios Pharmaceuticals announced that the FDA has granted orphan drug designation for AG-221, an oral firstin-class IDH2 mutant inhibitor for the treatment of patients with acute myelogenous leukemia. AG-221 is currently being evaluated in a phase 1 clinical trial in patients with advanced hematologic malignancies that carry an IDH2 mutation. For more information call (617) 649-8600 or visit Agios.com.

Neratinib Demonstrates Potential in Breast Cancer Trial Puma Biotechnology announced results from its phase 3 ExteNET trial of neratinib (PB272) for the extended adjuvant treatment of breast cancer. The ExteNET trial is a double-blind, placebo-controlled trial of neratinib vs.

placebo after adjuvant treatment with Herceptin (trastuzumab; Genentech) in women (n=2821) with early stage HER2positive breast cancer who had undergone surgery and adjuvant treatment with trastuzumab. After completion of adjuvant treatment with trastuzumab, patients were randomly assigned to receive extended adjuvant treatment with either neratinib or placebo for a period of 1 year. Patients were then followed for recurrent disease, ductal carcinoma in situ, or death for a period of 2 years after randomization in the trial. The primary endpoint of the trial was disease-free survival. For more information visit Pumabiotechnology.com.

NSCLC Therapy Granted Breakthrough Therapy Designation Clovis Oncology announced that the FDA has granted breakthrough therapy designation to CO-1686 as monotherapy for the treatment of second-line epidermal growth factor receptor (EGFR) mutantnon-small cell lung cancer (NSCLC) in patients with the T790M mutation. CO-1686 is a novel, oral, targeted irreversible inhibitor of mutant forms of the EGFR for the treatment of non-small cell lung cancer in patients with initial activating EGFR mutations as well as the dominant resistance mutation T790M. The designation was based on interim efficacy and safety results from an ongoing phase 1/2 study of CO-1686. An objective response rate of 64% in 14 of 22 evaluable T790M-positive patients was observed. There was no evidence of systemic wild-type EGFR inhibition. For more information visit ClovisOncology.com.

Mocetinostat Granted Orphan Drug for MDS Mirati Therapeutics announced that the FDA has granted orphan drug designation to mocetinostat, a selective HDAC inhibitor for the treatment of myelodysplastic syndrome (MDS). In addition to the ongoing phase 2 clinical trials, 13 clinical trials have been completed, which enrolled over 400 patients with a variety of hematologic malignancies and solid tumors. Mocetinostat being developed in a phase 2 dose confirmation study in combination with Vidaza as treatment for intermediate and high-risk MDS. Mirati also plans to initiate phase 2 studies of mocetinostat as a single agent in patients with mutations in histone acetyl transferases in bladder cancer and diffuse large B-cell lymphoma. For more information visit Mirati.com.

Elotuzumab Granted Breakthrough Therapy for Multiple Myeloma Bristol-Myers Squibb and AbbVie announced that the FDA has granted breakthrough therapy designation to elotuzumab, for use in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in patients who have received one or more prior therapies. The designation is based on results from a randomized phase 2, open-label study that evaluated two dose levels of elotuzumab in combination with lenalidomide and low-dose dexamethasone in previously treated patients, including the 10 mg/kg dose that is being studied in phase 3 trials. For more information visit BMS.com or AbbVie.com.

A8 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

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8/28/14 11:31 AM

CME ACTIVITY

MediBrief: From Drug Discovery to Clinical Use — The SNO Reporter on Quality Improvement with Current and Emerging Therapies for Patients with Glioblastoma EDUCATIONAL OBJECTIVES: After completing the activity, the participant should be better able to: • Explain how the advent of new combination treatments best supports an improved patient outcome for patients with GBM. • Identify the various novel imaging techniques that may be used to assess the response in patients with glioblastoma treated with antiangiogenic agents. • Describe how the most recently presented personalized and translational oncology research can make an impact on pathology, detection, prevention, and maintenance of GBM. COMPLETE THE POST-TEST: Go to myCME.com/glioblastoma and register.

Release Date: January 2014 Review Date: September 2014 Expiration Date: September 2015 This content was originally published on myCME.com in January 27, 2014. Estimated Time to Complete the Educational Activity: 1.25 hours Program Description: MediBrief: From Drug Discovery to Clinical Use -The SNO Reporter on Quality Improvement with Current and Emerging Therapies for Patients with Glioblastoma is a certified, opt-in, educational activity that briefly provides the busy U.S. clinician with summarized information of the key issues from the 2013 meeting of the Society for NeuroOncology. All information is prepared in brief, but concise and clinically accurate portions that are sensitive to the time constraints of busy clinicians. Additionally, each key issue is accompanied by suggested summary options that clinicians may digest and apply to real-life practice for personalized tumor care in an era of emerging data. Intended Audience: The primary target audience for this activity is U.S.based community medical oncologists, neuro-oncologists and neurosurgeons. The education will also, adult-learning-wise, be appropriately designed so that oncologists may share this information with the interdisciplinary healthcare team involved in the care of cancer patients. Faculty: N/A Accreditation Statement: Global Education Group is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Designation Statement: Global Education Group designates this enduring activity for a maximum of 1.25 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

related to the content of this activity. All identified conflicts of interest are thoroughly vetted by Global for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations. Planners and Managers Disclosures: Ashley Marostica, RN, MSN, Amanda Glazar, PhD, and Chirag Patel, PharmD, report nothing to disclose. Disclosure of Unlabeled Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. Global Education Group (Global) does not recommend the use of any agent outside of the labeled indications. Disclaimer: Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed in this activity should not be used by clinicians without evaluation of patient conditions and possible contraindications on dangers. Method of Participation: There are no fees for participating in this CME activity. To receive credit during the period January 2014 to September 2015, participants must (1) read the learning objectives and disclosure statements, (2) study the educational activity, and (3) complete the pre-test, post-test and activity evaluation form, including the certificate information section. To obtain a certificate, participants must receive a score of 70% or better on the post-test. The post-test can be accessed at myCME.com. If you have any questions relating to the accreditation of this activity, please contact Global Education Group at 303-395-1782 or inquire@globaleducationgroup.com. If you have any questions relating to other issues with this activity, please contact myCME.Support@haymarketmedical.com.

Disclosure of Conflicts of Interest: Global Education Group (Global) requires instructors, planners, managers and other individuals and their spouse/life partner who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as

A10 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

This activity is provided by Global Education Group.

CME ACTIVITY

Quality Improvement with Current and Emerging Therapies for Patients with Glioblastoma Reports from the 2013 Society for Neuro-Oncology (SNO) Annual Meeting discuss how newly discovered drugs for treating glioblastoma are moving into clinical practice.

ď ľABSTRACT AI-001 S1P: An alternative antiangiogenic target in GBM A nt i-a ng iogen ic t herapies have moved into the forefront of glioblastoma (GBM) targeted management, especially following the success of anti-vascular endothelial growth factor (VEGF) treatment in increasing progression-free survival (PFS) and quality

MICHELE GRAHAM

Angiogenesis is a hallmark of glioblastoma, as demonstrated in this image.

of life for patients. However, with the recurrence of GBMs, anti-V EGF treatment seems inadequate at blocking glioma induced angiogenesis single-handedly. Sphingosine-1-phosphate (S1P), a known pro-angiogenic lipid molecule formed by the enzyme sphingosine kinase 1 (Sphk1), has been shown to contribute to breast cancer induced angiogenesis. High SphK1 expression has been demonstrated in two independent studies to predict

an unfavorable prognosis in GBM. Nevertheless, S1P data in GBM and its role in angiogenesis remain limited. In this analysis, Abuhusain and colleagues further investigate SIP as an alternative anti-angiogenic target in GBM [Abuhusain 2013; abstr AI-001]. The authors measured the levels of SphK1 and S1P in normal grey matter (NGM; n=20), diffuse astrocytomas (AII; n=26), anaplastic astrocytomas (AIII; n=10), and GBM (n=20) tissue

CancerTherapyAdvisor.com | FALL 2014 | CANCER THERAPY ADVISOR A11

CME ACTIVITY samples using quantitative PCR and liquid chromatography-mass spectrometry (LC-MS), respectively. Cell based assays examining angiogenesis were performed, targeting SphK1 with siRNA and selective SphK1 inhibitors, including a stereoisomer control. An independent cohort of 47 GBM tissue samples, 43 matched GBM plasma samples, and 21 normal plasma samples were analyzed for S1P and correlation with patient survival outcomes were observed. S1P levels and SPHK1 expression were significantly elevated in gliomas compared to NGM. Plasma S1P levels are significantly elevated in GBM compared to normal healthy controls (p<0.001; Figure 1). Knockdown of SphK1 with siRNA and inhibitor, but not stereoisomer control, affected U87MG induced angiogenesis for HMEC-1 cell lines significantly. S1P in GBM tissue was elevated in short-term survivors, but was not statistically significant. KaplanMeier survival graphs for S1P levels in GBM tissue and plasma illustrated

an association between poor survival outcome and high S1P levels (P<0.05). VEGF levels were similar between all treatment groups, which were confirmed by VEGF ELISA. In summary, the results suggest that S1P is significantly elevated in GBM, a highly vascular tumor, compared to normal healthy controls. S1P inhibition requires tumor-induced angiogenesis in vitro. Inhibition of U87MG-induced angiogenesis occurs despite normal VEGF levels. High S1P levels in GBM tissue and plasma correlated with a poor survival outcome for patients; however, the potential role of S1P as a marker for survival requires further validation. S1P shows promising potential as an anti-angiogenic target and further research is warranted in assessing the efficacy of combining S1P and VEGF inhibitors, both in vitro and in vivo, in treating GBMs. Suggested Options for Practice • S1P levels and SPHK1 expression may be significantly elevated in GBM tissue compared to normal tissue

FIGURE 1. S1P Levels and SPHK1 Expression

S1P

SphK1 mRNA/18S rRNA

pmoles/mg tissue

SPHK1

100

0.1

0.01

0.1 NGM AII AIII GBM

Plasma S1P 1.5

pmoles/µl

1.0

0.5

0.0 NGM AII AIII GBM

Normal

A12 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

GBM

• Moving forward, validating the association between survival outcomes with the correlation of S1P levels in GBM tissue and plasma will be critical

ABSTRACT AI-004 Treatment Of GBM Xenograft Tumors With A Thrombospondin Mimetic Peptide, ABT-898: Comparison To Bevacizumab Anti-angiogenic therapy with bevacizumab, a monoclonal antibody toward VEGF-A, has demonstrated shortterm efficacy in many patients with GBM. Unfortunately, not all patients respond to treatment and of those who do respond, development of a more aggressive recurrent tumor phenotype has been reported. In this analysis, investigators Bae et al examine the anti-angiogenic effects of a recently developed thrombospondin-1 mimetic peptide (ABT-898) on brain microvessel endothelial cells (ECs) and on GBM xenograft tumors generated by intracerebral xenograft of patient-derived GBM neurospheres into nude mice [Bae 2013, abstr AI-004]. The primary objective of this study is to compare the anti-angiogenic and tumor cell invasion effect of ABT-898 to that of bevacizumab. Quantification of whether the stromal cell response participates in the phenotypic change of tumor cells by bevacizumab, Iba1+ activated microglial/macrophage response was evaluated. ABT-898 treatment inhibited tubulomorphogenesis of ECs in collagen gels in a dose- and CD36-dependent manner, and ABT-898 induced apoptosis of ECs in a dose-dependent manner. ABT-898 treatment of xenograft tumors (80 mg/ kg/day i.p.) significantly inhibited angiogenesis, increased TUNEL positivity,

CME ACTIVITY and prolonged mouse survival. Unlike bevacizumab-treated GBM xenografts, ABT-898-treated tumors did not exhibit increased invasive foci. Bevacizumabtreatment increased the number of Iba1+ cells in the tumor core and created a wider peri-tumoral rim composed of Iba1+ cells as compared to the vehicle-treated and ABT-898-treated tumors. Currently underway is the quantification of the chemokine and pro-inflammatory molecules secreted by Iba1+ cells in the two treatments vs. control. In conclusion, ABT-898 is an anti-angiogenic agent that prolongs survival of mice bearing GBM xenografts without inducing an invasive phenotype. Current evidence suggests a correlation between the number of Iba1+ activated microglial/ macrophages and glioma invasiveness. The reduced recruitment of Iba1+ cells to the tumor center with ABT-898 vs. bevacizumab likely contributes to the absence of an invasive phenotype with ABT-898. The authors hypothesize that ABT-898 inhibits Iba1+ cell recruitment to the tumor through a CD36-mediated mechanism. Knowing that bevacizumab may promote the invasive phenotype of tumor cells and has not shown to provide any long-term survival benefit for patients, these preliminary data are promising and suggests that ABT-898 may offer a novel advantage over bevacizumab as an anti-angiogenic therapeutic option. Suggested Options for Practice • Preliminary evidence in mice bearing GBM xenografts suggests that ABT-898 may have the potential to prolong survival without inducing an invasive phenotype as seen with anti-angiogenic agents such as bevacizumab • Moving forward, ABT-898 may have a potential therapeutic advantage over bevacizumab as a CD36-mediated antiangiogenic agent that inhibits Iba1+ cell recruitment to the GBM tumor center

ABSTRACT AI-032 Anti-Angiogenic Efficacy Of Bevacizumab Alone And In Combination With A Dual PI3K/ mTOR Inhibitor In An Orthotopic Model Of Malignant Glioma: A Multimodal Neuro-Imaging Approach Current evidence suggests that malignant gliomas can elude anti-angiogenic therapy with bevacizumab and may develop resistance via activation of complex molecular escape mechanisms (MET signalling cascade and/or the mTOR/PI3K pathway). Therefore, it is critical to evaluate novel combination treatment strategies in order to improve therapeutic outcomes. In this analysis, O’Halloran and colleagues analyze the anti-angiogenic efficacy of bevacizumab alone and in combination with a dual PI3K/mTOR inhibitor in an orthotopic model of malignant glioma [O’Halloran 2013; abstr AI-032]. The objective of this study is to mechanistically interrogate changes in tumor vasculature and proliferation after combination with bevacizumab and a PI3K/ mTOR inhibitor employing multi-modal imaging (PET, MRI, BLI). Human U87 glioma-luc cells were implanted into the cortex of nude mice (n=28). Animals were randomized as follows: Control; PIK3/ mTOR inhibitor (BEZ235) (45mg/kg p.o., daily 5/7, 2/7 off); bevacizumab (10mg/kg i.p., alternate days 12/7); combination. Pre- and post-treatment MRI [ADC; T2 and T2 with and without Very Small Superparamagnetic Iron Oxide Particle (VSOP)] was performed. PET, employing [18F]FET and [18F] FLT analyses was also implemented. Histological analyses comprised of Ki67, vWF, and TUNEL. A significant survival benefit was seen in the bevacizumab alone (p=0.0007)

and combined (p=0.0007) groups. Mice that were only treated by combination and bevacizumab showed a delayed tumor growth compared to PI3K/mTOR monotherapy (p=0.0404 and p =0.0253, respectively). T2WMRI revealed that overall the mice in the combined group had a significant reduction in tumor size (p=0.045) than compared to bevacizumab alone group. Vessel size index and vessel density index determined by MRI and [18F] FET revealed combination therapy significantly impacted tumor vessel formation vs. bevacizumab alone (p=0.005). Despite similar [18F]FLT uptake in the bevacizumab/combined groups, histological analyses showed a reduction of Ki67 staining and vWF positive endothelial cells in bevacizumab/combined groups. In summary, the results suggest that combined/bevacizumab group provides improved overall survival. Significant reduction in tumor size and vessel density was evident in the combined group vs. bevacizumab alone, which likely indicates that combined treatment has a greater effect on the microvasculature than bevacizumab alone. Hence, the combination of bevacizumab and dual PI3K/mTOR inhibitor therapy represents a novel treatment approach in the management of patients with malignant gliomas. Further investigation is warranted to validate the preliminary findings. Suggested Options for Practice • Preliminary evidence in mice suggests that tumor size and vessel density are significantly reduced by combination treatment of bevacizumab with PI3K/mTOR vs. bevacizumab treatment alone • Moving forward, the combination of bevacizumab and a dual PI3K/mTOR inhibitor may potentially represent a novel therapeutic strategy for the management of patients with malignant gliomas

CancerTherapyAdvisor.com | FALL 2014 | CANCER THERAPY ADVISOR A13

CME ACTIVITY ABSTRACT MR-006 Final Results Of A SingleInstitution Phase II Trial Of Radiation (RT), Temozolomide (TMZ), Erlotinib And Bevacizumab For Initial Treatment Of Glioblastoma (GBM) Glioblastoma (GBM) acounts for the majority of primary malignant brain tumors in adults. The epidermal growth factor receptor (EGFR) and VEGF pathways are both frequently overactive in GBM. Evidence suggests that the addition of erlotinib, an EGFR inhibitor, to radiotherapy (RT) and temozolomide (TMZ) provides modest improvement in survival. In this analysis, Clarke and colleagues combined bevacizumab, a VEGF inhibitor, and erlotinib with standard RT and TMZ, with the goal of improving overall survival (OS) in newly diagnosed patients with GBM [Clarke 2013; abstr MR-006]. This was a single-arm, single-institution phase II trial. Patients aged ≥18 years, newly diagnosed GBM and KPS ≥60 were eligible for the study. The primary objectives were OS and PFS from initial diagnosis. Secondary objective was safety analysis on the combination of TMZ, bevacizumab and erlotinib. Treatment consisted of

TABLE 1. Safety Profile GRADE

Lymphopenia

53%

12%

—

Thrombocytopenia

14%

—

Neutropenia

—

Infection

11%

Weight loss

11%

—

Diarrhea

12%

—

Fatigue

—

fractionated RT to 60 Gray, with daily TMZ at 75 mg/m2/d and erlotinib 150200 mg/d [or 500-600 mg/d for patients on enzyme-inducing antiepileptic drugs (EIAEDs)]. Bevacizumab was given at 10 mg/kg every 2 weeks, starting ≥ 4 weeks after surgery. After RT, adjuvant TMZ was given at 200 mg/m2/d × 5d per 28d cycle, with unchanged erlotinib and bevacizumab doses. Treatment was continued until progression or for 12 months (up to maximum 24 months). Efficacy was compared against institutional historical controls (N=133) treated on prospective phase II trials. 59 patients were enrolled into the primary efficacy cohort after 15 patients were treated on safety lead-in adding bevacizumab and erlotinib to adjuvant TMZ. For the efficacy group, median age was 54 years; median Karnofsky performance score (KPS) was 90. 15 patients had tumors with methylated MGMT (mMGMT), 26 with unmethylated (umMGMT), and 18 with unknown status. Median OS was 19.8 months (vs. 18 months, p= 0.33) and median PFS was 13.5 months (vs. 8.6 months, p= 0.03). Median OS in patients with mMGMT was 20.6 months vs. 17.5 months in patients with umMGMT. Patients whose tumors were both umMGMT and EGFR amplified (N=18) demonstrated improved PFS and a trend toward improved OS vs. historical controls (p = 0.0004 and p = 0.12, respectively). The most frequent related grade 3/4 AEs was lymphopenia, thrombocytopenia, neutropenia, diarrhea, weight loss, and fatigue (Table 1). 1 patient died of disseminated aspergillosis. In conclusion, the results of this phase II analysis suggest that the combination of bevacizumab, erlotinib, TMZ and RT is well-tolerated and demonstrated improved PFS but not OS vs. historical controls in a molecularly unselected GBM population. The combination may

A14 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

be potentially promising for patients whose tumors are EGFR amplified and MGMT unmethylated; however, this is a subset analysis and the results must be interpreted with caution. Suggested Options for Practice • The combination of bevacizumab, erlotinib, RT and TMZ does appear to provide improved PFS but does not provide OS benefit vs. historical GBM controls • Moving forward, combination of bevacizumab, erlotinib, RT and TMZ may be well tolerated and possibly beneficial for a subgroup of GBM patients with both umMGMT and EGFR amplification; however, further research is warranted for survival benefit

ABSTRACT MR-007 A Phase 1 Study Of Repeat Radiation, Minocycline, And Bevacizumab In Patients With Recurrent Glioma (RAMBO) Currently, no effective therapeutic options exist for patients with recurrent GBM after disease progression on bevacizumab. Pre-clinical data indicates that a potential mechanism of treatment resistance in recurrent GBM is from a mesenchymal shift due to microglia-mediated NF-κB activation. Minocycline has shown to inhibit NF-κB activation and reduce radiation resistance in GBM stem cell models in vitro and in vivo. Also, minocycline crosses the blood-brain barrier, which may be able to sensitize bevacizumab resistant GBM to re-irradiation. In this analysis, investigators Cohen and colleagues investigate the combination of repeat radiation, minocycline and bevacizumab in patients with recurrent GBM [Cohen 2013; abstr MR-007]. In this phase 1 study of re-irradiation, bevacizumab and minocycline in patients with recurrent GBM (RAMBO

CME ACTIVITY trial), adults with recurrent gliomas who have progressed on bevacizumab were eligible for the study. A 3+3 design was used with planned cohorts of 100 mg PO BID (cohort 1), 200 mg (cohort 2), and 400 mg PO BID (cohort 3) of minocycline. The primary objective is to establish the safety of adding minocycline to a commonly used combination of bevacizumab and repeat radiation. 6 patients were accrued to cohort 1, and 2 patients have been accrued to cohort 2 to date. No dose limiting toxicities have been encountered. No grade 3 toxicities unrelated to tumor progression have been seen other than one case of asymptomatic hypertension attributed to bevacizumab. Grade 2 toxicities include: 3 cases of fatigue; 1 case of anemia; 1case of hiccups; 3 cases of hypertension; 1 case of intracranial hemorrhage; 1 case of nausea; 1 case of thrush; 1 case of vertigo. Nausea, fatigue, and thrush were the only toxicities possibly thought to be minocycline-treatment related. 2 patients withdrew due to clinical progression during re-irradiation and went to hospice, and one person dropped out after 1 week due to unwillingness to take antiemetics for grade 1 nausea. Of the 3 patients from cohort 1 who completed re-irradiation, 2 are alive and progression free 6 months later. The maximum tolerated dose (MTD) has not been reached, and enrolment is ongoing. In conclusion, the analysis from the phase 1 RAMBO trial suggests that the treatment combination of minocycline, bevacizumab and re-irradiation is a tolerable and promising therapeutic approach for recurrent GBM. The optimal minocycline dose has not yet been established but this study serves as a pilot for a larger study to validate the safety and efficacy of the combination in patients with GBM who have limited options after disease progression on bevacizumab.

Suggested Options for Practice • Preliminary data from the RAMBO study indicates that the addition of minocycline to the common regimen of bevacizumab and re-irradiation is tolerable • Moving forward, the combination of minocycline, bevacizumab and re-irradiation may provide a promising therapeutic approach to treating patients with recurrent GBM who currently have no options after progressing on bevacizumab. However, MTD of minocycline must be established first in the ongoing analysis of RAMBO

ABSTRACT MR-024 Survival Outcomes And Prognostic Considerations Of Stereotactic Radiosurgery In The Treatment Of Recurrent Malignant Gliomas With And Without Bevacizumab Glioblastoma is associated with poor prognosis, severe neurological symptoms, cognitive deficits and impaired health-related quality of life (HRQoL). Salvage therapy involving combinations of surgery, RT, chemotherapy, or targeted therapy has shown to offer minimal survival benefit in recurrent GBM. Stereotactic radiosurgery (SRS) delivers high therapeutic doses of radiation to a specific target while minimizing dose toxicity to normal tissue; however, has not proven beneficial in the management of newly diagnosed GBM. Bevacizumab may also give an additional benefit to SRS. In this analysis, Rashed et al evaluate the survival outcomes and prognostic considerations of SRS in the treatment of recurrent GBM with and without bevacizumab [Rashed 2013; abstr MR-024]. This was a single-institution, retrospective study of 39 patients with recurrent malignant glioma treated

with SRS alone or with bevacizumab. Primary lesions were treated with 50.460 Gy of fractionated RT in all patients. SRS dose was 25 Gy in 5 fractions over a week. The primary objectives were to assess the OS and PFS from SRS. Also, other evaluations included age, gender, lesion volume and location, dexamethasone use, pre-SRS chemotherapeutic and surgical interventions, and bevacizumab use. Follow-up MRI scans were at 2-month intervals. Initial diagnosis was GBM in 25, gliomatosis cerebri 1, anaplastic astrocytomas (AA) 2, oligodendromas (OD) 6, anaplastic oligodendromas (AO) 4, anaplastic oligoastrocytomas (AOA) 1, and epithelial ependyoma (EE) 1. Six-month PFS and 12-month OS were 51.4% and 48.7%. Median PFS and OS were 5.51 and 12.3 months. GBM and AA had a statically significant OS of 9.5 months compared to 28.5 months for OD, AOD, and EE (p<0.001). OS and PFS were 13.1 months and 4.6 months without bevacizumab, 8.9 months and 4.6 months with pre-SRS bevacizumab, and 9.2 months and 6.1 months for postSRS bevacizumab (p=0.130). Hence, no statistically significant difference was observed in the presence or absence of bevacizumab. There was less dexamethasone use in patients receiving bevacizumab. OS was 18.1 months for age <40 years vs. 10.6 months for ages >40 (p=0.226). OS was 15.2 months for males vs. 9.5 months for females (p=0.0612). Frontal and temporal lobe recurrences had OS of 13.1 months and 12.3 months while parietal and thalamic lesions showed OS of 9.2 months and 8.7 months. OS was 18.7 months for tumor volumes <10cc and 9.2 months for lesions >10cc (p<0.002). Statistical analysis showed a linear correlation between post-SRS PFS and OS, suggesting PFS to be a valuable predictive index of survival.

CancerTherapyAdvisor.com | FALL 2014 | CANCER THERAPY ADVISOR A15

CME ACTIVITY In conclusion, bevacizumab conferred no survival advantage when added to SRS, however, it was found to decrease steroid use. Younger age, smaller lesions, female gender, and frontal lobe lesions fared better. This was a retrospective MRI review, and not a randomized study, hence it may not reflect the actual PFS measurements based on radiographic assessments during active surveillance. Further research is warranted upon the initial results of this study. Suggested Options for Practice • The addition of bevacizumab to SRS does not provide a statically significant survival advantage but may be useful in decreasing steroid use burden • Moving forward, larger randomized controlled studies are warranted to validate PFS and OS measurements in the individuals that fared better in this study with the addition of bevacizumab to SRS

ABSTRACT NO-014 Randomized, Phase IIIB Trial Evaluating Standard-Of-Care (SOC) Therapy With/Without Bevacizumab Continuation Beyond Disease Progression (PD) In Patients With Glioblastoma After First-Line Radiotherapy, Temozolomide And Bevacizumab (RT/T+BEV): Trial Rationale And Design After surgical resection, the current standard of care (SOC) for newly diagnosed GBM is TMZ concurrent with, and adjuvant to RT. While the SOC therapy has shown extended survival, GBM eventually recurs or progresses in almost all patients and further advances are still needed. Bevacizumab (BEV), a VEGF agent, is effective in newly diagnosed and recurrent GBM, and is associated with

stable/improved health-related quality of life (HRQoL) and reduced corticosteroid requirements. Based on its mode of action, continuing bevacizumab through multiple lines (TML) of therapy may provide additional benefits vs. stopping BEV at PD. A phase III study in colorectal cancer validated this approach, reporting longer PFS and OS when BEV plus chemotherapy was continued beyond first PD vs. chemotherapy alone [Bennouna 2013]. In this Phase IIIb (TAMIGA; MO28347)) study, Brandes et al present the trial design and rationale for SOC therapy with or without BEV continuation beyond PD in patients with GBM after first-line RT/T + BEV [Brandes 2013; abstr NO-014]. TAMIGA is a double-blind, placebo-controlled, randomized (at first PD), two-arm, multicenter, phase IIIb trial. The primary endpoint is superiority in OS, from randomization to continuous BEV plus SOC versus placebo plus SOC beyond first PD. Secondary endpoints include: PFS, 6-, 12- and 18-month OS, HRQoL, neurocognitive function and safety. Eligible patients included patients with newly diagnosed/histologically confirmed GBM, who previously were not treated with chemotherapy or RT. The target enrolment (n=510) will receive: firstline RT/T+BEV; T+BEV maintenance (x6); and single-agent bevacizumab until first PD (AVAglio regimen; Chinot 2013]. At PD, approximately 300 patients will be randomized to receive second-line BEV plus lomustine or receive placebo plus lomustine, with stratification based on: planned second-line SOC; performance status; time to PD during firstline treatment. At second PD, patients will continue to receive third-line BEV, or placebo, plus investigator’s choice of therapy (irinotecan, fotemustine, TMZ, carboplatin, etoposide, best supportive care). At third PD, patients have the following options: 1) BEV/placebo

A16 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

continued through subsequent lines of treatment at the investigator’s discretion in the absence of unacceptable toxicity or consent withdrawal; 2) Open-label BEV treatment after the third PD; 3) Investigational drugs which mandates discontinuation of BEV/placebo. Response will be assessed by modified Response Assessment in Neuro-Oncology Working Group criteria to minimize the impact of pseudoprogression. In summary, the authors present the phase IIIb (TAMIGA; M028347) study rationale and design. There is an unmet need for improved therapies to treat patients with recurrent GBM. Bevacizumab may continue to benefit patients with GBM beyond progression as shown in the treatment of metastatic CRC; hence, BEV has the potential to improve survival in GBM and provide a new treatment option. The TAMIGA trial is currently recruiting patients. Suggested Options for Practice • The TAMIGA study will provide critical data on the clinical benefit of continuing BEV beyond disease progression in patients with GBM as the benefit has been demonstrated in the treatment of mCRC • Moving forward, although OS is a gold standard endpoint, the design of the TAMIGA study acknowledges the importance of other measures of clinical benefit to support OS, such as PFS, HRQoL and neurocognitive function

ABSTRACT NO-016 Dual Phase I/II Study Of TH-302 And Bevacizumab In Recurrent Glioblastoma Following Bevacizumab Failure Glioblastoma (GBM) remains an incurable malignancy with poor survival despite resection and chemoradiation.

CME ACTIVITY

RANDOMIZATION

PRESURGERY 1 2

Placebo

TH-302 (575 mg/m2, single dose)

SURGERY + SAMPLING

FIGURE 2. Study Design

NO RANDOMIZATION OR SURGERY

Median PFS of patients with GBM who progress on bevacizumab and subsequently start a bevacizumab-containing regimen is approximately 1.2â&#x20AC;&#x201C;2 months [Quant 2009; Iwamoto 2009]. Preclinical studies have shown that antiangiogenic treatment leads to increased hypoxia and invasiveness. Given the hypoxic nature of GBM and potential increase of hypoxia by bevacizumab, the use of agents that have specific activity in the hypoxic tumor environment may benefit patients who have failed single-agent bevacizumab therapy. TH-302 is an investigational hypoxia-targeting prodrug that once activated releases the DNA cross-linking agent bromo-isophosphoramide mustard (Br-IPM). Investigators Brenner et al evaluate TH-302 in combination with bevacizumab in patients with recurrent GBM following bevacizumab failure [Brenner 2013; abstr NO-016]. This is a dual phase I/II, single center, dose-escalation, prospective study with randomization (2:1) with TH-302 single dose (575 mg/m2) vs. placebo administered pre-operatively (cohorts 1-3 only), followed by postoperative combination therapy of bevacizumab at 10 mg/kg every 2 weeks and TH-302 dose escalated 240-670 mg/m2 every 2 weeks (4 week cycle) until PD. Primary objectives are to determine the extent by which TH-302 is able to penetrate the BBB and affect

BEVACIZUMAB + TH-302 COHORT

NO.

POST-OPERATIVE TH-302 DOSE

3-6

240 mg/m2

3-6

340 mg/m2

3-6

480 mg/m2

3-6

480-670 mg/m2

tumor tissue, assess safety of the combination of TH-302 and bevacizumab, and to determine the maximum tolerated dose and dose-limiting toxicity (DLT). Secondary endpoint included the determination of PFS. Tumor assessments are performed after every even cycle during treatment. Resected tumor tissue was evaluated for hypoxia. 19 patients have been enrolled with 14 randomized and initiated TH-302 at doses of 240-480 mg/m2 plus bevacizumab in cohort 1, cohort 2 or cohort 3 (Figure 2). An additional 5 patients proceeded directly to combination therapy. 2 patients withdrew consent after surgery and 3 failed to recover sufficiently

to meet ongoing eligibility criteria so 9 of the 14 randomized patients received combination therapy of TH-302 plus bevacizumab, and 14 overall including the 5 patients without surgery. No DLTs (defined as occurring during Cycle 1) have been reported to date. No grade 4 AEs were observed at any dose. Two grade 3 AEs were observed at 340 mg/m2 and 670 mg/m2 of skin ulceration (second cycle) and thrombocytopenia (third cycle) respectively. 14 patients (mean age, 53.8 years) were evaluable for response, with 1 complete response (CR), 2 partial responses (PR), and 7 with stable disease (SD) (Table 2). The longest disease stabilization is currently ongoing at 22 months with the patient currently receiving Cycle 26. The median PFS for patients on TH-302 plus bevacizumab was 86 days (2.8 months). Histological assessment of resected tumors demonstrated extensive areas of hypoxia. Partial least square discriminant analysis from MR-spectra showed significant differences in metabolites before treatment and at progression. In conclusion, in patients with recurrent GBM following bevacizumab failure, TH-302 has a manageable safety

TABLE 2. Patientâ&#x20AC;&#x2122;s Progression Times, Prior Treatments and Best Responses PATIENTS EVALUABLE FOR RESPONSE (N=14)

MEDIAN

MEAN

RANGE

Age (years)

53.8

(43-70)

Number of Prior Therapies

2.8

(2-4)

72.5

100.7

(28-272)

Time from Surgery to C1D1 (days) (N=9)

(21-41)

PFS on TH-302 + Bevacizumab (days)

150

(59-681)

OS on TH-302 + Bevacizumab (days)

111

183

(64-681)

PFS 1st Bevacizumab Regimen (days)

3-month PFS on TH-302 + Bevacizumab (%) Best Response Clinical Benefit Rate

46% (95% CI: 18%-74%) 1 CR, 2 PR, 7 SD, 4 PD 71.40%

CancerTherapyAdvisor.com | FALL 2014 | CANCER THERAPY ADVISOR A17

CME ACTIVITY profile when used in combination with bevacizumab, with no DLTs observed at doses up to 670 mg/m2 every 2 weeks. Most AEs were mild and involved the mucosa, and were managed with conservative measures. Also, the longer PFS observed with the combination treatment in this analysis vs. the previously reported 1.2–2.0 months following a second bevacizumab regimen suggests clinical activity of the combination therapy in recurrent GBM after initial bevacizumab failure. The observed extensive tumor hypoxia may allow for hypoxia identification based on an endogenous marker. The dose escalation is ongoing with planned expansion at the MTD. Suggested Options for Practice • In patients with recurrent GBM following bevacizumab failure, preliminary data suggests that TH-302 has a manageable safety profile when used in combination with bevacizumab • Moving forward, combination of TH-302 with bevacizumab for treatment of recurrent GBM in patients who have failed bevacizumab may potentially provide clinically relevant improved PFS

ABSTRACT NO-080 Phase II Study Of Panobinostat In Combination With Bevacizumab For Recurrent Glioblastoma Despite treatment with the current standard of care therapies, patients with newly diagnosed GBM exhibit dismal prognoses. Bevacizumab is commonly used to treat recurrent GBM; however, responses are generally not durable and additional therapeutic options are needed [Norden 2008]. Panobinostat is a histone deacetylase inhibitor with anti-neoplastic and anti-angiogenic

TABLE 3. Grade ≥3 Toxicities Possibly, Probably or Definitely Associated with Panobinostat and/or Bevacizumab GRADE 3

GRADE 4

Lymphopenia

2 (8.3%)

Neutropenia

2 (8.3)

1 (4.2%)

2 (8.3%)

Hypophosphatemia

3 (12.5%)

ALT elevation

2 (8.3%)

Fatigue

1 (4.2%)

Hypertension

1 (4.2%)

QT interval prolongation

1 (4.2%)

Weight loss

1 (4.2%)

Pulmonary embolism

1 (4.2%)

CNS hemorrhage

1 (4.2%)

Hematologic

Thrombocytopenia

Non-Hematologic

effects in GBM and may work synergistically with bevacizumab [Drappatz 2012]. In this Phase II analysis, Lee and colleagues evaluate panobinostat in combination with bevacizumab in patients with recurrent GBM [Lee 2013; abstr NO-080]. This was a multicenter, single-arm, phase II study in patients with recurrent GBM. Adults ≥18 years old, life expectancy ≥8 weeks, KPS ≥60, and histologically confirmed glioblastoma with no prior anti-VEGF treatment were eligible for the study. The primary endpoint was 6-month PFS (PFS6) and the study was powered to discriminate between a 35% and 55% PFS6 rate (85% power at an alpha level of 0.07). Secondary objectives included determination of median PFS, median OS, and safety. Patients were treated with oral panobinostat 30 mg three times per week, every other week, in combination with bevacizumab 10 mg/kg every other week until PD or unacceptable toxicity.

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13 of the first 21 participants accrued has progressed within 6 months. At interim analysis, the study did not meet criteria for continued accrual and the study was closed. A total of 24 patients with GBM were accrued prior to study closure. Median age was 53 (range 22-66), median KPS was 85% (60%-100%), and median number of prior recurrences was 1 (range 1-3). PFS6 rate was 30.4% [95% CI 12.4%, 50.7%], median PFS was 5 months [95% CI 3 months, 9 months], and median OS was 9 months [95% CI 6 months, 19 months]. Radiographic responses by RANO criteria included 7 PR (29.2%), 14 SD (58.3%), and 3 PD (12.5%). The most common grade 3 or higher toxicities included hypophosphatemia (12.5%), thrombocytopenia (12.5%), lymphopenia (8.3%), neutropenia (8.3%), and ALT elevation (8.3%). There was one grade 4 CNS hemorrhage (4.2%) and one grade 4 pulmonary embolism (4.2%) (Table 3).

CME ACTIVITY In conclusion, the addition of panobinostat to bevacizumab in recurrent GBM did not meet the statistical endpoint, although it was reasonably well tolerated, and may not significantly improve PFS6 compared to historical controls of bevacizumab monotherapy. At study closure, 4 patients were still on active study treatment and no patients withdrew consent for participation on study. Suggested Options for Practice • For patients with recurrent GBM, the addition of panobinostat to bevacizumab may not significantly improve PFS6 • Moving forward, the addition of panobinostat to bevacizumab is reasonably well-tolerated; however, further larger study confirmation is needed on improvement of PFS6 measurements compared to historical controls of bevacizumab monotherapy

FIGURE 3. AVAglio Study Design RT 2Gy 5 days/week n=463

Debulking surgery or biopsy

Randomization N=921 Stratification • RPA class • Region

n=458

Treatment start 4-7 weeks post-surgery

TMZ 75mg/m2 qd

TMZ 150-200mg/m2 qd days 1-5 q28d

Placebo q2w

RT 2Gy 5 days/week

Placebo q3w

TMZ 75mg/m2 qd

TMZ 150-200mg/m2 qd days 1-5 q28d

BEV 10mg/kg q2w

Concurrent phase 6 weeks

Treatment break 4 weeks

Maintenance phase 6 cycles

BEV 15mg/kg q3w

Monotherapy phase until PD

TABLE 4. Summary of Treatment Exposure BEV + RT/TMZ (N=461)

PLACEBO + RT/TMZ (N=450)

Patients completing ≥90% of planned RT doses, n (%)

442 (95.9)

430 (95.6)

Patients completing ≥90% of planned concurrent TMZ doses, n (%)

414 (89.8)

404 (89.8)

Patients completing 6 cycles of maintenance TMZ, n (%)

298 (64.6)

166 (36.9)

Patients completing 6 cycles of maintenance BEV, n (%)

310 (67.2)

178 (39.6)

Median BEV doses (range)

19 (1-59)

—

12 (1-63)

ABSTRACT NO-119 Safety Results From AVAglio, A Phase III Randomized Study Of Bevacizumab (BEV) Plus Standard Combination Temozolomide (TMZ) And Radiotherapy (RT) In Newly Diagnosed Glioblastoma (GBM) The addition of bevacizumab (BEV) to first-line TMZ and RT in patients with newly diagnosed GBM has shown to significantly prolong PFS in the phase III (AVAglio study), randomized, double-blind, placebo-controlled trial [Chinot 2012]. Also, the results suggest a positive impact on other clinical measures such as health-related quality of life and functional independence in patients with newly diagnosed GBM. In this safety analysis of the AVAglio study, Saran et al report the incidence of adverse events of special interest (AESIs; on-target, class-specific

Median placebo doses (range)

BEVtoxicities): arterial thrombotic events (ATEs), wound healing complications (WHC), cerebral hemorrhage, and gastrointestinal perforations (GIP) [Saran 2013; abstr NO-119]. Patients aged ≥18 years with histologically confirmed GBM, WHO PS ≤2, stable/decreasing corticosteroid doses ≤5 days prior to randomization,

adequate healing of surgery and adequate hematologic, hepatic and renal function, were eligible for the study. Treatment comprised of concurrent, maintenance, and monotherapy phases (Figure 3). In the concurrent phase, patients received TMZ (75mg/m2/d) + RT (2Gy, 5d/wk) + placebo or BEV (10mg/kg, q2w) x6 wks. The concurrent phase

CancerTherapyAdvisor.com | FALL 2014 | CANCER THERAPY ADVISOR A19

CME ACTIVITY TABLE 5. Overall Incidences of AESIs (all Grades and Grade ≥3) AESI/AE, N (%) PATIENTS

BEV + RT/TMZ (N=461)

PLACEBO + RT/TMZ (N=450)

All grades

Grade ≥3

All grades

Grade ≥3

349 (75.7)

150 (32.5)

204 (45.3)

71 (15.8)

Cerebral hemorrhage

15 (3.3)

9 (2.0)

4 (0.9)

Other

171 (37.1)

6 (1.3)

88 (19.6)

4 (0.9)

WHCs

32 (6.9)

15 (3.3)

21 (4.7)

7 (1.6)

ATEs

27 (5.9)

22 (4.8)

7 (1.6)

6 (1.3)

Venous thromboembolic events

38 (8.2)

35 (7.6)

43 (9.6)

36 (8.0)

Hypertension

181 (39.3)

52 (11.3)

57 (12.7)

10 (2.2)

Proteinuria

72 (15.6)

25 (5.4)

19 (4.2)

0 (0.0)

GI perforation

8 (1.7)

5 (1.1)

2 (0.4)

1 (0.2)

Abscesses and fistulae

2 (0.4)

3 (0.7)

Congestive heart failure

2 (0.4)

1 (0.2)

0.0

Total patients with at least one AESI Bleeding

was followed by a 28-day treatment break starting at RT completion. In the maintenance phase, patients received TMZ (150–200mg/m 2/d, d1-5, q4w), placebo or BEV (10mg/kg, q2w) for six 4-week cycles. In the monotherapy phase, single-agent BEV (15mg/kg IV) or placebo was continued every 3 weeks until PD or unacceptable toxicity. AEs and AESIs for BEV were monitored for ≤90 days and ≤6 months after last treatment dose, respectively. The majority of patients received the planned treatment doses and overall duration of treatment and exposure to BEV/ placebo infusions was greater in the BEV arm than in the placebo arm (Table 4). The safety follow-up was a median of 12.3 months in the BEV arm and 8.5

months in the placebo arm. Overall incidences of AESIs (all grades) were increased with BEV vs. placebo (72.6% [28.7% grade ≥3; 7 patients grade 5] vs. 44.3% [15.2% grade ≥3; 3 patients grade 5]) (Table 5). ATEs were increased with BEV (5.0% [4.1% grade ≥3]) vs. placebo (1.6% [1.3% grade ≥3]). 70.3% and 42.8% ATEs (all grades) resolved in the BEV arm and the placebo arm, respectively. Similarly, the majority of grade ≥3 ATEs (68.2%) resolved in the BEV arm while 50% resolved in the placebo arm. While 40.9% (9/22) of the grade ≥3 ATEs with BEV occurred in patients ≥65 years, all grade ≥3 ATEs with placebo occurred in patients <65 years. Most ATEs were classified as stroke events: 19/27 (BEV)

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vs. 6/7 (placebo). Cerebral hemorrhage rates were similar (2.6% BEV vs. 2.2% placebo) between treatment arms. WHCs were more frequent with BEV than placebo (3.7% [1.5% grade ≥3] vs. 2.2% [0.7% grade ≥3]). All grade ≥3 WHCs were related to the craniotomy site and most resolved with treatment. GIP was reported for 1.7% (BEV) and 0.2% (placebo) of patients, and included one fatal large intestine perforation (BEV). In summary, the overall safety findings suggest an increase in toxicity in the experimental arm, related to the expected toxicity of BEV. However, this should be placed in context of the longer overall duration of safety follow-up and greater exposure to TMZ (more patients completing 6 cycles of maintenance TMZ) in the BEV arm vs. the placebo arm. The addition of BEV to RT/TMZ was well tolerated, with expected and manageable, on-target, class-specific toxicities. A small increase in fatal complications was evident; however, this did not offset the clinical benefit achieved. Suggested Options for Practice • Greater than 12 months of follow-up safety data from the AVAglio study suggests that the addition of BEV to RT/TMZ may lead to a slight increase in toxicity which may be class-specific but is manageable • Moving forward, the addition of BEV to RT/TMZ is well tolerated, with expected and manageable toxicities and the combination has previously shown to achieve significant PFS benefit for patients with newly diagnosed GBM References 1. Abuhusain H, Matin A, Qiao Q, et al. S1P: an alternative anti-angiogenic target in GBM. Poster Session No. AI-001 presented at: Society for Neuro-Oncology (SNO) 2013 Annual Meeting; November 21-24, 2013; San Francisco, CA.

CME ACTIVITY 2. Bae E, Smith L, Muller-Greven G, et al.

6. Cohen AL, Anker C, Shrieve D, et al. A phase

standard combination temozolomide (TMZ)

Treatment of GBM xenograft tumors with

1 study of Repeat rAdiation, Minocycline,

and radiotherapy (RT) in newly diagnosed

a thrombospondin mimetic peptide, ABT-

and Bevacizumab in patients with recurrent

glioblastoma (GBM). Poster Session No.

898: comparison to bevacizumab. Poster

gliOma (RAMBO). Poster Session No. MR-007

NO-119 presented at: Society for Neuro-

Session No. AI-004 presented at: Society for

presented at: Society for Neuro-Oncology

Oncology (SNO) 2013 Annual Meeting;

Neuro-Oncology (SNO) 2013 Annual Meeting;

(SNO) 2013 Annual Meeting; November 21-24,

November 21-24, 2013; San Francisco, CA.

2013; San Francisco, CA.

3. Brandes AA, Mason W, Pichler J, et al.

7. Oâ&#x20AC;&#x2122;Halloran P, Viel T, Schwegmann K, et al.

November 21-24, 2013; San Francisco, CA. 11. Chinot O, Wick W, Mason W et al. Phase III trial of bevacizumab added to standard radiother-

Randomized, phase IIIb trial evaluating stan-

Anti-angiogenic efficacy of bevacizumab

apy and temozolomide for newly-diagnosed

dard-of-care (SOC) therapy with/without

alone and in combination with a dual PI3K/

glioblastoma: mature progression-free survival

bevacizumab continuation beyond disease

mTOR inhibitor in an orthotopic model of

and preliminary overall survival results in

progression (PD) in patients with glioblas-

malignant glioma: A multimodal neuro-im-

AVAglio. Neuro Oncol. 2012;14 (suppl 6):vi101-

toma after first-line radiotherapy, temozolo-

aging approach. Poster Session No. AI-032

mide and bevacizumab (RT/T+BEV): trial

presented at: Society for Neuro-Oncology

rationale and design. Poster Session No.

(SNO) 2013 Annual Meeting; November

Continuation of bevacizumab after first

NO-014 presented at: Society for Neuro-

21-24, 2013; San Francisco, CA.

progression in metastatic colorectal cancer

Oncology (SNO) 2013 Annual Meeting; November 21-24, 2013; San Francisco, CA. 4. Brenner A, Sun J, Floyd J, et al. Dual phase

8. Rashed I, Melian E, Sethi A, et al. Survival outcomes and prognostic considerations of stereotactic radiosurgery in the treatment

vi105. Abstract OT-03. 12. Bennouna J, Sastre J, Arnold D, et al.

(ML18147): a randomised phase 3 trial.

Lancet Oncol. 2013;14:29-37. 13. Iwamoto FM, Abrey LE, Beal K, et al. Patterns

I/II study of TH-302 and bevacizumab in

of recurrent malignant gliomas with and

of relapse and prognosis after bevacizumab

recurrent glioblastoma following bevaci-

without bevacizumab. Poster Session No.

failure in recurrent glioblastoma. Neurology.

zumab failure. Poster Session No. NO-016

MR-024 presented at: Society for Neuro-

presented at: Society for Neuro-Oncology

Oncology (SNO) 2013 Annual Meeting;

(SNO) 2013 Annual Meeting; November 21-24, 2013; San Francisco, CA. 5. Clarke J, Molinaro A, Phillips J, et al. Final

November 21-24, 2013; San Francisco, CA.

of a second chemotherapy in recurrent malig-

9. Lee E, Reardon D, Schiff D, et al. Phase II study

nant glioma patient who progress on bevaci-

of panobinostat in combination with beva-

results of a single-institution phase II trial of

cizumab for recurrent glioblastoma. Poster

radiation (RT), temozolomide (TMZ), erlo-

Session No. NO-080 presented at: Society for

tinib and bevacizumab for initial treatment

Neuro-Oncology (SNO) 2013 Annual Meeting;

of glioblastoma (GBM). Poster Session No.

November 21-24, 2013; San Francisco, CA.

MR-006 presented at: Society for Neuro-

2009;73:1200-1206. 14. Quant EC, Norden AD, Drappatz J, et al. Role

10. Saran F, Chinot OL, Henriksson R, et al.

zumab. Neuro-Oncology. 2009;11:550-555. 15. Norden AD, Drappatz J, Wen PY. Novel anti-angiogenic therapies for malignant gliomas. Lancet Neurol. 2008;7(12):1152-1160. 16. Drappatz J, Lee EQ, Hammond S, et al. Phase 1 study of panobinostat in combination with

Oncology (SNO) 2013 Annual Meeting;

Safety results from AVAglio, a phase III ran-

bevacizumab for recurrent high-grade glio-

November 21-24, 2013; San Francisco, CA.

domized study of bevacizumab (BEV) plus

ma. J Neuro Oncol. 2012;107(1):133-138.

TO TAKE THE POST-TEST please go to myCME.com/glioblastoma

CancerTherapyAdvisor.com | FALL 2014 | CANCER THERAPY ADVISOR A21

FEATURE

BY BRYANT FURLOW

arly palliative care interventions can substantially improve cancer and cancer treatment–associated effects to the quality of life and psychological well-being of patients and family members, including patient pain, mobility impairment, shortness of breath, nausea and vomiting, anxiety, and depression. But implementation of early palliative care in clinical oncology has been slow. New payment reforms proposed by the American Society of Clinical Oncology (ASCO) would remove one important barrier to implementation by allowing bundled reimbursements. The majority of patients with cancer receive palliative care only in their last days of life, if at all. Attitudes among clinicians, patients, and family members still commonly and mistakenly equate palliative care with end-of-life hospice or surrender—something to be undertaken only after all efforts to prolong life, have failed.1,2 Political rhetoric surrounding health insurance reform has fueled some people’s concerns about palliative care and advanced care planning for patients with terminal disease.3 In reality, palliative care simply refers to interventions aimed at alleviating the effect of disease and treatment on the well-being and quality of life of patients and their family members.4,5

Palliative care is underutilized by oncologists and misunderstood by many patients and their families.

Et laborum quametur sam rerit rest dolorum, sit, occulparum Aped aborepelest inum

Patients with advanced cancer commonly suffer marked fatigue and weakness, loss of appetite and energy, pain, and emotional stress, which can profoundly affect their quality of life.6 Research indicates that initiating supportive care earlier, such as upon diagnosis with metastatic disease, can improve patients’ quality of life, pain, and mobility.4,6,7 There is even evidence that, among patients with terminal lung cancer, immediate initiation of palliative care can prolong median survival times by 2.7 months.4,7 Such findings led ASCO to issue a 2012 provisional clinical opinion recommending the integration of palliative care services into standard cancer care upon diagnosis with metastatic or advanced cancer.1 According to ASCO, physicians should regularly update patients about their prognosis and ask them about their quality of life and symptoms like fatigue, pain, and anxiety immediately upon diagnosis. Physicians should also explain the purpose of palliative care right away.1 Now, more than 2 years later, ASCO’s recommendation for early integration of palliative care has yet to be comprehensively implemented, and referrals continue to be made primarily near the end of patients’ lives.8,9 Truly patient-centered care requires the empowerment of patients with information and a role in clinical

THINKSTOCK

Palliative Care Integration and Expertise Are Pressing Goals for Oncologists

A22 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

Fall14_CTA_feature_F.indd 22

8/29/14 10:35 AM

FEATURE decision-making. Clinicians should not assume that patients will resist discussing palliative care, including psychosocial support, at the time of diagnosis instead of waiting until the end of life. A key message that must be conveyed to patients with cancer is that palliation does not mean end of life. Barriers to early integration abound. Medicare does not pay to train palliative specialists, leaving too few experts. (Two bills currently before Congress would address training and the development of palliative care centers.) Also, Medicare does not reimburse oncologists or practices that perform palliative care outside of the context of end-of-life hospice care, explained Jeffery Ward, MD, chair of ASCO’s Payment Reform Workgroup. That means that practices sometimes go unreimbursed for the time and effort they invest in supportive care for their patients. Dr. Ward’s workgroup recently proposed Medicare oncology payment reforms that would streamline billing (reducing the

A key message that must be conveyed to patients with cancer is that palliation does not mean end of life. current 58 cancer care billing codes to just 11 bundled-care codes) and reimburse oncology practices for integrating palliative care at the time of diagnosis.10 “Palliative care is not paid for in our system until you get to hospice,” Dr. Ward said. “We believe that when you bundle payments, you begin providing better palliative care. If I’m an oncologist spending

30% of my time giving palliative care but I’m not really trained and am not an expert in it, then I can develop palliative care in my practice and bring in a palliative physician. Bundling allows me to maximize efficiency.” ASCO is meeting with officials at the Centers for Medicare & Medicaid Services to discuss the possibility of a pilot project for the proposed payment reforms.10

2. Battley JE, Connell LC, O’Reilly S. Early specialty palliative care. N Engl J

Med.2014;370(11):1075. 3. Nyhan B, Reifler J, Ubel PA. The hazards of correcting myths about health care reform.

Med Care. 2013;51(2):127-132. 4. Irwin KE, Greer JA, Khatib J, et al. Early palliative care and metastatic non-small cell lung cancer: potential mechanisms of prolonged survival. Chron Respir Dis. 2013;10(1):35-47. 5. Ferris FD, Bruera F, Cherny N, et al. Palliative

Oncologists Should Seek Palliative Care Expertise W hile Dr. Ward emphasizes that ASCO’s proposed Medicaid payment reforms for cancer care would allow practices to hire palliative care physicians, others emphasize that oncologists must equip themselves with palliative care expertise, or even prepare to become the primary palliative care providers for their patients with advanced cancer.11,12 “General palliative care is mandatory for any physician who is caring for patients with incurable and advanced disease,” reported Jan Gaertner, MD, of the department of palliative care at University Medical Center Frieburg, in Freiburg, Germany, and colleagues.12 Communication is key to the successful integration of palliative care. Discussions about palliative care should be honest, simple, direct, and empathetic, acknowledging the patient’s physical and emotional suffering.12 While Dr. Gaertner’s team refers patients to a palliative care team, practice guidelines for symptom management are “readily available”, Dr. Gaertner noted, and these should be known and kept on hand by oncologists. ■

cancer care a decade later: accomplishments, the need, next steps—from the American Society of Clinical Oncology. J Clin

Oncol.2009;27(18):3052-3058. 6. Greer JA, Jackson VA, Meier DE, Temel JS. Early integration of palliative care services with standard oncology care for patients with advanced cancer. CA Cancer J Clin. 2013;63(5):349-363. 7. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733-742. 8. Lefkowits C, Binstock AB, CourtneyBrooks M, et al. Predictors of palliative care consultation on an inpatient gynecologic oncology service: are we following ASCO recommendations? Gynecol Oncol. 2014;133(2):319-325. 9. Committee on Improving the Quality of Cancer Care: Addressing the Challenges of an Aging Population; Board on Health Care Services; Institute of Medicine; et al. Delivering HighQuality Cancer Care: Charting a New Course for a System in Crisis. Washington (DC): National Academies Press (US); 2013. 10. Furlow B. New proposals to improve US cancer care and control costs. Lancet

Oncol.2014;15(9):921-922. 11. Rangachari D, Smith TJ. Integrating palliative care in oncology: the oncologist as a

Reference

primary palliative care provider. Cancer J.

1. Smith TJ, Temin S, Alesi ER, et al. American Society of Clinical Oncology provisional

2013;19(5):373-378. 12. Gaertner J, Weingärtner V, Wolf J, Voltz

clinical opinion: the integration of palliative

R. Early palliative care for patients with

care into standard oncology care. J Clin

advanced cancer: how to make it work. Curr

Oncol.2012;30(8):880-887.

Opin Oncol. 2013;25(4):342-352.

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IN THE CLINIC | BY C. ANDREW KISTLER, MD, P

harmD,

Everolimus Use in Sorafenib-Refractory Hepatocellular Carcinoma Researchers continue to search for a molecular pathway or biomarker to improve treatment options for patients with sorafenib-refractory HCC. intolerable side effects from the drug, disease progression, or treatment failure. Therefore, a common dilemma for patients and clinicians is determining what alternative treatment options are available if sorafenib treatment is ineffective. At this time, there is a very limited amount of clinical trial data to support the use of other systemic

chemotherapeutic agents such as doxorubicin, gemcitabine, or cisplatin in patients who are ineffectively treated with sorafenib. Patients with HCC typically do not respond well to systemic chemotherapy based on their overall level of hepatic dysfunction and resulting inability to tolerate these medications. In addition, drug resistance genes are expressed at a relatively high level in patients with HCC, making the risk of these treatments outweigh the benefits. In an effort to explore potential options for patients with HCC in whom sorafenib treatment is ineffective, Zhu et al recently published a clinical trial evaluating the use of everolimus in these patients.3 Everolimus is a mammalian target of rapamycin (mTOR) inhibitor, which has been approved for Continued on page A27

ÂŠ DU CANE MEDICAL IMAGING LTD. / SCIENCE SOURCE

epatocellu lar carci noma (HCC) is a relatively common malignancy worldwide, with approximately 750,000 new cases diagnosed in 2008.1 Surgical resection and/or liver transplantation are the best treatment options for patients with HCC; however, many patients are not candidates for these interventions based on their overall tumor burden and liver dysfunction. Nonsurgical treatment options for HCC include transarterial chemoembolization, radiofrequency ablation, and systemic chemotherapy. Unfortunately, advanced HCC does not have many systemic chemotherapy options. Sorafenib is an oral tyrosine kinase inhibitor that works to inhibit the vascular endothelial growth factor receptor and Raf kinase pathways.2 In the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SH A R P) clinical trial, sorafenib was shown to provide a benefit in both survival (10.7 months vs. 7.9 months, respectively) and median time to radiologic progression (5.5 months vs. 2.8 months, respectively) when compared with placebo. 2 However, some patients with HCC who are treated with sorafenib may experience

RPh

Colored axial computed tomography scan through a liver (light green, upper left). The patient has a large HCC (dark green) within the liver. The slice section is seen from below with the front of the body at top and the spine (blue) in the lower center.

A24 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

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VIEWPOINT | BY GREG OTIS

Topical Gel May Be as Effective as Oral Tamoxifen in DCIS A topical gel containing an active metabolite of tamoxifen suppressed cell proliferation equally as well as the oral form.

metabolite of tamoxifen, 4-OHT, applied as a gel to the breasts of women with ductal carcinoma in situ (DCIS) was as effective as oral tamoxifen in reducing a marker of cell proliferation, and may have less potential for toxicity, according to a study published in Clinical Cancer Research.1 “In this study, we have shown that the gel application of 4-OHT to the skin resulted in high drug levels in the breast but low drug levels in the circulation,” said Seema Khan, MD, professor of surgery at Northwestern University Feinberg School of Medicine in Chicago, IL, and leader of the research team. “This would maintain the effectiveness of the drug, but minimize the side effects.” Tamoxifen has been shown to reduce the risk of recurrence of estrogen receptor (ER)–positive DCIS and to reduce the incidence of primary breast cancer, but its adverse effects, including thromboembolism, endometrial changes, hot flashes, and vaginal symptoms, have limited its acceptance. Tamoxifen is broken down in the liver to 4-OHT and other metabolites. Some of these contribute to the potential adverse effects of the drug, including an increased risk of blood

clots. “Because the liver metabolism step is eliminated when the 4-OHT gel is directly applied to breast skin, the harmful effect of increasing the risk for blood clots should also be eliminated,” Dr. Khan said. In the phase 2 trial, 26 pre- and postmenopausal women with ER-positive

Plasma concentrations were more than 5-fold lower in the women who used the topical gel. DCIS were randomly assigned to receive topical 4-OHT, 4 mg/day, applied to both breasts, or oral tamoxifen, 20 mg/day, for 6 to 10 weeks before surger y. Concentrations of K i67, a marker of cell proliferation, were measured in breast tissue by immunohistochemistry. Plasma concentrations of tamoxifen and its major metabolites were also measured. After treatment, Ki67 decreased by 61% in the oral tamoxifen group and 52% in the 4-OHT topical gel group,

indicating that both treatments significantly reduced cell proliferation. In breast tissue, 4-OHT was found in similar concentrations in the two treatment groups, but plasma concentrations were more than 5-fold lower in the women who used the topical gel. Plasma concentrations of the coagulation-promoting proteins factor VIII and von Willebrand factor increased in women taking oral tamoxifen but not in women using 4-OHT topical gel, suggesting that women using the gel may have a lower risk of thromboembolism. In addition, measurement of insulin–like growth factor-1 and sex hormone-binding globulin suggested that the 4-OHT topical gel had fewer endocrine effects than oral tamoxifen. The two treatments had similar effects on quality of life. The frequency of vasomotor symptoms, including hot flashes, night sweats, and cold sweats, increased slightly in each group, and did not differ significantly between groups. Women using 4-OHT gel had slightly more gastrointestinal symptoms than women taking oral tamoxifen. “Oral tamoxifen is used by some women at high risk for breast cancer to prevent the development of the disease, and our data suggest that gel application of tamoxifen could replace this approach, thus encouraging more women to adhere to preventive therapy,” said Dr. Khan. ■ Reference 1. Lee O, Page K, Ivancic D, et al. A randomized phase II presurgical trial of transdermal 4-hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in situ of the breast. Clin Cancer Res. 2014;20(14);3672-3682.

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EXPERT PERSPECTIVE | BY STEVEN J. COHEN, MD

New Weapon Against Advanced Gastric/ Gastroesophageal Junction Dr. Cohen, CTA Advisory Board member, discusses the FDA approval of ramucirumab, a new therapy option for patients with gastric cancer.

amucirumab, an anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody, was recently approved by the U.S. Food and Drug Administration (FDA) as a single agent for patients with advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma with prior progression on or after platinum- or fluoropyrimidine-based chemotherapy. The FDA approval was based on the results of the REGARD trial, which was previously published in The Lancet. This well-designed trial randomly assigned 355 patients with previously treated advanced or metastatic gastric/ GEJ adenocarcinoma in a 2:1 fashion to ramucirumab or placebo.1 The primary endpoint was overall survival, and median survival was modestly improved with ramucirumab compared with placebo (5.2 vs. 3.8 months; hazard ratio [HR] = 0.78; P = 0.047). Six-month and 12-month survival were also improved with ramucirumab (42%

and 18% vs. corresponding rates of 32% and 11% in the placebo arm). Median progression-free survival was also longer in the ramucirumab arm (2.1 vs. 1.3 months; HR = 0.483, P < 0.0001). Further, stable disease was significantly improved with ramucirumab compared with placebo (~45% vs. ~20%), although objective responses were rare. Toxicities were manageable and as expected for an antiangiogenic agent. Hypertension, in particular, was increased in the ramucirumab arm (~16% vs. ~8% for placebo), although grade 3 or higher hy pertension occurred in 7.6% of patients. Diarrhea, headache, and hyponatremia were

all modestly increased in the ramucirumab arm. So, how should ramucirumab be utilized in clinical practice? Fit patients with advanced or metastatic gastric/GEJ cancers are typically treated initially with chemotherapy combinations including a platinum and a fluoropyrimidine (e.g., FOLFOX [leucovorin, 5-fluorouracil, oxaliplatin], DCF [docetaxel, cisplatin, 5-f luorouracil], ECF [epirubicin, cisplatin, 5-fluorouracil], and variants thereof ). For patients with HER2expressing cancers, trast uzumab is t y pically added to f irst-l i ne chemotherapy. However, second-line treatment after progression on first-line therapy has been more challenging. Randomized studies do support a modest benefit from chemotherapy, with either taxanes or irinotecan. Interestingly, the magnitude of the survival benefit for each of these chemotherapy agents is quite similar to that seen with ramucirumab (~1.5-month improvement in median survival). Thus, for patients with a good performance status, either chemotherapy or ramucirumab are reasonable second-line agents. Patients with contraindications to antiangiogenic therapy (thrombotic or bleeding complications) will probably not be good candidates for ramucirumab and should likely preferentially receive chemotherapy. A natural question is whether both chemotherapy and ramucirumab can be

Read more from our Advisory Board at CancerTherapyAdvisor.com/FromTheAdvisoryBoard

A26 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

EXPERT PERSPECTIVE administered concurrently in second-line advanced/metastatic gastric/GEJ adenocarcinoma therapy. Although not approved at this time for this indication, the combination of ramucirumab and

The combination of ramucirumab and paclitaxel was demonstrated to improve outcome compared with singleagent paclitaxel. paclitaxel was demonstrated to improve outcome compared with single-agent paclitaxel in the RAINBOW trial. In this randomized phase 3 trial, 665 patients in this setting were randomly assigned 1:1 to paclitaxel with

In the Clinic Continued from page A24

use in the United States in renal cell carcinoma, advanced breast cancer, pancreatic neuroendocrine tumors, and for the prevention of liver and kidney transplant rejection.4 The mTOR pathway has been implicated in the pathophysiology underlying HCC; therefore, it was hypothesized that everolimus may be a treatment option. The Everolimus for Liver Cancer Evaluation (EVOLVE-1) study included 546 adult patients with HCC who could not tolerate sorafenib or who had HCC progression during or after sorafenib treatment based on radiographic images. Patients received

or without ramucirumab. Those patients receiving the combination had improved median survival (primary endpoint) of 9.6 months compared with 7.4 months with single-agent paclitaxel (HR = 0.81; P = 0.02).2 As many patients are not well enough to receive third-line therapy, combining ramucirumab and chemotherapy in the second-line setting may be a natural step for some patients, although it is not currently approved as such. In summary, the approval of ramucirumab as a single agent in previously treated advanced/metastatic gastric/GEJ adenocarcinoma is a welcome addition to the therapeutic armamentarium in this disease. Oncologists now have a few second-line options, including ramucirumab monotherapy and taxane or irinotecan chemotherapy, or the combination of ramucirumab and a taxane. Although ramucirumab is not currently approved in combination with chemotherapy, supportive data from

supportive care and either 7.5 mg of everolimus daily or placebo. When everolimus was compared with placebo there was no difference in medial overall survival (7.6 months vs. 7.3 months, respectively) or median time to progression (3.0 months vs. 2.6 months, respectively). Patients in the everolimus group experienced more adverse events compared with patients who recieved placebo in numerous categories including stomatitis, anemia, asthenia, decreased appetite, and hepatitis B reactivation. Sorafenib-refractory HCC continues to be a challenging disease state to treat, with many prior and current clinical trials failing to identify new treatment options. Future studies will continue to

the RAINBOW trial and the reality that many patients are not well enough for third-line therapy may make this an attractive option for some patients. This is a welcome conundrum to have! â&#x2013; References 1. Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31-39. 2. Wilke H, Van Cutsem E, Oh SC, et al. RAINBOW: A global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-JVBE). J Clin

Oncol. 32, 2014 (suppl 3; abstr LBA7).

search for the next molecular pathway or biomarker that will prove useful in the development of systemic HCC medication. â&#x2013; References 1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-90. 2. Nexavar [prescribing information]. Wayne, NJ: Bayer Pharmaceuticals. 3. Zhu AX, Kudo M, Assenat E, et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial.

JAMA. 2014;312(1):57-67. 4. Afinitor [prescribing information]. Basel, Switzerland: Novartis Pharmaceuticals Corporation.

CancerTherapyAdvisor.com | FALL 2014 | CANCER THERAPY ADVISOR A27

REGIMEN & MONOGRAPH INDEX CANCER THERAPY REGIMENS & DRUG MONOGRAPHS 1

Bone Cancer

 Bone Cancer

7 Brain Cancer 10 Breast Cancer  Invasive  Recurrent or Metastatic

27 Endocrine Cancer 31 Gastrointestinal Cancer 37 Genitourinary Cancer  Bladder Cancer  Prostate Cancer  Renal Cell Carcinoma  Testicular Cancer

53 Gynecologic Cancer 57 Head and Neck Cancer

 Head and Neck Cancer

63 Hematologic Cancer 85 Lung Cancer 90 Sarcoma 91 Skin Cancer  Melanoma

Associated Hematological Disorders

A28 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

IMPORTANT INFORMATION FOR ALL READERS CANCER THERAPY ADVISOR (CTA) is an up-to-date guide to commonly prescribed pharmaceuticals, as well as certain OTC products. It has been produced to provide an easily accessible reminder of basic information useful to review when prescribing medications, such as specific indications for use, dosage, and a checklist of precautions, interactions, and adverse drug reactions. Reference should always be made to each drug being coadmin istered. The information it contains is intended solely for use by the medical profession. IT IS NOT INTENDED FOR LAY READERS. This reference has been assembled and edited by an experienced staff of pharmacists uti lizing information available from FDA-approved labeling. Distinctions have not necessarily been made between those reactions that are well-documented and/or clinically significant, and those that carry only a theoretical risk. A renowned board of consulting medical specialists has also independently reviewed the product references. However, although every effort is made to assure accuracy, the information in CTA is not necessarily reviewed by the supplier of a particular drug. If any questions arise about information in CTA, the physician should verify it against labeling or by contacting the company marketing the drug. The publisher and editors do not warrant or guarantee any of the products described or the information describing them. THE PUBLISHER AND EDITORS DO NOT ASSUME, AND HEREBY EXPRESSLY DISCLAIM ANY LIABILITY WHATSOEVER FOR ANY ERRORS OR OMISSIONS IN SUCH INFORMATION OR FOR ANY USE OF ANY OF THE PRODUCTS LISTED. No prescription drug should be used except on the advice of, and as directed by, a physician. The training and experience of a physician are essential to forming any opinion on the appropriateness of a specific drug for a specific patient. The information in this publication is not by itself sufficient for a lay person—or even a physician—to evaluate the risks and benefits of taking any particular drug. In reaching professional judgments on whether to prescribe a pharmaceutical, which to prescribe, and under what regimen, the physician should thoroughly understand the options available for any clinical application, the potential effectiveness of each product, and the associated risks and side effects. This knowledge should be considered in light of the special circumstances of the patient, for each patient is unique. No single reference can substitute for medical training and experience. The physician must be familiar with the full product labeling, provided by the manufacturer or distributor of the drug, of every product he or she prescribes, as well as the relevant medical literature. Certain additional qualifications are important in using this book. First, CTA has been deliberately kept concise, with a standardized format, so that it could be a convenient reference tool. This means that lengthy and detailed explanations about certain aspects of drugs commonly found in labeling are omitted or condensed. Second, by revising and reprinting quarterly, CTA should be one of the most up-to-date guides to prescription drugs now available in print. Only the current issue should be used. The prescribing decision is ultimately the responsibility of the physician. CTA is offered to assist physicians in this area. © 2014 Haymarket Media, Inc.

MASTER CANCER TREATMENT REGIMEN

BONE CANCER Bone Cancer Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

General Treatment Notes1

• Chemotherapy for Ewing’s sarcoma and osteosarcoma should include growth factor support. • Conventional chondrosarcoma (Grades 1–3) has no known standard chemotherapy options. • Mesenchymal chondrosarcoma: follow Ewing’s sarcoma regimens (category 2B). • High-grade undifferentiated pleomorphic sarcoma (UPS) of bone and dedifferentiated chondrosarcoma: follow osteosarcoma regimens (category 2B). • All recommendations are category 2A unless otherwise indicated.

Chordoma1 REGIMEN

DOSING

Imatinib

Imatinib 800mg orally once daily.

Imatinib with cisplatin4

Imatinib 400mg orally once daily and cisplatin 25mg/m2/week.

Imatinib with sirolimus5

Imatinib 400mg orally once daily and sirolimus 2mg/day orally once daily.

Erlotinib6

Erlotinib 150mg orally once daily.

Sunitinib7

Sunitinib 37.5mg orally once daily.

Lapatinib for EGFR-positive chordomas (category 2B)8

Lapatinib 1,500mg orally once daily.

2,3

Ewing’s Sarcoma and Mesenchymal Chondrosarcoma1 First-Line Therapy (Primary/Neoadjuvant/Adjuvant) VAC/IE (vincristine + doxorubicin* + cyclophosphamide alternating with ifosfamide + etoposide)9

Alternating VAC and IE cycles VAC cycles Day 1: Vincristine 2mg/m2 (max 2mg) IV + doxorubicin 75mg/m2 IVP + cyclophosphamide 1,200mg/m2 IV. Dactinomycin 1.25mg/m2 IV can be substituted for doxorubicin when a total doxorubicin dose of 375mg/m2 is reached. IE cycles Days 1–5: Ifosfamide 1,800mg/m2 IV + mesna + etoposide 100mg/m2 IV Repeat each cycle every 3 weeks for 17 cycles.

VAI (vincristine + ifosfamide + dactinomycin + doxorubicin)10

Day 1: Vincristine 1.5mg/m2 IV Days 1–3: Ifosfamide 2,000mg/m2 IV + mesna Days 1, 3, and 5: Dactinomycin 0.5mg/m2 IV Days 2 and 4: Doxorubicin 30mg/m2 IV. Repeat cycle every 3 weeks.

VIDE (vincristine + ifosfamide + doxorubicin + etoposide)11

Day 1: Vincristine 1.4mg/m2 (max 2mg) Days 1–3: Doxorubicin 20mg/m2 IV + ifosfamide 3mg/m2 IV + mesna 3g/m2 continuous IV infusion + etoposide 150mg/m2 IV. Repeat cycle every 3 weeks for up to 6 cycles.

Primary Therapy for Metastatic Disease at Initial Presentation VAC/IE (vincristine + doxorubicin* + cyclophosphamide alternating with ifosfamide + etoposide)9

Alternating VAC and IE cycles VAC cycles Day 1: Vincristine 2mg/m2 (max 2mg) IV + doxorubicin 75mg/m2 IV bolus + cyclophosphamide 1,200mg/m2 IV. Dactinomycin 1.25mg/m2 IV can be substituted for doxorubicin when a total doxorubicin dose of 375mg/m2 is reached. IE cycles Days 1–5: Ifosfamide 1,800mg/m2 IV + mesna + etoposide 100mg/m2 IV. Repeat each cycle every 3 weeks for 17 cycles. continued

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BONE CANCER Bone Cancer Treatment Regimens Ewing’s Sarcoma and Mesenchymal Chondrosarcoma1 (continued) Primary Therapy for Metastatic Disease at Initial Presentation (continued) REGIMEN

DOSING

VAI (vincristine + ifosfamide + dactinomycin [actinomycin D] + doxorubicin)10

Day 1: Vincristine 1.5mg/m2 IV Days 1–3: Ifosfamide 2,000mg/m2 IV + mesna Days 1, 3 and 5: Dactinomycin 0.5mg/m2 IV Days 2 and 4: Doxorubicin 30mg/m2 IV. Repeat cycle every 3 weeks.

VIDE (vincristine + ifosfamide + doxorubicin + etoposide)11

VAdriaC* (cyclophosphamide + vincristine + doxorubicin OR dactinomycin)12

Day 1: Vincristine 2mg/m2 IV + cyclophosphamide 1,200mg/m2 + doxorubicin 75mg/m2 (the first 5 cycles) OR dactinomycin 1.25mg/m2 IV (subsequent cycles). Repeat cycle every 3 weeks for 17 cycles.

Second-Line Therapy (Relapsed or Refractory Disease) Cyclophosphamide + topotecan13–16

Days 1–5: Cyclophosphamide 250mg/m2/day IV + topotecan 0.75mg/m2/day IV. Repeat cycle every 3 weeks for 12–14 cycles.

Irinotecan ± temozolomide17–23

Days 1–5: Temozolomide 100mg/m2/day orally, plus Days 1–5 and 8–12: Irinotecan 10–20mg/m2/day IV at least 1 hour after temozolomide. Repeat cycle every 3 or 4 weeks.

Ifosfamide + etoposide24

Days 1–5: Ifosfamide 1,800mg/m2/day IV + mesna Days 1–5: Etoposide 100mg/m2/day IV. Repeat every 3 weeks for 12 cycles.

Ifosfamide, carboplatin, and etoposide25

Days 1 and 2: Carboplatin 400mg/m2/day IV, plus Days 1–5: Ifosfamide 1,800mg/m2/day IV + mesna + etoposide 100mg/m2/day IV. Repeat cycle every 3 weeks for up to 12 cycles (median 1 cycle).

Docetaxel + gemcitabine26

Days 1 and 8: Gemcitabine 675mg/m2 IV, plus Day 8: Docetaxel 75–100mg/m2 IV. Repeat cycle every 3 weeks for up to 13 cycles (median 4 cycles).

Irinotecan, temozolomide + cefpodoxime23

Days 1–5 and Days 8–21: Irinotecan 20–30mg/m2 IV with continuous oral cefpodoxime 10mg/kg/day divided BID starting 2 days prior to irinotecan.

Cyclophosphamide + sirolimus27 (Category 2B)†

First cycle of treatment Days 1–7 and 15–21: Cyclophosphamide 100mg oral twice daily from first cycle of treatment Days 1–7: Sirolimus 1mg orally once daily Days 8–14: Sirolimus 1mg orally twice daily Days 15–21: Sirolimus 1mg orally three times daily. Second cycle of treatment Days 1–7 and 15-21: Cyclophosphamide 100mg oral twice daily from first cycle of treatment Days 1–21: Sirolimus 1mg orally three times daily. Repeat cycle every 4 weeks

Giant Cell Tumor of Bone1 Denosumab28,29

Denosumab 120mg subcutaneously every 4 weeks with additional doses on Days 8 and 15.

Interferon alfa30,31

Interferon alpha-2 or beta (3,000,000 units/m2) 48 to 72 hours postoperatively OR Increasing dosage from 4 × 106 units 3 times a week to 9 × 106 units 3 times a week.

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MASTER CANCER TREATMENT REGIMEN

BONE CANCER Osteosarcoma1 First-Line (Primary/Neoadjuvant/Adjuvant) or Primary Therapy for Metastatic Disease at Initial Presentation1 REGIMEN

DOSING

Cisplatin + doxorubicin32–34

Days 1–3: Doxorubicin 25mg/m2/day IV, plus Day 1: Cisplatin 100mg/m2 IV continuous IV infusion. Repeat cycle every 3 weeks for 6 cycles.

MAP (high-dose methotrexate + cisplatin + doxorubicin)35,36

Day 1: Methotrexate 8g/m2 IV (with leucovorin rescue 15mg every 6 hours for 11 doses, starting 24 hours after beginning methotrexate), followed by Days 7–9: Cisplatin 120mg/m2/day intra-arterially, followed by Day 9: Doxorubicin 60mg/m2 IV (48 hours after start of cisplatin infusion). Repeat cycle once after 4 weeks.

Doxorubicin + cisplatin + ifosfamide + high-dose methotrexate37

Days 0, 6, 18, 27, and 36: Methotrexate (MTX) 12g/m2 as a 4-hour infusion, increased by 2g/m2 if the hour-4 level of serum MTX in the previous course was <1000 µmol/L Days 1, 7, 19, 28, and 37: Cisplatin 60mg/m2/day as a 48-hour continuous IV infusion (total dose 120mg/m2) Days 1 and 7: Doxorubicin (ADM1) (preoperative): 75mg/m2 as a 24-hour continuous IV infusion Day 12: Surgery Days 13, 22, and 31: Doxorubicin (ADM2) (postoperative): 90mg/m2 as a 24-hour continuous IV infusion Days 4, 10, 16, 25, and 34: Ifosfamide: 3 g/m2/day as a 120-hour (5-day) continuous IV infusion (total dose 15 g/m2).

Ifosfamide + cisplatin + epirubicin38

Day 1: Epirubicin 90mg/m2, cisplatin 100mg/m2 Days 2–4: Ifosfamide 2.0 g/m2 with an equivalent dose of mesna, repeated every 21 days. Six cycles of this combination regimen were administered (3 cycles prior to surgery and 3 cycles postoperatively).

Second-Line Therapy (Relapsed or Refractory Disease) Carboplatin + ifosfamide + etoposide25

Days 1 and 2: Carboplatin 400mg/m2/day IV, plus Days 1–5: Ifosfamide 1,800mg/m2/day IV + mesna + etoposide 100mg/m2/day IV. Repeat cycle every 3 weeks for up to 12 cycles (median 1 cycles).

Gemcitabine + docetaxel26

Days 1 and 8: Gemcitabine 675mg/m2 IV, plus Day 8: Docetaxel 75–100mg/m2 IV. Repeat cycle every 3 weeks for up to 13 cycles (median 4 cycles).

Cyclophosphamide + topotecan16

Days 1–5: Cyclophosphamide 250mg/m2/dose followed by topotecan 0.75mg/m2/dose), each given as a 30-minute IV infusion once daily for 5 days.

Sorafenib39

Sorafenib 400mg orally twice daily.

Ifosfamide + etoposide24

Days 1–5: Ifosfamide 1,800mg/m2/day IV and etoposide 100mg/m2/day; 5-day cycles every 3 weeks for 12 cycles.

Cyclophosphamide + etoposide40

Day 1: Cyclophosphamide 4000mg/m2 3-hour IV infusion Days 2–4: Etoposide 100mg/m2 over 1 hour twice daily for 3 days on Days 2, 3, and 4 (total dose 600mg/m2).

* Dactinomycin can be substituted for doxorubicin because of concerns regarding cardiotoxicity. † Indicated for high-grade chondrosarcoma for systemic recurrence.

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Breast Cancer. v1.2014. Available at: http://www.nccn.org/ professionals/physician_gls/pdf/bone.pdf. Accessed April 15, 2014. 2. Casali PG, Messina A, Stacchiotti S, et al. Imatinib mesylate in chordoma. Cancer. 2004;101:2086–2097. 3. Stacchiotti S, Longhi A, Ferraresi V, et al. Phase II study of imatinib in advanced chordoma. J Clin Oncol. 2012;30:914–920. 4. Casali PG, Stacchiotti S, Sangalli C, et al. Chordoma. Current Opin Oncol. 2007;19:367–370.

5. Stacchiotti S, Marrari A, Tamborini E, et al. Response to imatinib plus sirolimus in advanced chordoma. Ann Oncol. 2009; 20:1886–1894. 6. Singhal N, Kotasek D, Parnis FX. Response to erlotinib in a patient with treatment refractory chordoma. Anti Cancer Drugs. 2009;20:953–955 7. George S, Merriam P, Maki RG, et al. Multicenter phase II trial of sunitinib in the treatment of nongastrointestinal stromal tumor sarcomas. J Clin Oncol. 2009;27:3154–3160. 8. Stacchiotti S, Tamborini E, LoVullo S, et al. A phase II study on lapatinib in advanced EGFR-positive chordoma. Ann Oncol. 2013;24(7):1931–1936.

continued

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BONE CANCER Bone Cancer Treatment Regimens References (continued) 9. Grier HE, Krailo MD, Tarbell NJ, et al. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med. 2003;348:694–701. 10. Paulussen M, Craft AW, Lewis I, et al; European Intergroup Cooperative Ewing’s Sarcoma Study-92. Results of the EICESS-92 Study: two randomized trials of Ewing’s sarcoma treatment—cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients. J Clin Oncol. 2008;26:4385–4393. 11. Juergens C, Weston C, Lewis I, et al. Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-E.W.I.N.G. 99 clinical trial. Pediatr Blood Cancer. 2006 Jul;47(1):22–29. 12. Miser JS, Krailo MD, Tarbell NJ, et al. Treatment of metastatic Ewing’s sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide—a Children’s Cancer Group and Pediatric Oncology Group study. J Clin Oncol. 2004;22:2873–2876. 13. Bernstein ML, Devidas M, Lafreniere D, et al. Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children’s Cancer Group Phase II Study 9457—a report from the Children’s Oncology Group. J Clin Oncol. 2006;24(1):152–159. 14. Hunold A, Weddeling N, Paulussen M, Ranft A, Liebscher C, Jürgens H. Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors. Pediatr Blood Cancer. 2006;47:795–800. 15. Kushner BH, Kramer K, Meyers PA, et al. Pilot study of topotecan and high-dose cyclophosphamide for resistant pediatric solid tumors. Med Pediatr Oncol. 2000;35(5):468–474. 16. Saylors RL 3rd, Stine KC, Sullivan J, et al; Pediatric Oncology Group. Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: a Pediatric Oncology Group phase II study. J Clin Oncol. 2001;19:3463–3469. 17. Casey DA, Wexler LH, Merchant MS, et al. Irinotecan and temozolomide for Ewing sarcoma: the Memorial Sloan-Kettering Experience. Pediatr Blood Cancer. 2009 Dec;53(6):1029–1034. 18. Wagner LM, McAllister N, Goldsby RE, Rausen AR, McNall- Knapp RY, McCarville MB, Albritton K. Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. Pediatr Blood Cancer. 2007;48:132–139. 19. Wagner LM, Crews KR, Iacono LC, et al. Phase I trial of temozolomide and protracted irinotecan in pediatric patients with refractory solid tumors. Clin Cancer Res. 2004;10(3):840–848. 20. McNall-Knapp RY, Williams CN, Reeves EN, et al. Extended phase I evaluation of vincristine, irinotecan, temozolomide, and antibiotic in children with refractory solid tumors. Pediatr Blood Cancer. 2010 Jul 1;54(7):909–915. 21. Blaney S, Berg SL, Pratt C, et al. A phase I study of irinotecan in pediatric patients: a pediatric oncology group study. Clin Cancer Res. 2001 Jan;7(1):32–37. 22. Furman WL, Stewart CF, Poquette CA, et al. Direct translation of a protracted irinotecan schedule from a xenograft model to a phase I trial in children. J Clin Oncol. 1999 Jun;17(6): 1815–1824. 23. McGregor LM, Stewart CF, Crews KR, et al. Dose escalation of intravenous irinotecan using oral cefpodoxime: a phase I study in pediatric patients with refractory solid tumors. Pediatr Blood Cancer. 2012;58:372–379. 24. Miser JS, Kinsella TJ, Triche TJ, et al. Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. J Clin Oncol. 1987;5:1191–1198.

25. Van Winkle P, Angiolillo A, Krailo M, et al. Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: the Children’s Cancer Group (CCG) experience. Pediatr Blood Cancer. 2005;44:338–347. 26. Navid F, Willert JR, McCarville MB, Furman W, Watkins A, Roberts W, Daw NC. Combination of gemcitabine and docetaxel in the treatment of children and young adults with refractory bone sarcoma. Cancer. 2008;113:419–425. 27. Bernstein-Molho R, Kollender Y, Issakov J, et al. Clinical activity of mTOR inhibition in combination with cyclophosphamide in the treatment of recurrent unresectable chondrosarcomas. Cancer Chemother Pharmacol. 2012;70:855–860. 28. Branstetter DG, Nelson SD, Manivel JC, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res. 2012 Aug 15; 18(16):4415–4424. 29. Thomas D, Henshaw R, Skubitz K, et al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010 Mar;11(3):275–280. 30. Kaiser U, Neumann K, Havemann K.Generalised giant-cell tumour of bone: successful treatment of pulmonary metastases with interferon alpha, a case report. J Cancer Res Clin Oncol. 1993;119(5):301–303. 31. Kaban LB, Troulis MJ, Ebb DJ, et al. Antiangiogenic therapy with interferon alpha for giant cell lesions of the jaws. Oral Maxillofac Surg. 2002 Oct;60(10):1103–1111; discussion 1111–1113. 32. Bramwell VH, Burgers M, Sneath R, et al. A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup. J Clin Oncol. 1992;10(10):1579–1591 33. Lewis IJ, Nooij MA, Whelan J, et al; MRC BO06 and EORTC 80931 collaborators; European Osteosarcoma Intergroup. Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst. 2007;99:112–128. 34. Souhami RL, Craft AW, Van der Eijken JW, et al. Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study of the European Osteosarcoma Intergroup. Lancet. 1997 Sep 27;350(9082):911–917. 35. Bacci G, Ferrari S, Bertoni F, et al. Long-term outcome for patients with nonmetastatic osteosarcoma of the extremity treated at the istituto ortopedico rizzoli according to the istituto ortopedico rizzoli/osteosarcoma-2 protocol: an updated report. J Clin Oncol. 2000;18:4016–4027. 36. Winkler K, Beron G, Delling G,Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. J Clin Oncol. 1988 Feb;6(2):329–337. 37. Bacci G, Briccoli A, Rocca M, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Ann Oncol. 2003 Jul;14(7): 1126–1134. 38. Basaran M, Bavbek ES, Saglam S, et al. A phase II study of cisplatin, ifosfamide and epirubicin combination chemotherapy in adults with nonmetastatic and extremity osteosarcomas. Oncology. 2007;72:255–260. 39. Grignani G, Palmerini E, Dileo P, et al. A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study. Ann Oncol. 2012;23:508–516. 40. Berger M, Grignani G, Ferrari S, et al. Phase 2 trial of two courses of cyclophosphamide and etoposide for relapsed high-risk osteosarcoma patients. Cancer. 2009;115:2980–2987.

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BONE CANCER COSMEGEN Recordati

℞

Actinomycin antibiotic. Dactinomycin 500mcg/ vial; lyophilized pwd for IV inj or regional perfusion after reconstitution; contains mannitol; preservative-free. Indications: In combination with other chemotherapy and/or multi-modality treatment regimen for childhood rhabdomyosarcoma, Ewing’s sarcoma. As a component of regional perfusion, for palliative and/or adjunctive treatment of locally recurrent or locoregional solid malignancies. Adults: Give by IV infusion. Childhood rhabdomyosarcoma, Ewing’s sarcoma: 15mcg/kg daily for 5 days. Regional perfusion: 50mcg/kg for lower extremity or pelvis; 35mcg/kg for upper extremity. Max 15mcg/kg/day per 2-week cycle or 400–600mcg/m2/day for five days. Use surface area to calculate dose for obese or edematous patients. Children: See literature. Contraindications: Current or recent chickenpox or herpes zoster. Warnings/Precautions: Myelosuppression; monitor bone marrow and hold treatment if platelets or WBCs decrease markedly. Extremely corrosive; avoid extravasation. Avoid skin, mucous membranes, eyes. Previous irradiation (esp. within 2 months of irradiation for treatment of rightsided Wilms’ tumor), cytotoxic chemotherapy. Monitor renal and hepatic function. Obese. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Avoid live vaccines. Concomitant radiotherapy in Wilms’ tumor: not recommended. Adverse reactions: GI upset, stomatitis, bone marrow suppression (neutropenia, thrombocytopenia), liver toxicity, infusion site reactions, malaise, fatigue, alopecia, possible second primary tumors (including leukemia); for perfusion therapy: infection, impaired wound healing, superficial ulceration of gastric mucosa, edema, soft tissue damage, possible venous thrombosis. How supplied: Vials–1

Doxorubicin HCl (various)

℞

arrhythmias). Recent MI. Previous treatment with max cumulative doses of anthracyclines, anthracenediones. Warnings/Precautions: Pre-existing heart disease or risk thereof. Obtain baseline CBC, bilirubin, AST, creatinine, LVEF. Hepatic dysfunction. Monitor cardiac function (LVEF, ECG echocardiogram), hepatic function, CBC, uric acid levels. Avoid extravasation. Children (cardiotoxicity, impaired myocardial growth). Elderly. Pregnancy (Cat.D; use adequate contraception). Nursing mothers: not recommended. Interactions: See Contraindications. Mediastinal irradiation, cyclophosphamide, calcium channel blockers, other anthracyclines increase risk of cardiac toxicity; limit lifetime dose to 400mg/m2. Necrotizing colitis with cytarabine. May increase toxicity of cyclophosphamide, mercaptopurine. May reduce serum digoxin levels. Doxorubicin toxicity increased with highdose IV progesterone, cyclosporine, streptozocin, and if given after paclitaxel infusion (give doxorubicin dose first). Elimination increased by phenobarbital. May decrease phenytoin levels. Recall pneumonitis with actinomycin and radiation in children. Adverse reactions: Local necrosis if extravasation occurs, myocardial toxicity (immediate or delayed), arrhythmias, leukemia, myelosuppression, hyperuricemia, urine discoloration, alopecia, hyperpigmentation, severe GI upset/ulceration, phlebosclerosis, facial flushing, fever, urticaria, peripheral neuropathy, anaphylaxis. How supplied: Contact supplier.

Methotrexate injection

℞

Bedford

Folic acid antagonist. Methotrexate 25mg/mL; soln for IV, IM, intra-arterial, or intrathecal administration after dilution; preservative-free. Also: Methotrexate for injection ℞ Methotrexate 1g/vial; pwd for IV, IM, intra-arterial, or intrathecal administration after dilution; preservative-free. Indications: Non-metastatic osteosarcoma in patients who have undergone surgical resection or amputation for the primary tumor (high-dose therapy with leucovorin rescue). Adults: Initially 12g/m2 IV infusion over 4 hours; may be increased to 15g/m2; see literature for leucovorin rescue dosing with high-dose methotrexate. Children: See literature. Contraindications: Pregnancy (Cat.X). Nursing mothers. Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function

every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration). Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity. Diabetes. Peptic ulcer. Ulcerative colitis. Infection. Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated. Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, non-absorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin). Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome). How supplied: Soln (2mL, 4mL, 8mL, 10mL)–10 (single-use vials); Pwd (1 gram)–1 (single-use vial)

VINCASAR PFS Teva

℞

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BONE CANCER Interactions: Concomitant radiotherapy through ports that include the liver: not recommended. Potentiated by CYP3A4 enzyme inhibitors (eg, itraconazole). Antagonizes phenytoin. Caution with other neurotoxic or platinum-containing agents. Separate L-asparaginase dose by 12–24hrs (administer after vincristine). Consider discontinuing drugs that cause urinary retention for the first few days following therapy. Adverse reactions: GI upset, paralytic ileus (esp. in children; discontinue temporarily if occurs), polyuria, dysuria, urinary retention, hypertension, hypotension, neuromuscular effects, dyspnea, bronchospasm, alopecia, rash, fever, headache, hypersensitivity reactions, acute uric acid nephropathy. How supplied: Single-use vials (1mL, 2mL)–1

VOTRIENT GlaxoSmithKline

℞

Kinase inhibitor. Pazopanib 200mg; tabs. Indications: Advanced soft tissue sarcoma in patients who have received prior chemotherapy. Adults: Take on an empty stomach. Swallow whole. 800mg once daily. Dose adjustments: see full labeling. Hepatic impairment: moderate: 200mg once daily; severe: not recommended. Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir, clarithromycin): avoid; if warranted, reduce dose of pazopanib to 400mg; may reduce further if toxicity occurs. Concomitant strong CYP3A4 inducers (eg, rifampin): avoid. Children: Not established (increased toxicity in developing organs). Warnings/Precautions: Not indicated for use in combination with other cancer agents. Not for treatment of adipocytic soft tissue sarcoma or gastrointestinal stromal tumors. Risk of severe and fatal hepatotoxicity. Monitor liver tests before starting and at least once every 4 weeks for at least the first 4 months of treatment, then periodically. If ALT between 3×ULN and 8×ULN continue therapy with weekly monitoring until ALT returns to Grade 1 or baseline. If ALT >8×ULN interrupt therapy until ALT returns to Grade 1 or baseline; may consider reintroducing at a reduced dose, measure liver tests weekly for 8 weeks; if ALT>3×ULN recurs, permanently discontinue. Permanently discontinue if ALT>3×ULN and bilirubin >2×ULN. Gilbert’s syndrome (see full labeling). History of QT prolongation. Cardiac dysfunction risk: evaluate LVEF at baseline and periodically; monitor for CHF. Monitor ECG, electrolytes (eg, calcium, magnesium, potassium), thyroid. History of hemoptysis, cerebral, or clinically significant GI hemorrhage in the past 6 months: not recommended. Risk of arterial thrombotic events (within previous 6 months: not recommended). Monitor for VTE, PE, infection, proteinuria (reduce dose if 24-hour urine protein ≥3g). Discontinue if severe and persistent hypertension (despite antihypertensives and

dose reduction) or if repeat episodes of proteinuria (despite dose reductions) occur. Stop therapy at least 7 days before surgery; discontinue in patients with wound dehiscence. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: See Adult dosing: Potentiated by strong CYP3A4 inhibitors, grapefruit juice. Antagonized by strong CYP3A4 inducers. Concomitant drugs with narrow therapeutic windows metabolized by CYP3A4, CYP2D6, or CYP2C8: not recommended. Increased risk of ALT elevations with concomitant simvastatin; caution and monitor closely; follow dosing guidelines or consider alternatives to pazopanib, or discontinuing simvastatin if develops. Caution with concomitant drugs that prolong QT interval (eg, antiarrhythmics). Adverse reactions: Diarrhea, hypertension, hair color changes, nausea, anorexia, vomiting, fatigue, decreased weight, decreased appetite, tumor pain, musculoskeletal pain, headache, dysgeusia, dyspnea, skin hypopigmentation; hepatoxicity, QT prolongation, hemorrhagic events, arterial thrombotic events (eg, MI, angina, ischemic stroke, TIA), venous thrombotic events (eg, VTE, PE), GI perforation or fistula, impaired wound healing, hypothyroidism, proteinuria, infection, reversible posterior leukoencephalopathy syndrome (discontinue if occurs). How supplied: Tabs–120

XGEVA Amgen

℞

Osteoclast inhibitor (RANKL inhibitor). Denosumab 120mg/vial (70mg/mL); soln for SC inj; preservative-free. Indications: Treatment of adults and skeletallymature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. Adults: Give by SC inj into upper arm, upper thigh, or abdomen. 120mg once every 4 weeks with additional 120mg doses on Days 8 and 15 of the 1st month of therapy. Children: Not established (interferes with bone growth and dentition). Contraindications: Pre-existing hypocalcemia. Warnings/Precautions: Correct hypocalcemia before starting; ensure adequate daily calcium, magnesium, and Vit.D intake, esp. in renal impairment (CrCl <30mL/min). Monitor calcium, phosphorus, magnesium levels in susceptible patients (eg, severe renal impairment, receiving dialysis). Monitor for osteonecrosis of the jaw. Perform oral exam and preventive dentistry before and regularly during therapy. Maintain good oral hygiene. Avoid invasive dental procedures during treatment. Evaluate for atypical fractures if thigh/groin pain develops; consider withholding therapy until risk/benefit assessment. Pregnancy (Cat.D); use highly effective contraception during therapy, and for at least 5 months after last dose. Nursing mothers:

avoid (may impair mammary gland development/ lactation). Interactions: Concomitant other denosumabcontaining products (eg, Prolia): not recommended. Concomitant drugs that can lower calcium levels; monitor. Adverse reactions: Fatigue, asthenia, hypophosphatemia, nausea, arthralgia, headache, back pain, pain in extremity, dyspnea; osteonecrosis of jaw, severe hypocalcemia (may be fatal), anaphylactic reactions (discontinue if occurs). How supplied: Single-use vial (1.7mL)–1

GENERIC NAME The active ingredients and strengths are listed under the name of each dosage form. If the product contains tartrazine, alcohol, flavors, or is alcohol-, sugar-, or dye-free, it is noted. Abbreviations are used to describe the dosage form and its formulation, e.g.: tabs = tablets caps = capsules e-c = enteric coated sust rel = sustained-release ext rel = extended-release

BRAND NAME The main name under which the product and all other dosage forms in the monograph are marketed.

LEGAL CATEGORY Federal schedule. The laws governing the prescribing/dispensing of products vary from state to state.

PHARMACOLOGIC CLASS The chemical/therapeutic class of the drug is listed in italics.

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BRAIN CANCER AFINITOR Novartis

℞

mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs. Indications: Subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC) in patients who require therapeutic intervention but are not candidates for curative surgical resection. Adults: Swallow whole with water or disperse tablet in 30mL of water and drink immediately. Take at the same time each day either consistently with or without food. BSA< 0.58m2: not studied. Initially: BSA: 0.5–1.2m2: 2.5mg once daily; 1.3–2.1m2: 5mg once daily; ≥2.2m2: 7.5mg once daily. Evaluate SEGA volume approx. 3 months after starting therapy and periodically thereafter; dose adjustments may be made at 2 week intervals. Trough concentrations should be assessed every 2 weeks, dosing should be titrated to attain a concentration of 5–10ng/mL (see literature). Severe adverse reactions: temporarily reduce dose or interrupt therapy; consider alternate day dosing for patients receiving 2.5mg daily. Severe hepatic impairment: not recommended. Concomitant strong CYP3A4 inhibitors: avoid; moderate CYP3A4 and/or PgP inhibitors: reduce dose by 50%, if CYP3A4 and/ or PgP inhibitor discontinued, return to dose used prior to initiating moderate inhibitor. Concomitant strong CYP3A4 inducers: avoid, if required, then double dose of everolimus; if discontinued, then return to dose used prior to initiating strong inducer. Continue as long as benefit observed or until unacceptable toxicity occurs. Children: <3yrs: not recommended. Contraindications: Sirolimus, temsirolimus, rapamycin allergy. Warnings/Precautions: Hepatic impairment (see Adult dose). Increased risk of infections; some may be severe or fatal. Pre-existing invasive fungal infections: treat before starting. Monitor CBCs, renal function, lipids, blood glucose, and for pneumonitis and infections: treat promptly if occur. Women of childbearing potential should use effective method of contraception during and up to 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Avoid live vaccines. Potentiated by strong CYP3A4 inhibitors, or P-glycoprotein inhibitors; avoid (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole, grapefruit juice). Caution with moderate CYP3A4 inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem) or P-glycoprotein inhibitors; reduce everolimus dose if used. Antagonized by strong CYP3A4 inducers; avoid (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s wort); increase everolimus dose if used. Adverse reactions: Pneumonitis (reduce dose and/or manage with corticosteroids; if severe, discontinue. May restart daily dose at approx. 50% lower than previously administered), infections

(discontinue if invasive systemic fungal infection develops), stomatitis (treat with non-alcoholic, non-peroxide mouthwash), GI upset, rash, fatigue, edema, fever, headache, asthenia, cough, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see literature). How supplied: Tabs–28 (4 blister cards × 7 tabs)

AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free. Indications: Glioblastoma, as a single agent for patients with progressive disease following prior therapy. Adults: Give by IV infusion after chemotherapy. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins. 10mg/kg every 2 weeks. Children: Not established. Warnings/Precautions: Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). History of hemoptysis of ≥ ½-teaspoon of red blood: do not administer. Discontinue if GI perforation, wound healing complications, serious hemorrhage, severe arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, non-GI fistula formation, or reversible posterior leukoencephalopathy syndrome occurs; suspend therapy if severe hypertension, moderate to severe proteinuria, or severe infusion reaction occurs. Cardiovascular disease. Diabetes. Renal or hepatic impairment. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis. Elderly. Increases risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy (Cat.C). Nursing mothers: not recommended. Adverse reactions: Epistaxis, headache, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome, infusion reactions, ovarian failure. How supplied: Single-use vial–1

BICNU Bristol-Myers Squibb

℞

Alkylating agent. Carmustine 100mg/vial; lyophilized pwd for IV infusion after reconstitution and dilution; preservative-free. Indications: Palliative therapy as a single agent or in combination with other chemotherapeutic agents for brain tumors (glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, metastatic brain tumors). Adults: Pretreat with antiemetics. Give by slow IV infusion. Previously untreated patients as a single

agent: Initially 150–200mg/m2 every 6 weeks. May give as one single dose or divided into daily injections (eg, 75–100mg/m2) on 2 consecutive days. Adjust subsequent doses based on hematologic response (see literature). In combination therapy: adjust doses accordingly (see literature). Children: Not recommended. Contraindications: Bone marrow suppression. Warnings/Precautions: Monitor blood counts weekly for > 6 weeks after a dose. Do not give repeat doses until platelets are >100,000/mm3 and leukocytes are 4000/mm3. Monitor liver and renal function. Perform pulmonary function tests prior to and during therapy. History of lung disease. Patients with baseline < 70% of the predicted Forced Vital Capacity or Carbon Monoxide Diffusing Capacity, and cumulative doses > 1400mg/m2 increase risk of pulmonary toxicity. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. Adverse reactions: Delayed myelosuppression leading to infection and bleeding, pulmonary toxicity, delayed pulmonary fibrosis, secondary malignancies, nausea, vomiting, hepatotoxicity, nephrotoxicity, neuroretinitis, chest pain, headache, hypersensitivity, hypotension, tachycardia. Intensive flushing of the skin and suffusion of the conjunctiva related to rapid IV infusion. How supplied: Single-use vial–1 (w. 3mL sterile diluent)

CEENU Bristol-Myers Squibb

℞

Alkylating agent. Lomustine 10mg, 40mg, 100mg; caps. Indications: Primary and metastatic brain tumors, in patients who have already received appropriate surgery and radiotherapy. Adults and Children: Pretreat with antiemetics and give on empty stomach. Give one dose every 6 weeks. Previously untreated (as a single agent): 130mg/m2. Compromised bone marrow function: 100mg/m2. Combination with other myelosuppressive drugs: adjust doses accordingly. Subsequent doses: adjust according to hematologic response (see literature). Warnings/Precautions: Monitor blood counts weekly for ≥6 weeks after a dose; repeat courses should not be given before 6 weeks (delayed hematologic toxicity) or until platelets are >100,000/mm3 or leukocytes >4000/mm3. Monitor liver and renal function. Perform pulmonary function tests prior to and frequently during therapy; increased risk of pulmonary toxicity in patients with baseline <70% of the predicted Forced Vital Capacity or Carbon Monoxide Diffusing Capacity. Pregnancy (Cat.D). Nursing mothers: not recommended. Adverse reactions: Delayed or cumulative myelosuppression (thrombocytopenia, leukopenia) leading to infection or bleeding, pulmonary toxicity, delayed pulmonary fibrosis, secondary malignancies, liver and renal dysfunction, nausea, vomiting, stomatitis, alopecia, optic atrophy, visual disturbances, disorientation, lethargy, ataxia, dysarthria. Note: Wear gloves when handling capsules. How supplied: Caps–20; Dose pack (100mg–2 caps, 40mg–2 caps, 10mg–2 caps)–1

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BRAIN CANCER Cyclophosphamide (various)

℞

Alkylating agent. Cyclophosphamide 25mg, 50mg; tabs. Indications: Neuroblastoma (disseminated disease). Adults: Initial and maintenance: 1–5mg/kg/day. Children: See literature. ℞ Also: CYTOXAN INJECTION Bristol-Myers Squibb Cyclophosphamide 500mg, 1g, 2g; per vial; pwd for inj after reconstitution; preservative-free. Adults: Initially 40–50mg/kg IV in divided doses over 2–5 days; or 10–15mg/kg IV every 7–10 days; or 3–5mg/kg IV twice weekly. Children: See literature. Contraindications: Severe bone marrow depression. Warnings/Precautions: Leukopenia. Thrombocytopenia. Tumor cell infiltration of bone marrow. Previous X-ray therapy or cytotoxic chemotherapy. Impaired renal or hepatic function. Infections. Adrenalectomy. General anesthesia within 10 days of therapy. Monitor hematologic profile (esp. neutrophils and platelets). Obtain urine sample (monitor for hemorrhagic cystitis); maintain adequate hydration. May interfere with wound healing. Elderly. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Potentiated by phenobarbital. Potentiates other myelosuppressives, radiotherapy, succinylcholine. May potentiate doxorubicin-induced cardiotoxicity. Adverse reactions: GI upset, alopecia, leukopenia, infections, thrombocytopenia, anemia, hemorrhagic cystitis (discontinue if occurs), renal tubular necrosis, interstitial pulmonary fibrosis, gonadal toxicity (amenorrhea, infertility), anaphylactic reactions. How supplied: Tabs–contact supplier Single-use vial–1

Doxorubicin HCl (various)

℞

Anthracycline. Doxorubicin HCl 10mg/vial, 20mg/vial, 50mg/vial; pwd for IV inj after reconstitution; contains lactose. ℞ Also: Doxorubicin HCl Solution Doxorubicin HCl 2mg/mL; soln for IV inj. Indications: Disseminated neoplasias (eg, neuroblastoma). Adults and Children: Monotherapy: usually 60–75mg/m2 IV every 21 days. Combination therapy: usually 40–60mg/m2 IV every 21 to 28 days. Hyperbilirubinemia, inadequate bone marrow reserves: reduce dose. Contraindications: Severe myelosuppression (baseline neutrophils <1500cells/mm3) or severe hepatic impairment. Cardiac disease (eg, severe myocardial insufficiency, arrhythmias). Recent MI. Previous treatment with max cumulative doses of anthracyclines, anthracenediones. Warnings/Precautions: Pre-existing heart disease or risk thereof. Obtain baseline CBC, bilirubin, AST, creatinine, LVEF. Hepatic dysfunction. Monitor cardiac function (LVEF, ECG echocardiogram), hepatic function, CBC, uric acid levels. Avoid extravasation. Children (cardiotoxicity,

impaired myocardial growth). Elderly. Pregnancy (Cat.D; use adequate contraception). Nursing mothers: not recommended. Interactions: See Contraindications. Mediastinal irradiation, cyclophosphamide, calcium channel blockers, other anthracyclines increase risk of cardiac toxicity; limit lifetime dose to 400mg/m2. Necrotizing colitis with cytarabine. May increase toxicity of cyclophosphamide, mercaptopurine. May reduce serum digoxin levels. Doxorubicin toxicity increased with high-dose IV progesterone, cyclosporine, streptozocin, and if given after paclitaxel infusion (give doxorubicin dose first). Elimination increased by phenobarbital. May decrease phenytoin levels. Recall pneumonitis with actinomycin and radiation in children. Adverse reactions: Local necrosis if extravasation occurs, myocardial toxicity (immediate or delayed), arrhythmias, leukemia, myelosuppression, hyperuricemia, urine discoloration, alopecia, hyperpigmentation, severe GI upset/ulceration, phlebosclerosis, facial flushing, fever, urticaria, peripheral neuropathy, anaphylaxis. How supplied: Contact supplier.

GLIADEL Eisai

℞

Nitrosurea. Carmustine 7.7mg, polifeprosan 20; per wafer. Indications: Newly-diagnosed high-grade malignant glioma as an adjunct to surgery and radiation. Recurrent glioblastoma multiforme as an adjunct to surgery. Adults: See literature. Place 8 wafers (61.6mg) in the resection cavity if the size and shape of it allows; max 8 wafers per surgical procedure. Children: Not recommended. Warnings/Precautions: Avoid communication between surgical resection cavity and ventricular system to prevent wafer from migrating and causing obstructive hydrocephalus. If communication larger than diameter of wafer exists, it should be closed prior to wafer implantation. Pregnancy (Cat.D). Nursing mothers: not recommended. Adverse reactions: Abdominal pain, back pain, chest pain, intracranial hypertension, abnormal healing, brain edema, meningitis or abscess; intracerebral mass effect. How supplied: Single-dose treatment box (8 wafers)–1

TEMODAR Merck

℞

Alkylating agent. Temozolomide 5mg, 20mg, 100mg, 140mg, 180mg, 250mg; caps. Indications: Newly diagnosed glioblastoma multiforme. Refractory anaplastic astrocytoma. Adults: See literature for monitoring and dose adjustment guidelines. Swallow whole with water; take on empty stomach at bedtime to reduce nausea, pretreat with antiemetics. Glioma: Concomitant phase, for newly diagnosed: 75mg/m2 daily for 42 days with focal radiotherapy; Maintenance phase, cycle 1: 150mg/m2 once daily for 5 consecutive days, then 23 days off; for cycles 2 through 6: increase to 200mg/m2 once daily for 5 consecutive days if tolerated, then 23 days off.

Anaplastic astrocytoma: 150mg/m2 once daily for 5 consecutive days per 28-day treatment cycle; increase dose in subsequent cycles to 200mg/m2 if tolerated; continue until disease progression, discontinue if minimum dose not tolerated. Children: Not recommended. Contraindications: Hypersensitivity to dacarbazine. Warnings/Precautions: Myelosuppression (higher risk in women or elderly, esp. in 1st cycle). Do not begin therapy unless hematology (ANC and platelets) is acceptable. Do CBC on day 22 of each cycle or within 48 hours of that day; repeat weekly until recovery if ANC or platelets fall below acceptable limits. Glioblastoma: monitor for and provide prophylaxis against P. carinii pneumonia (PCP). Severe renal or hepatic impairment. Avoid inhalation, and skin/mucous membrane contact, of capsule contents. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. See literature. Interactions: Valproic acid may increase temozolomide levels. Adverse reactions: Nausea, vomiting, anorexia, constipation, headache, other GI or CNS effects, alopecia, fatigue, convulsions, hemiparesis, fever, edema; myelosuppression (may be dose-limiting; see literature); others. How supplied: Caps 5mg, 20mg, 100mg, 140mg 180mg–5, 14; 250mg–5

VINCASAR PFS Teva

℞

Antimicrotubule agent. Vincristine sulfate 1mg/mL; soln for IV inj; contains mannitol; preservative-free. Indications: In combination with other chemotherapeutic agents for neuroblastoma. Adults: Usual dose: 1.4mg/m2 IV once weekly. Serum bilirubin >3mg/100mL: reduce dose by 50%. Children: ≤10kg: initially 0.05mg/kg IV once weekly. >10kg: usual dose: 2mg/m2 IV once weekly. Contraindications: Demyelinating form of Charcot-Marie-Tooth syndrome. Warnings/Precautions: For IV use only; fatal if given intrathecally. Hepatic dysfunction. Pre-existing neuromuscular disease. Obtain CBCs, platelets before each dose, then periodically. Monitor serum uric acid levels during first 3–4 weeks of treatment. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Concomitant radiotherapy through ports that include the liver: not recommended. Potentiated by CYP3A4 enzyme inhibitors (eg, itraconazole). Antagonizes phenytoin. Caution with other neurotoxic or platinum-containing agents. Separate L-asparaginase dose by 12–24hrs (administer after vincristine). Consider discontinuing drugs that cause urinary retention for the first few days following therapy. Adverse reactions: GI upset, paralytic ileus (esp. in children; discontinue temporarily if occurs), polyuria, dysuria, urinary retention, hypertension, hypotension, neuromuscular effects, dyspnea, bronchospasm, alopecia, rash, fever, headache, hypersensitivity reactions, acute uric acid nephropathy. How supplied: Single-use vials (1mL, 2mL)–1

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BREAST CANCER Breast Cancer (Invasive) Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are category 2A unless otherwise indicated.

Preferred Regimens for HER2-negative Disease1 REGIMEN

DOSING

Dose-dense AC followed by paclitaxel2

• Doxorubicin 60mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 14 days for 4 cycles. Followed by: • Paclitaxel 175mg/m2 via 3-hour IV infusion day 1 Cycled every 14 days for 4 cycles. (All cycles are with filgrastim support)

Dose-dense AC followed by weekly paclitaxel2

• Doxorubicin 60mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 14 days for 4 cycles. Followed by: • Paclitaxel 80mg/m2 via 1-hour IV infusion weekly for 12 weeks.

TC3

• Docetaxel 75mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days for 4 cycles. (All cycles are with filgrastim support)

Other Regimens for HER2-negative Disease1 AC4

• Doxorubicin 60mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days for 4 cycles.

TAC5

• Docetaxel 75mg/m2 IV day 1 • Doxorubicin 50mg/m2 IV day • Cyclophosphamide 500mg/m2 IV day 1 Cycled every 21 days for 6 cycles. (All cycles are with filgrastim support)

FAC6,7

• 5-fluorouracil 500mg/m2 IV days 1 and 8 or days 1 and 4 • Doxorubicin 50mg/m2 IV day 1 (or via 72-hour continuous infusion) • Cyclophosphamide 500mg/m2 IV day 1 Cycled every 21 days for 6 cycles.

CAF8

• Cyclophosphamide 100mg/m2 PO days 1–14 • Doxorubicin 30mg/m2 IV days 1 and 8 • 5-fluorouracil 500mg/m2 IV days 1 and 8 Cycled every 28 days for 6 cycles.

CEF9

• Cyclophosphamide 75mg/m2 PO days 1–14 • Epirubicin 60mg/m2 IV days 1 and 8 • 5-fluorouracil 500mg/m2 IV days 1 and 8 With cotrimoxazole support. Cycled every 28 days for 6 cycles.

CMF10

• Cyclophosphamide 100mg/m2 PO days 1–14 • Methotrexate 40mg/m2 IV days 1 and 8 • 5-fluorouracil 600mg/m2 IV days 1 and 8 Cycled every 28 days for 6 cycles.

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BREAST CANCER REGIMEN

DOSING

AC followed by docetaxel11

• Doxorubicin 60mg/m2 IV on day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days for 4 cycles. Followed by: • Docetaxel 100mg/m2 IV on day 1 • Cycled every 21 days for 4 cycles.

AC followed by weekly paclitaxel11

• Doxorubicin 60mg/m IV on day 1 • Cyclophosphamide 600mg/m IV on day 1 Cycled every 21 days for 4 cycles. Followed by: Paclitaxel 80mg/m by 1-hour IV infusion weekly for 12 weeks.

EC12

• Epirubicin 100mg/m2 IV day 1 • Cyclophosphamide 830mg/m2 IV day 1 Cycled every 21 days for 8 cycles.

FEC followed by docetaxel13

• 5-fluorouracil 500mg/m2 IV day 1 • Epirubicin 100mg/m2 IV day 1 • Cyclophosphamide 500mg/m2 IV day 1 Cycled every 21 days for 3 cycles. Followed by: • Docetaxel 100mg/m2 IV day 1 Cycled every 21 days for 3 cycles.

FEC followed by weekly paclitaxel14

• 5-fluorouracil 600mg/m2 IV day 1 • Epirubicin 90mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days for 4 cycles. Followed by: • 3 weeks of no treatment. Followed by: • Paclitaxel 100mg/m2 IV infusion weekly for 8 weeks.

FAC followed by weekly paclitaxel

• 5-fluorouracil 500mg/m2 IV days 1 and 8 (or days 1 and 4) • Doxorubicin 50mg/m2 IV day 1 (or via 72-hour continuous infusion) • Cyclophosphamide 500mg/m2 IV day 1 Cycled every 21 days for 6 cycles. Followed by: • Paclitaxel 80mg/m2 via 1-hour IV infusion weekly for 12 weeks.

Preferred Regimens for HER2-positive Disease1 AC followed by paclitaxel with trastuzumab15

• Doxorubicin 60mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days for 4 cycles. Followed by: • Paclitaxel 80mg/m2 via 1-hour IV infusion weekly for 12 weeks, with: • Trastuzumab 4mg/kg IV with first dose of paclitaxel Followed by: • Trastuzumab 2mg/kg IV weekly to complete 1 year of treatment. As an alternative, trastuzumab 6mg/kg IV every 21 days may be used following the completion of paclitaxel, and given to complete 1 year of trastuzumab treatment. Cardiac monitoring at baseline, 3, 6, and 9 months.

AC followed by paclitaxel with trastuzumab + pertuzumab

• Doxorubicin 60mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days for 4 cycles. Followed by: • Pertuzumab 840mg IV day 1 followed by 420mg IV • Trastuzumab 8mg/kg IV day 1 followed by 6mg/kg IV • Paclitaxel 80mg/m2 IV days 1, 8, and 15 Cycled every 21 days for 4 cycles. • Trastuzumab 6mg/kg IV day 1 Cycled every 21 days to complete 1 year of trastuzumab therapy. Cardiac monitoring at baseline, 3, 6, and 9 months. continued

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BREAST CANCER Breast Cancer (Invasive) Treatment Regimens Preferred Regimens for HER2-positive Disease1 (continued) REGIMEN

DOSING

Dose-dense AC followed by paclitaxel with trastuzumab16

• Doxorubicin 60mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 14 days for 4 cycles. Followed by: • Paclitaxel 175mg/m2 via 3-hour IV infusion day 1 (All cycles are with filgrastim support) Cycled every 14 days for 4 cycles, with: • Trastuzumab 4mg/kg IV with first dose of paclitaxel Followed by: • Trastuzumab 2mg/kg IV weekly to complete 1 year of treatment. As an alternative, trastuzumab 6mg/kg IV every 21 days may be used following the completion of paclitaxel, and given to complete 1 year of trastuzumab treatment. Cardiac monitoring at baseline, 3, 6, and 9 months.

TCH17

• Docetaxel 75mg/m2 IV day 1 • Carboplatin AUC 6 IV day 1 Cycled every 21 days for 6 cycles, with: • Trastuzumab 4mg/kg IV week 1 Followed by: • Trastuzumab 2mg/kg IV for 17 weeks Followed by: • Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. Cardiac monitoring at baseline, 3, 6, and 9 months.

TCH chemotherapy + pertuzumab18

• Trastuzumab 8mg/kg IV day 1 followed by 6mg/kg IV • Pertuzumab 840mg IV day 1 followed by 420mg IV • Docetaxel 75mg/m2 IV day 1 • Carboplatin AUC 6 IV day 1 Cycled every 21 days for 6 cycles. Followed by: • Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. Cardiac monitoring at baseline, 3, 6, and 9 months.

Other Regimens for HER2-positive Disease1 AC followed by docetaxel with trastuzumab17

• Doxorubicin 60mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 day 1 Cycled every 21 days for 4 cycles. Followed by: • Docetaxel 100mg/m2 IV day 1 Cycled every 21 days for 4 cycles, with: • Trastuzumab 4mg/kg IV week 1 Followed by: • Trastuzumab 2mg/kg IV weekly for 11 weeks Followed by: • Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. Cardiac monitoring at baseline, 3, 6, and 9 months.

AC followed by docetaxel with trastuzumab and pertuzumab

• Doxorubicin 60mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days for 4 cycles. Followed by: • Pertuzumab 840mg IV day 1 followed by 420mg IV • Trastuzumab 8mg/kg IV day I followed by 6mg/kg IV • Docetaxel 75–100mg/m2 IV day 1 Cycled every 21 days for 4 cycles. Followed by: • Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. Cardiac monitoring at baseline, 3, 6, and 9 months.

FEC followed by pertuzumab + trastuzumab + docetaxel18

• Fluorouracil 500mg/m2 IV day 1 • Epirubicin 100mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days for 3 cycles. Followed by: • Pertuzumab 840mg IV day 1 followed by 420mg IV • Trastuzumab 8mg/kg IV day 1 followed by 6mg/kg IV • Docetaxel 75–100mg/m2 IV day 1 Cycled every 21 days for 3 cycles. Followed by: • Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. Cardiac monitoring at baseline, 3, 6, and 9 months.

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MASTER CANCER TREATMENT REGIMEN

BREAST CANCER REGIMEN

DOSING

FEC followed by pertuzumab + trastuzumab + paclitaxel

• Fluorouracil 500mg/m2 IV day 1 • Epirubicin 100mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days for 3 cycles. Followed by: • Pertuzumab 840mg IV day 1 followed by 420mg IV • Trastuzumab 8mg/kg IV day 1 followed by 6mg/kg IV • Paclitaxel 80mg/m2 IV days 1, 8, and 15 Cycled every 21 days for 3 cycles. Followed by: • Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. Cardiac monitoring at baseline, 3, 6, and 9 months.

Pertuzumab + trastuzumab + docetaxel followed by FEC19

• Pertuzumab 840mg IV day 1 followed by 420mg IV • Trastuzumab 8mg/kg IV day 1 followed by 6mg/kg IV • Docetaxel 75–100mg/m2 IV day 1 Cycled every 21 days for 4 cycles. Followed by adjuvant therapy: • Fluorouracil 600mg/m2 IV day 1 • Epirubicin 90mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days for 3 cycles. Followed by: • Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. Cardiac monitoring at baseline, 3, 6, and 9 months.

Pertuzumab + trastuzumab + paclitaxel followed by FEC

• Pertuzumab 840mg IV day 1 followed by 420mg IV • Trastuzumab 8mg/kg IV day 1 followed by 6mg/kg IV • Paclitaxel 80mg/m2 IV days 1, 8, and 15 Cycled every 21 days for 4 cycles. Followed by adjuvant therapy: • Fluorouracil 600mg/m2 IV day 1 • Epirubicin 90mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days for 3 cycles. Followed by: • Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. Cardiac monitoring at baseline, 3, 6, and 9 months.

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.1.2014. Available at: http://www.nccn.org. Accessed February 14, 2014. 2. Citron ML, Berry DA, Cirrincione C, et al: Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21:1431–1439. 3. Jones S, Holmes F, O’Shaughnessey J, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-yearfollow-up of US Oncology Research trial 9735. J. Clin Oncol. 2009;27:1177–1183. 4. Fisher B, Brown AM, Dimitrov NV, et al: Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with six months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: Results from NSABP B-15. J Clin Oncol. 1990;8:1483–1496. 5. Martin. Pienkowski T, Mackey J, et al: Adjuvant docetaxel for node-positive breast cancer. N Engl J. Med. 2005;352:22. 6. Buzdar AU, Kau SW, Smith TL, Hortobagyi GN. Ten-year results of FAC adjuvant chemotherapy trial in breast cancer. Am J Clin Oncol. 1989;12:123–128. 7. Assikis V, Buzdar A, Yang Y, et al: A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003;97:2716–2723. 8. Bull JM, Tormey DC, Li SH, et al: A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer. 1978;41:1649–1657. 9. Levine MN, Bramwell VH, Pritchard KI, et al: Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer institute of Canada Clinical Trials Group. J Clin Oncol. 1998;16:2651–2658.

10. Goldrhirsch A, Colleoni M, Coates AS, et al: Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all CMFs alike? The International Breast Cancer Study Group (IBCSG). Ann Oncol. 1998;9:489–493. 11. Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in adjuvant treatment of breast cancer. N Engl J Med. 2008; 258:1663–1671. 12. Piccart MJ, Di Leo A, Beauduin M, et al: Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001;19:3103–3110. 13. Roche H, Fumoleau P, Spielmann M, et al. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: The FNCLCC PACS 001 trial. J Clin Oncol. 2006;24:5664–5671. 14. Martin M, Rodriguez-Lescure A, Ruiz A, et al: Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Nati Cancer Inst. 2008;100:805–814. 15. Romond EH, Perez EZ, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2 positive breast cancer. N Engl J Med. 2005;353:1673–1684. 16. Dang C, Fornier M, Sugarman S, et al: The Safety of Dose-Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel with Trastuzumab in HER-2/neu Overexpressed/Amplified Breast Cancer. J. Clin Oncol. 2008;26(8):1216–1222. 17. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365: 1273–1283. 18. Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline—containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24:2278–2284. 19. Gianni L, al e. Neoadjuvant pertuzumab (P) and trastuzumab (H): Antitumor and safety analysis of a randomized phase II study (NeoSphere) [abstract]. San Antonio Breast Cancer Symposium 2010;Abstract S3-2.

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MASTER CANCER TREATMENT REGIMEN

BREAST CANCER Breast Cancer (Recurrent or Metastatic) Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are category 2A unless otherwise indicated.

Preferred Single Agents1 REGIMEN

DOSING

Doxorubicin

60–75mg/m2 IV day 1 every 21 days2 OR 20mg/m2 IV day 1 weekly3

Pegylated liposomal doxorubicin4

50mg/m2 IV day 1 every 28 days

Paclitaxel

175mg/m2 IV day 1 every 21 days5 OR 80mg/m2 IV day 1 weekly6

Capecitabine7

1,000–1,250mg/m2 PO twice daily days 1–14 cycled every 28 days

Gemcitabine8

800–1,200mg/m2 IV days 1, 8, and 15 cycled every 28 days

Vinorelbine9

25mg/m2 IV day 1 weekly

Eribulin10

1.4mg/m2 IV days 1 and 8 cycled every 21 days

Other Single Agents1 Cyclophosphamide11

50mg PO daily on days 1–21 cycled every 28 days

Carboplatin

AUC 6 IV on day 1 cycled every 21–28 days

Docetaxel13,14

60–100mg/m2 IV day 1cycled every 21 days OR 40mg/m2 IV weekly for 6 weeks followed by a 2-week rest, then repeat15

Albumin-bound paclitaxel

100mg/m2 or 150mg/m2 IV days 1, 8, and 15 cycled every 28 days16,17 OR 260mg/m2 IV cycled every 21 days16

Cisplatin18

75mg/m2IV on day 1 cycled every 21 days

Epirubicin19

60–90mg/m2 IV day 1 cycled every 21 days

Ixabepilone20

40mg/m2 IV day 1 cycled every 21 days

Chemotherapy Combinations1 CAF21

• Cyclophosphamide 100mg/m2 PO days 1–14 • Doxorubicin 30mg/m2 IV days 1 and 8 • 5-fluorouracil 500mg/m2 IV days 1 and 8 Cycled every 28 days

FAC22

• 5-fluorouracll 500mg/m2 IV days 1 and 8 or days 1 and 4 • Doxorubicin 50mg/m2 IV day 1 (or by 72-hour continuous infusion) • Cyclophosphamide 500mg/m2 IV day 1 Cycled every 21 days for 6 cycles

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MASTER CANCER TREATMENT REGIMEN

BREAST CANCER REGIMEN

DOSING

FEC23

• Cyclophosphamide 400mg/m2 IV days 1 and 8 • Epirubicin 50mg/m2 IV days 1 and 8 • 5-fluorouracil 500mg/m2 IV days 1 and 8 Cycled every 28 days

AC24

• Doxorubicin 60mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days

EC25

• Epirubicin 75mg/m2 IV day 1 • Cyclophosphamide 600mg/m2 IV day 1 Cycled every 21 days

CMF26

• Cyclophosphamide 100mg/m2 PO days 1–14 • Methotrexate 40mg/m2 IV days 1 and 8 • 5-fluorouracll 600mg/m2 IV days 1 and 8 Cycled every 28 days

Docetaxel/capecitabine26

• Docetaxel 75mg/m2 IV day 1 • Capecitabine 950mg/m2 PO twice daily days 1–14 Cycled every 21 days

GT28

• Paclitaxel 175mg/m2 IV day 1 • Gemcitabine 1,250mg/m2 IV days 1 and 8 (following paclitaxel on day 1) Cycled every 21 days

Gemcitabine/carboplatin29

• Gemcitabine 1,000mg/m2 on days 1 and 8 • Carboplatin AUC 2 IV on days 1 and 8 Cycled every 21 days

Paclitaxel plus bevacizumab30

• Paclitaxel 90mg/m2 by 1-hour IV days 1, 8, and 15 • Bevacizumab 10mg/kg IV days 1 and 15 Cycled every 28 days

Preferred First-Line Agents for HER2-Positive Disease1 General treatment note: All trastuzumab-containing regimens require cardiac monitoring at baseline and at Months 3, 6, and 9.1

Pertuzumab + trastuzumab + docetaxel31

• Pertuzumab 840mg IV day 1 followed by 420mg IV • Trastuzumab 8mg/kg IV day 1 followed by 6mg/kg IV • Docetaxel 75–100mg/m2 IV day 1 Cycled every 21 days

Pertuzumab + trastuzumab + weekly paclitaxel32

• Pertuzumab 840mg IV day 1 followed by 420mg IV cycled every 21 days • Trastuzumab — 4mg/kg IV day 1 followed by 2mg/kg IV weekly OR — 8mg/kg IV day 1 followed by 6mg/kg IV cycled every 21 days32 • Paclitaxel 80mg/m2 IV day 1 weekly32 OR • Paclitaxel 175mg/m2 day 1 cycled every 21 days

Other First-Line Agents For HER2-Positlve Disease1 Paclitaxel/carboplatin + trastuzumab34

• Carboplatin AUC 6 IV day 1 • Paclitaxel 175mg/m2 IV day 1 cycled every 21 days • Trastuzumab — 4mg/kg IV day 1 followed by 2mg/kg IV weekly OR — 8mg/kg IV day 1 followed by 6mg/kg IV every 21 days33 continued

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BREAST CANCER Breast Cancer (Recurrent or Metastatic) Treatment Regimens Other First-Line Agents For HER2-Positlve Disease1 (continued) REGIMEN

DOSING

Weekly paclitaxel/carboplatin + trastuzumab35

• Paclitaxel 80mg/m2 IV days 1, 8, and 15 • Carboplatin AUC 2 IV days 1, 8, and 15 cycled every 28 days • Trastuzumab — 4mg/kg IV day 1 followed by 2mg/kg IV weekly OR — 8mg/kg IV day 1 followed by 6mg/kg IV every 21 days33

Trastuzumab + paclitaxel

• Paclitaxel — 175mg/m2 IV day 1 cycled every 21 days36 OR — 80-90mg/m2 IV day 1 weekly • Trastuzumab — 4mg/kg IV day 1 followed by 2mg/kg IV weekly OR — 8mg/kg IV day 1 followed by 6mg/kg IV every 21 days33

Trastuzumab + docetaxel

• Docetaxel — 80–100mg/m2 IV day 1 cycled every 21 days38 OR — 35mg/m2 IV days 1, 8, and 15 weekly39 • Trastuzumab — 4mg/kg IV day 1 followed by 2mg/kg IV weekly OR — 8mg/kg IV day 1 followed by 6mg/kg IV every 21 days33

Trastuzumab + vinorelbine40,41

• Vinorelbine — 25mg/m2 IV day 1 weekly OR — 30–35mg/m2 IV days 1 and 8 cycled every 21 days • Trastuzumab — 4mg/kg IV day 1 followed by 2mg/kg IV weekly OR — 8mg/kg IV day 1 followed by 6mg/kg IV every 21 days33

Trastuzumab + capecitabine42

• Capecitabine 1,000–1,250mg/m2 PO twice daily days 1–14 cycled every 21 days • Trastuzumab — 4mg/kg IV day 1 followed by 2mg/kg IV weekly36,43 OR — 8mg/kg IV day 1 followed by 6mg/kg IV every 21 days33

Preferred Agents for Trastuzumab-Exposed HER2-Positive Disease1 Ado-trastuzumab emtansine (T-DM1)44

3.6mg/kg IV day 1 cycled every 21 days

Other Agents for Trastuzumab-Exposed HER2-Positlve Disease1 Lapatinib + capecitabine45

• Lapatinib 1,250mg PO daily days 1–21 • Capecitabine 1,000mg/m2 PO twice daily days 1–14 cycled every 21 days

Trastuzumab + capecitabine46

Trastuzumab + lapatinib47

• Lapatinib 1,000mg PO daily • Trastuzumab — 4mg/kg IV day 1 followed by 2mg/kg IV weekly OR — 8mg/kg IV day 1 followed by 6mg/kg IV every 21 days33

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MASTER CANCER TREATMENT REGIMEN

BREAST CANCER References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.1.2014. Available at: http://www.nccn.org. Accessed February 14, 2014. 2. Chan S, Friedrichs K, Noel D, et al. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol. 1999;17:2341–2354. 3. Gundersen S, Kvinnsland S, Klepp O, et al. Weekly adriamycin versus VAC in advanced breast cancer. A randomized trial. Eur J Cancer Clin Oncol. 1986;22:1431–1434. 4. O’Brien ME, Wigler N, Inbar M, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCI (CAELYX/DoxiI) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15:440–449. 5. Seidman AD, Tiersten A, Hudis C, et al. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol. 1995;13:2575–2581. 6. Perez EA, Vogel CL, Irwin DH, et al. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001;19:4216–4223. 7. Bajetta E, Procopio G, Celio L, et al. Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol. 2005;23:2155–2161. 8. Seidman AD. Gemcitabine as single-agent therapy in the management of advanced breast cancer. Oncology. (Williston Park) 2001;15:11–14. 9. Zelek L, Barthier S, Riofrio M, et al. Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma. Cancer. 2001;92:2267–2272. 10. Cortes J, O’Shaughnessy J, Loesch O, et al. Eribulin monotherapy versus treatment of physicians choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomized study. Lancet. 2011;377:914–923. 11. Licchetta A, Correale P, Migali C, et al. Oral metronomic chemo- hormonal-therapy of metastatic breast cancer with cyclophosphamide and megestrol acetate. J Chemother. 2010;22(3):201–204. 12. Isakoff S J, Goss PE, Mayer EL, et al. TBCRCOO9: A multi-center phase II study of cisplatin or carboplatin for metastatic triple-negative breast cancer and evaluation of p631p73 as a biomarker of response [abstract). J Clin Oncol. 2011;29 (15_suppl): Abstract 1025. 13. Burriss HA 3rd. Single-agent docetaxel (Taxotere) in randomized phase Ill trials. Semin Oncol. 1999;26:1–6. 14. Harvey V, Mouridsen H, Semiglazov V, et al: Phase Ill trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol. 2006;24(31):4963–4970. 15. Burstein HJ, Manola J, Younger J, et al. Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol. 2000;18:1212–1219. 16. Gradishar W, Tjulandin S. Davidson N, et al. Phase Ill trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005;23:7794–7803. 17. Gradishar W, Dimitry K, Sergey C, et al: Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009;27(22):3611–3619. 18. Silver DR, Richardson AL, EkIund AC, et al. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol. 2010;28(7):1145–1153. 19. Bastholt L, Dalmark M, Gjedde SB, et al. Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer a randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 1996;14:1146–1155. 20. Perez E, Lerzo G, Pivot X, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007;25(23):3407–3414. 21. Bull JM, Tormey DC, Li SH, et al. A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer. 1978;41:1649–1657. 22. Hortobagyi GN, Gutterman JU, Blumenschein GR, et al: Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG. Cancer. 1979;43:1225–33. 23. Ackland SR, Anton A, Breithach GR, et al. Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer a randomized multinational study. J Clin Oncol. 2001;19:943–953. 24. Nabholtz JM, Falkson C, Campos O, et al: Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer results of a randomized, multicenter, phase Ill trial. J Clin Oncol. 2003;21(6):968–975.

25. Langley RE, Carmichel J, Jones AL, et al. Phase Ill trial of epirubicin plus paclitaxel compared with epirubicin plus cyclophosphamide as first-line chemotherapy for metastatic breast cancer United Kingdom Cancer Research Institute. J Clin Oncol. 2005;23:8322–8330. 26. Bonadonna G, Brusamolino E, Valagussa P, et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976;294:405–410. 27. O’Shaughnessy J, Miles D, Vukelja S, et al. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer phase Ill thai results. J Clin Oncol. 2002;20:2812–2823. 28. Albain KS, Nag S, Calderillo-Ruiz G, et al Gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol. 2008;26(24):3950–3957. 29. O’Shaughnessy J, Schwartzberg LS, Danso MA, et al. A randomized phase ill study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (GIC) in metastatic triple-negative breast cancer (TNBC). [abstract]. J Clin Oncol. 2011;29(Suppl_15):Abstract 1007. 30. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizurriab versus paclitaxel alone for metastatic breast cancer. N EngI J Med. 2007;357:2666–2676. 31. Baselga J, Cones J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N EngI J Med. 2012;366:109–119. 32. Datko F, D’Andrea G, Dickler M, et al. Phase II study of pertuzumab, trastuzumab, and weekly paclitaxel in patients with metastatic HER2-overexpressing metastatic breast cancer [abstract]. Cancer Research. 2012;72: Abstract P5-18–20. 33. Leyland-Jones B, Gelmon K, Ayoub JP, et al. Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol. 2003;21: 3965–3971. 34. Robert N, Leyland-Jones B, Asmar L, et al. Randomized phase III study of trastuzumab, paclitaxel, and carboplatin compared with trastuzumab and paclitaxel in women with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2006;24: 2786–2792. 35. Perez EA, Suman VJ, Rowland KM, et al. Two concurrent phase II trials of paclitaxel/ carboplatin/trastuzumab (weekly or every-3-week schedule) as first-line therapy in women with HER2-overexpressing metastatic breast cancer: NCCTG study 983252. Clin Breast Cancer. 2005;6:425–432. 36. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N EngI J Med. 2001; 344:783–792. 37. Seidman A, Berry DA, Cirrincione C, et al. Randomized phase Ill trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008;26: 1642–1649. 38. Marty M, Cognetti F, Maraninchi O, et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005;23:4265–4274. 39. Esteva FJ, Valero V, Booser O, et al. Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20: 1800–1808. 40. Burstein HJ, Keshaviah A, Baron AD, et al. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer the trastuzumab and vinorelbine or taxane study. Cancer. 2007;110:965–972. 41. Andersson M, Lidbrink E, Bjerre K, et al. Phase III randomized study comparing docetaxel plus trastuzumab with vinorelbine plus trastuzumab as first-line therapy for metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer: the HERNATA study. J Clin Oncol. 2011;29: 264–271. 42. von Minckwitz G, du Bois A, Schmidt M, et al. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer a German breast group 26/breast international group 03-05 study. J Clin Oncol. 2009;27:1999–2006. 43. Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational study of the efficacy and safety of humanized anti-l-IER2 ruonodonal antibody in women who have HER2overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999;17:2639–2648. 44. Verma S, Miles O, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer (supplementary appendix available online]. N EngI J Med. 2012;367:1783–1791. 45. Geyer C, Forster J, Undquist O, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006:355:2733–2743. 46. Bartsch R, Wenzel C, Altorjai G, et al. Capecitabine and trastuzumab in heavily pretreated metastatic breast cancer. J Clin Oncol. 2007;25:3853–3858. 47. Blackwell KL, Burstein H, Storniolo AM, et al. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive. Trastuzumabrefractory metastatic breast cancer. J Clin Oncol. 2010;28(7):1124–1130. (Revised 2/2014) © 2014 Haymarket Media, Inc.

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BREAST CANCER ABRAXANE Celgene

℞

Taxane antimicrotubule. Paclitaxel [bound to albumin (human)] 100mg/vial; pwd for IV infusion after reconstitution; solvent-free. Indications: Treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy (prior therapy should have included an anthracycline unless clinically contraindicated). Adults: Do not treat if neutrophil count <1,500 cells/mm3 or platelets <100,000 cells/mm3. 260mg/m2 by IV infusion over 30 minutes every 3 weeks. If severe neutropenia (neutrophil <500 cells/mm3 for ≥1week) or severe sensory neuropathy occurs: reduce subsequent doses to 220mg/m2; reduce to 180mg/m2 if severe neutropenia or sensory neuropathy recurs. If grade 3 sensory neuropathy occurs, suspend use until resolution to grade 1 or 2; reduce subsequent doses. Hepatic impairment: see full labeling. Avoid extravasation. Children: Not evaluated. Contraindications: Baseline neutrophil count <1,500 cells/mm3. Prior severe hypersensitivity reaction (do not rechallenge). Warnings/Precautions: Do not substitute for, or with, other paclitaxel products (due to formulation differences). Do frequent complete blood cell counts. Monitor for sensory neuropathy, sepsis, or pneumonitis. Hepatic or renal dysfunction. Contains human albumin; remote risk of viral transmission. Use appropriate contraception (men and women). Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May potentiate or be potentiated by CYP2C8 and/or CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, efavirenz, nevirapine) and/or inhibitors (eg, ketoconazole, other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, nelfinavir). Adverse reactions: Bone marrow suppression (eg, neutropenia, anemia), infections, alopecia, sensory neuropathy (may require dose reduction or interruption), peripheral neuropathy, GI upset, mucositis, fatigue/asthenia, myalgia/arthralgia, abnormal ECG; alkaline phosphatase or AST elevation; dyspnea, edema, hypotension, rash (may be serious); rare: thrombotic events. How supplied: Single-use vial–1

ADRUCIL Teva

℞

of treatment; or give a maintenance dose of 10–15mg/kg per week as a single dose; max: 1g/ week. Poor risk patients: see literature for dose adjustments. Children: Not recommended. Contraindications: Poor nutritional state. Depressed bone marrow function. Potentially serious infections. Warnings/Precautions: Narrow margin of safety; monitor for toxicity. Consider hospitalization for 1st course. History of highdose pelvic irradiation. Previous use of alkylating agents. Widespread involvement of bone marrow by metastatic tumors. Renal or hepatic impairment. Discontinue if signs of toxicity appear (eg, stomatitis, esophagopharyngitis, leukopenia, intractable vomiting, diarrhea, GI ulceration or bleeding, thrombocytopenia, hemorrhage). Monitor WBCs with differential before each dose. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Potentiated by leucovorin. Adverse reactions: Stomatitis, esophagopharyngitis, GI upset, anorexia, leukopenia, alopecia, dermatitis, hand-foot syndrome; others. Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase) How supplied: Single-dose vials (10mL)–10

AFINITOR Novartis

℞

mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs. Indications: Postmenopausal women with advanced hormone receptor-positive, HER2negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole. Adults: Swallow whole with water or disperse tablet in 30mL of water and drink immediately. Take at the same time each day either consistently with or without food. 10mg once daily. Mild hepatic impairment (Child-Pugh class A): 7.5mg daily, may reduce to 5mg if not tolerated. Moderate hepatic impairment (Child-Pugh class B), or adverse reactions: reduce to 5mg daily, may be reduce to 2.5mg if not tolerated. Severe hepatic impairment (Child-Pugh class C): max 2.5mg daily if benefits outweigh risk. Concomitant moderate CYP3A4 or P-glycoprotein inhibitors: reduce to 2.5mg once daily; may consider increasing to 5mg if tolerated. If moderate inhibitor is discontinued, allow 2–3 days washout period before increasing everolimus dose; return to dose used prior to initiating the moderate inhibitor. Concomitant strong CYP3A4 inducers: may increase from 10–20mg once daily by increments of 5mg. If strong inducer is discontinued, should return to dose used prior to initiating the strong inducer. Continue as long as benefit observed or until unacceptable toxicity occurs. Children: Not recommended.

Contraindications: Sirolimus, temsirolimus, rapamycin allergy. Warnings/Precautions: Hepatic impairment (see Adult dose). Increased risk of infections; some may be severe or fatal. Pre-existing invasive fungal infections: treat before starting. Monitor CBCs, renal function, lipids, blood glucose, and for pneumonitis and infections: treat promptly if occur. Women of childbearing potential should use effective method of contraception during and up to 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Avoid live vaccines. Potentiated by strong CYP3A4 inhibitors, or P-glycoprotein inhibitors; avoid (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole, grapefruit juice). Caution with moderate CYP3A4 inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem) or P-glycoprotein inhibitors; reduce everolimus dose if used. Antagonized by strong CYP3A4 inducers; avoid (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s wort); increase everolimus dose if used. Adverse reactions: Pneumonitis (reduce dose and/or manage with corticosteroids; if severe, discontinue. May restart daily dose at approx. 50% lower than previously administered), infections (discontinue if invasive systemic fungal infection develops), stomatitis (treat with non-alcoholic, non-peroxide mouthwash), GI upset, rash, fatigue, edema, fever, headache, asthenia, cough, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see literature). How supplied: Tabs–28 (4 blister cards × 7 tabs)

ARIMIDEX AstraZeneca

℞

Aromatase inhibitor. Anastrozole 1mg; tabs. Indications: In postmenopausal women: adjuvant treatment of hormone receptor-positive early breast cancer; first-line treatment of hormone receptor-positive or unknown locally advanced or metastatic breast cancer; advanced breast cancer with disease progression after tamoxifen therapy. Adults: 1mg once daily. Advanced disease: continue until tumor progression. Children: Not applicable. Contraindications: Women who are or may become pregnant. Pregnancy (Cat.X). Warnings/Precautions: Pre-existing ischemic heart disease. Severe hepatic impairment. Monitor bone mineral density, cholesterol. Nursing mothers: not recommended. Interactions: Antagonized by tamoxifen, estrogens; do not give concomitantly. Adverse reactions: Hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis,

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BREAST CANCER hypertension, depression, nausea, vomiting, rash, osteoporosis, fractures, back pain, insomnia, headache, peripheral edema, lymphedema, dyspnea, dizziness, paresthesia, vaginal bleeding, cough, hypercholesterolemia. How supplied: Tabs–30

AROMASIN Pfizer

℞

Aromatase inactivator. Exemestane 25mg; tabs. Indications: In postmenopausal women: adjuvant treatment of estrogen-receptor positive early breast cancer after 2–3 years of tamoxifen therapy to complete a total of 5 years of hormonal therapy; advanced breast cancer with disease progression after tamoxifen therapy. Adults: Give after a meal. 25mg once daily. Concomitant potent CYP3A4 inducer (eg, rifampicin, phenytoin): 50mg once daily. Advanced disease: continue until tumor progression is evident. Children: Not established. Contraindications: Pregnancy (Cat.X). Premenopausal women. Warnings/Precautions: Hepatic or renal insufficiency. Perform routine assessment of Vit. D levels prior to initiation; supplement if deficient. Nursing mothers. Interactions: May be antagonized by estrogens (avoid), CYP3A4 inducers. Avoid concomitant bisphosphonates, Vit. D supplements, calcium. Adverse reactions: Hot flashes, fatigue, arthralgia, headache, insomnia, increased sweating, nausea, increased appetite; reductions in bone mineral density. How supplied: Tabs–30

Cyclophosphamide (various)

℞

Alkylating agent. Cyclophosphamide 25mg, 50mg; tabs. Indications: Carcinoma of the breast. Adults: Initial and maintenance: 1–5mg/kg/day. Children: See literature. ℞ Also: CYTOXAN INJECTION Bristol-Myers Squibb Cyclophosphamide 500mg, 1g, 2g; per vial; pwd for inj after reconstitution; preservative-free. Adults: Initially 40–50mg/kg IV in divided doses over 2–5 days; or 10–15mg/kg IV every 7–10 days; or 3–5mg/kg IV twice weekly. Children: See literature. Contraindications: Severe bone marrow depression. Warnings/Precautions: Leukopenia. Thrombocytopenia. Tumor cell infiltration of bone marrow. Previous X-ray therapy or cytotoxic chemotherapy. Impaired renal or hepatic function. Infections. Adrenalectomy. General anesthesia within 10 days of therapy. Monitor hematologic profile (esp. neutrophils and platelets). Obtain urine sample (monitor for hemorrhagic cystitis); maintain adequate hydration. May interfere with wound healing. Elderly. Pregnancy (Cat.D). Nursing mothers: not recommended.

Interactions: Potentiated by phenobarbital. Potentiates other myelosuppressives, radiotherapy, succinylcholine. May potentiate doxorubicin-induced cardiotoxicity. Adverse reactions: GI upset, alopecia, leukopenia, infections, thrombocytopenia, anemia, hemorrhagic cystitis (discontinue if occurs), renal tubular necrosis, interstitial pulmonary fibrosis, gonadal toxicity (amenorrhea, infertility), anaphylactic reactions. How supplied: Tabs–contact supplier Single-use vial–1

Doxorubicin HCl (various)

℞

Anthracycline. Doxorubicin HCl 10mg/vial, 20mg/vial, 50mg/vial; pwd for IV inj after reconstitution; contains lactose. ℞ Also: Doxorubicin HCl Solution Doxorubicin HCl 2mg/mL; soln for IV inj. Indications: Disseminated neoplasias (eg, breast carcinoma). Adjunct in breast cancer after resection. Adults and Children: Monotherapy: usually 60–75mg/m2 IV every 21 days. Combination therapy: usually 40–60mg/m2 IV every 21 to 28 days. Hyperbilirubinemia, inadequate bone marrow reserves: reduce dose. Contraindications: Severe myelosuppression (baseline neutrophils <1500cells/mm3) or severe hepatic impairment. Cardiac disease (eg, severe myocardial insufficiency, arrhythmias). Recent MI. Previous treatment with max cumulative doses of anthracyclines, anthracenediones. Warnings/Precautions: Pre-existing heart disease or risk thereof. Obtain baseline CBC, bilirubin, AST, creatinine, LVEF. Hepatic dysfunction. Monitor cardiac function (LVEF, ECG echocardiogram), hepatic function, CBC, uric acid levels. Avoid extravasation. Children (cardiotoxicity, impaired myocardial growth). Elderly. Pregnancy (Cat.D; use adequate contraception). Nursing mothers: not recommended. Interactions: See Contraindications. Mediastinal irradiation, cyclophosphamide, calcium channel blockers, other anthracyclines increase risk of cardiac toxicity; limit lifetime dose to 400mg/m2. Necrotizing colitis with cytarabine. May increase toxicity of cyclophosphamide, mercaptopurine. May reduce serum digoxin levels. Doxorubicin toxicity increased with high-dose IV progesterone, cyclosporine, streptozocin, and if given after paclitaxel infusion (give doxorubicin dose first). Elimination increased by phenobarbital. May decrease phenytoin levels. Recall pneumonitis with actinomycin and radiation in children. Adverse reactions: Local necrosis if extravasation occurs, myocardial toxicity (immediate or delayed), arrhythmias, leukemia, myelosuppression, hyperuricemia, urine discoloration, alopecia, hyperpigmentation, severe GI upset/ulceration, phlebosclerosis, facial flushing, fever, urticaria, peripheral neuropathy, anaphylaxis. How supplied: Contact supplier.

ELLENCE Pfizer

℞

Anthracycline. Epirubicin HCl 2mg/mL; soln for IV infusion; preservative-free. Indications: Adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer. Adults: Give by IV infusion over 15–20 minutes. Administer in repeated 3–4 week cycles for a total of 6 cycles. Total dose may be given on Day 1 of each cycle; or divided equally and given on Days 1 and 8 of each cycle. Initially 100–120mg/m2. Bone marrow dysfunction: consider lower starting dose (75–90mg/m2). Renal or hepatic impairment, dose adjustments: see full labeling. Children: Not established. Contraindications: Baseline neutrophil count <1500 cells/mm3. Cardiomyopathy and/or heart failure. Recent MI. Severe arrhythmias. Previous treatment with anthracyclines (max cumulative doses). Severe hepatic dysfunction. Warnings/Precautions: Cardiovascular disease. Prior or concomitant radiotherapy to mediastinal/pericardial area. Previous anthracycline therapy. Renal or hepatic impairment. Monitor CBCs, platelets, cardiac, renal, and hepatic function before and during each treatment cycle. Consider monitoring serum uric acid, potassium, calcium, phosphate after starting therapy. Avoid extravasation. Elderly (esp. female ≥70yrs). Advise women of childbearing potential to avoid becoming pregnant during treatment and use effective contraceptive methods. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Caution with other cardiotoxic drugs. Avoid concomitant live vaccines. Potentiated by cimetidine; stop cimetidine during therapy. Inflammatory recall reaction possible with previous radiation therapy. Adverse reactions: Myelosuppression (leukopenia, neutropenia, anemia, thrombocytopenia), amenorrhea, lethargy, nausea, vomiting, mucositis, diarrhea, infection, conjunctivitis/keratitis, alopecia, local toxicity, rash/itch; cardiotoxicity, hyperuricemia, acute myelogenous leukemia. How supplied: Single-use vials (25mL, 100mL)–1

ESTRACE Warner Chilcott

℞

Estrogen. Estradiol 0.5mg, 1mg, 2mg+; scored tabs; +contains tartrazine. Indications: Palliative treatment of metastatic breast cancer in select patients (see literature). Adults: 10mg 3 times daily for at least 3 months. Children: Not applicable. Contraindications: Thrombophlebitis. Thromboembolic disorders. Cerebrovascular disorders. Abnormal undiagnosed genital bleeding. Estrogen-depended neoplasias. Liver dysfunction or disease. Pregnancy (Cat.X). Warnings/Precautions: Asthma (2mg tabs). Hepatic dysfunction. Conditions aggravated

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MASTER DRUG MONOGRAPHS

BREAST CANCER by fluid retention. Cardiovascular disorders, arterial vascular disease, and risks factors (eg, hypertension, diabetes, obesity, SLE). Familial hyperlipoprotenemia. Monitor BP. Discontinue if jaundice occurs and before prolonged immobilization (eg, surgery). Nursing mothers. Adverse reactions: See literature. GI upset, headache, hypertension, edema, hypercalcemia, gallbladder or thromboembolic disease, gynecomastia, impotence, impaired glucose tolerance. How supplied: Tabs–100

EVISTA Lilly

℞

Selective estrogen receptor modulator (SERM). Raloxifene HCl 60mg; tabs. Indications: Reduction in risk of invasive breast cancer in postmenopausal women: with osteoporosis and/or at high risk for invasive breast cancer. Adults: 60mg once daily. Children: Not recommended. Contraindications: Active or history of venous thromboembolic events. Nursing mothers. Pregnancy (Cat.X). Women who may become pregnant. Warnings/Precautions: Not for use in premenopausal women. Concomitant systemic estrogen therapy: not recommended. Discontinue 72 hours before, and during prolonged immobilization; resume when fully ambulatory. Coronary heart disease or risk of coronary event (increased risk of death due to stroke). Hepatic dysfunction. Moderate to severe renal impairment. Interactions: May antagonize warfarin; monitor. Avoid concomitant cholestyramine, other anion exchange resins. Caution with other highly protein-bound drugs (eg, diazepam, diazoxide, lidocaine). Adverse reactions: Hot flashes, leg cramps, peripheral edema, flu syndrome, arthralgia, sweating; rare: venous thromboembolic events. How supplied: Tabs–30, 100, 2000

FARESTON ProStrakan

Interactions: Caution with drugs that decrease renal calcium excretions (eg, thiazide diuretics). Monitor anticoagulants (eg, warfarin). Potentiated by CYP3A4 inhibitors (eg, ketoconazole, erythromycin, other macrolides). Antagonized by CYP3A4 inducers (eg, phenobarbital, phenytoin, carbamazepine). Adverse reactions: Hot flashes, sweating, GI upset, vaginal discharge, dizziness, edema, vaginal bleeding; hypercalcemia, tumor flare, endometrial hyperplasia; rare: leukopenia, thrombocytopenia. How supplied: Tabs–30, 100

℞

Nonsteroidal antiestrogen. Toremifene (as citrate) 60mg; tabs. Indications: Metastatic breast cancer in postmenopausal women with estrogen-receptor positive or unknown tumors. Adults: 60mg once daily. Continue until disease progression is observed. Children: Not applicable. Warnings/Precautions: History of thromboembolic disease: not recommended. Bone metastases; monitor for hypercalcemia during first weeks of treatment, discontinue if severe. Pre-existing endometrial hyperplasia; long-term therapy not recommended. Leukopenia, thrombocytopenia; obtain leukocyte and platelet counts. Monitor CBCs, calcium levels, liver function tests periodically. Pregnancy (Cat.D). Nursing mothers.

FASLODEX AstraZeneca

℞

Estrogen receptor antagonist. Fulvestrant 50mg/mL; soln for IM inj. Indications: Hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Adults: Give by IM inj slowly (1–2 mins/ injection). 500mg (as two 5mL injections, one in each buttock) on days 1, 15, 29, then once per month thereafter. Moderate hepatic impairment: 250mg (as one 5mL injection) on days 1, 15, 29, then once per month thereafter. Children: Not applicable. Warnings/Precautions: Bleeding diatheses, thrombocytopenia, or anticoagulant use. Moderate to severe hepatic impairment. Pregnancy (Cat.D; avoid); exclude pregnancy before starting. Nursing mothers: not recommended. Adverse reactions: Inj site pain, GI upset, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, constipation; increased hepatic enzymes, hypersensitivity reactions. How supplied: Prefilled syringe kit (2 × 5mL)–1

FEMARA Novartis

℞

Aromatase inhibitor. Letrozole 2.5mg; tabs. Indications: In postmenopausal women: Adjuvant treatment of hormone receptor positive early breast cancer; Extended adjuvant treatment of early breast cancer after 5 years of adjuvant tamoxifen therapy; First-line treatment of hormone receptor positive or unknown, locally advanced or metastatic breast cancer; Treatment of advanced breast cancer with disease progression following antiestrogen therapy. Adults: 2.5mg once daily. Continue until tumor progression is evident. Adjuvant or extended adjuvant therapy: treat for at least 24 months (see literature). Severe hepatic impairment or cirrhosis: 2.5mg every other day. Children: Not applicable. Contraindications: Women of premenopausal endocrine status. Pregnancy (Cat.X). Warnings/Precautions: Severe renal or hepatic impairment. Monitor bone mineral density, serum cholesterol. Nursing mothers.

Adverse reactions: Pain (bone, musculoskeletal, and others), hot flashes, arthralgia, flushing, asthenia, edema, headache, dizziness, hypercholesterolemia, sweating increased, GI upset, fatigue, dyspnea, cough, insomnia, hypertension, alopecia, anorexia, weight changes, hypercalcemia, pleural effusion, vertigo; thromboembolic or cardio- or cerebrovascular events (rare). How supplied: Tabs–30

Fluorouracil (various)

℞

Antimetabolite. Fluorouracil 50mg/mL; soln for IV inj. Indications: Palliative management of carcinoma of the breast. Adults: Give by IV inj. 12mg/kg once daily for 4 successive days; max 800mg/day. If no toxicity is observed, 6mg/kg are given on the 6th, 8th, 10th, and 12th days unless toxicity occurs. Maintenance therapy: repeat dosage of 1st course every 30 days after the last day of the previous course of treatment; or give a maintenance dose of 10–15mg/kg per week as a single dose; max: 1g/ week. Poor risk patients: see literature for dose adjustments. Children: Not recommended. Contraindications: Poor nutritional state. Depressed bone marrow function. Potentially serious infections. Warnings/Precautions: Narrow margin of safety; monitor for toxicity. Consider hospitalization for 1st course. History of highdose pelvic irradiation. Previous use of alkylating agents. Widespread involvement of bone marrow by metastatic tumors. Renal or hepatic impairment. Discontinue if signs of toxicity appear (eg, stomatitis, esophagopharyngitis, leukopenia, intractable vomiting, diarrhea, GI ulceration or bleeding, thrombocytopenia, hemorrhage). Monitor WBCs with differential before each dose. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Potentiated by leucovorin. Adverse reactions: Stomatitis, esophagopharyngitis, GI upset, anorexia, leukopenia, alopecia, dermatitis, hand-foot syndrome; others. Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase). How supplied: Contact supplier.

Fluoxymesterone (various)

CIII

Androgen. Fluoxymesterone 10mg; tabs. Indications: Palliation of androgen responsive recurrent mammary cancer in women who are more than one year but less than five years postmenopausal, or who have been proven to have a hormone-dependent tumor as shown by previous beneficial response to castration. Adults: Individualize. 10–40mg/day; may be given in divided doses to ensure more stable

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BREAST CANCER blood levels. Continue therapy for at least 1 month for subjective response, 2–3 months for objective response. Children: Not applicable. Contraindications: Pregnancy (Cat.X). Serious cardiac, hepatic or renal disease. Warnings/Precautions: Discontinue if cholestatic hepatitis, jaundice, or hypercalcemia develops. Pre-existing cardiac, renal or hepatic disease. Monitor urine and serum calcium levels frequently. Obtain LFTs periodically. Long-term therapy: check hemoglobin and hematocrit levels, cholesterol. Nursing mothers: not recommended. Interactions: May need to reduce concomitant anticoagulant dose. May potentiate oxyphenbutazone. May alter insulin requirements. Adverse reactions: Amenorrhea, inhibition of gonadotropin secretion, virilization, nausea, jaundice, altered LFTs, hirsutism, acne, headache, anxiety, depression, paresthesias, altered libido, fluid and electrolyte disturbances, suppression of clotting factors, increased serum cholesterol; rare: hepatic adenomas, hepatocellular carcinoma, peliosis hepatis. How supplied: Contact supplier.

GEMZAR Lilly

℞

Antimetabolite. Gemcitabine HCl 200mg, 1g; per vial; pwd for IV infusion after reconstitution; contains mannitol. Indications: First-line treatment of metastatic breast cancer (in combination with paclitaxel) after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were contraindicated. Adults: Infuse over 30 minutes (increased toxicity if infusion goes beyond 60 minutes). 1250mg/m2 on Days 1 and 8 of each 21 day cycle. Adjust dose based on toxicity (see literature). Children: Not recommended. Warnings/Precautions: Not for use in combination with radiation therapy. Discontinue immediately if severe lung toxicity, hemolytic uremic syndrome, or capillary leak syndrome occurs. Renal or hepatic impairment. Evaluate renal and hepatic function prior to therapy, then periodically thereafter. Discontinue if severe liver injury develops. Monitor for myelosuppression; obtain CBCs, platelets prior to each dose. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: See Warnings/Precautions. Concomitant radiation therapy: may cause severe radiation toxicity. Adverse reactions: Myelosuppression, nausea, vomiting, elevated transaminases, proteinuria, hematuria, rash, pruritus, dyspnea, edema, flulike symptoms, infection, alopecia, neurotoxicity, others; rare: renal or liver failure, hemolytic uremic syndrom, capillary leak syndrome. Testing considerations: ERCC1 overexpression for response and prognosis; RRM1 How supplied: Single-use vials–1

HALAVEN Eisai

℞

Non-taxane microtubule dynamics inhibitor. Eribulin mesylate 0.5mg/mL, soln for IV inj. Indications: Treatment of metastatic breast cancer in patients who have previously received at least two chemotherapeutic regimens for metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. Adults: Give by IV injection over 2–5mins. 1.4mg/m2 on Days 1 and 8 of a 21-day cycle. Mild hepatic impairment (Child-Pugh A) or moderate renal impairment (CrCl 30–50mL/min): 1.1mg/m2 on Days 1 and 8 of a 21-day cycle. Moderate hepatic impairment (Child-Pugh B): 0.7mg/m2 on Days 1 and 8 of a 21-day cycle. Hold dose for ANC <1000/mm3, platelets <75000/mm3, or grade 3 or 4 non-hematological toxicities. Delay or reduce dose according to toxicities; see full labeling. Do not re-escalate dose after it is reduced. Children: <18yrs: not established. Warnings/Precautions: Monitor CBCs; increase frequency of monitoring if grade 3 or 4 cytopenias develop, delay and reduce subsequent doses if febrile neutropenia or grade 4 neutropenia lasting >7 days develops. Monitor for peripheral neuropathy; withhold dose if grade 3 or 4 peripheral neuropathy develops until resolution to grade 2 or less. Congenital long QT syndrome: avoid. CHF, bradyarrhythmias, electrolyte abnormalities: monitor ECG for prolonged QT interval. Correct electrolyte abnormalities (K+, Mg+) before treatment; monitor. Severe hepatic impairment (Child-Pugh C) or severe renal impairment (CrCl<30mL/min): insufficient data. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Caution with other drugs that prolong QT interval (eg, Class IA and III antiarrhythmics); monitor. Adverse reactions: Neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, constipation, febrile neutropenia; possible QT prolongation, elevated liver enzymes. Note: Do not mix with dextrose-containing solutions. Do not administer in same line as other drugs or fluids. How supplied: Single-use vial (2mL)–1

HERCEPTIN Genentech

℞

Human epidermal growth factor receptor (HER2) inhibitor. Trastuzumab 440mg/vial; lyophilized pwd for IV infusion after reconstitution and dilution; preservative-free. Indications: HER2-overexpressing metastatic breast cancer as a single agent in patients who have received one or more chemotherapy regimens; or in combination with paclitaxel in patients who have not received chemotherapy. Adjuvant treatment in HER2-overexpressing, node-positive or node-negative breast cancer (as a single agent following multi-modality

anthracycline based therapy; in combination with doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; or in combination with docetaxel and carboplatin). Adults: Give as IV infusion. Initially 4mg/kg over 90 minutes, followed by 2mg/kg over 30 minutes weekly; administer until tumor progression. Adjuvant treatment (administer trastuzumab weekly for 52 weeks); In combination therapy: with doxorubicin and cyclophosphamide, followed by either paclitaxel or docetaxel; or with docetaxel/carboplatin: initially 4mg/kg over 90 minutes, followed by 2mg/kg over 30 minutes once weekly for the 1st 12 weeks (concurrently w. paclitaxel or docetaxel) or 1st 18 weeks (concurrently w. docetaxel/carboplatin). One week after the last trastuzumab weekly dose, give trastuzumab 6mg/kg over 30–90 minutes every 3 weeks. Following multi-modality anthracycline based therapy: initially 8mg/kg over 90 minutes, then 6mg/kg over 30–90 minutes every 3 weeks. Infusion reactions or cardiomyopathy: see literature. Children: Not recommended. Warnings/Precautions: Increased risk of cardiomyopathy. Conduct cardiac assessment (eg, history, physical exam, LVEF) at baseline, every 3 months during and after therapy; repeat LVEF at 4 week intervals if dose is withheld due to significant left ventricular cardiac dysfunction. Interrupt therapy if dyspnea or significant hypotension occurs; consider discontinuing permanently if severe infusion reactions, CHF, pulmonary toxicity, or significant left ventricular myocardial dysfunction develops. Symptomatic intrinsic lung disease. Extensive tumor involvement of the lungs. Test for HER2 protein overexpression and HER2 gene amplification using FDA-approved tests for specific tumor type (breast or gastric/gastroesophageal adenocarcinoma). Elderly. Pregnancy (Cat.D); use adequate contraception during and at least 6 months after therapy. Nursing mothers: not recommended. Interactions: Increased cardiomyopathy with anthracycline-containing chemotherapy. Increased toxicity with other myelosuppressives. Potentiated by paclitaxel. Adverse reactions: Fever, GI upset, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, myalgia, thrombosis/ embolism; severe infusion reactions, febrile neutropenia/exacerbation of chemotherapyinduced neutropenia, pulmonary toxicity (eg, interstitial pneumonitis), cardiomyopathy (eg, left ventricular myocardial dysfunction); pregnant women (2nd & 3rd trimesters): possible oligohydramnios (monitor). Note: Enroll pregnant women with breast cancer who are using trastuzumab in the Cancer and Childbirth Registry (800) 690-6720. Testing considerations: HER2 protein overexpression How supplied: Vial–1 (w. diluent)

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BREAST CANCER IXEMPRA Bristol-Myers Squibb

℞

Epothilone microtubule inhibitor. Ixabepilone 15mg/vial, 45mg/vial; pwd for IV infusion after constitution and dilution; diluent contains alcohol, polyoxyethylated castor oil. Indications: Metastatic or locally advanced breast cancer: In combination with capecitabine after failure of an anthracycline and a taxane; and as monotherapy after failure of an anthracycline, a taxane, and capecitabine. Adults: Pretreat with both H1 and H2 blockers 1hr before infusion; and with steroid if previous hypersensitivity reaction occurred. 40mg/m2 by IV infusion over 3hrs, once every 3wks. Use max body surface area (BSA) of 2.2m2 to calculate dose if BSA >2.2m2. Moderate hepatic impairment (as monotherapy): initially 20mg/m2 per dose; max 30mg/m2 per dose (see literature). Neuropathy, myelosuppression, concomitant strong CYP3A4 inhibitors: reduce dose. Concomitant strong CYP3A4 inducers: consider gradual dose increases. See literature. Children: Not recommended. Contraindications: Baseline neutrophils <1500cells/mm3 or platelets <100,000cells/mm3. AST or ALT >2.5×ULN or bilirubin >1×ULN (in combination with capecitabine). Warnings/Precautions: Monitor CBC and liver function at baseline, then periodically. Hepatic impairment (ALT or AST >10×ULN or bilirubin >3×ULN: not recommended; ALT or AST >5×ULN: limited data, use caution). Diabetes. Neuropathy. Cardiac disease (discontinue if cardiac ischemia or cardiac dysfunction occurs). Monitor for signs/symptoms of neuropathy, neutropenia. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Potentiated by strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, certain macrolides, nefazodone, grapefruit juice); avoid. Caution with mild or moderate CYP3A4 inhibitors; consider alternative agents. Antagonized by strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, dexamethasone, phenobarbital); avoid. Avoid St. John’s wort. Adverse reactions: Peripheral sensory neuropathy, fatigue, asthenia, myalgia, arthralgia, alopecia, GI upset, stomatitis, mucositis, musculoskeletal pain, palmarplantar erythrodysesthesia syndrome, anorexia, abdominal pain, nail disorder, constipation; myelosuppression (neutropenia, leukopenia, anemia, thrombocytopenia); hypersensitivity reactions; others. How supplied: Kit–1 vial (w. diluent)

KADCYLA Genentech

℞

HER2-targeted antibody-drug conjugate. Adotrastuzumab emtansine 100mg, 160mg; per vial; powder; for IV infusion after reconstitution.

Indications: Treatment in patients with HER2positive (+), metastatic breast cancer (MBC) who previously received trastuzumab and a taxane, separately or in combination. Patients should have either: received prior therapy for metastatic disease or developed disease recurrence during or within 6 months of completing adjuvant therapy. Adults: Give by IV infusion only over 90 minutes 3.6mg/kg max every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. Subsequent infusions may be given over 30 minutes if previously tolerated. Monitor closely for possible SC infiltration during infusion. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: Do not substitute for or with trastuzumab. Hepatotoxicity; monitor serum transaminases and bilirubin prior to starting and to each dose; reduce dose or discontinue if occurs. Risk of left ventricular dysfunction. Assess LVEF prior to initiation and every 3 months during treatment; interrupt and discontinue as appropriate. Risk of embryofetal toxicity. Permanently discontinue if interstitial lung disease or pneumonitis occurs. Monitor for signs/symptoms of extravasation, infusion-related or hypersensitivity reactions; if significant, slow or interrupt infusion; discontinue if life-threatening. Monitor platelets at baseline and prior to each dose; if platelets <50,000/mm3, delay dose until recovery to ≥75,000/mm3; if platelets <25,000/mm3, delay until recovery to ≥75,000/mm3 and reduce dose. If thrombocytopenia occurs <100,000/mm3 and concomitant anticoagulants, monitor closely. Monitor for neurotoxicity; withhold temporarily if Grade 3 or 4 peripheral neuropathy occurs. Test for HER2 protein overexpression or gene amplification using FDA-approved tests by labs with demonstrated proficiency. Pregnancy (Category D); use adequate contraception during and at least 6 months after last dose. Nursing mothers: not recommended. Interactions: Avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, clarithromycin, atazanavir, indinavir, ritonavir, nefazodone, nelfinavir, saquinavir, telithromycin); if unavoidable, consider delaying therapy (see full labeling). Adverse reactions: Fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache; increased transaminases, constipation. How supplied: Single-use vial–1

Megestrol acetate (various) Progestin. Megestrol acetate 20mg, 40mg; scored tabs. Indications: Palliative treatment of advanced breast carcinoma. Adults: 40mg 4 times daily. Children: Not applicable. Warnings/Precautions: History of thromboembolic disease. Diabetes. Monitor for

adrenal insufficiency. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May increase insulin requirements. Decreases indinavir levels. Adverse reactions: Weight gain, thromboembolic events, heart failure, GI upset, edema, breakthrough menstrual bleeding, dyspnea, tumor flare, hyperglycemia, alopecia, hypertension, carpal tunnel syndrome, mood changes, hot flashes, malaise, asthenia, lethargy, sweating, rash. How supplied: Contact supplier.

Pamidronate disodium

Injection (various)

Bisphosphonate. Pamidronate disodium 30mg, 90mg; per vial; pwd for IV infusion after reconstitution; contains mannitol. Indications: Osteolytic bone metastases of breast cancer. Adults: Give by IV infusion. 90mg infused over 2hrs every 3–4wks. Max single dose: 90mg. Children: Not recommended. Warnings/Precautions: Severe renal impairment in patients with bone metastases: not recommended. Renal or hepatic insufficiency. Check serum creatinine before each dose: withhold until serum creatinine is within 10% of baseline if serum creatinine increases 0.5mg/dL from normal pre-treatment levels, or by 1mg/dL from an abnormal pre-treatment level. Monitor electrolytes (esp. calcium, magnesium, phosphate, potassium), CBC/ differential, hematocrit/hemoglobin. Preexisting blood disorders (eg, anemia, leukopenia, thrombocytopenia); monitor closely for first 2 weeks after treatment. Avoid dental surgery (do preventative dental work before therapy). Evaluate if thigh or groin pain develops and consider discontinuing if atypical femur fracture is suspected. Pregnancy (Cat.D): not recommended. Nursing mothers. Interactions: Caution with other nephrotoxic drugs (eg, thalidomide). Adverse reactions: Infusion-site reactions, fever, headache, dizziness, paresthesia, increased sweating, GI upset, anemia, fatigue, musculoskeletal pain (may be severe), electrolyte disturbances, hypertension, dyspnea, renal toxicity; jaw osteonecrosis, atypical subtrochanteric and diaphyseal femoral fractures. How supplied: Contact supplier.

PERJETA Genentech ℞

℞

Human epidermal growth factor receptor (HER2) dimerization inhibitor. Pertuzumab 420mg/14mL (30mg/mL); soln for IV infusion; preservativefree. Indications: In combination with trastuzumab and docetaxel: to treat patients with HER2positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease; for

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BREAST CANCER the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either >2cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. Limitations of use: not established as part of a doxorubicin-containing regimen. Not established in administration for >6 cycles for early breast cancer. Adults: In combination with trastuzumab and docetaxel: initially 840mg IV over 60 minutes, followed every 3 weeks thereafter by a dose of 420mg IV over 30–60 minutes. Pertuzumab should be withheld or discontinued if trastuzumab is withheld or discontinued. If docetaxel is discontinued, treatment with pertuzumab and trastuzumab may continue. Neoadjuvant treatment: give every 3 weeks for 3 to 6 cycles as part of one of the treatment regimens for early breast cancer: see full labeling. Dose modification (missed dose, LVEF, or infusion reactions): see full labeling. Children: Not established. Warnings/Precautions: Risk of embryo-fetal toxicity. Pretreatment LVEF value of ≤50%, history of CHF, decreases in LVEF to <50% during prior trastuzumab therapy, uncontrolled hypertension, recent MI, serious cardiac arrythmia requiring treatment or a cumulative prior anthracycline exposure to >360mg/m2 of doxorubicin or its equivalent: not studied. Assess LVEF at baseline and at regular intervals (eg, every 3 months in metastatic setting, and every 6 weeks in the neoadjuvant setting) during treatment; if LVEF is <45%, or is 45% to 49% with a ≥10% absolute decrease below the pretreatment value, withhold (pertuzumab + trastuzumab) and repeat LVEF within 3 weeks; discontinue if LVEF has not improved. Monitor for signs/symptoms of infusion reactions; slow or interrupt infusion and treat if occurs; discontinue if severe. Test and confirm for HER2 protein overexpression using FDA-approved tests by labs with demonstrated proficiency. Pregnancy (Cat.D); use adequate contraception during and at least 6 months after therapy. Nursing mothers: not recommended. Adverse reactions: Diarrhea, alopecia, neutropenia, nausea, fatigue, rash, peripheral neuropathy; hypersensitivity (monitor), decreases in LVEF; pregnant women: possible oligohydramnios (monitor). Encourage women who are exposed to Perjeta during pregnancy to enroll in the MotHER Pregnancy Registry: (800) 690-6720. How supplied: Single-use vial–1

PREMARIN Pfizer

℞

Estrogen. Conjugated estrogens 0.3mg, 0.45mg, 0.625mg, 0.9mg, 1.25mg; tabs. Indications: Treatment of breast cancer (for palliation only) in appropriately selected women and men with metastatic disease. Adults: 10mg 3 times daily for at least 3 months. Children: Not applicable.

Contraindications: Known, suspected, or history of breast cancer, except in appropriately selected patients being treated for metastatic disease. Known or suspected estrogen-dependent neoplasia. Undiagnosed abnormal genital bleeding. Pulmonary embolism/DVT (active or history of). Arterial thromboembolism (eg, stroke, MI; active or history of). Liver dysfunction or disease. Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. Known or suspected pregnancy (Cat.X). Warnings/Precautions: Not for prevention of cardiovascular disease. Use for shortest duration consistent with treatment goals and risks. Reevaluate periodically. Patients with an intact uterus should almost always receive a progestin with systemic estrogens to avoid endometrial hyperplasia. Discontinue if cardiovascular events occur or are suspected; if jaundice occurs; and during immobilization or at least 4–6 weeks before surgery associated with thromboembolism. Hepatic dysfunction. Conditions aggravated by fluid retention. Gallbladder disease. Bone disease associated with hypercalcemia. Hereditary angioedema. Do initial complete physical and repeat annually (include BP, mammogram, PAP smear). Adolescents. Nursing mothers: not recommended. Adverse reactions: See literature. Increased risk of cardiovascular events, estrogen-dependent carcinoma, gallbladder disease, thromboembolic disorders, hepatic tumors. GI upset, breakthrough bleeding, edema, weight changes, mastodynia, hypertension, depression, anaphylactic reactions, angioedema, intolerance to contact lenses. How supplied: Tabs 0.3mg, 0.625mg, 1.25mg–100, 1000; 0.45mg, 0.9mg–100

SOLTAMOX ORAL

SOLUTION DARA BioSciences

℞

Antiestrogen. Tamoxifen (as citrate) 10mg/5mL; licorice and aniseed flavors; sugar-free; contains alcohol. Indications: Treatment of metastatic breast cancer in men and women. Axillary node-positive breast cancer in postmenopausal women after surgery + irradiation. Axillary node-negative breast cancer in women after surgery + irradiation. Reduction in risk of invasive breast cancer in women with ductal carcinoma in situ (DCIS) after surgery + radiation. Reduction in breast cancer incidence in high-risk women. Adults: Treatment: 20–40mg/day; give doses >20mg in divided doses (AM and PM). Reduction of incidence in high-risk women or DCIS: 20mg once daily for 5 years. Children: Not recommended. Contraindications: For reduction in incidence in high-risk women and women with DCIS: concomitant coumarin anticoagulants, history of deep vein thrombosis or pulmonary embolism. Warnings/Precautions: See literature. Do gynecological exam at least annually. DCIS and

risk reduction: consider increased risk of uterine cancer (endometrial adenocarcinoma, uterine sarcoma), stroke and pulmonary embolism. Women with advanced disease: discontinue if severe hypercalcemia occurs. Monitor blood, lipids, liver function, for thromboembolism symptoms (eg, leg swelling, unexplained shortness of breath), and for uterine changes/ cancer (eg, pelvic pain or pressure); promptly investigate any abnormal vaginal bleeding. Breast cancer treatment: history of thromboembolic events. Pregnancy (Cat.D); avoid. Premenopausal: use effective non-hormonal contraception during and within 2 months of discontinuing therapy; begin therapy during menses or, if irregular menses, obtain (−) B-hCG pregnancy test first. Nursing mothers: not recommended. Interactions: See Contraindications. May potentiate oral anticoagulants; if co-administered, monitor PT. Concomitant anastrozole: not recommended. Antagonizes letrozole. Plasma levels reduced by CYP3A4 inducers (eg, rifampin, aminoglutethimide). Cytotoxic drugs increase risk of thrombotic events. Potentiated by bromocriptine. Adverse reactions: Hot flashes, vaginal discharge, altered menses, oligomenorrhea, nausea, cough, edema, fatigue, abdominal cramps, bone and tumor pain (in advanced disease), local disease flare, hypercalcemia, thrombotic events, ovarian cysts, uterine fibroids or cancer (endometrial adenocarcinoma, uterine sarcoma), endometrial or visual changes, liver abnormalities, hypertriglyceridemia, blood dyscrasias, hair loss. How supplied: Soln–150mL

Tamoxifen (various)

℞

Antiestrogen. Tamoxifen (as citrate) 10mg, 20mg; tabs. Indications: Treatment of metastatic breast cancer in men and women. Axillary node-positive breast cancer in postmenopausal women after surgery + irradiation. Axillary node-negative breast cancer in women after surgery + irradiation. Reduction in risk of invasive breast cancer in women with ductal carcinoma in situ (DCIS) after surgery + radiation. Reduction in breast cancer incidence in high-risk women. Adults: Treatment: 20–40mg/day; give doses >20mg in divided doses (AM and PM). Reduction of incidence in high-risk women or DCIS: 20mg once daily for 5 years. Children: McCune-Albright Syndrome, precocious puberty: see literature. Contraindications: For risk reduction: concomitant coumarin anticoagulants, history of deep vein thrombosis or pulmonary embolism, planned pregnancy. Pregnancy (Cat.D). Nursing mothers. Warnings/Precautions: See literature. Do gynecological exam at least annually. DCIS and risk reduction: consider increased risk of uterine cancer (endometrial adenocarcinoma,

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BREAST CANCER uterine sarcoma) and thrombotic events. Women with advanced disease: discontinue if severe hypercalcemia occurs. Monitor blood, lipids, liver function, for thromboembolism symptoms (eg, leg swelling, unexplained shortness of breath), and for uterine changes/ cancer (eg, pelvic pain or pressure); promptly investigate any abnormal vaginal bleeding. Breast cancer treatment: history of thromboembolic events. Premenopausal: use effective non-hormonal contraception during and within 2 months of discontinuing therapy; begin therapy during menses or, if irregular menses, obtain (−) B-hCG pregnancy test first. Interactions: May potentiate oral anticoagulants (see Contraindications). Antagonizes anastrozole (avoid concomitant use); letrozole. Plasma levels reduced by CYP3A4 inducers (eg, rifampin). Cytotoxic drugs increase risk of thrombotic events. Potentiated by bromocriptine. Adverse reactions: Hot flashes, vaginal discharge, altered menses, rash, headache, nausea, cough, edema, fatigue, abdominal cramps, bone and tumor pain (in advanced disease), local disease flare, hypercalcemia, thrombotic events, ovarian cysts, uterine fibroids or cancer (endometrial adenocarcinoma, uterine sarcoma), endometrial or visual changes, jaundice, hypertriglyceridemia, blood dyscrasias, hair loss. How supplied: Contact supplier.

TAXOL Bristol-Myers Squibb

℞

Antimicrotubule agent. Paclitaxel 6mg/mL; soln for IV infusion after dilution; contains Cremophor EL (polyoxyethylated castor oil), dehydrated alcohol. Indications: Adjuvant treatment of nodepositive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy. Breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Adults: See literature. Premedicate with corticosteroids, diphenhydramine, H2 antagonists. Breast cancer (node-positive): 175mg/m2 IV over 3 hours every 3 weeks for 4 courses administered sequentially to doxorubicin-containing combination chemotherapy. Breast cancer (after failure of initial chemotherapy for metastatic disease or relapse): 175mg/m2 IV over 3 hours every 3 weeks. Hepatic impairment or neutropenia: see literature for dose modifications. Do not treat if neutrophil count <1,500cells/mm3 or platelets <100,000cells/mm3. Children: Not recommended. Contraindications: Baseline neutrophil count <1,500cells/mm3. Warnings/Precautions: Do frequent peripheral blood cell counts. Hepatic dysfunction. Conduction abnormalities: monitor cardiac

function. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: May potentiate or be potentiated by CYP2C8 or CYP3A4 substrates, inducers and/or inhibitors. Potentiated by cisplatin. May potentiate doxorubicin. Adverse reactions: Bone marrow suppression (eg, neutropenia, leukopenia, thrombocytopenia, anemia), inj site reactions, infections, hypotension, bradycardia, hypersensitivity reactions (if severe, do not rechallenge), peripheral neuropathy, myalgia, arthralgia, GI upset, mucositis, alopecia, abnormal ECG, elevated liver enzymes. How supplied: Multidose vial (5mL, 16.7mL, 50mL)–1

TAXOTERE Sanofi Aventis

℞

Antimicrotubule agent. Docetaxel 20mg/mL; soln for IV infusion after dilution; contains polysorbate 80; diluent contains alcohol. Indications: Locally advanced or metastatic breast cancer after failure of prior chemotherapy. In combination with doxorubicin and cyclophosphamide: adjuvant treatment of operable node (+) breast cancer. Adults: Give by IV infusion over 1hr once every 3 weeks. Breast cancer: 60–100mg/m2. Adjuvant in operable node (+) breast cancer (treat for 6 courses): 75mg/m2. Premedicate with oral corticosteroid. Adjust dose based on tolerability and effect (see full labeling); allow neutrophils and platelets to recover before subsequent cycles. Children: Not established. Contraindications: Neutrophil count <1500 cells/mm3. Hypersensitivity to polysorbate 80. Warnings/Precautions: Hepatic dysfunction; bilirubin >ULN, SGOT and/or SGPT >1.5×ULN concomitant with alkaline phosphatase >2.5×ULN: not recommended. Obtain bilirubin, AST/ALT, and alkaline phosphatase values prior to each cycle. Monitor peripheral blood counts frequently (esp. neutrophils, platelets). Monitor for hypersensitivity reactions (esp. during 1st and 2nd infusions). Pre-existing effusions. Adjust dose if severe neurosensory symptoms (eg, paresthesia, dysesthesia, pain) occur; discontinue if symptoms persist. Monitor for eye disorders; discontinue if cystoid macular edema is diagnosed (consider alternative non-taxane chemotherapy). Elderly. Pregnancy (Cat.D; use adequate contraception); nursing mothers: not recommended. Interactions: May affect, or be affected by, other CYP3A4 inhibitors, inducers, or substrates (eg, ketoconazole, ritonavir). Adverse reactions: Infections, neutropenia, anemia, febrile neutropenia, hypersensitivity/ infusion site reactions, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis,

alopecia, myalgia; cutaneous reactions (eg, erythema, edema, desquamation), acute myeloid leukemia, death (septic and nonseptic), cystoid macular edema. How supplied: Single-dose vials (1mL, 4mL, 8mL)–1 (w. diluent, supplies)

Thiotepa (various)

℞

Alkylating agent. Thiotepa 15mg; per vial; lyophilized pwd for IV, intravesical, or intracavitary administration after reconstitution. Indications: Adenocarcinomas of the breast. Intracavitary effusion due to neoplasm of serosal cavities. Adults: 0.3–0.4mg/kg IV once every 1–4 weeks. Intracavitary administration: 0.6–0.8mg/kg through same tube used to remove fluid from cavity. Children: Not recommended. Contraindications: Renal, hepatic, or bone marrow dysfunction; if need outweighs risk, may be used in low dosage with close monitoring. Warnings/Precautions: Bone marrow suppression; monitor blood and platelets weekly during and for at least 3 weeks after therapy. Discontinue if WBC ≤3000/mm3 or platelets ≤150,000/mm3. Monitor renal and hepatic function. Use effective contraception if patient or partner is of childbearing potential. Elderly. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Increased toxicity with concomitant or sequential alkylating agents (nitrogen mustards, cyclophosphamide), radiation, myelosuppressants. Prolonged apnea with succinylcholine. Adverse reactions: Myelosuppression, fatigue, febrile or allergic reactions, inj site reactions, urinary retention, dysuria, GI disturbances, anorexia, alopecia, dizziness, headache, drowsiness, blurred vision, amenorrhea, interferes with spermatogenesis. Intravesical administration: rare: chemical or hemorrhagic cystitis. How supplied: Contact supplier.

TREXALL Teva

℞

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BREAST CANCER Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration). Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity. Diabetes. Peptic ulcer. Ulcerative colitis. Infection. Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated. Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, non-absorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin). Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome). How supplied: Tabs–30 Soln (2mL, 4mL, 8mL, 10mL)–10 (single-use vials) Pwd (1 gram)–1 (single-use vial)

TYKERB GlaxoSmithKline

℞

Tyrosine kinase inhibitor. Lapatinib 250mg; tabs. Indications: In combination with capecitabine, for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Limitation of use: patients

should have disease progression on trastuzumab before initiating Tykerb in combination with capecitabine. In combination with letrozole for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer that overexpresses HER2 for whom hormonal therapy is indicated. Adults: Take 1hr before or 1hr after a meal (capecitabine should be taken with food or within 30mins after food). HER2 metastatic breast cancer: 1250mg (5 tabs) once daily on Days 1–21 continuously in combination with capecitabine 2000mg/m2/day (administered orally in 2 doses approx. 12hrs apart) on Days 1–14 in a repeating 21 day cycle; continue until disease progression or unacceptable toxicity occurs. After recovery from left ventricular ejection fraction (LVEF) decrease: 1000mg/day. Severe hepatic dysfunction (Child-Pugh Class C): 750mg/day (no clinical data for this dose adjustment). Concomitant potent CYP3A4 inducers: may titrate up to 4500mg/day (no clinical data for this dose adjustment). Hormone receptor positive, HER2 positive metastatic breast cancer: 1500mg (6 tabs) once daily continuously in combination with letrozole 2.5mg once daily. After recovery from LVEF decrease: 1250mg/day. Severe hepatic dysfunction: 1000mg/day (no clinical data for this dose adjustment). Concomitant potent CYP3A4 inducers: may titrate up to 5500mg/day (no clinical data for this dose adjustment). For both: Concomitant potent CYP3A4 inhibitors: 500mg/day (no clinical data for this dose adjustment). Interrupt if diarrhea is NCI CTC grade 3, or grade 1 or 2 with complicating features develop; may restart at lower dose (reduced from 1250mg/day to 1000mg/day or from 1500mg/day to 1250mg/day) when resolves ≤ grade 1; permanently discontinue if diarrhea is grade 4. Other toxicities: discontinue if ≥grade 2 NCI CTC toxicity occurs; may restart at 1250mg/day if toxicity improves to grade 1; if recurs, may restart at 1000mg/day (with capecitabine); 1250mg/day (w. letrozole). Children: Not established. Warnings/Precautions: Confirm normal LVEF before starting. Discontinue if ≥grade 2 decrease in LVEF occurs, or if LVEF falls below institution’s lower limit of normal; may restart after at least 2 weeks at reduced dose if asymptomatic and LVEF recovers. Conditions that impair left ventricular function, or risk factors for QT prolongation (eg, hypokalemia, hypomagnesemia, congenital long QT syndrome, concomitant antiarrhythmics, cumulative high dose anthracyclines); correct electrolyte disturbances before starting. Monitor for interstitial lung disease or pneumonitis;

discontinue if pulmonary symptoms ≥grade 3 (NCI CTCAE). Monitor liver function tests before, every 4–6 weeks during therapy and as indicated; discontinue if hepatotoxicity occurs; do not retreat. Severe hepatic impairment: consider dose reduction. Diarrhea: promptly treat with anti-diarrheal agents; if severe, may require fluids, electrolytes, antibiotics and therapy interruption/discontinuation. Monitor ECG. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Avoid potent CYP3A4 inhibitors (eg, ketoconazole), grapefruit; reduce dose if unavoidable. Avoid potent CYP3A4 inducers (eg, carbamazepine); slowly titrate dose up if unavoidable. May affect drugs that are affected by p-glycoprotein, CYP2C8, CYP3A4. Adverse reactions: Diarrhea (may be severe), nausea, vomiting, hand/foot syndrome, rash, fatigue; decreased LVEF, QT prolongation, interstitial lung disease, pneumonitis, hepatotoxicity (may be fatal). Testing considerations: HER2 protein overexpression How supplied: Tabs–150

Vinblastine for injection

℞

Bedford

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BREAST CANCER Avoid in elderly with cachexia or ulcerated skin; or in patients with malignant-cell infiltration of the bone marrow. Pre-existing pulmonary dysfunction. Progressive dyspnea requiring chronic therapy (do not re-administer). Ischemic cardiac disease. Bone marrow suppression; monitor WBC before and during treatment. Avoid contamination of the eyes or injecting into an extremity with poor circulation (thrombosis possible). Avoid extravasation. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May be potentiated by CYP3A inhibitors (eg, erythromycin). Antagonizes phenytoin. Adverse reactions: Leukopenia, alopecia, GI upset, paresthesias, malaise, pain; dyspnea, severe bronchospasm. How supplied: Pwd–10 Soln–1

XELODA Roche

℞

Fluoropyrimidine. Capecitabine (prodrug of 5-fluorouracil) 150mg, 500mg; tabs. Indications: Metastatic breast cancer resistant to both paclitaxel and an anthracyclinecontaining chemotherapy regimen or resistant to paclitaxel when further anthracycline therapy is not indicated (eg, prior cumulative doses of 400mg/m2 of doxorubicin or its equivalents). With docetaxel for metastatic breast cancer after failure of prior anthracycline-containing regimen. Adults: See literature. Give cyclically (2 weeks on, 1 week off). Take with water within 30 minutes after AM & PM meals. ≥18yrs:

1250mg/m2 twice daily. Combination therapy: give with docetaxel 75mg/m2 IV infused over 1 hour every 3 weeks. Interrupt, adjust dose, and/or treat symptoms if toxicity occurs (eg, hyperbilirubinemia, diarrhea, nausea, vomiting, hand-and-foot syndrome, stomatitis) (see literature); do not increase dose afterwards. Renal impairment (CrCl 51–80mL/min): monitor carefully; (CrCl 30–50mL/min): reduce capecitabine dose to 75% of starting dose (ie, 950mg/m2 twice daily). Children: <18yrs: not recommended. Contraindications: Severe renal impairment (CrCl <30mL/min). Dihydropyrimidine dehydrogenase deficiency. Pregnancy (Cat.D), nursing mothers: not recommended. Warnings/Precautions: Hepatic or renal dysfunction. Coronary artery disease. Elderly (≥80years). Interactions: Potentiated by leucovorin. Monitor warfarin, other CYP2C9 substrates, phenytoin. Adverse reactions: Diarrhea, lymphopenia, necrotizing enterocolitis, hand-and-foot syndrome, GI upset, stomatitis, fatigue, dermatitis, anorexia, cardiotoxicity, bone marrow suppression, blood dyscrasias, hyperbilirubinemia, paresthesias, eye irritation, fever, headache, edema, dizziness, insomnia, myalgia, dehydration, nail disorder, limb pain, skin discoloration, alopecia. Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase) How supplied: Tabs 150mg–60 500mg–120

ZOLADEX AstraZeneca

℞

GnRH agonist. Goserelin (as acetate) 3.6mg; SC implant. Indications: Palliative treatment of advanced breast cancer in pre- and perimenopausal women. Adults: Implant SC into anterior abdominal wall. One 3.6mg implant every 28 days. Children: Not established. Contraindications: Pregnancy (Cat.D). Warnings/Precautions: Males: increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood glucose and for signs/symptoms of CVD during therapy. Risk of ureteral obstruction or spinal cord compression; monitor during 1st month of therapy. Females: nondiagnosed abnormal vaginal bleeding: not recommended. Risk factors for decreased bone mineral density (eg, chronic alcohol, tobacco, anticonvulsants, corticosteroids). Premenopausal women: use nonhormonal contraception during and for 12 weeks after therapy or until menses resume. Nursing mothers: not recommended. Interactions: May affect tests of pituitarygonadotropic and gonadal functions. Adverse reactions: Females: hypoestrogenism (eg, hot flashes, headache, sweating, acne, emotional lability, depression, decreased libido, vaginitis, breast atrophy, seborrhea). Males: decreased testosterone levels (eg, hot flashes, sexual dysfunction, decreased erections, gynecomastia), lower urinary tract symptoms. Both: transient worsening of symptoms (eg, bone pain), tumor flare, diarrhea, nausea, edema, malaise, hyperglycemia, hypercalcemia, decreased bone mineral density. How supplied: Implant (in syringe)–1

DOSAGES FOR THE ELDERLY Special caution is advised when prescribing drugs for elderly patients. Keep the following points in mind when prescribing drugs for patients of approximately 60 years or older:

1. Renal Function: Glomerular filtration rate, renal tubular secretion and blood flow tend to decrease with advancing age, while the incidence of renal pathology increases. 2. Drug Sensitivity: Elderly patients may show unusual sensitivity or paradoxical reactions to a number of drugs. Refer to the complete prescribing information. 3. Drug Distribution: The ratio of fat to lean body weight may increase in the elderly, which affects the volume of distribution of fat-soluble drugs. Plasma albumin concentrations may be decreased in the elderly. This potentiates plasma-protein bound drugs and increases the potential for drug interactions caused by plasma-protein displacement. 4. Polypharmacy: It is important to determine the patient’s current medication use, including nonprescription products, before adding any medication to determine any possible interactions. 5. Hepatic Function: Reduced function of metabolic enzymes in the liver may occur in the elderly.

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ENDOCRINE CANCER ABRAXANE Celgene

℞

Taxane antimicrotubule. Paclitaxel [bound to albumin (human)] 100mg/vial; pwd for IV infusion after reconstitution; solvent-free. Indications: First-line treatment of metastatic adenocarcinoma of the pancreas, in combination with gemcitabine. Adults: Do not treat if neutrophil count <1,500 cells/mm3 or platelets <100,000 cells/mm3. 125mg/m2 IV over 30–40 minutes on Days 1, 8, and 15 of each 28-day cycle. Dose reductions for hematologic and neurologic adverse reactions, hepatic impairment: see full labeling. Avoid extravasation. Children: Not evaluated. Contraindications: Baseline neutrophil count <1,500 cells/mm3. Prior severe hypersensitivity reaction (do not rechallenge). Warnings/Precautions: Do not substitute for, or with, other paclitaxel products (due to formulation differences). Do frequent complete blood cell counts. Monitor for sensory neuropathy, sepsis, or pneumonitis. Hepatic or renal dysfunction. Contains human albumin; remote risk of viral transmission. Use appropriate contraception (men and women). Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May potentiate or be potentiated by CYP2C8 and/or CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, efavirenz, nevirapine) and/or inhibitors (eg, ketoconazole, other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, nelfinavir). Adverse reactions: Bone marrow suppression (eg, neutropenia, anemia), infections, alopecia, sensory neuropathy (may require dose reduction or interruption), peripheral neuropathy, GI upset, mucositis, fatigue/asthenia, myalgia/arthralgia, abnormal ECG; alkaline phosphatase or AST elevation; dyspnea, edema, hypotension, rash (may be serious); rare: thrombotic events. How supplied: Single-use vial–1

ADRUCIL Teva

℞

Warnings/Precautions: Narrow margin of safety; monitor for toxicity. Consider hospitalization for 1st course. History of highdose pelvic irradiation. Previous use of alkylating agents. Widespread involvement of bone marrow by metastatic tumors. Renal or hepatic impairment. Discontinue if signs of toxicity appear (eg, stomatitis, esophagopharyngitis, leukopenia, intractable vomiting, diarrhea, GI ulceration or bleeding, thrombocytopenia, hemorrhage). Monitor WBCs with differential before each dose. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Potentiated by leucovorin. Adverse reactions: Stomatitis, esophagopharyngitis, GI upset, anorexia, leukopenia, alopecia, dermatitis, hand-foot syndrome; others. Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase) How supplied: Single-dose vials (10mL)–10

AFINITOR Novartis

℞

mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs. Indications: Progressive neuroendocrine tumors of pancreatic origin (PNET) in patients with unresectable, locally advanced or metastatic disease. Adults: Swallow whole with water or disperse tablet in 30mL of water and drink immediately. Take at the same time each day either consistently with or without food. 10mg once daily. Mild hepatic impairment (Child-Pugh class A): 7.5mg daily, may reduce to 5mg if not tolerated. Moderate hepatic impairment (Child-Pugh class B), or adverse reactions: reduce to 5mg daily, may be reduce to 2.5mg if not tolerated. Severe hepatic impairment (Child-Pugh class C): max 2.5mg daily if benefits outweigh risk. Concomitant moderate CYP3A4 or P-glycoprotein inhibitors: reduce to 2.5mg once daily; may consider increasing to 5mg if tolerated. If moderate inhibitor is discontinued, allow 2–3 days washout period before increasing everolimus dose; return to dose used prior to initiating the moderate inhibitor. Concomitant strong CYP3A4 inducers: may increase from 10–20mg once daily by increments of 5mg. If strong inducer is discontinued, should return to dose used prior to initiating the strong inducer. Continue as long as benefit observed or until unacceptable toxicity occurs. Children: Not recommended. Contraindications: Sirolimus, temsirolimus, rapamycin allergy. Warnings/Precautions: Hepatic impairment (see Adult dose). Increased risk of infections; some may be severe or fatal. Pre-existing invasive fungal infections: treat before starting. Monitor CBCs, renal function, lipids, blood glucose, and for pneumonitis and infections: treat promptly

if occur. Women of childbearing potential should use effective method of contraception during and up to 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Avoid live vaccines. Potentiated by strong CYP3A4 inhibitors, or P-glycoprotein inhibitors; avoid (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole, grapefruit juice). Caution with moderate CYP3A4 inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem) or P-glycoprotein inhibitors; reduce everolimus dose if used. Antagonized by strong CYP3A4 inducers; avoid (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s wort); increase everolimus dose if used. Adverse reactions: Pneumonitis (reduce dose and/or manage with corticosteroids; if severe, discontinue. May restart daily dose at approx. 50% lower than previously administered), infections (discontinue if invasive systemic fungal infection develops), stomatitis (treat with non-alcoholic, non-peroxide mouthwash), GI upset, rash, fatigue, edema, fever, headache, asthenia, cough, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see literature). How supplied: Tabs–28 (4 blister cards × 7 tabs)

CAPRELSA AstraZeneca

℞

Kinase inhibitor. Vandetanib 100mg, 300mg, tabs. Indications: Symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease. Adults: Do not crush tabs. May disperse tabs in 2oz noncarbonated water for oral or NGT administration; avoid contact of dispersion with skin, mucous membranes. 300mg once daily. Renal impairment (CrCl<50mL/min): initially 200mg once daily. Reduce dose if severe toxicity or QTc interval prolongation occurs (see full labeling). Do not take a missed dose within 12 hours of the next dose. Children: Not recommended. Contraindications: Congenital long QT syndrome. Warnings/Precautions: Hypocalcemia, hypokalemia, hypomagnesemia, QTcF interval >450msec, history of torsades de pointes, bradyarrhythmias, uncompensated heart failure, recent hemoptysis: not recommended. Ventricular arrhythmias. Recent MI. Monitor electrolytes (esp. K+, Ca++, Mg++), TSH, and ECG for QT prolongation at baseline, 2–4 weeks and 8–12 weeks after starting, then every 3 months, and after dose reductions or dose interruptions >2 weeks; reduce dose as needed. Correct electrolyte disturbances before starting. Maintain serum K+ at least 4mEq/mL. Hepatic impairment

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ENDOCRINE CANCER (Child-Pugh B or C): not recommended. Interrupt therapy and follow-up if acute or worsening pulmonary symptoms, or QTcF >500msec develop. Discontinue if confirmed interstitial lung disease, severe ischemic cerebrovascular event, hemorrhage, heart failure, diarrhea, uncontrolled hypertension, or posterior leukoencephalopathy symptoms (RPLS) occur. Avoid sun, UV light. Elderly. Pregnancy (Cat.D) (may cause fetal harm; use appropriate effective contraception during and for 4 months after stopping therapy), nursing mothers: not recommended. Interactions: Avoid strong CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenytoin, phenobarbital, rifampin, rifabutin, rifapentine, St. John’s Wort). Avoid other drugs that can prolong QT interval (eg, amiodarone, disopyramide, procainamide, sotalol, dofetilide, chloroquine, clarithromycin, dolasetron, granisetron, haloperidol, pimozide, methadone, moxifloxacin). Adverse reactions: Diarrhea/colitis (suspend if severe), rash, acne, nausea, hypertension, headache, upper respiratory tract infections, decreased appetite, abdominal pain, decreased calcium or glucose, increased ALT; QT prolongation, torsades de pointes, sudden death, severe skin reactions (eg, Stevens-Johnson syndrome; discontinue if occurs). Note: Prescribers and pharmacies must enroll in the Caprelsa REMS program by calling (800) 2369933 or visit www.caprelsarems.com. How supplied: Tabs–30

COMETRIQ Exelixis

℞

Kinase inhibitor. Cabozantinib 20mg, 80mg; caps. Indications: Treatment of progressive, metastatic medullary thyroid cancer (MTC). Adults: Swallow whole. 140mg daily. Do not eat at least 2 hours before or 1 hour after dose. Continue until disease progression or unacceptable toxicity. Withhold for Grade 4 hematologic adverse reactions, ≥Grade 3 non-hematologic reactions or intolerable Grade 2 reactions. Upon improvement to Grade 1 or to baseline, reduce dose as follows: previously on 140mg daily, resume at 100mg daily; previously on 100mg daily, resume at 60mg daily; previously on 60mg daily, resume at 60mg if tolerated, otherwise discontinue. Concomitant strong CYP3A4 inhibitor: reduce daily dose by 40mg; resume dose used prior to starting inhibitor 2–3 days after discontinuation of inhibitor. Concomitant strong CYP3A4 inducers: increase daily dose by 40mg; resume dose used prior to starting inducer 2–3 days after discontinuation of inducer. Max daily dose: 180mg. Children: Not studied. Warnings/Precautions: Permanently discontinue if the following occurs: GI or non-GI perforation/fistula formation, severe hemorrhage, serious arterial thromboembolic events (eg, MI, cerebral infarction), nephrotic syndrome, malignant hypertension, hypertensive

crisis, persistent uncontrolled hypertension despite optimal medical management, osteonecrosis of the jaw, reversible posterior leukoencephalopathy syndrome. Moderate to severe hepatic impairment: not recommended. Recent history of hemorrhage, hemoptysis: avoid. Stop treatment at least 28 days prior to scheduled surgery (including invasive dental procedures); withhold dose if dehiscence or wound healing complications require medical intervention. Monitor for bleeding, hypertension, proteinuria (measure urine protein regularly). Use effective contraception during and up to 4 months after completion of therapy. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Avoid concomitant strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole, grapefruit or grapefruit juice) and strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s Wort): see Adult dose. Adverse reactions: Diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome, decreased weight/appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, constipation, increased AST, ALT, alkaline phosphatase, lymphopenia, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, hyperbilirubinemia. How supplied: 140mg daily-dose carton–4 blister cards (each: 7×80mg and 21×20mg caps); 100mg daily-dose carton–4 blister cards (each: 7×80mg and 7×20mg caps); 60mg daily-dose carton–4 blister cards (each: 21×20mg caps)

Doxorubicin HCl (various)

℞

Anthracycline. Doxorubicin HCl 10mg/vial, 20mg/vial, 50mg/vial; pwd for IV inj after reconstitution; contains lactose. ℞ Also: Doxorubicin HCl Solution Doxorubicin HCl 2mg/mL; soln for IV inj. Indications: Disseminated neoplasias (eg, thyroid carcinoma). Adults and Children: Monotherapy: usually 60–75mg/m2 IV every 21 days. Combination therapy: usually 40–60mg/m2 IV every 21 to 28 days. Hyperbilirubinemia, inadequate bone marrow reserves: reduce dose. Contraindications: Severe myelosuppression (baseline neutrophils <1500cells/mm3) or severe hepatic impairment. Cardiac disease (eg, severe myocardial insufficiency, arrhythmias). Recent MI. Previous treatment with max cumulative doses of anthracyclines, anthracenediones. Warnings/Precautions: Pre-existing heart disease or risk thereof. Obtain baseline CBC, bilirubin, AST, creatinine, LVEF. Hepatic dysfunction. Monitor cardiac function (LVEF, ECG echocardiogram), hepatic function, CBC, uric acid levels. Avoid extravasation. Children (cardiotoxicity, impaired myocardial

growth). Elderly. Pregnancy (Cat.D; use adequate contraception). Nursing mothers: not recommended. Interactions: See Contraindications. Mediastinal irradiation, cyclophosphamide, calcium channel blockers, other anthracyclines increase risk of cardiac toxicity; limit lifetime dose to 400mg/m2. Necrotizing colitis with cytarabine. May increase toxicity of cyclophosphamide, mercaptopurine. May reduce serum digoxin levels. Doxorubicin toxicity increased with high-dose IV progesterone, cyclosporine, streptozocin, and if given after paclitaxel infusion (give doxorubicin dose first). Elimination increased by phenobarbital. May decrease phenytoin levels. Recall pneumonitis with actinomycin and radiation in children. Adverse reactions: Local necrosis if extravasation occurs, myocardial toxicity (immediate or delayed), arrhythmias, leukemia, myelosuppression, hyperuricemia, urine discoloration, alopecia, hyperpigmentation, severe GI upset/ulceration, phlebosclerosis, facial flushing, fever, urticaria, peripheral neuropathy, anaphylaxis. How supplied: Contact supplier.

Fluorouracil (various)

℞

Antimetabolite. Fluorouracil 50mg/mL; soln for IV inj. Indications: Palliative management of carcinoma of the pancreas. Adults: Give by IV inj. 12mg/kg once daily for 4 successive days; max 800mg/day. If no toxicity is observed, 6mg/kg are given on the 6th, 8th, 10th, and 12th days unless toxicity occurs. Maintenance therapy: repeat dosage of 1st course every 30 days after the last day of the previous course of treatment; or give a maintenance dose of 10–15mg/kg per week as a single dose; max: 1g/ week. Poor risk patients: see literature for dose adjustments. Children: Not recommended. Contraindications: Poor nutritional state. Depressed bone marrow function. Potentially serious infections. Warnings/Precautions: Narrow margin of safety; monitor for toxicity. Consider hospitalization for 1st course. History of highdose pelvic irradiation. Previous use of alkylating agents. Widespread involvement of bone marrow by metastatic tumors. Renal or hepatic impairment. Discontinue if signs of toxicity appear (eg, stomatitis, esophagopharyngitis, leukopenia, intractable vomiting, diarrhea, GI ulceration or bleeding, thrombocytopenia, hemorrhage). Monitor WBCs with differential before each dose. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Potentiated by leucovorin. Adverse reactions: Stomatitis, esophagopharyngitis, GI upset, anorexia, leukopenia, alopecia, dermatitis, hand-foot syndrome; others.

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ENDOCRINE CANCER Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase). How supplied: Contact supplier.

GEMZAR Lilly

℞

Antimetabolite. Gemcitabine HCl 200mg, 1g; per vial; pwd for IV infusion after reconstitution; contains mannitol. Indications: First-line treatment of locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) pancreatic cancer. Adults: Infuse over 30 minutes (increased toxicity if infusion goes beyond 60 minutes). 1000mg/m2 once weekly for up to 7 weeks, followed by a week of rest; subsequent cycles: infuse once weekly for 3 consecutive weeks out of every 4 weeks. Adjust dose based on toxicity (see literature). Children: Not recommended. Warnings/Precautions: Not for use in combination with radiation therapy. Discontinue immediately if severe lung toxicity, hemolytic uremic syndrome, or capillary leak syndrome occurs. Renal or hepatic impairment. Evaluate renal and hepatic function prior to therapy, then periodically thereafter. Discontinue if severe liver injury develops. Monitor for myelosuppression; obtain CBCs, platelets prior to each dose. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: See Warnings/Precautions. Concomitant radiation therapy: may cause severe radiation toxicity. Adverse reactions: Myelosuppression, nausea, vomiting, elevated transaminases, proteinuria, hematuria, rash, pruritus, dyspnea, edema, flulike symptoms, infection, alopecia, neurotoxicity, others; rare: renal or liver failure, hemolytic uremic syndrom, capillary leak syndrome. Testing considerations: ERCC1 overexpression for response and prognosis; RRM1 How supplied: Single-use vials–1

LYSODREN Bristol-Myers Squibb

℞

Adrenal cytotoxic agent. Mitotane 500mg; tabs; scored. Indications: Inoperable adrenal cortical carcinoma. Adults: 2–6g/day in divided doses (3–4 times/day). Doses may be increased incrementally to 9–10g/day. Max: 18–19g/day. Continue as long as clinical benefit observed. Children: Not recommended. Warnings/Precautions: Discontinue temporarily following shock or severe trauma. Hepatic disease. Remove any tumor tissues from metastatic masses prior to therapy to minimize possible infarction and hemorrhage. Long-term administration of high doses: assess behavioral and neurological function. May need concomitant steroid replacement. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Monitor oral anticoagulants. Caution with other drugs susceptible to hepatic enzyme induction. Adverse reactions: GI upset, lethargy, somnolence, dizziness, vertigo, rash. How supplied: Tabs–100

Mitomycin (various)

℞

Cytotoxic antibiotic. Mitomycin 5mg/vial, 20mg/vial, 40mg/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol. Indications: Disseminated adenocarcinoma of the pancreas. Adults: Give by IV infusion. 20mg/m2 as a single dose every 6–8 weeks. Discontinue if disease progresses after two courses. Myelosuppression: see literature for dose adjustments. Children: Not recommended. Contraindications: Thrombocytopenia. Coagulation disorders. Bleeding tendencies. Warnings/Precautions: Renal toxicity; serum creatinine >1.7mg: not recommended. Monitor platelets, WBCs, differential, hemoglobin repeatedly during and for at least 8 weeks after therapy. Avoid extravasation. Monitor fluid balance and avoid overhydration. Pregnancy, nursing mothers: not recommended. Interactions: Caution with vinca alkaloids, other chemotherapy. Adverse reactions: Thrombocytopenia, leukopenia (cumulative myelosuppression); inj site reactions (eg, cellulitis), stomatitis, alopecia, renal toxicity, pulmonary toxicity (eg, pulmonary infiltrates); discontinue if occurs; hemolytic uremic syndrome, CHF, fever, anorexia, nausea, vomiting. How supplied: Contact supplier.

NEXAVAR Bayer and Onyx

℞

Multikinase inhibitor. Sorafenib 200mg; tabs. Indications: Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment. Adults: Take on an empty stomach. 400mg twice daily. If toxicity occurs, may reduce dose to 400mg and 200mg 12hrs apart (either dose can come first); if second reduction is required, may reduce dose to 200mg twice daily; if third reduction is required, may reduce to 200mg once daily (see full labeling). Concomitant strong CYP3A4 inducers: consider increasing dose, monitor for toxicity. Children: Not established. Contraindications: Concomitant carboplatin/ paclitaxel in patients with squamous cell lung cancer. Warnings/Precautions: Avoid in congenital long QT syndrome. Monitor patients with CHF, bradyarrhythmias, drugs known to prolong the QT interval, electrolyte abnormalities. Discontinue if severe dermatologic toxicity, hypertension, GI perforation, hemorrhage, cardiac ischemia, MI occurs. Suspend therapy before major surgery.

Monitor BP weekly during the first 6 weeks and thereafter. Monitor hepatic function regularly; discontinue if transaminases significantly elevated. Severe hepatic impairment (ChildPugh C) or on dialysis. Monitor TSH levels monthly and adjust thyroid therapy. Use effective contraception during and for 2 weeks after stopping treatment. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: See Contraindications. Avoid strong CYP3A4 inducers (eg, St. John’s Wort, dexamethasone, phenytoin, carbamazepine, rifabutin, rifampin, phenobarbital) and neomycin; may decrease sorafenib levels. May potentiate warfarin (monitor PT & INR), other drugs metabolized by UGT1A1 or UGT1A9 pathway, or substrates of CYP2B6, CYP2C8, CYP2C9, P-gp. Concomitant Class Ia and III antiarrhythmics; may prolong QT interval. Adverse reactions: Dermatologic toxicity (eg, rash, hand-foot skin reaction, alopecia, pruritus, dry skin, Stevens-Johnson syndrome, toxic epidermal necrolysis), fatigue, weight loss, diarrhea, anorexia, abdominal pain, hypertension, hemorrhage, electrolyte abnormalities; druginduced hepatitis, QT prolongation. How supplied: Tabs–120

SUTENT Pfizer

℞

Multikinase inhibitor. Sunitinib (as malate) 12.5mg, 25mg, 50mg; gelatin caps. Indications: Progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with unresectable locally advanced or metastatic disease. Adults: 37.5mg once daily continuously without a scheduled off-treatment period. May adjust dose in increments or decrements of 12.5mg. Concomitant strong CYP3A4 inhibitors (see Interactions): may reduce dose to 25mg daily. Concomitant strong CYP3A4 inducers (see Interactions): may increase to max 62.5mg daily. Children: Not established. Warnings/Precautions: Hepatotoxicity; may be severe or fatal. Monitor liver function tests before starting, during each cycle of treatment and as clinically needed; interrupt if Grade 3 or 4 hepatic adverse events occur and discontinue if no resolution; if severe liver function changes or signs/symptoms of failure, do not restart. Cardiovascular disease: monitor LVEF at baseline and periodically thereafter; interrupt or reduce dose if LVEF <50% and >20% below baseline; discontinue if CHF occurs. History of QT prolongation or proarrythmic conditions (eg, bradycardia, electrolyte disturbances); perform periodic ECG, monitor electrolytes. Monitor BP. Suspend therapy if severe hypertension, seizures, or pancreatitis develops. Obtain CBCs, platelets, serum chemistries at start of each cycle. Concomitant exposure to risk factors (eg, IV bisphosphonates therapy or dental disease) may increase the risk of osteonecrosis of the jaw; avoid or consider preventive dentistry prior to

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ENDOCRINE CANCER treatment. Risk of tumor lysis syndrome: monitor closely in RCC and GIST patients with high tumor burden. Monitor for thyroid dysfunction; obtain baseline levels prior to treatment. Undergoing major surgery. Stress (monitor for adrenal insufficiency). Renal or hepatic impairment. Pregnancy (Cat.D; avoid). Nursing mothers: not recommended. Interactions: May be potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole); grapefruit. May be antagonized by CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital); St. John’s wort: not recommended. Adverse reactions: Fatigue, asthenia, fever, diarrhea, nausea, vomiting, mucositis/stomatitis, dyspepsia, abdominal pain, constipation, hypertension, peripheral edema, rash, handfoot syndrome, skin discoloration, dry skin, hair color changes, altered taste, headache, back pain, arthralgia, extremity pain, cough, dyspnea, anorexia, bleeding; hepatotoxicity, left ventricular dysfunction, QT prolongation, hemorrhage, hypertension, osteonecrosis of the jaw, tumor lysis syndrome, thyroid dysfunction, impaired wound healing, others (see full labeling). How supplied: Caps–28

TARCEVA Genentech

℞

Human epidermal growth factor receptor type 1/ epidermal growth factor receptor tyrosine kinase inhibitor. Erlotinib (as HCl) 25mg, 100mg, 150mg; tabs. Indications: In combination with gemcitabine: first-line treatment of locally advanced, unresectable or metastatic pancreatic cancer. Adults: Take on empty stomach. 100mg once daily + gemcitabine (see literature). Use until disease progression or unacceptable toxicity occurs. Diarrhea unresponsive to loperamide, severe skin reactions, strong CYP3A4 inhibitors (see Interactions), hepatic impairment: reduce in 50mg decrements. CYP3A4 inducers (see Interactions): consider increased dose (see literature). Children: Not recommended. Warnings/Precautions: Discontinue if interstitial lung disease, hepatic failure, or GI perforation occurs; interrupt or discontinue therapy in patients with dehydration at risk for renal failure, or with severe bullous, blistering or exfoliative skin conditions, or with acute/ worsening ocular disorders. Hepatic impairment. Monitor liver function tests periodically; if tests worsen, consider withholding or reducing dose; interrupt or discontinue therapy if severe changes (eg, total bilirubin >3×ULN, and/or transaminases >5×ULN) occur. Monitor renal function, serum electrolytes, pulmonary function, INR, prothrombin time. History of peptic ulcers or diverticular disease. Pregnancy (Cat.D); use

adequate contraception (see literature). Nursing mothers: not recommended. Interactions: Potentiated by CYP3A4 inhibitors (eg, clarithromycin, ritonavir, ketoconazole). Plasma levels decreased by CYP3A4 inducers (eg, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort), proton pump inhibitors or H2 blockers, and smoking. Antagonizes midazolam. Increased risk of GI perforation with concomitant anti-angiogenic agents, steroids, NSAIDs, taxane-based chemotherapy. Monitor for bleeding with oral anticoagulants, NSAIDs. Adverse reactions: Rash, diarrhea, GI upset, anorexia, fatigue, elevated LFTs, unexplained pulmonary symptoms (eg, dyspnea, cough, fever; discontinue and follow-up if occurs), stomatitis, infection; rare: GI perforation (may be fatal), ocular disorders (eg, conjunctivitis, keratitis, corneal ulceration/perforation), MI/ischemia, hemolytic anemia, cerebrovascular accidents, interstitial lung disease; hepatic or renal failure and hepatorenal syndrome (may be fatal); bullous, blistering and exfoliative skin conditions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis). Testing considerations: K-RAS mutation analysis, EGFR amplification analysis How supplied: Tabs–30

THYROGEN Genzyme

℞

Thyroid stimulating hormone (recombinant). Thyrotropin alfa 1.1mg/vial; lyophilized pwd for IM inj after reconstitution; contains mannitol. Indications: Adjunctive diagnostic tool for serum thyroglobin (Tg) testing with or without radioiodine imaging in the follow-up of patients with well-differentiated thyroid cancer. Adjunctive treatment for radioiodine ablation of thyroid tissue remnants in patients who have undergone a near-total or total thyroidectomy for welldifferentiated thyroid cancer and who do not have evidence of metastatic thyroid cancer. Adults: ≥16yrs: Give by IM inj into the buttock. 0.9mg, followed by a second 0.9mg injection 24 hours later. For radioiodine imaging or remnant ablation, give radioiodine 24 hours after the second Thyrogen injection. Children: <16yrs: not established. Warnings/Precautions: See full labeling. Reports of death in patients who are not thyroidectomized or with distant metastatic thyroid cancer wthin 24hrs after administration. Heart disease, extensive metastatic disease, or other serious underlying illnesses; increased risk of Thyrogen-induced hyperthyroidism, consider hospitalization for administration and postadministration observation. Caution patients regarding possible neurologic symptoms. Consider pretreatment with glucocorticoids in those whose tumor expansion may compromise vital anatomic structures (eg, trachea, CNS, lung metastases). Thyroglobulin (Tg) antibodies may render Tg levels uninterpretable; consider further evaluation with thyroid hormone withdrawal scan. Previous bovine

TSH treatment. Residual thyroid tissue. End-stage renal disease. Elderly (increased risk of cardiac effects). Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Nausea, headache, fatigue, influenza-like symptoms; death (in nonthyroidectomized or with distant metastatic thyroid cancer), stroke and other neurologic events, sudden rapid tumor enlargement in distant metastatic thyroid cancer. How supplied: 2-vial kit–2 vials of Thyrogen; 4-vial kit–2 vials of Thyrogen + 2 vials of diluent

ZANOSAR Teva

℞

Anthracycline (nitrosourea). Streptozocin 1g/ vial; pwd for IV inj or infusion after reconstitution/ dilution; preservative-free. Indications: Symptomatic or progressive metastatic pancreatic islet cell cancer. Adults: 1g/m2 IV once weekly for 2 weeks; may repeat weekly; max 1.5g/m2 per dose. Or, 500mg/m2 IV daily for 5 days every 6 weeks until max benefit or toxicity. Children: Not recommended. Warnings/Precautions: Renal dysfunction or disease. Monitor renal function (eg, urinalysis, BUN, creatinine, electrolytes) before, weekly during, and for 4 weeks after therapy; discontinue or reduce dose if significant renal toxicity occurs (see literature). Obtain CBCs, liver function tests weekly. Avoid extravasation. Ensure adequate hydration. Elderly. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Avoid concomitant nephrotoxic agents. Additive toxicity with other cytotoxic drugs. Severe bone marrow toxicity with doxorubicin. Phenytoin may reduce cytotoxicity. Adverse reactions: GI upset (may be severe); hematological, hepatic and renal (cumulative and dose-related; may be fatal) toxicity; glucose intolerance, nephrogenic diabetes insipidus, inj site reactions, CNS effects (eg, confusion, lethargy, depression). How supplied: Single-use vial–1

DOSAGE Recommended adult dosage and, where appropriate, the dosage for children. Doses are given for children <12 years of age unless stated otherwise. Assume the adult dosage for children ≥12 years. Dosages for children are presented in ascending age order.

CARE OF DRUGS Patients should be advised that all drug preparations require careful storage.

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GASTROINTESTINAL CANCER ADRUCIL Teva

℞

Antimetabolite. Fluorouracil 50mg/mL; soln for IV inj. Indications: Palliative management of carcinoma of the colon, rectum, and stomach. Adults: Give by IV inj. 12mg/kg once daily for 4 successive days; max 800mg/day. If no toxicity is observed, 6mg/kg are given on the 6th, 8th, 10th, and 12th days unless toxicity occurs. Maintenance therapy: repeat dosage of 1st course every 30 days after the last day of the previous course of treatment; or give a maintenance dose of 10–15mg/kg per week as a single dose; max: 1g/ week. Poor risk patients: see literature for dose adjustments. Children: Not recommended. Contraindications: Poor nutritional state. Depressed bone marrow function. Potentially serious infections. Warnings/Precautions: Narrow margin of safety; monitor for toxicity. Consider hospitalization for 1st course. History of highdose pelvic irradiation. Previous use of alkylating agents. Widespread involvement of bone marrow by metastatic tumors. Renal or hepatic impairment. Discontinue if signs of toxicity appear (eg, stomatitis, esophagopharyngitis, leukopenia, intractable vomiting, diarrhea, GI ulceration or bleeding, thrombocytopenia, hemorrhage). Monitor WBCs with differential before each dose. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Potentiated by leucovorin. Adverse reactions: Stomatitis, esophagopharyngitis, GI upset, anorexia, leukopenia, alopecia, dermatitis, hand-foot syndrome; others. Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase) How supplied: Single-dose vials (10mL)–10

AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free. Indications: Metastatic colorectal carcinoma, in combination with 5-FU-based chemotherapy for first- or second-line treatment; or in combination with fluoropyrimidine-irinotecanor fluoropyrimidine oxaliplatin-based therapy for second-line treatment in patients who have progressed on a first-line Avastin-containing regimen. Limitation of use: not for adjuvant treatment of colon cancer. Adults: Give by IV infusion after chemotherapy. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins. 5mg/kg (when used with bolus-IFL) or 10mg/kg (when used with FOLFOX-4) once every 2 weeks until disease progression detected;

5mg/kg every 2 weeks or 7.5mg/kg every 3 weeks (when used with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based therapy). Children: Not established. Warnings/Precautions: Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). History of hemoptysis of ≥ ½-teaspoon of red blood: do not administer. Discontinue if GI perforation, wound healing complications, serious hemorrhage, severe arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, non-GI fistula formation, or reversible posterior leukoencephalopathy syndrome occurs; suspend therapy if severe hypertension, moderate to severe proteinuria, or severe infusion reaction occurs. Cardiovascular disease. Diabetes. Renal or hepatic impairment. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis. Elderly. Increases risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy (Cat.C). Nursing mothers: not recommended. Adverse reactions: Epistaxis, headache, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome, infusion reactions, ovarian failure. How supplied: Single-use vial–1

CAMPTOSAR Pfizer

℞

Topoisomerase 1 inhibitor. Irinotecan HCl 20mg/mL; soln for IV infusion after dilution. Indications: Metastatic colorectal cancer, as 1st line therapy with 5-FU and leucovorin, or as monotherapy if disease recurs or progresses after fluorouracil-based therapy. Adults: See literature. Give by IV infusion over 90 minutes. Combination therapy: 125mg/m2 on days 1, 8, 15, 22; or, 180mg/m2 on days 1, 15, 29; both: give every 6 weeks. Monotherapy: 125mg/m2 on days 1, 8, 15, 22, then 2-week rest; or, 350mg/m2 once every 3 weeks. Elderly (≥65 years), pelvic or abdominal radiotherapy, performance status of 2, increased bilirubin, homozygous UGT1A1*28 allele, or toxicity: reduce initial dose. May pretreat with antiemetics and/ or atropine. Children: See literature. Contraindications: During or within 2 weeks of St. John’s wort, or 1 week of ketoconazole. Warnings/Precautions: Not for use as part of 5-FU/LV “Mayo Clinic” regimen except in certain circumstances (see literature). Renal or hepatic impairment. Dialysis: not recommended. Diabetes. Gilbert’s syndrome or abnormal glucuronidation. Monitor blood counts; suspend if neutropenic fever or ANC <1000/mm3 occurs. If late diarrhea occurs, may treat with loperamide;

suspend until bowel function normalizes. Avoid extravasation. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: See Contraindications. Avoid live vaccines. Concomitant irradiation: not recommended. Antagonized by CYP3A4 inducers (eg, phenytoin, phenobarbital, carbamazepine, rifampin, St. John’s wort). Hyperglycemia, lymphocytopenia increased with dexamethasone. Increased risk of renal toxicity with diuretics (esp. in dehydration). May affect neuromuscular blocking agents. May be potentiated by atazanavir. Adverse reactions: GI upset, myelosuppression, fever, infection, asthenia, renal or hepatic dysfunction, dyspnea, dizziness, somnolence, hypotension, thromboembolic events, rash, alopecia, hand-and-foot syndrome, edema, cholinergic effects, flushing, ileus, local or hypersensitivity reactions. Testing considerations: UGT1A1 mutation analysis How supplied: Single-dose vial (2mL, 5mL)–1

Doxorubicin HCl (various)

℞

Anthracycline. Doxorubicin HCl 10mg/vial, 20mg/vial, 50mg/vial; pwd for IV inj after reconstitution; contains lactose. ℞ Also: Doxorubicin HCl Solution Doxorubicin HCl 2mg/mL; soln for IV inj. Indications: Disseminated neoplasias (eg, gastric carcinoma). Adults and Children: Monotherapy: usually 60–75mg/m2 IV every 21 days. Combination therapy: usually 40–60mg/m2 IV every 21 to 28 days. Hyperbilirubinemia, inadequate bone marrow reserves: reduce dose. Contraindications: Severe myelosuppression (baseline neutrophils <1500cells/mm3) or severe hepatic impairment. Cardiac disease (eg, severe myocardial insufficiency, arrhythmias). Recent MI. Previous treatment with max cumulative doses of anthracyclines, anthracenediones. Warnings/Precautions: Pre-existing heart disease or risk thereof. Obtain baseline CBC, bilirubin, AST, creatinine, LVEF. Hepatic dysfunction. Monitor cardiac function (LVEF, ECG echocardiogram), hepatic function, CBC, uric acid levels. Avoid extravasation. Children (cardiotoxicity, impaired myocardial growth). Elderly. Pregnancy (Cat.D; use adequate contraception). Nursing mothers: not recommended. Interactions: See Contraindications. Mediastinal irradiation, cyclophosphamide, calcium channel blockers, other anthracyclines increase risk of cardiac toxicity; limit lifetime dose to 400mg/m2. Necrotizing colitis with cytarabine. May increase toxicity of cyclophosphamide, mercaptopurine. May reduce serum digoxin levels. Doxorubicin toxicity increased with high-dose IV progesterone, cyclosporine, streptozocin, and if given after paclitaxel infusion (give doxorubicin dose first). Elimination increased by phenobarbital. May

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GASTROINTESTINAL CANCER decrease phenytoin levels. Recall pneumonitis with actinomycin and radiation in children. Adverse reactions: Local necrosis if extravasation occurs, myocardial toxicity (immediate or delayed), arrhythmias, leukemia, myelosuppression, hyperuricemia, urine discoloration, alopecia, hyperpigmentation, severe GI upset/ulceration, phlebosclerosis, facial flushing, fever, urticaria, peripheral neuropathy, anaphylaxis. How supplied: Contact supplier.

ELOXATIN Sanofi Aventis

℞

Alkylating agent (organoplatinum complex). Oxaliplatin 5mg/mL; soln for IV infusion after dilution; preservative-free. Indications: Adjuvant treatment for Stage III colon cancer in patients who have undergone complete resection of the primary tumor (in combination with infusional 5-FU/LV). Treatment of advanced colorectal cancer (in combination with infusional 5-FU/LV). Adults: See literature. Premedicate with antiemetics. Give by IV infusion every two weeks for a total of 6 months (eg, 12 cycles). Day 1: 85mg/m2 + leucovorin, followed by 5-FU. Day 2: Leucovorin followed by 5-FU. Severe renal impairment: initially 65mg/m2. Neuropathy, other toxicities: see literature for dose adjustments. Children: Not recommended. Warnings/Precautions: Have epinephrine, corticosteroids, antihistamines available during infusion. Discontinue if interstitial lung disease or pulmonary fibrosis suspected. Monitor for neuropathy; reduce dose or discontinue if needed. Renal impairment. Monitor WBCs with differential, hemogloblin, platelets, blood chemistries (including ALT, AST, bilirubin, creatinine) before each treatment. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Caution with concomitant nephrotoxic agents. Monitor oral anticoagulants. Adverse reactions: Peripheral sensory neuropathy, neutropenia, thrombocytopenia, anemia, GI upset, increased liver enzymes, emesis, fatigue, stomatitis; hypersensitivity reactions (monitor), pulmonary fibrosis (may be fatal), hepatotoxicity. Testing considerations: ERCC1 overexpression How supplied: Single-use vials (50mg, 100mg, 200mg)–1

ERBITUX Bristol-Myers Squibb

℞

Epidermal growth factor receptor blocker. Cetuximab 100mg/vial, 200mg/vial; soln for IV infusion; preservative-free. Indications: K-Ras mutation-negative (wildtype), EGFR-expressing metastatic colorectal carcinoma: for use in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment, or in combination with irinotecan (if refractory to irinotecan-based chemotherapy), or

as a single agent (after failure of both irinotecanand oxaliplatin-based regimens or if irinotecanintolerant). Not recommended for use with K-Ras mutation-positive or K-Ras somatic mutations in codon 12 or 13. Adults: Pretreat with H1 blocker. Give by IV infusion (use filter); max rate: 10mg/min. Initial dose: 400mg/m2 once over 2 hours; then 250mg/m2 once weekly over 1 hour until disease progression or unacceptable toxicity. Complete administration 1 hour prior to FOLFIRI. Permanently reduce infusion rate by 50% if Grade 1 or 2 and non-serious Grade 3 infusion reaction occurs; permanently discontinue if Grade 3 or 4 serious reaction occurs. Monitor patient during and for 1 hr post-infusion. Skin toxicity: see full labeling. Children: Not recommended. Warnings/Precautions: Confirm K-Ras mutation status and EGFR expression for colorectal cancer. Discontinue if severe infusion reactions or interstitial lung disease occur. Monitor for infusion reactions, cardiopulmonary arrest, pulmonary toxicity, skin inflammation/ infection; avoid sun, UV light. Additive cutaneous reactions with irradiation. Cardiovascular diseases (w. irradiation or platinum-based therapy with 5-FU). Monitor electrolytes (eg, magnesium, potassium, calcium) during and after cetuximab therapy. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Increased mucositis (Grade 3–4), radiation recall syndrome, acneiform rash, cardiac events, and electrolyte disturbances with radiation and cisplatin. Adverse reactions: Cutaneous reactions (pruritus, nail changes), acneform rash, headache, diarrhea, infection, asthenia, mucositis, weight loss, xerostomia, dehydration, electrolyte abnormalities; infusion reactions (may be severe: eg, bronchospasm, dyspnea), interstitial lung disease, cardiopulmonary arrest, hypomagnesemia, fever, sepsis, kidney failure, pulmonary embolus; others (see full labeling). Testing considerations: EGFR amplification analysis, K-RAS mutation analysis, B-RAF mutation analysis. How supplied: Single-use vials–1

Floxuridine (various) Antimetabolite. Floxuridine 500mg/vial; lyophilized pwd for intra-arterial infusion after reconstitution and dilution. Indications: Palliative therapy of GI adenocarcinoma with liver metastases in select patients (see literature). Adults: Continuous arterial infusion 0.1–0.6mg/kg per day. Hepatic artery infusion: 0.4–0.6mg/kg per day. May give until adverse reactions occur; treat as long as response continues. See literature. Children: Not recommended. Contraindications: Poor nutritional state. Myelosuppression. Serious infections.

℞

Warnings/Precautions: Hospitalize for 1st course. Hepatic or renal dysfunction. History of high-dose pelvic irradiation or alkylation therapy. Monitor blood (esp WBC, platelets). Discontinue for myocardial ischemia, stomatitis or esophagopharyngitis, WBC <3500 or rapidly falling, intractable vomiting, GI ulcer/bleeding, diarrhea, platelets <100000, hemorrhage. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Adverse reactions: GI upset, enteritis, stomatitis, localized erythema, myelosuppression, liver dysfunction, GI bleeding/ulcer, duodenitis, gastroenteritis, glossitis, pharyngitis, intraand extrahepatic biliary sclerosis, acalculous cholecystitis, alopecia, dermatitis, myocardial ischemia, fever, malaise; lab abnormalities (eg, anemia, leukopenia, thrombocytopenia, abnormal PT, total proteins, ESR, ALT/SGOT, bilirubin, lactic dehydrogenase); procedural complications (eg, arterial aneurysm, ischemia, thrombotic events, fibromyositis, thrombophlebitis, hepatic necrosis, abscess). How supplied: Contact supplier.

Fluorouracil (various)

℞

Antimetabolite. Fluorouracil 50mg/mL; soln for IV inj. Indications: Palliative management of carcinoma of the colon, rectum, and stomach. Adults: Give by IV inj. 12mg/kg once daily for 4 successive days; max 800mg/day. If no toxicity is observed, 6mg/kg are given on the 6th, 8th, 10th, and 12th days unless toxicity occurs. Maintenance therapy: repeat dosage of 1st course every 30 days after the last day of the previous course of treatment; or give a maintenance dose of 10–15mg/kg per week as a single dose; max: 1g/week. Poor risk patients: see literature for dose adjustments. Children: Not recommended. Contraindications: Poor nutritional state. Depressed bone marrow function. Potentially serious infections. Warnings/Precautions: Narrow margin of safety; monitor for toxicity. Consider hospitalization for 1st course. History of highdose pelvic irradiation. Previous use of alkylating agents. Widespread involvement of bone marrow by metastatic tumors. Renal or hepatic impairment. Discontinue if signs of toxicity appear (eg, stomatitis, esophagopharyngitis, leukopenia, intractable vomiting, diarrhea, GI ulceration or bleeding, thrombocytopenia, hemorrhage). Monitor WBCs with differential before each dose. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Potentiated by leucovorin. Adverse reactions: Stomatitis, esophagopharyngitis, GI upset, anorexia, leukopenia, alopecia, dermatitis, hand-foot syndrome; others.

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GASTROINTESTINAL CANCER Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase). How supplied: Contact supplier.

FUSILEV Spectrum

℞

Folate analogue. Levoleucovorin (as calcium pentahydrate) 50mg/vial; pwd for IV inj after reconstitution; contains mannitol 50mg/vial; 175mg/17.5mL; soln for IV inj; preservative-free. Indications: Palliative treatment of advanced metastatic colorectal cancer in combination with 5-fluorouracil (5-FU). Adults: Administer levoleucovorin and 5-FU separately to avoid precipitate formation. Regimen 1: give levoleucovorin at 100mg/m2 by slow IV inj over a minimum of 3 minutes, followed by 5-FU at 370mg/m2 by IV inj. Regimen 2: give levoleucovorin at 10mg/m2 by IV inj, followed by 5-FU at 425mg/m2 by IV inj. Both: Treat daily for 5 days. Five-day treatment course may be repeated at 4 week (28 days) intervals for 2 courses, and then repeated at 4–5 week (28–35 days) intervals provided that patient recovered completely from toxic effects from prior treatment course. Dose adjustments for subsequent treatment course: see literature. Children: Not recommended. Warnings/Precautions: Not for treating pernicious anemia and megaloblastic anemia. Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers. Interactions: Potentiates 5-fluorouracil toxicity. Antagonizes TMP/SMZ. Antagonizes anticonvulsants (eg, phenobarbital, primidone, phenytoin). May be affected by drugs that affect MTX elimination. Adverse reactions: Stomatitis, nausea, diarrhea. How supplied: Single-use vial (pwd, soln)–1

GLEEVEC Novartis

℞

Kinase inhibitor. Imatinib (as mesylate) 100mg, 400mg; tabs. Indications: Kit (CD117) (+) unresectable and/or metastatic malignant GI stromal tumors (GIST). Adjuvant treatment of adults following complete gross resection of Kit (CD117) (+) GIST. Adults: Take with food and water. May disperse tab in water or apple juice and take promptly. ≥18yrs: GIST: 400mg once daily; up to 800mg daily (given as 400mg twice daily) may be considered if clinically indicated. Adjuvant GIST treatment: 400mg once daily; 36 months of treatment recommended (see full labeling). If severe non-hematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction. Severe hepatic impairment: reduce dose by 25%. Renal or hematologic reactions: see full labeling. Potent CYP3A4 inducers (eg, rifampin): increase imatinib dose by at least 50%. Children: Not recommended.

Warnings/Precautions: Hepatic or renal impairment. Monitor weight and for fluid retention regularly; CBCs weekly for 1st month, bi-weekly for 2nd month, then periodically (eg, every 2–3 months); liver function at baseline then monthly or as needed; GI symptoms at baseline. Cardiovascular disease or risk factors; monitor. Immunosuppression from long-term use. Monitor for tumor lysis syndrome; correct clinically significant dehydration and treat high uric acid levels before initiating therapy. Monitor growth in children. Possible cardiogenic shock/LV dysfunction in conditions with high eosinophil levels (eg, HES/CEL, MDS/MPD, ASM); consider concomitant systemic steroid prophylaxis (1–2mg/kg) for 1 or 2 wks if abnormal ECG or serum troponin. Monitor TSH levels in thyroidectomy patients undergoing levothyroxine replacement. Pregnancy (Cat.D); avoid. Use highly effective contraception during treatment. Nursing mothers: not recommended. Interactions: Avoid grapefruit juice. Potentiated by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin). May potentiate drugs metabolized by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain statins, sirolimus, tacrolimus), CYP2D6, or CYP2C9 (use heparin instead of warfarin). Adverse reactions: Edema (may be severe), nausea, vomiting, musculoskeletal pain, diarrhea, muscle cramps, rash (may be severe; eg, erythema multiforme, Stevens-Johnson syndrome), fatigue, abdominal pain, dizziness, blurred vision, somnolence, fever, headache, cough, arthralgia/myalgia, dyspnea, hypokalemia, night sweats, anorexia, pruritus, hemorrhage, anemia, neutropenia, thrombocytopenia, weight gain, renal or hepatotoxicity, immunosuppression, hypothyroidism; rare: severe CHF, LV dysfunction. How supplied: 100mg–90; 400mg–30

HERCEPTIN Genentech

℞

Human epidermal growth factor receptor (HER2) inhibitor. Trastuzumab 440mg/vial; lyophilized pwd for IV infusion after reconstitution and dilution; preservative-free. Indications: HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, in combination with cisplatin and capecitabine or 5-fluorouracil, in patients who have not received prior treatment. Adults: Give as IV infusion. Initially 8mg/kg over 90 minutes, followed by 6mg/kg over 30–90 minutes every 3 weeks until disease progression. Infusion reactions or cardiomyopathy: see literature. Children: Not recommended.

Warnings/Precautions: Increased risk of cardiomyopathy. Conduct cardiac assessment (eg, history, physical exam, LVEF) at baseline, every 3 months during and after therapy; repeat LVEF at 4 week intervals if dose is withheld due to significant left ventricular cardiac dysfunction. Interrupt therapy if dyspnea or significant hypotension occurs; consider discontinuing permanently if severe infusion reactions, CHF, pulmonary toxicity, or significant left ventricular myocardial dysfunction develops. Symptomatic intrinsic lung disease. Extensive tumor involvement of the lungs. Test for HER2 protein overexpression and HER2 gene amplification using FDA-approved tests for specific tumor type (breast or gastric/gastroesophageal adenocarcinoma). Elderly. Pregnancy (Cat.D); use adequate contraception during and at least 6 months after therapy. Nursing mothers: not recommended. Interactions: Increased cardiomyopathy with anthracycline-containing chemotherapy. Increased toxicity with other myelosuppressives. Potentiated by paclitaxel. Adverse reactions: Fever, GI upset, infections, stomatitis, weight loss, upper respiratory tract infections, thrombocytopenia, mucosal inflammation, nasopharyngitis, dysgeusia, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, myalgia, thrombosis/ embolism; severe infusion reactions, febrile neutropenia/exacerbation of chemotherapyinduced neutropenia, pulmonary toxicity (eg, interstitial pneumonitis), cardiomyopathy (eg, left ventricular myocardial dysfunction); pregnant women (2nd & 3rd trimesters): possible oligohydramnios (monitor). Testing considerations: HER2 protein overexpression How supplied: Vial–1 (w. diluent)

Leucovorin Teva

℞

Folic acid derivative. Leucovorin calcium 100mg/vial, 350mg/vial; lyophilized pwd for IV or IM inj after reconstitution; preservative-free. Indications: Palliative treatment of advanced colorectal cancer in combination with 5-fluorouracil. Adults: Max IV infusion rate: 160mg/min. 200mg/m2 by slow IV inj over a minimum of 3 minutes, followed by 5-fluorouracil (370mg/m2); or 20mg/m2 IV followed by 5-fluorouracil (425mg/m2); both regimens: daily for 5 days, may be repeated at 4-week intervals for 2 courses and then repeated at 4–5 week intervals (if completely recovered from toxic effects of previous course). Children: See literature. Contraindications: Pernicious anemia and other megaloblastic anemias due to Vit. B12 deficiency. Warnings/Precautions: Do not administer intrathecally. CNS metastases. Monitor CBCs with differential, platelets, electrolytes, liver function

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MASTER DRUG MONOGRAPHS

GASTROINTESTINAL CANCER tests prior to each treatment, then periodically. Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers. Interactions: Potentiates toxicity of 5-fluorouracil; use lower 5-fluorouracil dose. May antagonize phenobarbital, phenytoin, and primidone. Caution with trimethoprim-sulfamethoxazole. Adverse reactions: Leukopenia, thrombocytopenia, infection, GI upset, stomatitis, constipation, lethargy, malaise, fatigue, alopecia, dermatitis, anorexia; seizures, syncope. How supplied: Single-use vials–1

Mitomycin (various)

℞

Cytotoxic antibiotic. Mitomycin 5mg/vial, 20mg/vial, 40mg/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol. Indications: Disseminated adenocarcinoma of the stomach. Adults: Give by IV infusion. 20mg/m2 as a single dose every 6–8 weeks. Discontinue if disease progresses after two courses. Myelosuppression: see literature for dose adjustments. Children: Not recommended. Contraindications: Thrombocytopenia. Coagulation disorders. Bleeding tendencies. Warnings/Precautions: Renal toxicity; serum creatinine >1.7mg: not recommended. Monitor platelets, WBCs, differential, hemoglobin repeatedly during and for at least 8 weeks after therapy. Avoid extravasation. Monitor fluid balance and avoid overhydration. Pregnancy, nursing mothers: not recommended. Interactions: Caution with vinca alkaloids, other chemotherapy. Adverse reactions: Thrombocytopenia, leukopenia (cumulative myelosuppression); inj site reactions (eg, cellulitis), stomatitis, alopecia, renal toxicity, pulmonary toxicity (eg, pulmonary infiltrates); discontinue if occurs; hemolytic uremic syndrome, CHF, fever, anorexia, nausea, vomiting. How supplied: Contact supplier.

NEXAVAR Bayer and Onyx

℞

Multikinase inhibitor. Sorafenib 200mg; tabs. Indications: Unresectable hepatocellular carcinoma. Adults: Take on an empty stomach. 400mg twice daily. If toxicity occurs, may reduce dose to 400mg once daily; if further dose reduction required, may reduce dose to 400mg every other day (see full labeling). Concomitant strong CYP3A4 inducers: consider increasing dose, monitor for toxicity. Children: Not established. Contraindications: Concomitant carboplatin/ paclitaxel in patients with squamous cell lung cancer. Warnings/Precautions: Avoid in congenital long QT syndrome. Monitor patients with CHF, bradyarrhythmias, drugs known to prolong the QT interval, electrolyte abnormalities. Discontinue

if severe dermatologic toxicity, hypertension, GI perforation, hemorrhage, cardiac ischemia, MI occurs. Suspend therapy before major surgery. Monitor BP weekly during the first 6 weeks and thereafter. Monitor hepatic function regularly; discontinue if transaminases significantly elevated. Severe hepatic impairment (Child-Pugh C) or on dialysis. Use effective contraception during and for 2 weeks after stopping treatment. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: See Contraindications. Avoid strong CYP3A4 inducers (eg, St. John’s Wort, dexamethasone, phenytoin, carbamazepine, rifabutin, rifampin, phenobarbital) and neomycin; may decrease sorafenib levels. May potentiate warfarin (monitor PT & INR), other drugs metabolized by UGT1A1 or UGT1A9 pathway, or substrates of CYP2B6, CYP2C8, CYP2C9, P-gp. Concomitant Class Ia and III antiarrhythmics; may prolong QT interval. Adverse reactions: Dermatologic toxicity (eg, rash, hand-foot skin reaction, alopecia, pruritus, dry skin, Stevens-Johnson syndrome, toxic epidermal necrolysis), fatigue, weight loss, diarrhea, anorexia, abdominal pain, hypertension, hemorrhage, electrolyte abnormalities; druginduced hepatitis, QT prolongation. How supplied: Tabs–120

PHOTOFRIN Pinnacle Biologics

℞

Photosensitizing agent. Porfimer (as sodium) 75mg/vial; pwd for IV inj after reconstitution; preservative-free. Indications: Palliation of patients with completely obstructing esophageal cancer or partially obstructing esophageal cancer who cannot be satisfactorily treated with Nd:YAG laser therapy. Ablation of high-grade dysplasia in Barrett’s esophagus patients who do not undergo esophagectomy. Adults: See literature. Give by slow IV inj over 3–5 minutes. 2mg/kg then illumination with laser light 40–50 hours following injection. Esophageal cancer: 2nd course may be given at a minimum of 30 days after initial therapy; max 3 courses (separated by ≥30 days). Ablation of high-grade dysplasia in Barrett’s esophagus: 2nd course may be given at a minimum of 90 days after initial therapy; max 3 courses (separated by ≥90 days). Children: Not recommended. Contraindications: Porphyria. Existing tracheoesophageal or bronchoesophageal fistula. Tumors eroding into a major blood vessel. Emergency treatment of patients with severe acute respiratory distress caused by an obstructing endobronchial lesion. Esophageal or gastric varices. Esophageal ulcers >1cm in diameter. Warnings/Precautions: Avoid direct sunlight or bright indoor light; wear dark sunglasses when outdoors. Increased risk of fatal massive hemoptysis with large, centrally located tumors,

cavitating tumors, extensive tumor extrinsic to the bronchus. Caution with endobronchial tumors in locations where treatment-induced inflammation could obstruct airway. Avoid extravasation. Pregnancy (Cat.C; use adequate contraception), nursing mothers: not recommended. Interactions: Increased risk of photosensitivity reactions with other photosensitizing agents (eg, tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics, griseofulvin, fluoroquinolones). May be antagonized by dimethyl sulfoxide, β-carotene, ethanol, formate, mannitol, allopurinol, calcium channel blockers, prostaglandin synthesis inhibitors, drugs that decreased clotting, vasoconstriction or platelet aggregation (eg, thromboxane A2 inhibitors), glucocorticoid hormones. Separate radiotherapy by 2–4 weeks. Adverse reactions: Photosensitivity reactions (eg, erythema, swelling, itching, burning sensation, feeling hot, blisters), fluid imbalance, chest pain, fever, pain, abdominal pain, GI upset, constipation, mucositis, ocular sensitivity, dyspnea, pleural effusion, anemia, fistula formation, fatal massive hemoptysis, others. How supplied: Vial–1

STIVARGA Bayer

℞

Kinase inhibitor. Regorafenib 40mg; tablets. Indications: Treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. Treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate or sunitinib malate. Adults: Swallow whole with a low-fat breakfast (contains <30% fat). 160mg once daily for the first 21 days of each 28-day cycle; until disease progression or unacceptable toxicity. Dose modifications: see full prescribing information. Children: <18yrs: not established. Warnings/Precautions: Risk of severe hepatotoxicity (may be fatal). Monitor hepatic function before starting and at least every 2 weeks during first 2 months of treatment; interrupt and reduce or discontinue if hepatotoxicity or hepatocellular necrosis occurs. Severe hepatic impairment: not recommended. Increased risk of hemorrhage; permanently discontinue if severe or life-threatening. Interrupt and reduce or permanently discontinue if dermatological toxicity occurs (eg, hand-foot skin reaction [a.k.a. palmar-plantar erythrodysesthesia], rash). Ensure BP is controlled before starting; monitor weekly for the first 6 weeks then every cycle or as clinically indicated; withhold if severe or uncontrolled. Myocardial ischemia/infarction: withhold if new or acute onset develops; resume when resolved. Discontinue if reversible posterior

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GASTROINTESTINAL CANCER leukoencephalopathy syndrome (RPLS) or GI perforation/fistula develops. Wound healing complications: stop treatment at least 2 weeks before surgery; discontinue if wound dehiscence occurs. Fetal toxicity. Pregnancy (Cat.D); use effective contraception during treatment and up to 2 months after completion. Nursing mothers: not recommended. Interactions: Avoid concomitant strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, St. John’s Wort). Avoid concomitant strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, voriconazole). Monitor INR levels with concomitant warfarin. Adverse reactions: Asthenia/fatigue, decreased appetite and food intake, hand-foot skin reaction, diarrhea, mucositis, weight loss, infection, hypertension, dysphonia, GI and abdominal pain, rash, fever, nausea; hepatotoxicity, hemorrhage, GI perforation, cardiac ischemia/infarction, RPLS. How supplied: Tabs–84 (3 × 28)

SUTENT Pfizer

℞

Multikinase inhibitor. Sunitinib (as malate) 12.5mg, 25mg, 50mg; gelatin caps. Indications: Gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate. Adults: 50mg once daily for 4 weeks, then 2 weeks off (see full labeling). May adjust dose in increments or decrements of 12.5mg. Concomitant strong CYP3A4 inhibitors (see Interactions): may reduce dose to 37.5mg daily. Concomitant strong CYP3A4 inducers (see Interactions): may increase to max 87.5mg daily. Children: Not established. Warnings/Precautions: Hepatotoxicity; may be severe or fatal. Monitor liver function tests before starting, during each cycle of treatment and as clinically needed; interrupt if Grade 3 or 4 hepatic adverse events occur and discontinue if no resolution; if severe liver function changes or signs/symptoms of failure, do not restart. Cardiovascular disease: monitor LVEF at baseline and periodically thereafter; interrupt or reduce dose if LVEF <50% and >20% below baseline; discontinue if CHF occurs. History of QT prolongation or proarrythmic conditions (eg, bradycardia, electrolyte disturbances); perform periodic ECG, monitor electrolytes. Monitor BP. Suspend therapy if severe hypertension, seizures, or pancreatitis develops. Obtain CBCs, platelets, serum chemistries at start of each cycle. Concomitant exposure to risk factors (eg, IV bisphosphonates therapy or dental disease) may increase the risk of osteonecrosis of the jaw;

avoid or consider preventive dentistry prior to treatment. Risk of tumor lysis syndrome: monitor closely in RCC and GIST patients with high tumor burden. Monitor for thyroid dysfunction; obtain baseline levels prior to treatment. Undergoing major surgery. Stress (monitor for adrenal insufficiency). Renal or hepatic impairment. Pregnancy (Cat.D; avoid). Nursing mothers: not recommended. Interactions: May be potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole); grapefruit. May be antagonized by CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital); St. John’s wort: not recommended. Adverse reactions: Fatigue, asthenia, fever, diarrhea, nausea, vomiting, mucositis/stomatitis, dyspepsia, abdominal pain, constipation, hypertension, peripheral edema, rash, handfoot syndrome, skin discoloration, dry skin, hair color changes, altered taste, headache, back pain, arthralgia, extremity pain, cough, dyspnea, anorexia, bleeding; hepatotoxicity, left ventricular dysfunction, QT prolongation, hemorrhage, hypertension, osteonecrosis of the jaw, tumor lysis syndrome, thyroid dysfunction, impaired wound healing, others (see full labeling). How supplied: Caps–28

TAXOTERE Sanofi Aventis

℞

Antimicrotubule agent. Docetaxel 20mg/mL; soln for IV infusion after dilution; contains polysorbate 80; diluent contains alcohol. Indications: In combination with cisplatin and fluorouracil: advanced gastric adenocarcinoma without previous chemotherapy. Adults: Give by IV infusion over 1hr once every 3 weeks. 75mg/m2. Premedicate with oral corticosteroid. Adjust dose based on tolerability and effect (see full labeling); allow neutrophils and platelets to recover before subsequent cycles. Children: Not established. Contraindications: Neutrophil count <1500 cells/mm3. Hypersensitivity to polysorbate 80. Warnings/Precautions: Hepatic dysfunction; bilirubin >ULN, SGOT and/or SGPT >1.5×ULN concomitant with alkaline phosphatase >2.5×ULN: not recommended. Obtain bilirubin, AST/ALT, and alkaline phosphatase values prior to each cycle. Monitor peripheral blood counts frequently (esp. neutrophils, platelets). Monitor for hypersensitivity reactions (esp. during 1st and 2nd infusions). Pre-existing effusions. Adjust dose if severe neurosensory symptoms (eg, paresthesia, dysesthesia, pain) occur;

discontinue if symptoms persist. Monitor for eye disorders; discontinue if cystoid macular edema is diagnosed (consider alternative non-taxane chemotherapy). Elderly. Pregnancy (Cat.D; use adequate contraception); nursing mothers: not recommended. Interactions: May affect, or be affected by, other CYP3A4 inhibitors, inducers, or substrates (eg, ketoconazole, ritonavir). Adverse reactions: Infections, neutropenia, anemia, febrile neutropenia, hypersensitivity/ infusion site reactions, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, myalgia; cutaneous reactions (eg, erythema, edema, desquamation), acute myeloid leukemia, death (septic and nonseptic), cystoid macular edema. How supplied: Single-dose vials (1mL, 4mL, 8mL)–1 (w. diluent, supplies)

VECTIBIX Amgen

℞

Human epidermal growth factor receptor (EGFR) inhibitor. Panitumumab 20mg/mL; soln for IV infusion after dilution; preservative-free. Indications: First-line treatment of wild-type KRAS metastatic colorectal carcinoma (mCRC) in combination with FOLFOX, or as monotherapy following disease progression after prior fluoropyrimidine-, oxaliplatin-, and irinotecancontaining chemotherapy as determined by an FDA-approved test. Limitation of use: not for treating KRAS-mutant mCRC or for whom KRAS mutation status is unknown. Adults: 6mg/kg by IV infusion over 60 mins once every 14 days. If 1st infusion is tolerated, give subsequent infusions over 30–60 mins. Doses >1000mg: infuse over 90 mins. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: Confirm absence of a KRAS mutation using an FDA-approved test prior to initiation. Withhold or discontinue therapy for dermatologic or soft tissue toxicity associated with severe inflammatory or infectious complications; monitor. Discontinue if severe infusion reactions develop. Interrupt therapy if acute onset or worsening of pulmonary symptoms; discontinue if interstitial lung disease (ILD) is confirmed. Limit sun exposure. Monitor electrolytes (eg, magnesium, calcium) prior to initiation, during, and for 8 weeks after completing therapy. Monitor for ocular toxicities (eg, keratitis); interrupt or discontinue if occur. May impair fertility in women; use effective contraception during treatment and for 6 months following last dose. Pregnancy (Cat.C). Nursing

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GASTROINTESTINAL CANCER mothers: not recommended; discontinue during therapy and for 2 months after last dose. Interactions: Concomitant bevacizumab and chemotherapy: increased mortality and toxicity may occur. Adverse reactions: Skin rash, paronychia, fatigue, nausea, diarrhea; hypomagnesemia, hypocalcemia, hypokalemia, dermatologic toxicities with possible infection (may be fatal), infusion reactions, immunogenicity, ILD, pulmonary fibrosis, keratitis, photosensitivity, possible acute renal failure w. chemotherapy. Testing considerations: EGFR amplification analysis, K-RAS mutation analysis. How supplied: Single-use vial (5mL, 10mL, 20mL)–1

XELODA Roche

℞

Fluoropyrimidine. Capecitabine (prodrug of 5-fluorouracil) 150mg, 500mg; tabs. Indications: First-line treatment of metastatic colorectal carcinoma when fluoropyrimidine therapy alone is preferred. Adjuvant treatment of Dukes’ C colon cancer after complete resection of the primary tumor when fluoropyrimidine therapy alone is preferred. Adults: See literature. Give cyclically (2 weeks on, 1 week off). Take with water within 30 minutes after AM & PM meals. ≥18yrs: 1250mg/m2 twice daily. Continue for a total of 8 cycles. Interrupt, adjust dose, and/or treat symptoms if toxicity occurs (eg, hyperbilirubinemia, diarrhea, nausea, vomiting, hand-and-foot syndrome, stomatitis) (see literature); do not increase dose afterwards. Renal impairment (CrCl 51–80mL/min): monitor carefully; (CrCl 30–50mL/min): reduce capecitabine dose to 75% of starting dose (ie, 950mg/m2 twice daily). Children: <18yrs: not recommended.

Contraindications: Severe renal impairment (CrCl <30mL/min). Dihydropyrimidine dehydrogenase deficiency. Pregnancy (Cat.D), nursing mothers: not recommended. Warnings/Precautions: Hepatic or renal dysfunction. Coronary artery disease. Elderly (≥80years). Interactions: Potentiated by leucovorin. Monitor warfarin, other CYP2C9 substrates, phenytoin. Adverse reactions: Diarrhea, lymphopenia, necrotizing enterocolitis, hand-and-foot syndrome, GI upset, stomatitis, fatigue, dermatitis, anorexia, cardiotoxicity, bone marrow suppression, blood dyscrasias, hyperbilirubinemia, paresthesias, eye irritation, fever, headache, edema, dizziness, insomnia, myalgia, dehydration, nail disorder, limb pain, skin discoloration, alopecia. Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase) How supplied: Tabs 150mg–60 500mg–120

ZALTRAP

℞

Regeneron and Sanofi Aventis

Fusion protein. Ziv-aflibercept 25mg/mL; soln for IV infusion after dilution; preservative-free. Indications: In combination with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen. Adults: Start ziv-aflibercept prior to any component of the FOLFIRI regimen on treatment day. Give 4mg/kg as an IV infusion over 1hr every 2 weeks; continue until disease progression or unacceptable toxicity. For recurrent or severe hypertension, suspend until controlled. Upon

resumption, permanently reduce to 2mg/kg. For recurrent proteinuria, suspend until proteinuria <2g per 24hrs, then permanently reduce to 2mg/kg. Children: Not established. Warnings/Precautions: Increased risk of hemorrhage; monitor for signs/symptoms. Do not start in patients with severe hemorrhage; discontinue if develops. Monitor for GI perforation, fistula formation, compromised wound healing; discontinue if occurs. Suspend therapy at least 4 weeks prior to elective surgery; do not resume for at least 4 weeks following major surgery and until wound is fully healed. Monitor BP every 2 weeks and treat appropriately if hypertension occurs; temporarily suspend until controlled; discontinue if hypertensive crisis/encephalopathy occurs. Discontinue if arterial thromboembolic events (eg, transient ischemic attack, cerebrovascular accident, angina pectoris) occur. Monitor for proteinuria; suspend if proteinuria ≥2g per 24hrs; discontinue if nephrotic syndrome or thrombotic microangiopathy occurs. Monitor CBC with differential at baseline and prior to start of each cycle; delay until neutrophils ≥1.5×109/L. Risk of severe diarrhea and dehydration esp. in elderly (monitor). Discontinue if reversible posterior leukoencephalopathy syndrome occurs. Pregnancy (Cat.C). Use effective contraception during and up to 3 months after the last dose. Nursing mothers: not recommended. Adverse reactions: Leukopenia, diarrhea, neutropenia, proteinuria, AST/ALT increased, stomatitis, fatigue, thrombocytopenia, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, headache. How supplied: Single-use vials (100mg/4mL)–1, 3; (200mg/8mL)–1

FDA PREGNANCY CATEGORIES When pregnancy appears as a contraindication or precaution to the use of a drug, it is usually qualified by a category as assigned by the FDA.

A: Adequate and well-controlled studies in pregnant women have failed to show a risk to the fetus in the first trimester of pregnancy and there is no evidence of risk in later trimesters. B: Animal studies have failed to show a risk to the fetus and there are no adequate and well-controlled studies in pregnant women; or animal studies have shown an adverse effect but adequate and wellcontrolled studies in pregnant women have failed to demonstrate a risk to the fetus during the first trimester of pregnancy and there is no evidence of a risk in later trimesters. C: Animal studies have shown an adverse effect on the fetus, there are no adequate and well-controlled studies in humans, and the potential benefits may outweigh the risks; or there are no animal studies and no adequate and well-controlled studies in humans. D: Positive evidence of human fetal risk but the benefits may outweigh the risks. X: Animal or human studies have shown fetal abnormalities or toxicity, or both, and the risks clearly outweigh any possible benefits.

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MASTER CANCER TREATMENT REGIMEN

GENITOURINARY CANCER Bladder Cancer Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Perioperative Chemotherapy (Neoadjuvant or Adjuvant)1 REGIMEN

DOSING

Dose-dense methotrexate + vinblastine + doxorubicin + cisplatin (DDMVAC) with growth factor support2,3

Day 1: Methotrexate 30mg/m2 IV Day 2: Vinblastine 3mg/m2 IV, plus doxorubicin 30mg/m2 IV, plus cisplatin 70mg/m2 IV Day 4: Granulocyte colony-stimulating factor (G-CSF) 240μg/m2 SQ for 7 consecutive days (days 4 through 10). May be extended for up to a total of 14 consecutive days. Repeat every 2 weeks for 3–4 cycles.

Gemcitabine + cisplatin4–6

Days 1, 8 and 15: Gemcitabine 1,000mg/m2 IV over 30–60 minutes Day 2: Cisplatin 70mg/m2. Repeat every 4 weeks for a maximum of 6 cycles.

Cisplatin + methotrexate + vinblastine (CMV)7

Day 1: Methotrexate 30mg/m2 IV bolus plus vinblastine 4mg/m2 IV bolus Day 2: Cisplatin 100mg/m2 IV infusion; followed by hydration; followed by leucovorin 15mg PO or IV every 6 hours for 4 doses (commencing 24 hours after methotrexate on day 1). Day 8: Methotrexate 30mg/m2 IV bolus plus vinblastine 4mg/m2 IV bolus. Day 9: Leucovorin 15mg PO every 6 hours for 4 doses after methotrexate on day 8. Repeat every 3 weeks for 3 cycles.

Principals of Chemotherapy Management • Randomized trials and meta-analyses show a survival benefit for cisplatin-based neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer.2,8,9 • Meta-analysis suggests a survival benefit to adjuvant therapy for pathologic T3, T4 or N+ disease at cystectomy.9 • Neoadjuvant chemotherapy is preferred over adjuvant-based chemotherapy on a higher level of evidence data. • DDMVAC is preferred over standard MVAC based on category I evidence showing DDMVAC to be better tolerated and more effective than conventional MVAC in advanced disease.3,10 Based on these data, the traditional dose and schedule for MVAC is no longer recommended. • Perioperative gemcitabine and cisplatin is a reasonable alternative to DDMVAC based on category I evidence showing equivalence to conventional MVAC in the setting of advanced disease.5,6 • For gemcitabine/cisplatin, both 21- and 28-day regimens are acceptable. Better dose compliance may be achieved with fewer delays in dosing using the 21-day schedule.11 • Neoadjuvant chemotherapy may be considered for select patients with upper tract urothelial carcinoma, particularly for higher stage and/or grade tumors, as renal function will decline after nephroureterectomy and may preclude adjuvant therapy. • Carboplatin should not be substituted for cisplatin in the perioperative setting. — For patients with borderline renal function or minimal dysfunction, a split-dose administration of cisplatin may be considered (such as 35mg/m2 on days 1 and 2 or days 1 and 8; category 2B). Although safer, the relative efficacy of the cisplatin-containing combination administered with such modifications remains undefined. — For patients who are not candidates for cisplatin, there are no data to support a recommendation for perioperative chemotherapy.

First-Line Chemotherapy for Metastatic Disease1 Gemcitabine + cisplatin5

Days 1, 8 and 15: Gemcitabine 1,000mg/m2 IV over 30–60 minutes Day 2: Cisplatin 70mg/m2. Repeat every 4 weeks for a maximum of 6 cycles.

DDMVAC with growth factor support 3,10

Day 1: Methotrexate 30mg/m2 IV Day 2: Vinblastine 3mg/m2 IV, plus doxorubicin 30mg/m2 IV, plus cisplatin 70mg/m2 IV Day 4: G-CSF 240μg/m2 SQ for 7 consecutive days (days 4 through 10). May be extended for up to a total of 14 consecutive days. Repeat every 2 weeks for 3–4 cycles. OR Day 1: Methotrexate 30mg/m2 IV Day 2: Vinblastine 3mg/m2 IV, plus doxorubicin 30mg/m2 IV, plus cisplatin 70mg/m2 IV Day 3: G-CSF SQ for 5 consecutive days (days 3 through 7). Repeat cycle every 15 days.

Principals of Chemotherapy Management • The presence of both visceral metastases and Eastern Cooperative Oncology Group performance score ≥ 2 strongly predict poor outcome with chemotherapy. Patients without these adverse prognostic factors have the greatest benefit from chemotherapy. • For most patients, the risks of adding paclitaxel to gemcitabine and cisplatin outweigh the limited benefit seen in the randomized trial.12 • A substantial proportion of patients cannot receive cisplatin-based chemotherapy due to renal impairment or other comorbidities. — Participation in clinical trials of new or more tolerable therapy is recommended. — Carboplatin-/taxane-based regimens, or single-agent therapy can be considered as alternative regimens for these patients.

continued

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GENITOURINARY CANCER Bladder Cancer Treatment Regimens Second-Line (Palliative) Chemotherapy for Metastatic Disease1* Preferred Treatment Single-agent taxane or gemcitabine Additional Single-Agent Treatment Options • Cisplatin • Carboplatin

• Doxorubicin • 5-fluorouracil (5-FU)

• Ifosfamide • Methotrexate

• Pemetrexed • Vinblastine

First-Line Radiosensitizing Chemotherapy Regimens1† Cisplatin13

Cisplatin 100mg/m2 IV every 2 weeks for 3 cycles.

Cisplatin + 5-FU14,15

Days 1, 2, 3, 15, 16, and 17: IV hydration at a rate of 500mL/hour; followed by 5-FU 400mg/m2 IV push; followed by cisplatin 15mg/m2 IV over 1 hour as induction and consolidation therapy.‡

5-FU + mitomycin C15-17

Day 1 of radiotherapy: Mitomycin 12mg/m2 IV bolus, plus Week 1 (fractions 1–5) and Week 4 (fractions 16–20) of radiotherapy: 5-FU 500mg/m2 continuous IV infusion (10 days total).

Cisplatin + paclitaxel17

Days 1, 8 and 15: Paclitaxel 50mg/m2 Days 1–3, 8–10, 15–17: Cisplatin 15mg/m2; followed by twice-daily radiotherapy for 8 days∥

Radiosensitizing Chemotherapy with Conventionally Fractionated radiation1§ • Cisplatin • Docetaxel or paclitaxel

• 5-FU • 5-FU and mitomycin C

• Capecitabine • Low-dose gemcitabine

* No standard therapy exists in this setting, thus participation in clinical trials of new agents is recommended. † For bladder-preserving chemoradiation following a maximal transurethral resection of bladder tumor. ‡ On days 1, 3, 15, and 17, radiation was given immediately following the chemotherapy using twice-a-day 3 Gy per fraction cores to the pelvis for a total radiation dose of 24 Gy (with at least a 4-hour inter-fraction interval). § For palliation of metastases or for pelvic recurrence after cystectomy. ∥ Upon complete or near complete response, patients received consolidation chemoradiation consisting of 1.5 Gy pelvic radiotherapy twice a day for 8 days to 24 Gy (total dose: 64.3 Gy to the tumor and 44.8 Gy to the pelvic lymph nodes) and paclitaxel 50mg/m2 days 1 and 8 and cisplatin15mg/m2 on days 1, 2, 8, and 9.

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Bladder Cancer. v 1.2014. Available at: http://www.nccn.org/ professionals/physician_gls/PDF/bladder.pdf. Accessed April 4, 2014. 2. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349(9):859–866. 3. Sternberg CN, de Mulder PH, Schornagel JH, et al. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol. 2001;19(10):2638–2646. 4. Dash A, Pettus JA, Herr HW, et al. A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer. 2008;113(9):2471–2477. 5. von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18(17):3068–3077. 6. von der Maase H, Sengelov L, Roberts JT, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602–4608. 7. Griffiths G, Hall R, Sylvester R, et al. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011;29(16):2171–2177. 8. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol. 2005;48(2):202–205.

9. Adjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis of individual patient data Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Eur Urol. 2005;48(2):189–199. 10. Sternberg CN, de Mulder P, Schornagel JH, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006;42(1):50–54. 11. Soto Parra H, Cavina R, Latteri F, et al. Three-week versus four-week schedule of cisplatin and gemcitabine: results of a randomized phase II study. Ann Oncol. 2002;13(7): 1080–1086. 12. Bellmunt J, von der Maase H, Mead GM, et al. Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC Intergroup Study 30987. J Clin Oncol. 2012;30:1107–1113. 13. Coppin CM, Gospodarowicz MK, James K, et al. Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. J Clin Oncol. 1996;14:2901–2907. 14. Kaufman DS, Winter KA, Shipley WU, et al. The initial results in muscle-invading bladder cancer of RTOG 95-06: phase I/II trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response. The Oncologist. 2000;5:471–476. 15. James ND, Hussain SA, Hall E, et al; BC200I Investigators. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N EngI J Med. 2012;366:1477–1488. 16. Hussain SA, Stocken DD, Peake DR, et al. Long-term results of a phase II study of synchronous chemoradiotherapy in advanced muscle invasive bladder cancer. Br J Cancer. 2004;90:2106–2111. 17. Mitin T, Hunt D, Shipley W, et al. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomized multicentre phase 2 trial. Lancet Oncol. 2013;14:863–872. (Revised 4/2014) © 2014 Haymarket Media, Inc.

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GENITOURINARY CANCER Prostate Cancer Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

First-Line Therapy1 REGIMEN

DOSING

Docetaxel + prednisone2,3

Day 1: Docetaxel 75mg/m2 IV once every 3 weeks, plus Day 1: Prednisone 5mg orally twice daily. Repeat for up to 10 cycles if tolerated.

Sipuleucel-T4,5

Sipuleucel-T three complete doses (50 million autologous CD54+ cells), given at 2-week intervals (range 1–15 weeks).*

Second-Line Therapy1 Abiraterone acetate6–8

Abiraterone 1,000mg orally once daily, plus prednisone 5mg orally twice daily on an empty stomach.5

Cabazitaxel + prednisone9–11

Day 1: Cabazitaxel 25mg/m2 IV, every 3 weeks, plus Day 1: Prednisone 10mg orally daily or 5mg twice daily throughout cabazitaxel treatment.10 Repeat for up to 10 cycles if tolerated.

Enzalutamide12,13

Enzalutamide 160mg/day orally without regard to food intake; with or without prednisone.1

Mitoxantrone + prednisone (palliative option)2,9

Day 1: Mitoxantrone 12mg/m2 IV, every 3 weeks, plus Day 1: Prednisone 10mg orally daily or 5mg twice daily. Repeat for up to 10 cycles if tolerated.

Sipuleucel-T4,5

Sipuleucel-T three complete doses (50 million autologous CD54+ cells), given at 2-week intervals (range 1–15 weeks).*

General treatment notes: Encourage men with advanced prostate cancer to participate in clinical trials and refer early to a medical oncologist. Reserve systemic chemotherapy for men with castration-recurrent metastatic prostate cancer except when enrolled in a clinical trial. * The maximum dosing interval has not been established.4

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in 8. Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic Oncology™. Prostate Cancer. v 2.2014. Available at: http://www.nccn.org/profescastration-resistant prostate cancer: final overall survival analysis of the COUsionals/physician_gls/pdf/prostate.pdf. Accessed April 6, 2014. AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13:983–992. 2. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–1512. 9. de Bono JS, Oudard S, Ozguroglu M, et al; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer 3. Tannock IF, Fizazi K, Ivanov S, et al; VENICE investigators. Aflibercept versus placebo progressing after docetaxel treatment: a randomised open-label trial. Lancet. in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised 2010;376:1147–1154. Jevtana [prescribing information] Bridgewater, NJ: sanotrial. Lancet Oncol. 2013;14:760–768. fi-aventis US LLC; 2014. 4. Provenge [prescribing information]. Seattle, WA: Dandreon Corp.; 2011. 10. Heidenreich A, Scholz HJ, Rogenhofer S, et al. Cabazitaxel plus prednisone for metastatic castration-resistant prostate cancer progressing after docetaxel: results 5. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castrafrom the German compassionate-use programme. Eur Urol. 2013;63:977–982. tion-resistant prostate cancer. N Engl J Med. 2010;363:411–422. 11. Xtandi [prescribing information]. Northbrook, IL: Astellas Pharma US, Inc.; 2013. 6. Zytiga [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; 2013. 12. Scher HI, Fizazi K, Saad F, et al; AFFIRM Investigators. Increased survival with enzalut7. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005. amide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–1197. (Revised 4/2014) © 2014 Haymarket Media, Inc.

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GENITOURINARY CANCER Renal Cell Carcinoma Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

General treatment notes:1 • Targeted therapy using tyrosine kinase inhibitors is now widely used as first- and second-line treatments in renal cell carcinoma (RCC). To date, seven such agents have been approved by the FDA for the treatment of advanced RCC: sunitinib, bevacizumab (+ interferon), pazopanib, temsirolimus, sorafenib, everolimus, and axitinib. • Prior to targeted therapies, systemic treatment options were limited to cytokine therapy, notably interleukin-2 (IL-2) and interferon-α-2A (IFN-α-2a).

First-line Targeted Therapy for Patients with Predominantly Clear Cell Carcinoma1 REGIMEN

DOSING

Sunitinib

Sunitinib 50mg/day PO for 4 weeks on, and 2 weeks off.

Bevacizumab + IFN-∥α-2a4–6

Bevacizumab 10mg/kg IV every 2 weeks; plus IFN-α-2a 9 million IU SQ three times a week.

Pazopanib4,7,8

Pazopanib 800mg PO once daily.

Temsirolimus9,10

Temsirolimus 25mg IV over 30–60 minutes once weekly.

Sorafenib11

Sorafenib 400mg PO twice daily.*

2,3

Subsequent Therapy for Patients with Predominantly Clear Cell Carcinoma1 Everolimus12,13

Everolimus 10mg PO once daily.

Axitinib14,15

Axitinib 5mg PO every 12 hours.†

Sorafenib16–19

Sorafenib 400mg PO twice daily.

Sunitinib2,20,21

Sunitinib 50mg/day PO for 4 weeks on, and 2 weeks off.

Pazopanib

Pazopanib 800mg PO once daily.

7,8

Temsirolimus22,23

Temsirolimus 25, 75, or 250mg IV over 30 minutes.

Bevacizumab24

Bevacizumab 3 or 10mg/kg IV over 30–120 minutes.

Cytokine Therapy (first-line) for Patient with Predominantly Clear Cell Carcinoma1 High-dose IL-225,26

IL-2 720,000 IU/kg IV every 8 hours (max 15 consecutive doses/cycle)‡ OR Days 1–5 and Days 15–19: IL-2 600,000 IU/kg IV every 8 hours (max 14 doses). Repeat cycle every 4 weeks for max 3 cycles.

* Patients who progressed were dose-escalated to 600 mg twice daily. † May increase to 7mg every 12 hours after 2 weeks based on criteria; may increase to 10mg every 12 hours after 2 weeks based on criteria. ‡ Treatments divided into 60-day courses, with each IV treatment course consisting of 2 cycles of therapy, separated by approximately 7–10 days of rest with no other therapy during the remainder of the 60 days.

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Kidney. v 2.2014. Available at: http://www.nccn.org/professionals/ physician_gls/pdf/kidney.pdf. Accessed April 22, 2014. 2. Sutent [package insert]. New York, NY: Pfizer Labs; 2011.

3. Gore ME, Szczylik C, Porta C, et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009;10:757–763. 4. Avastin [package insert]. San Francisco, CA: Genentech; 2011.

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GENITOURINARY CANCER 5. Escudier B, Pluzanska A, Koralewski P, et al; AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370:2103–2111. 6. Rini BI, Halabi S, Rosenberg JE, et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol. 2010;28:2137–2143. 7. Votrient [package insert].Research Triangle Park, NC: GSK; 2012. 8. Sternberg CN, Davis ID, Mardiak J et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28:1061–1068. 9. Torisel [package insert]. Philadelphia, PA: Wyeth; 2011. 10. Hudes G, Carducci M, Tomczak P, et al; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271–2281. 11. Escudier B, Szczylik C, Hutson TE, et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(8):1280–1289. 12. Afinitor [package insert]. East Hanover, NJ: Novartis; 2011. 13. Motzer RJ, Escudier B, Oudard S, et al; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008;372:449–456. 14. Inlyta [package insert]. New York, NY: Pfizer Inc; 2012. 15. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomized phase 3 trial. Lancet. 2011;378:1931–1939. 16. Nexavar [package insert]. Wayne, NJ: Bayer HealthCare; 2011.

17. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2): 125–134. 18. Di Lorenzo G, Carteni G, Autorino R, et al. Phase II study of sorafenib in patients with sunitinib-refractory metastatic renal cell cancer. J Clin Oncol. 2009;27(27):4469–4474. 19. Garcia JA, Hutson TE, Elson P, et al. Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab. Cancer. 2010;116(23):5383–5390. 20. Motzer RJ, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24(1):16–24. 21. Motzer RJ, Rini BI, Bukowski RM, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA. 2006;295(21): 2516–2524. 22. Atkins MB, Hidalgo M, Stadler WM, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol. 2004;22(5):909–918. 23. Hutson TE, Escudier B, Esteban E, et al. Temsirolimus vs Sorafenib as Second Line Therapy in Metastatic Renal Cell Carcinoma: Results from the INTORSECT Trial [abstract]. Ann Oncol. 2012;23:Abstract: LBA22. 24. Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003; 349(5):427–434. 25. Yang JC, Sherry RM, Steinberg SM, et al. Randomized study of high-dose and lowdose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol. 2003;21:3127–3132. 26. McDermott DF, Regan MM, Clark JI, et al. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol. 2005;23:133–141.

Testicular Cancer Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Primary Chemotherapy for Germ Cell Tumors1 REGIMEN

DOSING

Etoposide + cisplatin2

Days 1–5: Etoposide 100mg/m2 IV + cisplatin 20mg/m2 IV Repeat cycle every 3 weeks for 4 cycles.

Bleomycin + etoposide + cisplatin3

Days 1–5: Cisplatin 20mg/m2 IV + etoposide 100mg/m2 IV Days 1, 8 and 15*: Bleomycin 30 units IV weekly Repeat cycle every 3 weeks for 3 cycles.

Etoposide + ifosfamide + cisplatin + mesna4

Day 1: (prior to ifosfamide) mesna 120mg/m2 by slow IV push Days 1–5: Etoposide 75mg/m2 IV + mesna 1,200mg/m2 continuous IV infusion + ifosfamide 1,200mg/m2 IV + cisplatin 20mg/m2 Repeat cycle every 3 weeks for 4 cycles. continued

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GENITOURINARY CANCER Bladder Cancer Treatment Regimens Second-Line Chemotherapy For Metastatic Germ Cell Tumors1 Conventional-dose Chemotherapy Regimens Vinblastine + ifosfamide + cisplatin + mesna5

Days 1 and 2: Vinblastine 0.11mg/kg IV push; plus Days 1–5: Mesna 400mg/m2 IV every 8 hours + ifosfamide 1,200mg/m2 IV + cisplatin 20mg/m2 IV Repeat cycle every 3 weeks.

Paclitaxel + ifosfamide + mesna + cisplatin6

Day 1: Paclitaxel 250mg/m2 IV Days 2–5: Ifosfamide 1,500mg/m2 + cisplatin 25mg/m2 IV daily + mesna 500mg/m2 IV before ifosfamide, and then 4 and 8 hours after each dose of ifosfamide. Repeat cycle every 3 weeks.

High-dose Chemotherapy Regimens Carboplatin + etoposide7

Carboplatin 700mg/m2 IV + etoposide 750mg/m2 IV Administer 5, 4, and 3 days before peripheral blood stem cell infusion for 2 cycles.

Paclitaxel + ifosfamide + mesna + carboplatin + etoposide8

Day 1: Paclitaxel 200mg/m2 IV over 24 hours. Days 2–4: Ifosfamide 2,000mg/m2 over 4 hours with mesna protection Repeat every 14 days for 2 cycles; followed by Days 1–3: Carboplatin AUC 7–8 IV over 60 minutes Days 1–3: Etoposide 400mg/m2 IV Administer with peripheral blood stem cell support at 14- to 21-day intervals for 3 cycles.

Subsequent Chemotherapy For Metastatic Germ Cell Tumors1 Gemcitabine + oxaliplatin9–11

Days 1 and 8: Gemcitabine 1,000mg/m2 IV, plus Day 1: Oxaliplatin 130mg/m2 IV Repeat cycle every 3 weeks. OR Days 1 and 8: Gemcitabine 1,250mg/m2 IV, plus Day 1: Oxaliplatin 130mg/m2 IV Repeat cycle every 3 weeks.

Gemcitabine + paclitaxel12,13

Days 1, 8 and 15: Gemcitabine 1,000mg/m2 IV over 30 minutes + paclitaxel 100mg/m2 IV over 1 hour Repeat every 4 weeks for a max 6 cycles.

Gemcitabine + paclitaxel + oxaliplatin14

Days 1 and 8: Gemcitabine 800mg/m2 IV + paclitaxel 80mg/m2 IV Day 1: Oxaliplatin 130mg/m2 IV Repeat every 3 weeks for at least 2 cycles.

Etoposlde15

Etoposlde 50mg/m2 PO daily until progression or toxicity.

* Some NCCN institutions give bleomycin on Days 2, 9 and 16.

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Testicular Cancer. v 1.2014. Available at: http://www.nccn.org/ professionals/physician_gls/pdf/testicular.pdf. Accessed April 22, 2014. 2. Xiao H, Mazumdar M, Bajorin DF, et al. Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin. J Clin Oncol. 1997;15:2553–2558. 3. Saxman SB, Finch D, Gonin R, Einhorn LH, et al. Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-prognosis germ-cell tumors: the Indiana University experience. J Clin Oncol. 1998;16:702–706. 4. Nichols CR, Catalano PJ, Crawford ED, et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol. 1998;16:1287–1293. 5. Loehrer PJ Sr, Lauer R, Roth BJ, et al. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med. 1988;109:540–546. 6. Kondagunta GV, Bacik J, Donadio A, et al. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol. 2005;23:6549–6555. 7. Einhorn LH, Williams SD, Chamness A, et al. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. 2007;357:340–348. 8. Feldman DR. Sheinfeld J, Bajorin DF, et al. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol. 2010;28:1706–1713.

9. Pectasides D, Pectasides M, Farmakis D, et al. Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study. Ann Oncol. 2004;15: 493–497. 10. Kollmannsberger C, Beyer J, Liersch R, et al. Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: a study of the German Testicular Cancer Study Group. J Clin Oncol. 2004;22:108–114. 11. De Giorgi U, Rosti G, Aieta M, et al. Phase II study of oxaliplatin and gemcitabine salvage chemotherapy in patients with cisplatin-refractory nonseminomatous germ cell tumor. Eur Urol. 2006;50(5):1032–1038. 12. Einhorn LH, Brames MJ, Juliar B, et al. Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after progression following high-dose chem therapy with tandem transplant. J Clin Oncol. 2007;25: 513–516. 13. Mulherin B, Brames MJ, Einhorn L. Long-term survival with paclitaxel and gemcitabine for germ cell tumors after progression following high-dose chemotherapy with tandem transplants [abstract]. J Clin Oncol. 2011;29: Abstract 4562. 14. Bokemeyer C, Oechsle K, Honecker F, et al. Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ- cell tumors: a study of the German Testicular Cancer Study Group. Ann Oncol. 2008;19:448–453. 15. Miller JC, Einhorn LH. Phase II study of daily oral etoposide in refractory germ cell tumors. Semin Oncol. 1990;17:36–39. (Revised 5/2014) © 2014 Haymarket Media, Inc.

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MASTER DRUG MONOGRAPHS

GENITOURINARY CANCER AFINITOR Novartis

℞

mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs. Indications: Advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. Adults: Swallow whole with water or disperse tablet in 30mL of water and drink immediately. Take at the same time each day either consistently with or without food. RCC or renal angiomyolipoma with TSC: 10mg once daily. Mild hepatic impairment (Child-Pugh class A): 7.5mg daily, may reduce to 5mg if not tolerated. Moderate hepatic impairment (Child-Pugh class B), or adverse reactions: reduce to 5mg daily, may be reduce to 2.5mg if not tolerated. Severe hepatic impairment (Child-Pugh class C): max 2.5mg daily if benefits outweigh risk. Concomitant moderate CYP3A4 or P-glycoprotein inhibitors: reduce to 2.5mg once daily; may consider increasing to 5mg if tolerated. If moderate inhibitor is discontinued, allow 2–3 days washout period before increasing everolimus dose; return to dose used prior to initiating the moderate inhibitor. Concomitant strong CYP3A4 inducers: may increase from 10–20mg once daily by increments of 5mg. If strong inducer is discontinued, should return to dose used prior to initiating the strong inducer. Continue as long as benefit observed or until unacceptable toxicity occurs. Children: Not recommended. Contraindications: Sirolimus, temsirolimus, rapamycin allergy. Warnings/Precautions: Hepatic impairment (see Adult dose). Increased risk of infections; some may be severe or fatal. Pre-existing invasive fungal infections: treat before starting. Monitor CBCs, renal function, lipids, blood glucose, and for pneumonitis and infections: treat promptly if occur. Women of childbearing potential should use effective method of contraception during and up to 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Avoid live vaccines. Potentiated by strong CYP3A4 inhibitors, or P-glycoprotein inhibitors; avoid (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole, grapefruit juice). Caution with moderate CYP3A4 inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem) or P-glycoprotein inhibitors; reduce everolimus dose if used. Antagonized by strong CYP3A4 inducers; avoid (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s wort); increase everolimus dose if used. Adverse reactions: Pneumonitis (reduce dose and/or manage with corticosteroids; if severe, discontinue. May restart daily dose at approx.

50% lower than previously administered), infections (discontinue if invasive systemic fungal infection develops), stomatitis (treat with non-alcoholic, non-peroxide mouthwash), GI upset, rash, fatigue, edema, fever, headache, asthenia, cough, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see literature). How supplied: Tabs–28 (4 blister cards × 7 tabs)

AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free. Indications: Metastatic renal cell carcinoma (mRCC) in combination with interferon alfa. Adults: Give by IV infusion after chemotherapy. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins. 10mg/kg every 2 weeks with interferon alfa. Children: Not established. Warnings/Precautions: Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). History of hemoptysis of ≥ ½-teaspoon of red blood: do not administer. Discontinue if GI perforation, wound healing complications, serious hemorrhage, severe arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, non-GI fistula formation, or reversible posterior leukoencephalopathy syndrome occurs; suspend therapy if severe hypertension, moderate to severe proteinuria, or severe infusion reaction occurs. Cardiovascular disease. Diabetes. Renal or hepatic impairment. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis. Elderly. Increases risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy (Cat.C). Nursing mothers: not recommended. Adverse reactions: Epistaxis, headache, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome, infusion reactions, ovarian failure. How supplied: Single-use vial–1

Bleomycin (various) Cytotoxic glycopeptide antibiotic. Bleomycin 15units/vial, 30units/vial; lyophilized pwd for IM, IV, SC, or intrapleural administration after reconstitution. Indications: Palliative treatment for squamous cell carcinoma (penis), testicular carcinoma (embryonal cell, choriocarcinoma, teratocarcinoma).

℞

Adults: 0.25–0.5 units/kg IV, IM, or SC weekly or twice weekly. Renal impairment: see literature. Total doses >400 units: increased risk of pulmonary toxicity. Children: Not recommended. Warnings/Precautions: Renal impairment. Compromised pulmonary function. Monitor renal function. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: May be potentiated by nephrotoxic drugs. Adverse reactions: Erythema, rash, striae, vesiculation, hyperpigmentation, tenderness of the skin, hyperkeratosis, nail changes, alopecia, pruritus, stomatitis; pneumonitis, pulmonary fibrosis, idiosyncratic reaction (hypotension, mental confusion, fever, chills, wheezing). How supplied: Contact supplier.

CASODEX AstraZeneca

℞

Antiandrogen. Bicalutamide 50mg; tabs. Indications: In combination with luteinizing hormone-releasing hormone (LHRH) analogue in stage D2 metastatic prostate carcinoma. Adults: Take at the same time each day. 50mg daily. Start treatment at same time as starting LHRH analogue. Children: Not applicable. Contraindications: Women of childbearing potential. Pregnancy (Cat.X). Warnings/Precautions: Moderate to severe hepatic impairment. Monitor prostate specific antigen and hepatic function (discontinue if ALT >2×ULN or if jaundice occurs). Nursing mothers. Interactions: Monitor oral anticoagulants. Adverse reactions: Hot flashes, gynecomastia, breast pain, diarrhea, pain, asthenia, infection, dyspnea, impotence, loss of libido, others (see literature); rare: hepatitis. How supplied: Tabs–30, 100

Cisplatin (various)

℞

Platinum coordination complex. Cisplatin 1mg/mL; soln for IV infusion after dilution. Indications: As a single agent, for treating transitional cell bladder cancer. Adults: Give by IV infusion over 6–8 hours. 50–70mg/m2 IV per cycle once every 3–4 weeks; heavily pretreated patients: initially 50mg/m2 IV per cycle every 4 weeks. Usual max: 100mg/m2 per cycle. Subsequent cycles: give as tolerated, withhold dose if serum creatinine, BUN, platelets, WBCs, or auditory acuity out of normal limits; see literature. Children: Not recommended. Contraindications: Renal or hearing impairment. Myelosuppression. Pregnancy (Cat.D). Nursing mothers. Warnings/Precautions: Have epinephrine, antihistamine available. Monitor baseline and pretreatment renal function, electrolytes, auditory function; do periodic CBCs (weekly), liver function

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GENITOURINARY CANCER tests, neurologic exam. Hydrate patient before dosing. Avoid extravasation. Elderly. Interactions: Potentiates nephrotoxicity with other nephrotoxic drugs (eg, aminoglycosides). May antagonize anticonvulsants. May be antagonized by pyridoxine. Adverse reactions: Nephrotoxicity, neurotoxicity (eg, peripheral neuropathies), ototoxicity, myelosuppression, hemolytic anemia, marked nausea and vomiting, vascular toxicity (eg, MI, TIA), electrolyte disturbances, hyperuricemia, SIADH, hepatotoxicity, anaphylactic-like reactions, others; see literature. Note: Avoid contact with aluminum (eg, needles). How supplied: Contact supplier.

COSMEGEN Recordati

DELESTROGEN JHP

℞

Actinomycin antibiotic. Dactinomycin 500mcg/ vial; lyophilized pwd for IV inj or regional perfusion after reconstitution; contains mannitol; preservative-free. Indications: In combination with other chemotherapy and/or multi-modality treatment regimen for Wilms’ tumor. As a component of regional perfusion, for palliative and/or adjunctive treatment of locally recurrent or locoregional solid malignancies. Adults: Give by IV infusion. Wilms’ tumor: 15mcg/kg daily for 5 days. Regional perfusion: 50mcg/kg for lower extremity or pelvis; 35mcg/kg for upper extremity. Max 15mcg/kg/day per 2-week cycle or 400–600mcg/m2/day for five days. Use surface area to calculate dose for obese or edematous patients. Children: See literature. Contraindications: Current or recent chickenpox or herpes zoster. Warnings/Precautions: Myelosuppression; monitor bone marrow and hold treatment if platelets or WBCs decrease markedly. Extremely corrosive; avoid extravasation. Avoid skin, mucous membranes, eyes. Previous irradiation (esp. within 2 months of irradiation for treatment of right-sided Wilms’ tumor), cytotoxic chemotherapy. Monitor renal and hepatic function. Obese. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Avoid live vaccines. Concomitant radiotherapy in Wilms’ tumor: not recommended. Adverse reactions: GI upset, stomatitis, bone marrow suppression (neutropenia, thrombocytopenia), liver toxicity, infusion site reactions, malaise, fatigue, alopecia, possible second primary tumors (including leukemia); for perfusion therapy: infection, impaired wound healing, superficial ulceration of gastric mucosa, edema, soft tissue damage, possible venous thrombosis. How supplied: Vials–1

℞

Estrogen. Estradiol valerate 10mg/mL (in a vehicle containing chlorobutanol 5mg and sesame oil), 20mg/mL (in a vehicle containing benzyl benzoate 224mg, benzyl alcohol 20mg, and castor oil), 40mg/mL (in a vehicle containing benzyl benzoate 447mg, benzyl alcohol 20mg, and castor oil); soln for IM inj. Indications: Advanced androgen-dependent carcinoma of the prostate (for palliation only). Adults: Give by deep IM inj into upper, outer quadrant of gluteal muscle. 30mg or more every 1 or 2 weeks. Children: Not applicable. Contraindications: Thrombophlebitis. Thromboembolic disorders. Cerebrovascular disorders. Abnormal undiagnosed genital bleeding. Estrogen-depended neoplasias. Liver dysfunction or disease. Pregnancy (Cat.X). Warnings/Precautions: Hepatic dysfunction. Conditions aggravated by fluid retention. Cardiovascular disorders, arterial vascular disease, and risks factors (eg, hypertension, diabetes, obesity, SLE). Familial hyperlipoprotenemia. Monitor BP. Discontinue if jaundice occurs and before prolonged immobilization (eg, surgery). Adverse reactions: See literature. GI upset, headache, hypertension, edema, hypercalcemia, gallbladder or thromboembolic disease, gynecomastia, impotence, impaired glucose tolerance. How supplied: Multi-dose vials (5mL)–1

Doxorubicin HCl (various)

℞

Interactions: See Contraindications. Mediastinal irradiation, cyclophosphamide, calcium channel blockers, other anthracyclines increase risk of cardiac toxicity; limit lifetime dose to 400mg/m2. Necrotizing colitis with cytarabine. May increase toxicity of cyclophosphamide, mercaptopurine. May reduce serum digoxin levels. Doxorubicin toxicity increased with high-dose IV progesterone, cyclosporine, streptozocin, and if given after paclitaxel infusion (give doxorubicin dose first). Elimination increased by phenobarbital. May decrease phenytoin levels. Recall pneumonitis with actinomycin and radiation in children. Adverse reactions: Local necrosis if extravasation occurs, myocardial toxicity (immediate or delayed), arrhythmias, leukemia, myelosuppression, hyperuricemia, urine discoloration, alopecia, hyperpigmentation, severe GI upset/ulceration, phlebosclerosis, facial flushing, fever, urticaria, peripheral neuropathy, anaphylaxis. How supplied: Contact supplier.

ELIGARD 7.5mg 1-MONTH

℞

Sanofi Aventis

GnRH analogue. Leuprolide acetate 7.5mg per inj; ext-rel susp; for SC inj. ℞ Also: ELIGARD 22.5mg 3-MONTH Leuprolide acetate 22.5mg per inj; ext-rel susp; for SC inj. ℞ Also: ELIGARD 30mg 4-MONTH Leuprolide acetate 30mg per inj; ext-rel susp; for SC inj. ℞ Also: ELIGARD 45mg 6-MONTH Leuprolide acetate 45mg per inj; ext-rel susp; for SC inj. Indications: Palliative treatment of advanced prostate cancer. Adults: Allow product to reach room temperature before using; inject within 30 minutes of mixing. Use correct formulation. 7.5mg SC once per month; or 22.5mg SC once every 3 months; or 30mg SC once every 4 months; or 45mg SC once every 6 months. Rotate inj site. Children: Not established. Contraindications: Women. Pregnancy (Cat.X). Warnings/Precautions: May worsen metastatic vertebral lesions and/or urinary tract obstruction; monitor closely during first few weeks. Increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood glucose, HbA1c, and for signs/symptoms of CVD during therapy. Monitor serum testosterone, PSA periodically. Adverse reactions: Malaise, fatigue, hot flashes/sweats, testicular atrophy, gynecomastia, local reactions, asthenia, pain, spinal cord compression, decreased bone density; transient worsening of signs/symptoms (eg, bone pain, neuropathy, hematuria, bladder outlet obstruction); rare: pituitary apoplexy. How supplied: Single-use kit–1

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GENITOURINARY CANCER EMCYT Pfizer

℞

Estramustine phosphate sodium (prodrug of estradiol) 140mg; caps. Indications: Palliative of metastatic, progressive prostate cancer. Adults: Take 1 hour before or 2 hours after meals. 14mg/kg in 3 or 4 divided doses; reevaluate after 30 to 90 days. Continue as long as favorable response maintained. Children: Not applicable. Contraindications: Active thrombophlebitis or thromboembolic disorders (except when tumor mass caused by thromboembolic phenomenon). Allergy to estradiol, nitrogen mustard. Warnings/Precautions: History of thrombophlebitis, thrombosis, thromboembolic disorders. Cerebro- or cardiovascular disease. Diabetes. Hypertension. Conditions aggravated by fluid retention. Renal or hepatic dysfunction. Monitor bilirubin and hepatic enzymes during and for 2 months after treatment is discontinued. Metabolic bone diseases associated with hypercalcemia. Use effective contraception. Interactions: Absorption impaired by calcium. Adverse reactions: Edema, dyspnea, leg cramps; nausea, diarrhea, GI upset; pruritus, dry skin, easy bruising; breast tenderness and enlargement; lethargy, emotional lability, insomnia; leucopenia; abnormal bilirubin, LDH, SGOT. Thrombosis, MI. How supplied: Caps–100

ESTRACE Warner Chilcott

℞

Estrogen. Estradiol 0.5mg, 1mg, 2mg+; scored tabs; +contains tartrazine. Indications: Palliative treatment of androgendependent advanced prostate cancer. Adults: 1–2mg 3 times daily. Children: Not applicable. Contraindications: Thrombophlebitis. Thromboembolic disorders. Cerebrovascular disorders. Abnormal undiagnosed genital bleeding. Estrogen-depended neoplasias. Liver dysfunction or disease. Pregnancy (Cat.X). Warnings/Precautions: Asthma (2mg tabs). Hepatic dysfunction. Conditions aggravated by fluid retention. Cardiovascular disorders, arterial vascular disease, and risks factors (eg, hypertension, diabetes, obesity, SLE). Familial hyperlipoprotenemia. Monitor BP. Discontinue if jaundice occurs and before prolonged immobilization (eg, surgery). Nursing mothers. Adverse reactions: See literature. GI upset, headache, hypertension, edema, hypercalcemia, gallbladder or thromboembolic disease, gynecomastia, impotence, impaired glucose tolerance. How supplied: Tabs–100

ETOPOPHOS Bristol-Myers Squibb

℞

Topoisomerase inhibitor. Etoposide (as phosphate) 100mg/vial; pwd for IV infusion after reconstitution and dilution. Indications: Refractory testicular tumors after appropriate radiation, surgery, and other chemotherapy. Adults: See literature. Give by IV infusion over 5 to 210 minutes; use doses equivalent to those used for VePesid (eg, 50–100mg/m2 per day on days 1 through 5 to 100mg/m2 per day on days 1, 3, 5.). Repeat course every 3 to 4 weeks after recovery (esp myelosuppression). Toxicity unknown at doses >175mg/m2 per day. Renal impairment (CrCl ≤50mL/min): reduce dose (see literature). Consider dose reduction with existing myelosuppression due to previous radiation or chemotherapy. Children: Not recommended. Warnings/Precautions: Monitor blood (esp. CBCs/differential, platelets, hemoglobin) before each cycle and during therapy; renal function. Withhold dose if platelet count <50,000/mm3 or ANC <500/mm3. Hypoalbuminemia. Elderly. Pregnancy (Cat.D); nursing mothers: not recommended. Interactions: Caution with levamisole, others that inhibit phosphatase activity. May be potentiated by cyclosporine. Additive toxicity with radiation, other cytotoxic therapies. Adverse reactions: Hypersensitivity/ infusion reactions (eg, fever/chills, hypotension, bronchospasm), GI upset, mucositis, myelosuppression (esp. neutropenia, thrombocytopenia; may be fatal), asthenia, alopecia, fever, infections, peripheral neurotoxicity; rare: acute leukemia; others. How supplied: Single-dose vials–1

FIRMAGON Ferring

℞

GnRH receptor antagonist. Degarelix 80mg/vial, 120mg/vial; pwd for SC inj after reconstitution. Indications: Advanced prostate cancer. Adults: Give by SC inj in abdomen once every 28 days; avoid waist and rib areas. Two 120mg injections once, then one 80mg inj once every 28 days. Children: Not established. Contraindications: Pregnancy (Cat.X). Warnings/Precautions: Severe renal or hepatic impairment. Congenital long QT syndrome. Electrolyte imbalances. CHF. Monitor serum PSA. Discontinue if serious hypersensitivity reaction occurs; do not rechallenge. Nursing mothers: not recommended. Interactions: Caution with Class IA (eg, quinidine, procainamide) or Class III (eg, amiodarone, sotalol) antiarrhythmics.

Adverse reactions: Inj site reactions (eg, pain, erythema, swelling, induration), hot flashes, increased weight, fatigue, increased transaminases, increased gammaglutamyltransferase; QT prolongation. How supplied: Treatment Initiation pack (120mg/vial)–2 (w. supplies) Treatment Maintenance pack (80mg/vial)–1 (w. supplies)

Flutamide (various)

℞

Antiandrogen. Flutamide 125mg; caps. Indications: In combination with LHRH agonists (GnRH analogues) in locally confined stage B2–C and stage D2 metastatic prostate carcinoma. Adults: 250mg every 8 hrs. Children: Not applicable. Contraindications: Severe hepatic impairment. ALT ≥2×ULN: not recommended. Warnings/Precautions: Monitor liver function at baseline, monthly for first 4 months, then periodically, and if liver dysfunction occurs; if ALT >2×ULN or jaundice occurs, discontinue and monitor closely until resolution. Monitor prostate specific antigen (PSA). Consider monitoring methemoglobin levels in patients susceptible to aniline toxicity (eg, G6PD deficiency, smokers, hemoglobin M disease). Pregnancy (Cat.D); not for use in women. Interactions: Monitor warfarin. Adverse reactions: Diarrhea, hot flashes, loss of libido, impotence, GI disturbances, gynecomastia, rash, edema, hypertension, CNS effects, blood dyscrasias, urine discoloration, liver failure. How supplied: Contact supplier.

IFEX Bristol-Myers Squibb

℞

Alkylating agent. Ifosfamide 1g, 3g; per vial; pwd for IV infusion after reconstitution. Also: IFEX w. MESNEX COMBINATION PACK ℞ Alkylating agent + uroprotectant. Ifosfamide 1g, 3g; per vial; pwd for IV infusion after reconstitution, + mesna 1g/vial. Indications: Third-line adjunctive treatment of germ cell testicular cancer. Adults: Give by slow IV infusion over at least 30 minutes. 1.2g/m2 per day for 5 consecutive days; repeat every 3 weeks or after hematological recovery (platelets ≥100000/microliter, WBC ≥4000/microliter). Children: Not recommended. Contraindications: Severe bone marrow depression. Warnings/Precautions: Discontinue if neurologic effects (eg, somnolence, confusion, hallucinations) occur. Do urinalysis before each dose, postpone dose if hematuria occurs. Give mesna and at least 2L fluids daily. Do hematologic

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GENITOURINARY CANCER profile before each dose; discontinue if WBCs <2000/microliter or platelets <50000/microliter. May interfere with wound healing. Impaired hepatic, renal, or hematopoetic function. Prior radiation therapy or other cytotoxic agents. Ensure adequate hydration. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Increased risk of myelosuppression with other chemotherapy agents. Adverse reactions: Alopecia, GI upset, hematuria, CNS toxicity, infection, renal or liver dysfunction, phlebitis, fever, urotoxicity (eg, hemorrhagic cystitis), leukopenia, thrombocytopenia. How supplied: Ifex single-dose vials–1 Combination Pack w. Mesnex: Ifex 5×1g single-dose vials + Mesnex 3×1g multidose vials Ifex 10×1g single-dose vials + Mesnex 10×1g multidose vials Ifex 2×3g single-dose vials + Mesnex 6×1g multidose vials

INLYTA Pfizer

℞

Kinase inhibitor. Axitinib 1mg, 5mg; tabs. Indications: Treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy. Adults: Take 12hrs apart. Swallow whole with a glass of water. Initially 5mg twice daily. If tolerated for at least two consecutive weeks with no adverse reactions >Grade 2, normotensive, and not receiving antihypertensives, may increase dose to 7mg twice daily, then 10mg twice daily. May reduce dose from 5mg twice daily to 3mg twice daily, then 2mg twice daily if additional dose reduction required. Concomitant strong CYP3A4/5 inhibitors: avoid; if warranted, decrease Inlyta dose by approximately ½. If strong CYP3A4/5 inhibitor discontinued, return Inlyta dose (after 3–5 half-lives of the inhibitor) to that used prior to CYP3A4/5 inhibitor initiation. Moderate hepatic impairment: decrease dose by approximately ½. Children: Not studied. Warnings/Precautions: Control and monitor BP prior to and during therapy; discontinue if severe and persistent hypertension (despite antihypertensive therapy and dose reduction). Risk of thromboembolic events. Untreated brain metastasis, recent active GI bleed: not recommended. Interrupt therapy if bleeding requires medical intervention. GI perforation and fistula formation; monitor. Monitor thyroid, liver function (ALT, AST, bilirubin), and for proteinuria before starting therapy, then periodically. Reduce dose or temporarily interrupt for moderate to severe proteinuria. Risk of reversible posterior leukoencephalopathy syndrome (permanently discontinue if occurs). Stop treatment at least 24hrs prior to scheduled surgery. Severe hepatic impairment. End-stage renal disease. Pregnancy (Cat.D); avoid. Use adequate

contraception during therapy. Nursing mothers: not recommended. Interactions: See Adult dose. Avoid strong CYP3A4/5 inhibitors (eg, grapefruit juice, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), CYP3A4/5 inducers (eg, rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, St. John’s wort), moderate CYP3A4/5 inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin). Adverse reactions: Diarrhea, nausea, vomiting, hypertension, fatigue, decreased appetite, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, asthenia, constipation, proteinuria. How supplied: Tabs 1mg–180; 5mg–60

JEVTANA Sanofi Aventis

℞

Taxane antimicrotubule. Cabazitaxel 60mg/1.5mL; soln for IV infusion after dilution; contains polysorbate 80, diluent contains ethanol. Indications: In combination with prednisone, hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. Adults: Pretreat with IV antihistamine, corticosteroid, and H2 blocker 30 min before each dose (see literature) and with antiemetic (IV or oral as needed). 25mg/m2 by IV infusion over 1 hour every 3 weeks, with oral prednisone 10mg/day during treatment. Do not treat if neutrophil count ≤1,500 cells/mm3. Prolonged grade ≥3 neutropenia (>1 week), febrile neutropenia, grade ≥3 diarrhea: delay treatment and/or reduce dose to 20mg/m2 (see literature). Discontinue if reactions persist after dosing at 20mg/m2. Children: Not recommended. Contraindications: Baseline neutrophil count ≤1,500cells/mm3. Allergy to polysorbate 80. Warnings/Precautions: Do CBC weekly in 1st cycle and before each subsequent cycle. Increased risk of neutropenia complications; consider G-CSF prophylaxis. Hepatic impairment: not recommended. Severe renal impairment (CrCl <30mL/min) or ESRD. Elderly (increased susceptibility to adverse reactions); monitor closely. Pregnancy (Cat.D; avoid). Nursing mothers: not recommended. Interactions: Avoid strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, atazanavir, nefazodone, nelfinavir, ritonavir, saquinavir, voriconazole) (may potentiate cabazitaxel); caution with moderate CYP3A4 inhibitors. Avoid strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, phenobarbital) (may antagonize cabazitaxel). Avoid St. John’s Wort. Adverse reactions: Bone marrow suppression (esp. neutropenia, anemia, leukopenia, thrombocytopenia), febrile neutropenia, GI upset (esp. diarrhea, may be fatal), renal failure,

fatigue, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, arthralgia, alopecia, hypersensitivity reactions (eg, rash, hypotension, bronchospasm). How supplied: Kit (single-use vial + diluent)–1

Leuprolide acetate (various)

℞

GnRH analogue. Leuprolide acetate 5mg/mL; soln for SC inj; contains benzyl alcohol. Indications: Palliative treatment of advanced prostatic carcinoma. Adults: 1mg SC daily. Rotate inj site. Children: Not applicable. Contraindications: Women. Pregnancy (Cat.X). Warnings/Precautions: Metastatic vertebral lesions. Urinary obstruction. Monitor serum testosterone, PSA, acid phosphatase. Increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood glucose, HbA1c, and for signs/ symptoms of CVD during therapy. Risk of QT prolongation: long-term androgen deprivation therapy, congenital long QT syndrome, electrolyte abnormalities, or CHF, and concomitant Class IA or III antiarrhythmics. Instruct patient on correct self administration. Interactions: Concomitant Class IA (eg, quinidine, procainamide) or Class III (eg, amiodarone, sotalol) antiarrhythmics may prolong the QT interval. Adverse reactions: Hot flashes/sweats, inj site reaction, initial worsening of signs/symptoms (eg, bone pain, urinary tract obstruction, hematuria), edema, GI upset, pain, cardiovascular events, CNS and antiandrogenic effects, asthenia, spinal cord compression; hyperglycemia, anaphylactoid, photosensitivity. How supplied: Contact supplier.

LUPRON DEPOT 7.5mg AbbVie ℞ GnRH analogue. Leuprolide acetate 7.5mg; depot susp for IM inj. Indications: Palliative treatment of advanced prostatic carcinoma. Adults: 7.5mg IM once a month. Rotate inj site. Children: Not applicable. ℞ Also: LUPRON DEPOT-3 MONTH 22.5mg Leuprolide acetate 22.5mg; depot susp for IM inj. Adults: 22.5mg IM inj every 3 months (84 days). Do not split doses. Children: Not applicable. ℞ Also: LUPRON DEPOT-4 MONTH 30mg Leuprolide acetate 30mg; depot susp for IM inj; preservative-free. Adults: 30mg as single IM inj every 4 months (16 weeks). Do not split doses. Children: Not applicable. ℞ Also: LUPRON DEPOT-6 MONTH 45mg Leuprolide acetate 45mg; depot susp for IM inj. Adults: 45mg as single IM inj every 6 months (24 weeks). Do not split doses. Children: Not applicable. Contraindications: Women. Pregnancy (Cat.X).

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GENITOURINARY CANCER Warnings/Precautions: Metastatic vertebral lesions. Urinary obstruction. Monitor serum testosterone, PSA, acid phosphatase. Increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood glucose, HbA1c, and for signs/ symptoms of CVD during therapy. Risk of QT prolongation: long-term androgen deprivation therapy, congenital long QT syndrome, electrolyte abnormalities, or CHF, and concomitant Class IA or III antiarrhythmics. Instruct patient on correct self administration. Interactions: Concomitant Class IA (eg, quinidine, procainamide) or Class III (eg, amiodarone, sotalol) antiarrhythmics may prolong the QT interval. Adverse reactions: Hot flashes/sweats, inj site reaction, initial worsening of signs/symptoms (eg, bone pain, urinary tract obstruction, hematuria), edema, GI upset, pain, cardiovascular events, CNS and antiandrogenic effects, asthenia, spinal cord compression; hyperglycemia, anaphylactoid, photosensitivity. How supplied: Depot kit–1 (prefilled dualchamber syringe w. supplies)

MENEST King

℞

Estrogen. Esterified estrogens 0.3mg, 0.625mg, 1.25mg, 2.5mg; tabs. Indications: Palliative treatment of androgendependent advanced prostate cancer. Adults: 1.25–2.5mg 3 times daily. Children: Not applicable. Contraindications: Thrombophlebitis. Thromboembolic disorders. Cerebrovascular or coronary artery disease. Pregnancy (Cat.X). Warnings/Precautions: Hepatic dysfunction. Gallbladder disease. Conditions aggravated by fluid retention. Familial hyperlipoproteinemia. Discontinue if jaundice occurs. Nursing mothers. Adverse reactions: See literature. Migraine, depression, edema, weight changes, hypertension, GI upset, gynecomastia, impotence. How supplied: Tabs 2.5mg–50 0.3mg, 0.625mg, 1.25mg–100

Mitoxantrone HCl (various)

℞

Topoisomerase II inhibitor. Mitoxantrone (as HCl) 2mg/mL; soln for IV infusion after dilution; preservative-free. Indications: Treatment of pain in advanced hormone-refractory prostrate cancer in combination with corticosteroids. Adults: Give as a short IV infusion. 12–14mg/m2 every 21 days. Children: Not established. Warnings/Precautions: Risk of myelosuppression esp. in high doses (>14mg/m2 daily for 3 days); do not administer if baseline neutrophil count <1500 cell/mm3, except in ANLL. Increased risk of cardiotoxicity with pre-existing cardiovascular disease, prior radiotherapy to mediastinal/pericardial area, or previous anthracycline therapy. Assess cardiac history,

physical exam, ECG, and LVEF prior to therapy. Increased risk of secondary acute myeloid leukemia. Hepatic impairment. Monitor CBCs, platelets, liver function tests prior to each course. Monitor for signs of infection. Avoid extravasation. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Caution with concomitant cardiotoxic drugs. Adverse reactions: Myelosuppression, nausea, vomiting, infection, fever, fatigue, alopecia, dyspnea, hypersensitivity reactions, bluishgreen urine, sclera discoloration, hyperuricemia (monitor), menstrual disorders, amenorrhea, interstitial pneumonitis; cardiotoxicity (eg, CHF). How supplied: Contact supplier.

NEXAVAR Bayer and Onyx

℞

Multikinase inhibitor. Sorafenib 200mg; tabs. Indications: Advanced renal cell carcinoma. Adults: Take on an empty stomach. 400mg twice daily. If toxicity occurs, may reduce dose to 400mg once daily; if further dose reduction required, may reduce dose to 400mg every other day (see full labeling). Concomitant strong CYP3A4 inducers: consider increasing dose, monitor for toxicity. Children: Not established. Contraindications: Concomitant carboplatin/ paclitaxel in patients with squamous cell lung cancer. Warnings/Precautions: Avoid in congenital long QT syndrome. Monitor patients with CHF, bradyarrhythmias, drugs known to prolong the QT interval, electrolyte abnormalities. Discontinue if severe dermatologic toxicity, hypertension, GI perforation, hemorrhage, cardiac ischemia, MI occurs. Suspend therapy before major surgery. Monitor BP weekly during the first 6 weeks and thereafter. Monitor hepatic function regularly; discontinue if transaminases significantly elevated. Severe hepatic impairment (Child-Pugh C) or on dialysis. Use effective contraception during and for 2 weeks after stopping treatment. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: See Contraindications. Avoid strong CYP3A4 inducers (eg, St. John’s Wort, dexamethasone, phenytoin, carbamazepine, rifabutin, rifampin, phenobarbital) and neomycin; may decrease sorafenib levels. May potentiate warfarin (monitor PT & INR), other drugs metabolized by UGT1A1 or UGT1A9 pathway, or substrates of CYP2B6, CYP2C8, CYP2C9, P-gp. Concomitant Class Ia and III antiarrhythmics; may prolong QT interval. Adverse reactions: Dermatologic toxicity (eg, rash, hand-foot skin reaction, alopecia, pruritus, dry skin, Stevens-Johnson syndrome, toxic epidermal necrolysis), fatigue, weight loss, diarrhea, anorexia, abdominal pain, hypertension, hemorrhage, electrolyte abnormalities; druginduced hepatitis, QT prolongation. How supplied: Tabs–120

NILANDRON Covis

℞

Antiandrogen. Nilutamide 150mg; tabs. Indications: Metastatic prostate cancer (Stage D2), as an adjunct to surgical castration. Adults: 300mg once daily for 30 days then 150mg once daily, starting day of or day after surgical castration. Children: Not applicable. Contraindications: Severe hepatic impairment or respiratory insufficiency. Warnings/Precautions: Obtain baseline liver and pulmonary function tests and chest X-ray. Monitor for interstitial pneumonitis; discontinue if occurs. Monitor liver function for first 4 months then periodically; discontinue if ALT > 2×ULN or jaundice occurs. May discolor urine or sclera. Pregnancy (Cat.C): not for use in women. Nursing mothers. Interactions: Monitor drugs metabolized by CYP450 (eg, Vit. K antagonists, theophylline, phenytoin); may need to adjust dose. May cause alcohol intolerance. Adverse reactions: Hot flushes, impaired night vision, GI upset, increased liver enzymes, constipation, dizziness, abnormal vision, hypertension, hepatitis, interstitial pneumonitis. How supplied: Tabs–30

PREMARIN Pfizer

℞

Estrogen. Conjugated estrogens 0.3mg, 0.45mg, 0.625mg, 0.9mg, 1.25mg; tabs. Indications: Treatment of advanced androgendependent carcinoma of the prostate (for palliation only). Adults: 1.25mg–2.5mg 3 times daily. Children: Not applicable. Contraindications: Known, suspected, or history of breast cancer, except in appropriately selected patients being treated for metastatic disease. Known or suspected estrogen-dependent neoplasia. Undiagnosed abnormal genital bleeding. Pulmonary embolism/DVT (active or history of). Arterial thromboembolism (eg, stroke, MI; active or history of). Liver dysfunction or disease. Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. Known or suspected pregnancy (Cat.X). Warnings/Precautions: Not for prevention of cardiovascular disease. Use for shortest duration consistent with treatment goals and risks. Reevaluate periodically. Patients with an intact uterus should almost always receive a progestin with systemic estrogens to avoid endometrial hyperplasia. Discontinue if cardiovascular events occur or are suspected; if jaundice occurs; and during immobilization or at least 4–6 weeks before surgery associated with thromboembolism. Hepatic dysfunction. Conditions aggravated by fluid retention. Gallbladder disease. Bone disease associated with hypercalcemia. Hereditary angioedema. Do initial complete physical and repeat annually (include

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GENITOURINARY CANCER BP, mammogram, PAP smear). Adolescents. Nursing mothers: not recommended. Adverse reactions: See literature. Increased risk of cardiovascular events, estrogen-dependent carcinoma, gallbladder disease, thromboembolic disorders, hepatic tumors. GI upset, breakthrough bleeding, edema, weight changes, mastodynia, hypertension, depression, anaphylactic reactions, angioedema, intolerance to contact lenses. How supplied: Tabs 0.3mg, 0.625mg, 1.25mg–100, 1000; 0.45mg, 0.9mg–100

PROLEUKIN Prometheus

℞

Interleukin-2, recombinant. Aldesleukin 22 million IU/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol; preservative-free. Indications: Metastatic renal cell carcinoma. Adults: ≥18yrs: 600,000 IU/kg (0.037mg/kg) every 8 hours by IV infusion over 15 minutes for a max of 14 doses, followed by 9 days rest, then repeat for another 14 doses (max 28 doses/ course), as tolerated. Retreatment and dose adjustments: see literature. Children: <18yrs: not established. Contraindications: Abnormal thallium stress test or pulmonary function tests. Organ allografts. Previous drug related toxicity (eg, sustained ventricular tachycardia [≥5 beats], uncontrolled or unresponsive arrhythmias, chest pain with ECG changes consistent with angina, or MI, cardiac tamponade, intubation >72hrs, renal failure requiring dialysis >72hrs, coma or toxic psychosis >48hrs, repetitive or difficult seizures, bowel ischemia or perforation, GI bleeding requiring surgery). Warnings/Precautions: See literature. History of cardiac or pulmonary disease. Renal, hepatic, or CNS impairment. Seizure disorder. Bacterial infections (treat prior to starting therapy; esp. patients with indwelling central lines). Withhold dose if organ perfusion is not maintained, urine output is reduced, systolic BP <90mmHg, CHF, cardiac ischemia or arrhythmias occur; or if moderate-to-severe lethargy or somnolence (continuing may result in coma) develops. Evaluate and treat CNS metastases; obtain negative scan before starting treatment. Do thallium stress test; monitor vital signs, weight, fluid intake and output daily. Correct hypovolemia or fluid accumulations if occur. Obtain CBCs, differential and platelets, blood chemistries (electrolytes, renal and hepatic function tests), chest X-rays, serum creatinine (should be ≤1.5mg/dL before starting therapy), pulmonary function tests, arterial blood gases. Monitor for capillary leak syndrome, mental status changes, thyroid changes, diabetes onset. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Psychotropics may increase CNS toxicity. Increased toxicity with other nephrotoxic, hepatotoxic, myelotoxic, or

cardiotoxic drugs. Hypersensitivity reactions with other antineoplastics. Myocardial injury and rhabdomyolysis risk increased with interferonalfa. Antagonized by glucocorticoids (avoid). β-blockers and other antihypertensives may potentiate hypotension. Delayed reactions to iodinated contrast media. May increase risk of allograft rejection. Adverse reactions: Hypotension, GI upset, oliguria, flu-like syndrome, respiratory disorders (eg, dyspnea), CNS effects (eg, confusion, somnolence), rash, metabolic and nutritional disorders (eg, bilirubinemia, increased creatinine), hyperglycemia, thyroid disorder, thrombocytopenia, anemia, impaired neutrophil function, capillary leak syndrome, cardiotoxicity, exacerbation of autoimmune and inflammatory disease, eosinophilia, possible antibody formation; others. How supplied: Single-use vials–1

PROVENGE Dendreon

℞

Autologous cellular immunotherapy. Sipuleucel-T (autologous CD54+ cells activated with PAP-GMCSF); minimum 50 million cells/dose; suspension for IV infusion. Indications: Asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer. Adults: Autologous use only. Obtain product release from manufacturer, match patient identity on product and Cell Product Disposition form, check expiration date and time on product before infusing. Premedicate 30 minutes before infusion with acetaminophen and antihistamine. Give three doses at 2-week intervals. For each dose: give entire contents of bag by IV infusion over 60 minutes; do not use filter; do not use if clumps do not disperse with gentle mixing. Observe patient for at least 30 minutes after infusion. May interrupt or slow infusion if acute transfusion reaction occurs; do not restart if product at room temp for >3 hours. Children: Not applicable. Warnings/Precautions: Cardiac or pulmonary conditions. Each dose requires a standard leukapheresis procedure about 3 days before infusion. If scheduled infusion is missed, do an additional leukapheresis procedure if treatment course is to be continued. Risk of disease transmission. Pregnancy, lactation: not applicable. Interactions: May be antagonized by concomitant chemotherapy or immunosuppressive therapy. Adverse reactions: Infusion reactions (eg, chills, fever, respiratory events, GI upset, hypertension, tachycardia), fatigue, back pain, joint ache, headache. Note: If product sterility tests indicate microbial contamination, manufacturer will contact physician (tests are incomplete at time of infusion). How supplied: Patient-specific bag (250mL)–1

SUTENT Pfizer

℞

Multikinase inhibitor. Sunitinib (as malate) 12.5mg, 25mg, 50mg; gelatin caps. Indications: Advanced renal cell carcinoma (RCC). Adults: 50mg once daily for 4 weeks, then 2 weeks off (see full labeling). May adjust dose in increments or decrements of 12.5mg. Concomitant strong CYP3A4 inhibitors (see Interactions): may reduce dose to 37.5mg daily. Concomitant strong CYP3A4 inducers (see Interactions): may increase to max 87.5mg daily. Children: Not established. Warnings/Precautions: Hepatotoxicity; may be severe or fatal. Monitor liver function tests before starting, during each cycle of treatment and as clinically needed; interrupt if Grade 3 or 4 hepatic adverse events occur and discontinue if no resolution; if severe liver function changes or signs/symptoms of failure, do not restart. Cardiovascular disease: monitor LVEF at baseline and periodically thereafter; interrupt or reduce dose if LVEF <50% and >20% below baseline; discontinue if CHF occurs. History of QT prolongation or proarrythmic conditions (eg, bradycardia, electrolyte disturbances); perform periodic ECG, monitor electrolytes. Monitor BP. Suspend therapy if severe hypertension, seizures, or pancreatitis develops. Obtain CBCs, platelets, serum chemistries at start of each cycle. Concomitant exposure to risk factors (eg, IV bisphosphonates therapy or dental disease) may increase the risk of osteonecrosis of the jaw; avoid or consider preventive dentistry prior to treatment. Risk of tumor lysis syndrome: monitor closely in RCC and GIST patients with high tumor burden. Monitor for thyroid dysfunction; obtain baseline levels prior to treatment. Undergoing major surgery. Stress (monitor for adrenal insufficiency). Renal or hepatic impairment. Pregnancy (Cat.D; avoid). Nursing mothers: not recommended. Interactions: May be potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole); grapefruit. May be antagonized by CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital); St. John’s wort: not recommended. Adverse reactions: Fatigue, asthenia, fever, diarrhea, nausea, vomiting, mucositis/stomatitis, dyspepsia, abdominal pain, constipation, hypertension, peripheral edema, rash, handfoot syndrome, skin discoloration, dry skin, hair color changes, altered taste, headache, back pain, arthralgia, extremity pain, cough, dyspnea, anorexia, bleeding; hepatotoxicity, left ventricular dysfunction, QT prolongation, hemorrhage, hypertension, osteonecrosis of the jaw, tumor lysis syndrome, thyroid dysfunction, impaired wound healing, others (see full labeling). How supplied: Caps–28

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GENITOURINARY CANCER TAXOTERE Sanofi Aventis

℞

Antimicrotubule agent. Docetaxel 20mg/mL; soln for IV infusion after dilution; contains polysorbate 80; diluent contains alcohol. Indications: In combination with prednisone: hormone-refractory metastatic prostate cancer. Adults: Give by IV infusion over 1hr once every 3 weeks. 75mg/m2. Premedicate with oral corticosteroid. Adjust dose based on tolerability and effect (see full labeling); allow neutrophils and platelets to recover before subsequent cycles. Children: Not established. Contraindications: Neutrophil count <1500 cells/mm3. Hypersensitivity to polysorbate 80. Warnings/Precautions: Hepatic dysfunction; bilirubin >ULN, SGOT and/or SGPT >1.5×ULN concomitant with alkaline phosphatase >2.5×ULN: not recommended. Obtain bilirubin, AST/ALT, and alkaline phosphatase values prior to each cycle. Monitor peripheral blood counts frequently (esp. neutrophils, platelets). Monitor for hypersensitivity reactions (esp. during 1st and 2nd infusions). Pre-existing effusions. Adjust dose if severe neurosensory symptoms (eg, paresthesia, dysesthesia, pain) occur; discontinue if symptoms persist. Monitor for eye disorders; discontinue if cystoid macular edema is diagnosed (consider alternative non-taxane chemotherapy). Elderly. Pregnancy (Cat.D; use adequate contraception); nursing mothers: not recommended. Interactions: May affect, or be affected by, other CYP3A4 inhibitors, inducers, or substrates (eg, ketoconazole, ritonavir). Adverse reactions: Infections, neutropenia, anemia, febrile neutropenia, hypersensitivity/ infusion site reactions, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, myalgia; cutaneous reactions (eg, erythema, edema, desquamation), acute myeloid leukemia, death (septic and nonseptic), cystoid macular edema. How supplied: Single-dose vials (1mL, 4mL, 8mL)–1 (w. diluent, supplies)

THERACYS Sanofi Pasteur

℞

BCG Live. Live Bacillus Calmette and Guerin (BCG) strain of attenuated Mycobacterium bovis; 81mg per vial; pwd for intravesical administration after reconstitution and dilution; preservative-free. Indications: Treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder. Prophylaxis of stage Ta and/or T1 papillary tumors following transurethral resection (TUR). Adults: Drain bladder via urethral catheter prior to instillation. Induction: Instill 1 dose intravesically once per week for 6 weeks. Maintenance: one dose at 3, 6, 12, 18, and 24 months after initial dose. Retain in bladder for up

to 2 hours, then void seated. Increase fluid intake to flush bladder. Children: Not recommended. Contraindications: Immunosuppressed. Active TB. Febrile illness. UTI (withhold until complete resolution). Gross hematuria. Do not give within 7–14 days after biopsy, TUR, or traumatic catheterization. Warnings/Precautions: Not for the prevention of cancer or TB. Determine PPD status prior to therapy; rule out active TB if (+). Not for stage TaG1 papillary tumors unless high tumor recurrence risk. Not for IV, IM, or SC injection. Monitor for systemic BCG reaction; may occur as a hypersensitivity reaction (eg, malaise, fever, chills) or active infection (eg, fever ≥101.3°F, or acute localized inflammation such as epididymitis, prostatitis, or orchitis persisting ≥2 days); if persistent fever or acute febrile illness consistent with BCG infection occurs, discontinue BCG permanently and treat with ≥2 antimycobacterial drugs (except pyrazinamide). Local irritative effects: do not use antimycobacterial drugs prophylactically. Preexisting arterial aneurysm or prosthetic devices: risk of ectopic BCG infection. High-risk for HIV. Latex allergy. Small bladder. PPD seroconversion may occur with treatment. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: See contraindications. Immunosuppressants, myelosuppressants, radiation, antimicrobial therapy may reduce efficacy. Adverse reactions: Bladder irritation, inflammation (begins after 4 hrs and last up to 72 hrs), dysuria, urinary frequency, malaise, hematuria, fever, chills, cystitis, anemia, UTI, GI upset, renal toxicity, genital pain, arthralgia, incontinence, cramps, flu-like syndrome, systemic BCG infection. How supplied: Vial–1 (w. diluent)

Thiotepa (various)

℞

Alkylating agent. Thiotepa 15mg; per vial; lyophilized pwd for IV, intravesical, or intracavitary administration after reconstitution. Indications: Superficial papillary carcinoma of the urinary bladder. Intracavitary effusion due to neoplasm of serosal cavities. Adults: Avoid fluids 8–12 hrs prior to treatment. 60mg once weekly for 4 weeks; may repeat up to a total of 3 courses. Retain in bladder for 2 hours. Intracavitary administration: 0.6–0.8mg/kg through same tube used to remove fluid from cavity. Children: Not recommended. Contraindications: Renal, hepatic, or bone marrow dysfunction; if need outweighs risk, may be used in low dosage with close monitoring. Warnings/Precautions: Bone marrow suppression; monitor blood and platelets weekly during and for at least 3 weeks after therapy. Discontinue if WBC ≤3000/mm3 or platelets ≤150,000/mm3. Monitor renal and hepatic function.

Use effective contraception if patient or partner is of childbearing potential. Elderly. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Increased toxicity with concomitant or sequential alkylating agents (nitrogen mustards, cyclophosphamide), radiation, myelosuppressants. Prolonged apnea with succinylcholine. Adverse reactions: Myelosuppression, fatigue, febrile or allergic reactions, inj site reactions, urinary retention, dysuria, GI disturbances, anorexia, alopecia, dizziness, headache, drowsiness, blurred vision, amenorrhea, interferes with spermatogenesis. Intravesical administration: rare: chemical or hemorrhagic cystitis. How supplied: Contact supplier.

TICE BCG Merck

℞

BCG Live. Bacillus of Calmette and Guerin (BCG) strain of Mycobacterium bovis live, attenuated culture preparation; 50mg per vial; pwd for intravesical administration after reconstitution and dilution; preservative-free. Indications: Treatment and prophylaxis of carcinoma in situ (CIS) of the urinary bladder. Prophylaxis of stage Ta and/or T1 papillary tumor of the urinary bladder. Adults: 1 vial in 50mL preservative-free saline intravesically once per week for 6 weeks (may repeat this regimen once if remission not achieved); then monthly for 6–12 months if needed. Avoid fluid at least 4 hrs before treatment and void immediately before administration. Retain in bladder for 2 hours. Children: Not recommended. Contraindications: Immunosuppressed. Active TB. Febrile illness. UTI. Gross hematuria. Do not give within 7 days after bladder biopsy, transurethral resection (TUR), or traumatic catheterization. Warnings/Precautions: Not a vaccine for prevention of cancer or TB. Not for IV or SC use. Determine PPD status prior to therapy; rule out active TB if (+). Monitor for signs of systemic BCG infection: flu-like symptoms >72 hrs, fever ≥103°F, persistent LFT abnormalities; prostatitis, epididymitis, orchitis >2 days; treat with at least 2 antimycobacterial drugs (except pyrazinamide). Local irritative toxicities: do not treat with antimycobacterials. Bleeding bladder mucosa, small bladder. Disinfect fluid voided after therapy with bleach. PPD seroconversion may occur with treatment. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Immunosuppressants, myelosuppressants, radiation, antimicrobial therapy may reduce efficacy. Adverse reactions: Urine discoloration, bladder irritation, inflammation (begins after 4 hrs and last up to 72 hrs), malaise, fever, chills, flu-like syndrome, systemic BCG infection, dysuria, urinary frequency, hematuria, cystitis, urgency, nocturia, cramps, pain, incontinence, rigors, arthralgia. How supplied: Vial–1

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GENITOURINARY CANCER TOPOSAR Teva

℞

Topoisomerase inhibitor. Etoposide 20mg/mL; soln for IV infusion; contains dehydrated alcohol 33.2%, polysorbate 80. Indications: Refractory testicular tumors after appropriate radiation, surgery, and other chemotherapy. Adults: Give by slow IV infusion over 30–60mins. Range 50–100mg/m2 per day on days 1 through 5 to 100mg/m2 per day on days 1, 3, and 5. Repeat course every 3 to 4 weeks after recovery from any toxicity. Renal impairment (CrCl 15–50mL/min): reduce dose to 75%; (CrCl <15mL/min): see literature. Consider dose reduction with existing myelosuppression due to previous radiation or chemotherapy. Children: Not recommended. Warnings/Precautions: Monitor for myelosuppression; obtain CBCs with differential, platelets, hemoglobin at baseline, prior to each subsequent dose, during and after therapy. Withhold dose if platelet count <50,000/mm3 or ANC <500/mm3. Renal impairment. Hypoalbuminemia. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Potentiated by cyclosporine. Additive toxicity with radiation, other cytotoxic therapies. Adverse reactions: Hypersensitivity/ infusion reactions (eg, fever/chills, hypotension, bronchospasm), GI upset, anorexia, mucositis, myelosuppression (esp neutropenia, thrombocytopenia; may be fatal), alopecia, fever, infections, peripheral neurotoxicity; rare: acute leukemia; others. How supplied: Multi-dose vials (5mL, 25mL, 50mL)–1

TORISEL Pfizer

℞

mTOR kinase inhibitor. Temsirolimus 25mg/mL; ethanolic soln for IV infusion after two dilutions (first w. supplied diluent); contains alcohol, polysorbate 80. Indications: Advanced renal cell carcinoma. Adults: 25mg once weekly. Infuse IV over 30–60min, using an infusion pump. Continue until disease progression or unacceptable toxicity occurs. Premedicate with IV antihistamine (eg, diphenydramine). Hold dose if ANC <1000/mm3, platelets <75000/mm3, or NCI CTCAE ≥grade 3 adverse reaction occurs; may restart at a dose reduced by 5mg/week (no lower than 15mg/wk) if adverse reactions resolve to ≤grade 2. See Interactions. Children: Not recommended. Warnings/Precautions: Sirolimus or related allergy. Hepatic insufficiency. Perioperative period (may interfere with wound healing). CNS tumors. Monitor CBCs weekly and chemistry panels every 2 weeks, blood glucose, lipids, renal function, and for worsening respiratory or GI symptoms (eg, acute abdomen, blood in stool). Elderly.

Pregnancy (Cat.D) (avoid pregnancy during and for 3 months after therapy, male patients should use appropriate contraception), nursing mothers: not recommended. Interactions: Avoid strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice); if used, consider reducing temsirolimus dose to 12.5mg/week (allow 1 week after discontinuing CYP3A4 inhibitor before readjusting temsirolimus dose). Avoid strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital, St. John’s Wort); if used, consider increasing temsirolimus dose to 50mg/week. Avoid live vaccines, close contact with vaccinees. Additive toxicity with sunitinib (rash, gout/ cellulitis), anticoagulants (intracerebral bleeding). Adverse reactions: Rash, asthenia, mucositis, nausea, edema, anorexia, infection, pain, anemia, hyperglycemia, hyperlipemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, leukopenia; hypersensitivity/infusion reactions (anaphylaxis, dyspnea, flushing, chest pain), immunosuppression, interstitial lung disease, bowel perforation, acute renal failure, abnormal wound healing; others (see literature). How supplied: Kit (vial + diluent)–1

TRELSTAR Actavis

℞

GnRH analogue. Triptorelin pamoate 3.75mg, 11.25mg, 22.5mg; pwd for IM inj after reconstitution; contains mannitol. Indications: Palliative treatment of advanced prostate cancer. Adults: Give by IM inj in buttock. 3.75mg every 4 weeks, or 11.25mg every 12 weeks, or 22.5mg every 24 weeks. Children: Not established. Contraindications: Women. Pregnancy (Cat.X). Warnings/Precautions: Must administer under physician supervision. Discontinue if hypersensitivity occurs. Initial transient increase in serum testosterone may result in worsening of symptoms. Spinal cord compression. Renal or hepatic impairment. Metastatic vertebral lesions. Upper or lower urinary tract obstruction. Increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood glucose and for signs/symptoms of CVD during therapy. Interactions: Avoid hyperprolactinemic drugs. Adverse reactions: Inj site reactions, hot flushes, skeletal pain, fatigue, hypertension, headache, dizziness, diarrhea, vomiting, leg edema, insomnia, impotence, emotional lability, anemia, pruritus, urinary retention, UTI, erectile dysfunction, testicular atrophy; hyperglycemia. How supplied: Single-dose vial–1 MixJect system–1 (vial + vial adapter + prefilled syringe)

VALSTAR Endo

℞

Anthracycline. Valrubicin 40mg/mL; soln for intravesical instillation after dilution; contains 50% polyoxyl castor oil/50% dehydrated alcohol; preservative-free. Indications: Intravesical therapy of BCGrefractory carcinoma in situ (CIS) of the urinary bladder in patients for whom immediate cystectomy would be associated with unacceptable morbidity or mortality. Adults: Drain bladder before instilliation. 800mg given intravesically via urethral catheter once weekly for 6 weeks. Retain drug for 2 hours before voiding, then void. Children: Not recommended. Contraindications: Concurrent UTI. Small bladder capacity (eg, unable to tolerate a 75mL instillation). Warnings/Precautions: Monitor for disease recurrence or progression with cystoscopy, biopsy, and urine cytology every 3 months; if there is not a complete response of CIS to treatment after 3 months or if CIS recurs, cystectomy must be reconsidered. Severe irritable bladder symptoms. Perforated bladder. Bladder mucosa compromised. Delay administration for at least 2 weeks after transurethral resection and/or fulguration. Maintain adequate hydration. Pregnancy (Cat.C); avoid, both males and females should use effective birth control. Nursing mothers: not recommended. Adverse reactions: Bladder symptoms (eg, urinary frequency, dysuria, urinary urgency, spasm, hematuria, pain, incontinence, cystitis, nocturia, local burning, urethral pain, pelvic pain, UTI). How supplied: Single-use vials–4, 24

VANTAS Endo

℞

GnRH analogue. Histrelin acetate 50mg; SC implant. Indications: Palliative treatment of advanced prostate cancer. Adults: Insert 1 implant SC in the inner aspect of the upper arm. Remove after 12 months; may replace. Children: Not applicable. Contraindications: Pregnancy (Cat.X). Nursing mothers. Not for use in women or children. Warnings/Precautions: Metastatic vertebral lesions, urinary tract obstruction (monitor closely in 1st few weeks). Avoid wetting inserted arm for 24hrs and heavy lifting or strenuous exertion for 1st week. Increased risk of developing diabetes; monitor blood glucose and HbA1c periodically; treat if occurs. Increased risk of developing MI, sudden cardiac death, stroke; monitor for signs/symptoms of cardiovascular disease. Measure serum testosterone, PSA levels periodically. Implant not visible on X-ray.

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GENITOURINARY CANCER Interactions: May interfere with pituitary gonadotropic and gonadal function tests. Adverse reactions: Hot flashes, initial worsening of signs/symptoms (eg, bone pain, urinary tract obstruction, hematuria), fatigue, local reactions, CNS or antiandrogenic effects, renal impairment, constipation; hyperglycemia, diabetes, cardiovascular disease. How supplied: Kit–1 (w. implant and supplies)

Vinblastine for injection

VINCASAR PFS Teva

℞

Bedford

Antimicrotubule agent. Vinblastine (as sulfate) 10mg/vial; lyophilized pwd for IV inj or infusion after reconstitution. Also: Vinblastine injection Fresenius Kabi ℞ Vinblastine (as sulfate) 1mg/mL; soln for IV inj or infusion; contains benzyl alcohol. Indications: Frequently responsive: palliative treatment of advanced carcinoma of the testis. Adults: See literature. Give by IV once weekly. 1st dose: 3.7mg/m2 as a single dose, continue to increase dose by increments (2nd dose: 5.5mg/m2, 3rd dose: 7.4mg/m2, 4th dose: 9.25mg/m2, 5th dose: 11.1mg/m2, max dose: 18.5mg/m2) until WBC 3,000cells/mm3 reached, stop at this dose, then administer a dose one increment smaller at weekly intervals for maintenance. Usual weekly dosage: 5.5–7.4mg/m2. Do not give the next dose, even if 7 days have elapsed, unless WBC ≥4,000cells/mm3. If oncolytic effect occurs before leukopenia, do not increase the size of subsequent doses. Hepatic impairment: reduce dose by 50% if serum bilirubin >3mg/100mL. Children: See literature. IV use only. Testicular germ cell carcinomas: initially 3mg/m2. Adjust dose according to hematologic tolerance. Contraindications: Significant granulocytopenia (unless result of disease being treated). Bacterial infections (treat first). Warnings/Precautions: For IV use only; fatal if given intrathecally. Hepatic impairment. Avoid in elderly with cachexia or ulcerated skin; or in patients with malignant-cell infiltration of the bone marrow. Pre-existing pulmonary dysfunction. Progressive dyspnea requiring chronic therapy (do not re-administer). Ischemic cardiac disease. Bone marrow suppression; monitor WBC before and during treatment. Avoid contamination of the eyes or injecting into an extremity with poor circulation (thrombosis possible). Avoid extravasation. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May be potentiated by CYP3A inhibitors (eg, erythromycin). Antagonizes phenytoin. Adverse reactions: Leukopenia, alopecia, GI upset, paresthesias, malaise, pain; dyspnea, severe bronchospasm. How supplied: Pwd–10 Soln–1

℞

Antimicrotubule agent. Vincristine sulfate 1mg/mL; soln for IV inj; contains mannitol; preservative-free. Indications: In combination with other chemotherapeutic agents for Wilms’ tumor. Adults: Usual dose: 1.4mg/m2 IV once weekly. Serum bilirubin >3mg/100mL: reduce dose by 50%. Children: ≤10kg: initially 0.05mg/kg IV once weekly. >10kg: usual dose: 2mg/m2 IV once weekly. Contraindications: Demyelinating form of Charcot-Marie-Tooth syndrome. Warnings/Precautions: For IV use only; fatal if given intrathecally. Hepatic dysfunction. Preexisting neuromuscular disease. Obtain CBCs, platelets before each dose, then periodically. Monitor serum uric acid levels during first 3–4 weeks of treatment. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Concomitant radiotherapy through ports that include the liver: not recommended. Potentiated by CYP3A4 enzyme inhibitors (eg, itraconazole). Antagonizes phenytoin. Caution with other neurotoxic or platinum-containing agents. Separate L-asparaginase dose by 12–24hrs (administer after vincristine). Consider discontinuing drugs that cause urinary retention for the first few days following therapy. Adverse reactions: GI upset, paralytic ileus (esp. in children; discontinue temporarily if occurs), polyuria, dysuria, urinary retention, hypertension, hypotension, neuromuscular effects, dyspnea, bronchospasm, alopecia, rash, fever, headache, hypersensitivity reactions, acute uric acid nephropathy. How supplied: Single-use vials (1mL, 2mL)–1

VOTRIENT GlaxoSmithKline

℞

Kinase inhibitor. Pazopanib 200mg; tabs. Indications: Advanced renal cell carcinoma. Adults: Take on an empty stomach. Swallow whole. 800mg once daily. Dose adjustments: see full labeling. Hepatic impairment: moderate: 200mg once daily; severe: not recommended. Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir, clarithromycin): avoid; if warranted, reduce dose of pazopanib to 400mg; may reduce further if toxicity occurs. Concomitant strong CYP3A4 inducers (eg, rifampin): avoid. Children: Not established (increased toxicity in developing organs). Warnings/Precautions: Not indicated for use in combination with other cancer agents. Not for treatment of adipocytic soft tissue sarcoma or gastrointestinal stromal tumors. Risk of severe and fatal hepatotoxicity. Monitor liver tests before starting and at least once every 4 weeks for at least the first 4 months of treatment, then

periodically. If ALT between 3×ULN and 8×ULN continue therapy with weekly monitoring until ALT returns to Grade 1 or baseline. If ALT >8×ULN interrupt therapy until ALT returns to Grade 1 or baseline; may consider reintroducing at a reduced dose, measure liver tests weekly for 8 weeks; if ALT>3×ULN recurs, permanently discontinue. Permanently discontinue if ALT>3×ULN and bilirubin >2×ULN. Gilbert’s syndrome (see full labeling). History of QT prolongation. Cardiac dysfunction risk: evaluate LVEF at baseline and periodically; monitor for CHF. Monitor ECG, electrolytes (eg, calcium, magnesium, potassium), thyroid. History of hemoptysis, cerebral, or clinically significant GI hemorrhage in the past 6 months: not recommended. Risk of arterial thrombotic events (within previous 6 months: not recommended). Monitor for VTE, PE, infection, proteinuria (reduce dose if 24-hour urine protein ≥3g). Discontinue if severe and persistent hypertension (despite antihypertensives and dose reduction) or if repeat episodes of proteinuria (despite dose reductions) occur. Stop therapy at least 7 days before surgery; discontinue in patients with wound dehiscence. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: See Adult dosing: Potentiated by strong CYP3A4 inhibitors, grapefruit juice. Antagonized by strong CYP3A4 inducers. Concomitant drugs with narrow therapeutic windows metabolized by CYP3A4, CYP2D6, or CYP2C8: not recommended. Increased risk of ALT elevations with concomitant simvastatin; caution and monitor closely; follow dosing guidelines or consider alternatives to pazopanib, or discontinuing simvastatin if develops. Caution with concomitant drugs that prolong QT interval (eg, antiarrhythmics). Adverse reactions: Diarrhea, hypertension, hair color changes, nausea, anorexia, vomiting, fatigue, decreased weight, decreased appetite, tumor pain, musculoskeletal pain, headache, dysgeusia, dyspnea, skin hypopigmentation; hepatoxicity, QT prolongation, hemorrhagic events, arterial thrombotic events (eg, MI, angina, ischemic stroke, TIA), venous thrombotic events (eg, VTE, PE), GI perforation or fistula, impaired wound healing, hypothyroidism, proteinuria, infection, reversible posterior leukoencephalopathy syndrome (discontinue if occurs). How supplied: Tabs–120

XOFIGO Bayer

℞

Alpha particle-emitting radioactive therapeutic agent. Radium Ra 223 dichloride 1000 kBq/mL (27 microcurie/mL) with a total radioactivity of 6000 kBq/vial (162 microcurie/vial) at the reference date; IV injection. Indications: Treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.

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GENITOURINARY CANCER Adults: See full labeling. Administer by slow IV over 1 min. 50kBq (1.35 microcurie) per kg given at 4 week intervals for 6 injections. Children: <18yrs: not established. Contraindications: Women who are or may become pregnant. Pregnancy (Cat.X). Warnings/Precautions: Not for use in women. Bone marrow suppression. Perform hematologic evaluation at baseline and prior to every dose. Before 1st dose, the ANC should be ≥1.5 ×109/L, platelets ≥100 ×109/L and hemoglobin ≥10g/dL. Before subsequent doses, the ANC should be ≥1 ×109/L and platelets ≥50 ×109/L; discontinue if no recovery within 6–8 weeks after last dose despite receiving supportive care. Monitor closely if evidence of compromised bone marrow reserve. Discontinue if life-threatening complications occur despite supportive care for bone marrow failure. Monitor oral intake and fluid status carefully. Males (use condoms) and female partners of reproductive potential should use highly effective contraceptive method during and 6 months after completion. Nursing mothers: not recommended. Interactions: Concomitant chemotherapy: not established. Discontinue if concomitant with chemotherapy, other systemic radioisotopes or hemibody external radiotherapy. Adverse reactions: Nausea, diarrhea, vomiting, peripheral edema, anemia, lymphocytopenia, leukopenia, thrombocytopenia, neutropenia. How supplied: Single-use vials (6mL)–1

XTANDI Astellas

℞

Androgen receptor inhibitor. Enzalutamide 40mg; caps. Indications: Treatment of metastatic castrationresistant prostate cancer in patients who have previously received docetaxel. Adults: Swallow whole. 160mg once daily. Dose modifications: ≥Grade 3 toxicity or intolerable side effect: withhold dosing for 1 week or until symptoms improve to ≤Grade 2, then resume at same or reduced dose, if warranted. Concomitant strong CYP2C8 inhibitors: avoid if possible. If co-administration necessary, reduce Xtandi dose to 80mg once daily; if inhibitor is discontinued, return Xtandi dose to dose used prior to initiation of inhibitor. Children: Not established. Contraindications: Pregnancy (Cat.X). Warnings/Precautions: Seizure risk. Severe renal or hepatic impairment. Nursing mothers. Interactions: Potentiated by strong CYP2C8 inhibitors (eg, gemfibrozil), CYP3A4 inhibitors (itraconazole). May be antagonized by CYP2C8 inducers (eg, rifampin), CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, bosentan, efavirenz, etravirine, modafinil, nafcillin, St. John’s Wort). Antagonizes midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate). Avoid concomitant drugs with narrow therapeutic indexes metabolized by CYP3A4 (eg, alfentanil, cyclosporine,

dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus), CYP2C9 (eg, phenytoin, warfarin), CYP2C19 (eg, S-mephenytoin); enzalutamide may decrease their exposure. Caution with concomitant drugs that may lower the seizure threshold. Monitor INR if concomitant warfarin cannot be avoided. Adverse reactions: Asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, hypertension, neutropenia; seizures. How supplied: Caps–120

ZOLADEX AstraZeneca

℞

GnRH agonist. Goserelin (as acetate) 3.6mg; SC implant. ℞ Also: ZOLADEX 3-MONTH 10.8mg Goserelin (as acetate) 10.8mg; SC implant. Indications: Palliative treatment of advanced prostate carcinoma. In combination with flutamide for management of locally confined Stage T2b-T4 (Stage B2-C) prostate carcinoma. Adults: Implant SC into anterior abdominal wall. Prostate cancer: one 3.6mg implant every 28 days or one 10.8mg implant every 12 weeks. Stage B2-C prostatic carcinoma (in combination with flutamide): Treat 8 weeks prior to and during radiotherapy. Initially one 3.6mg implant, followed in 28 days by one 10.8mg implant; or may use one 3.6mg implant every 28 days (two before and two during radiotherapy). Children: Not established. Contraindications: Pregnancy (Cat.D). Warnings/Precautions: Increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood glucose and for signs/symptoms of CVD during therapy. Risk of ureteral obstruction or spinal cord compression; monitor during 1st month of therapy. Risk factors for decreased bone mineral density (eg, chronic alcohol, tobacco, anticonvulsants, corticosteroids). Nursing mothers: not recommended. Interactions: May affect tests of pituitarygonadotropic and gonadal functions. Adverse reactions: Decreased testosterone levels (eg, hot flashes, sexual dysfunction, decreased erections, gynecomastia), lower urinary tract symptoms, transient worsening of symptoms (eg, bone pain), tumor flare, diarrhea, nausea, edema, malaise, hyperglycemia, hypercalcemia, decreased bone mineral density. How supplied: Implant (in syringe)–1

ZYTIGA Janssen Biotech

℞

CYP17 inhibitor. Abiraterone acetate 250mg; tablets. Indications: In combination with prednisone for the treatment of metastatic castration-resistant prostate cancer.

Adults: Take on empty stomach (no food 2 hours before or 1 hour after administration). Swallow whole with water. 1g once daily (in combination with prednisone 5mg twice daily). Moderate hepatic impairment (Child-Pugh Class B): 250mg once daily. If hepatotoxicity occurs: interrupt, then restart at reduced dose; discontinue if severe (see full labeling). If concomitant strong CYP3A4 inducer necessary, increase abiraterone dose frequency to twice daily during co-administration period (eg, from 1g once daily to 1g twice daily); reduce back to previous dose/frequency when CYP3A4 inducer is discontinued. Children: Not recommended. Contraindications: Pregnancy (Cat.X). Women who are or may become pregnant. Warnings/Precautions: Risk of mineralocorticoid excess: patients with history of cardiovascular disease, LVEF <50%, Class III or IV heart failure, recent MI, ventricular arrhythmias. Monitor BP, serum potassium, and for fluid retention monthly. Control hypertension and correct hypokalemia before and during treatment. Monitor for adrenocortical insufficiency. Stress (may need higher corticosteroid dose). Baseline severe hepatic impairment (Child-Pugh Class C); avoid. Monitor liver function (ALT/AST, bilirubin) prior to starting treatment, every 2 weeks for the first 3 months, and monthly thereafter; interrupt, reduce dose, or discontinue if hepatic dysfunction occurs. Nursing mothers: not recommended. Interactions: CYP2D6 substrates with narrow therapeutic index (eg, thioridazine); avoid. Potentiates dextromethorphan. May affect, or be affected by, strong inhibitors or inducers of CYP3A4; avoid or use caution. Concomitant CYP2C8 substrates: monitor closely for signs of toxicity. Adverse reactions: Joint swelling or discomfort, hypokalemia, edema, myalgia, hot flush, GI upset, UTI, cough, hypertension, arrhythmias, urinary frequency, nocturia, URI, adrenocortical insufficiency, hepatotoxicity. Note: Pregnant women and those of childbearing potential should not handle Zytiga tablets without protection (eg, gloves). Partners must use appropriate barrier contraception. How supplied: Tabs–120

ALPHABETICAL INDEX A complete list of products and conditions, fully indexed by brand name, generic name and indication, can be found at the back of this reference.

MANUFACTURERS INDEX A complete list of names and contact information for companies can be found at the back of this reference.

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GYNECOLOGIC CANCER ALKERAN GlaxoSmithKline

℞

Nitrogen mustard derivative. Melphalan 2mg; scored tabs. Indications: For the palliation of non-resectable epithelial ovarian cancer. Adults: 0.2mg/kg per day for 5 days; repeat course every 4–5 weeks. Continue treatment as hematological recovery permits (esp. WBCs and platelets); for other regimens: see literature. Children: Not recommended. Contraindications: Prior resistance to melphalan. Warnings/Precautions: Prior irradiation or chemotherapy. Bone marrow suppression. Azotemia. Monitor platelets, hemoglobin, WBC and differential at start of therapy and prior to each course; discontinue if WBC <3,000cells/ µL or platelets <100,000cells/µL. Moderate to severe renal impairment. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Radiotherapy potentiates antineoplastic effect. For IV: caution with cyclosporine, cisplatin, BCNU, nalidixic acid. Adverse reactions: Bone marrow suppression, GI upset, hepatic dysfunction, anemia, blood dyscrasias, secondary malignancies (eg, nonlymphocytic leukemia), rash, alopecia, pulmonary fibrosis, interstitial pneumonitis, gonadal toxicity (amenorrhea, infertility); hypersensitivity reactions, cardiac arrest (rare). How supplied: Tabs–50 Single-use vial–1 (w. diluent)

Bleomycin (various)

℞

Cytotoxic glycopeptide antibiotic. Bleomycin 15units/vial, 30units/vial; lyophilized pwd for IM, IV, SC, or intrapleural administration after reconstitution. Indications: Palliative treatment for squamous cell carcinoma (cervix, vulva). Adults: 0.25–0.5 units/kg IV, IM, or SC weekly or twice weekly. Renal impairment: see literature. Total doses >400 units: increased risk of pulmonary toxicity. Children: Not recommended. Warnings/Precautions: Renal impairment. Compromised pulmonary function. Monitor renal function. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: May be potentiated by nephrotoxic drugs. Adverse reactions: Erythema, rash, striae, vesiculation, hyperpigmentation, tenderness of the skin, hyperkeratosis, nail changes, alopecia, pruritus, stomatitis; pneumonitis, pulmonary fibrosis, idiosyncratic reaction (hypotension, mental confusion, fever, chills, wheezing). How supplied: Contact supplier.

Carboplatin (various) Platinum coordination complex. Carboplatin 10mg/mL; soln for IV infusion.

℞

Indications: Initial treatment of advanced ovarian cancer in combination with other chemotherapy. Secondary treatment of recurrent ovarian cancer after prior chemotherapy, including patients previously treated with cisplatin. Adults: See literature. Give by IV infusion over ≥15 minutes. Combination therapy with cyclophosphamide (previously untreated): 300mg/m2 on Day 1 every 4 weeks for 6 cycles. As a single agent for recurrent ovarian carcinoma: 360mg/m2 on Day 1 every 4 weeks. In either case the Calvert equation may be used (Total Dose [mg]=[target area under the curve (AUC)] × [glomerular filtration rate + 25]). Use Calvert equation for elderly patients. Adjust dose for renal insufficiency and blood counts (see literature). Children: Not recommended. Contraindications: Severe bone marrow suppression. Significant bleeding. Pregnancy (Cat.D). Nursing mothers. Warnings/Precautions: Dose-related bone marrow suppression. Elderly. Renal dysfunction. Monitor blood counts frequently; do not repeat dose until neutrophil count is >2,000 and platelets are >100,000. Anemia (transfusions may be needed). Premedicate with antiemetics; increasing infusion time or dividing total daily dose over 5 days may reduce emesis. Previous platinum-containing therapy. Loss of vision with higher than recommended doses. Interactions: Potentiates nephrotoxicity with other nephrotoxic drugs (eg, aminoglycosides). Caution with other myelosuppressives. Adverse reactions: Bone marrow suppression with possible infectious or hemorrhagic complications, anemia, vomiting, abdominal pain, anorexia, diarrhea, constipation, peripheral neuropathies, ototoxicity, visual disturbances, taste perversion, CNS symptoms, nephrotoxicity, hepatotoxicity, electrolyte changes, hypersensitivity reactions, injection site reactions, pain, asthenia, alopecia, malaise, hypertension; respiratory, genitourinary, mucosal, cardiovascular events; rare: hemolytic uremic syndrome. Note: Avoid contact with aluminum (eg, needles). How supplied: Contact supplier.

Cisplatin (various) Platinum coordination complex. Cisplatin 1mg/mL; soln for IV infusion after dilution. Indications: As a single agent, for secondary therapy of metastatic ovarian tumor. Adjunctive therapy for ovarian tumor. Adults: Give by IV infusion over 6–8 hours. 100mg/m2 IV per cycle once every 4 weeks; or, (when given with cyclophosphamide): 75–100mg/m2 IV per cycle once every 4 weeks. Usual max: 100mg/m2 per cycle. Subsequent cycles: give as tolerated, withhold dose if serum creatinine, BUN, platelets, WBCs, or auditory acuity out of normal limits; see literature. Children: Not recommended.

℞

Contraindications: Renal or hearing impairment. Myelosuppression. Pregnancy (Cat.D). Nursing mothers. Warnings/Precautions: Have epinephrine, antihistamine available. Monitor baseline and pretreatment renal function, electrolytes, auditory function; do periodic CBCs (weekly), liver function tests, neurologic exam. Hydrate patient before dosing. Avoid extravasation. Elderly. Interactions: Potentiates nephrotoxicity with other nephrotoxic drugs (eg, aminoglycosides). May antagonize anticonvulsants. May be antagonized by pyridoxine. Adverse reactions: Nephrotoxicity, neurotoxicity (eg, peripheral neuropathies), ototoxicity, myelosuppression, hemolytic anemia, marked nausea and vomiting, vascular toxicity (eg, MI, TIA), electrolyte disturbances, hyperuricemia, SIADH, hepatotoxicity, anaphylactic-like reactions, others; see literature. Note: Avoid contact with aluminum (eg, needles). How supplied: Contact supplier.

COSMEGEN Recordati

℞

Actinomycin antibiotic. Dactinomycin 500mcg/ vial; lyophilized pwd for IV inj or regional perfusion after reconstitution; contains mannitol; preservative-free. Indications: Gestational trophoblastic neoplasia. Adults: Give by IV infusion. 12mcg/kg daily for 5 days as a single agent; 500mcg on Days 1 and 2 as combination regimen with etoposide, methotrexate, folinic acid, vincristine, cyclophosphamide, and cisplatin. Max 15mcg/kg/day per 2-week cycle or 400–600mcg/m2/day for five days. Use surface area to calculate dose for obese or edematous patients. Children: See literature. Contraindications: Current or recent chickenpox or herpes zoster. Warnings/Precautions: Myelosuppression; monitor bone marrow and hold treatment if platelets or WBCs decrease markedly. Extremely corrosive; avoid extravasation. Avoid skin, mucous membranes, eyes. Previous irradiation (esp. within 2 months of irradiation for treatment of rightsided Wilms’ tumor), cytotoxic chemotherapy. Monitor renal and hepatic function. Obese. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Avoid live vaccines. Concomitant radiotherapy in Wilms’ tumor: not recommended. Adverse reactions: GI upset, stomatitis, bone marrow suppression (neutropenia, thrombocytopenia), liver toxicity, infusion site reactions, malaise, fatigue, alopecia, possible second primary tumors (including leukemia); for perfusion therapy: infection, impaired wound healing, superficial ulceration of gastric mucosa, edema, soft tissue damage, possible venous thrombosis. How supplied: Vials–1

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GYNECOLOGIC CANCER Cyclophosphamide (various)

℞

Alkylating agent. Cyclophosphamide 25mg, 50mg; tabs. Indications: Adenocarcinoma of the ovary. Adults: Initial and maintenance: 1–5mg/kg/day. Children: See literature. ℞ Also: CYTOXAN INJECTION Bristol-Myers Squibb Cyclophosphamide 500mg, 1g, 2g; per vial; pwd for inj after reconstitution; preservative-free. Adults: Initially 40–50mg/kg IV in divided doses over 2–5 days; or 10–15mg/kg IV every 7–10 days; or 3–5mg/kg IV twice weekly. Children: See literature. Contraindications: Severe bone marrow depression. Warnings/Precautions: Leukopenia. Thrombocytopenia. Tumor cell infiltration of bone marrow. Previous X-ray therapy or cytotoxic chemotherapy. Impaired renal or hepatic function. Infections. Adrenalectomy. General anesthesia within 10 days of therapy. Monitor hematologic profile (esp. neutrophils and platelets). Obtain urine sample (monitor for hemorrhagic cystitis); maintain adequate hydration. May interfere with wound healing. Elderly. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Potentiated by phenobarbital. Potentiates other myelosuppressives, radiotherapy, succinylcholine. May potentiate doxorubicin-induced cardiotoxicity. Adverse reactions: GI upset, alopecia, leukopenia, infections, thrombocytopenia, anemia, hemorrhagic cystitis (discontinue if occurs), renal tubular necrosis, interstitial pulmonary fibrosis, gonadal toxicity (amenorrhea, infertility), anaphylactic reactions. How supplied: Tabs–contact supplier Single-use vial–1

DOXIL Janssen Biotech

℞

Anthracycline. Doxorubicin HCl (liposomal) 2mg/mL; dispersion for IV infusion after dilution; preservative-free. Indications: Ovarian cancer refractory to platinum-based chemotherapy. Adults: Give by IV infusion at initial rate of 1mg/min; may increase rate to complete infusion over 1hr if no infusion reactions occur; may premedicate with antiemetics. 50mg/m2 once every 4 weeks; continue for at least 4 cycles as tolerated. Hepatic dysfunction (serum bilirubin ≥1.2mg/dL), hand-foot syndrome, hematologic toxicity (esp. ANC, platelets), or stomatitis: reduce dose. Consider total anthracycline and anthracenedione doses and irradiation when calculating total cumulative dose. See full labeling. Children: Not established. Warnings/Precautions: Not substitutable on a mg/mg basis with other doxorubicin products. Cardiotoxicity, acute infusion-related reactions, myelosuppression may occur. Have resuscitative/

antiallergic equipment and expertise available. Hepatic impairment. Monitor blood (esp. CBC + platelets), hepatic (esp. SGOT/SGPT, alkaline phosphatase), and cardiac function (esp. myocardial biopsy). Monitor periodically for secondary oral cancers with long-term use. Avoid extravasation. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Caution with cyclosporine, phenobarbital, phenytoin, streptozocin, digoxin, myelosuppressants, others. Previous mediastinal irradiation, cyclophosphamide, other cardiotoxic drugs: monitor for cardiotoxicity and hepatotoxicity. Adverse reactions: Asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand and foot syndrome, rash, neutropenia, thrombocytopenia, anemia; infusion reactions, cardiovascular events (eg, cardiomyopathy, CHF, acute LV failure), recall of skin reaction from prior radiation therapy, toxoplasmosis, urine discoloration (red/orange). How supplied: Single-use vials (10mL, 25mL)–1

Doxorubicin HCl (various)

℞

Anthracycline. Doxorubicin HCl 10mg/vial, 20mg/vial, 50mg/vial; pwd for IV inj after reconstitution; contains lactose. ℞ Also: Doxorubicin HCl Solution Doxorubicin HCl 2mg/mL; soln for IV inj. Indications: Disseminated neoplasias (eg, ovarian carcinoma). Adults and Children: Monotherapy: usually 60–75mg/m2 IV every 21 days. Combination therapy: usually 40–60mg/m2 IV every 21 to 28 days. Hyperbilirubinemia, inadequate bone marrow reserves: reduce dose. Contraindications: Severe myelosuppression (baseline neutrophils <1500cells/mm3) or severe hepatic impairment. Cardiac disease (eg, severe myocardial insufficiency, arrhythmias). Recent MI. Previous treatment with max cumulative doses of anthracyclines, anthracenediones. Warnings/Precautions: Pre-existing heart disease or risk thereof. Obtain baseline CBC, bilirubin, AST, creatinine, LVEF. Hepatic dysfunction. Monitor cardiac function (LVEF, ECG echocardiogram), hepatic function, CBC, uric acid levels. Avoid extravasation. Children (cardiotoxicity, impaired myocardial growth). Elderly. Pregnancy (Cat.D; use adequate contraception). Nursing mothers: not recommended. Interactions: See Contraindications. Mediastinal irradiation, cyclophosphamide, calcium channel blockers, other anthracyclines increase risk of cardiac toxicity; limit lifetime dose to 400mg/m2. Necrotizing colitis with cytarabine. May increase toxicity of cyclophosphamide, mercaptopurine. May reduce serum digoxin levels. Doxorubicin toxicity increased with high-dose IV progesterone, cyclosporine, streptozocin, and if given after paclitaxel infusion (give doxorubicin dose first). Elimination increased by phenobarbital. May decrease phenytoin levels. Recall pneumonitis with actinomycin and radiation in children.

Adverse reactions: Local necrosis if extravasation occurs, myocardial toxicity (immediate or delayed), arrhythmias, leukemia, myelosuppression, hyperuricemia, urine discoloration, alopecia, hyperpigmentation, severe GI upset/ulceration, phlebosclerosis, facial flushing, fever, urticaria, peripheral neuropathy, anaphylaxis. How supplied: Contact supplier.

GEMZAR Lilly

℞

Antimetabolite. Gemcitabine HCl 200mg, 1g; per vial; pwd for IV infusion after reconstitution; contains mannitol. Indications: Advanced ovarian cancer (in combination with carboplatin) that has relapsed at least 6 months after completion of platinumbased therapy. Adults: Infuse over 30 minutes (increased toxicity if infusion goes beyond 60 minutes). 1000mg/m2 on Days 1 and 8 of each 21 day cycle. Adjust dose based on toxicity (see literature). Children: Not recommended. Warnings/Precautions: Not for use in combination with radiation therapy. Discontinue immediately if severe lung toxicity, hemolytic uremic syndrome, or capillary leak syndrome occurs. Renal or hepatic impairment. Evaluate renal and hepatic function prior to therapy, then periodically thereafter. Discontinue if severe liver injury develops. Monitor for myelosuppression; obtain CBCs, platelets prior to each dose. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: See Warnings/Precautions. Concomitant radiation therapy: may cause severe radiation toxicity. Adverse reactions: Myelosuppression, nausea, vomiting, elevated transaminases, proteinuria, hematuria, rash, pruritus, dyspnea, edema, flulike symptoms, infection, alopecia, neurotoxicity, others; rare: renal or liver failure, hemolytic uremic syndrom, capillary leak syndrome. Testing considerations: ERCC1 overexpression for response and prognosis; RRM1 How supplied: Single-use vials–1

HEXALEN Eisai

℞

S-triazine derivative. Altretamine 50mg; caps. Indications: Palliative treatment of persistent or recurrent ovarian cancer following first-line therapy with a cisplatin and/or alkylating agentbased combination. Adults: 260mg/m2 daily in four divided doses (after meals and at bedtime), for either 14 or 21 consecutive days in a 28-day cycle. Discontinue for >14 days if GI intolerance is unresponsive to treatment, WBC count <2000/mm3 or granulocyte count <1000/mm3, platelet count <75000/mm3, or progressive neurotoxicity occurs. Restart at 200mg/m2 daily. Discontinue indefinitely if neurologic symptoms fail to stabilize. Children: Not recommended.

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GYNECOLOGIC CANCER Contraindications: Severe myelosuppression or neurologic toxicity, except cisplatin-related neuropathy. Warnings/Precautions: Monitor for myelosuppression (do monthly CBCs) and neurotoxicity. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Avoid pyridoxine. Severe orthostatic hypotension with MAOIs. Adverse reactions: Nausea, vomiting, peripheral neuropathy, CNS symptoms (eg, mood disorders, ataxia, dizziness), myelosuppression, renal dysfunction, increased alkaline phosphatase. How supplied: Caps–100

HYCAMTIN GlaxoSmithKline

℞

Topoisomerase inhibitor. Topotecan (as HCl) 4mg/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol; preservative-free. Indications: Metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy. Stage IV-B, recurrent or persistent carcinoma of the cervix in combination with cisplatin. Adults: Confirm baseline neutrophils >1,500cells/mm3 and platelets >100,000cells/mm3 prior to 1st course of therapy. Give by IV infusion over 30 minutes. Ovarian cancer: 1.5mg/m2 daily for 5 consecutive days starting on Day 1 of a 21-day cycle. Cervical cancer: 0.75mg/m2 on Days 1, 2, and 3; followed by cisplatin. Dose adjustments, renal impairment: see literature. Children: Not recommended. Contraindications: Severe bone marrow depression. Pregnancy (Cat.D). Nursing mothers. Warnings/Precautions: Monitor peripheral blood cell counts during therapy; hold subsequent doses until neutrophils >1,000cells/mm3, platelets >100,000cells/mm3, and hemoglobin ≥9g/dL. History of interstitial lung disease, pulmonary fibrosis, lung cancer, thoracic exposure to radiation, use of pneumotoxic drugs and/or colony stimulating factors: increased risk of interstitial lung disease; monitor, discontinue if occurs. Moderate to severe renal impairment. Avoid extravasation. Elderly. Interactions: Myelosuppression potentiated with platinum agents. Neutropenia potentiated by G-CSF. Adverse reactions: See literature. Neutropenia, leukopenia, thrombocytopenia, anemia, GI upset, anorexia, abdominal pain, stomatitis, headache, dyspnea, cough, pyrexia, alopecia, fatigue; infection, sepsis, interstitial lung disease, neutropenic colitis (may be fatal). How supplied: Single-use vials–1, 5

HYDREA Bristol-Myers Squibb

℞

Substituted urea. Hydroxyurea 500mg; caps. Indications: Recurrent metastatic or inoperable ovarian carcinoma. Adults: See literature. Intermittant therapy for solid tumors: 80mg/kg as single dose every 3rd day. Continuous therapy for solid tumors: 20–30mg/kg/day as single dose. Renal impairment: reduce dose. Children: Not recommended. Contraindications: Marked bone marrow depression. Warnings/Precautions: Previous irradiation therapy or chemotherapy. Correct anemia before starting. Monitor hematologic, renal, hepatic function before and during treatment. Marked renal dysfunction. Myeloproliferative disorders; discontinue if cutaneous vasculitic ulcerations develop and use alternative agents. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [monitor], fatal hepatotoxicity, peripheral neuropathy). Myelosuppressives potentiate antineoplastic effect. May antagonize antigout agents. Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated urease, uricase, lactate dehydrogenase. Adverse reactions: Leukopenia, anemia, erythrocytic abnormalities, thrombocytopenia, GI upset, rash, erythema, fever, CNS effects, temporary renal impairment, acute pulmonary reactions, secondary leukemias, skin cancer. Note: Wear disposable gloves when handling caps or bottle. How supplied: Caps–100

Megestrol acetate (various)

℞

Progestin. Megestrol acetate 20mg, 40mg; scored tabs. Indications: Palliative treatment of advanced endometrial carcinoma. Adults: 40–320mg daily in divided doses. Children: Not applicable. Warnings/Precautions: History of thromboembolic disease. Diabetes. Monitor for adrenal insufficiency. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May increase insulin requirements. Decreases indinavir levels. Adverse reactions: Weight gain, thromboembolic events, heart failure, GI upset, edema, breakthrough menstrual bleeding, dyspnea, tumor flare, hyperglycemia, alopecia, hypertension, carpal tunnel syndrome, mood

changes, hot flashes, malaise, asthenia, lethargy, sweating, rash. How supplied: Contact supplier.

TAXOL Bristol-Myers Squibb

℞

Antimicrotubule agent. Paclitaxel 6mg/mL; soln for IV infusion after dilution; contains Cremophor EL (polyoxyethylated castor oil), dehydrated alcohol. Indications: First-line therapy (in combination with cisplatin) and subsequent therapy for advanced carcinoma of the ovary. Adults: See literature. Premedicate with corticosteroids, diphenhydramine, H2 antagonists. Previously untreated ovarian cancer: 175mg/m2 IV over 3 hours + cisplatin every 3 weeks; or 135mg/m2 IV over 24 hours + cisplatin every 3 weeks. Previously treated ovarian cancer: 135mg/m2 or 175mg/m2 IV over 3 hours every 3 weeks. Hepatic impairment or neutropenia: see literature for dose modifications. Do not treat if neutrophil count <1,500cells/mm3 or platelets <100,000cells/mm3. Children: Not recommended. Contraindications: Baseline neutrophil count <1,500cells/mm3. Warnings/Precautions: Do frequent peripheral blood cell counts. Hepatic dysfunction. Conduction abnormalities: monitor cardiac function. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: May potentiate or be potentiated by CYP2C8 or CYP3A4 substrates, inducers and/or inhibitors. Potentiated by cisplatin. May potentiate doxorubicin. Adverse reactions: Bone marrow suppression (eg, neutropenia, leukopenia, thrombocytopenia, anemia), inj site reactions, infections, hypotension, bradycardia, hypersensitivity reactions (if severe, do not rechallenge), peripheral neuropathy, myalgia, arthralgia, GI upset, mucositis, alopecia, abnormal ECG, elevated liver enzymes. How supplied: Multidose vial (5mL, 16.7mL, 50mL)–1

Thiotepa (various)

℞

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GYNECOLOGIC CANCER Contraindications: Renal, hepatic, or bone marrow dysfunction; if need outweighs risk, may be used in low dosage with close monitoring. Warnings/Precautions: Bone marrow suppression; monitor blood and platelets weekly during and for at least 3 weeks after therapy. Discontinue if WBC ≤3000/mm3 or platelets ≤150,000/mm3. Monitor renal and hepatic function. Use effective contraception if patient or partner is of childbearing potential. Elderly. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Increased toxicity with concomitant or sequential alkylating agents (nitrogen mustards, cyclophosphamide), radiation, myelosuppressants. Prolonged apnea with succinylcholine. Adverse reactions: Myelosuppression, fatigue, febrile or allergic reactions, inj site reactions, urinary retention, dysuria, GI disturbances, anorexia, alopecia, dizziness, headache, drowsiness, blurred vision, amenorrhea, interferes with spermatogenesis. Intravesical administration: rare: chemical or hemorrhagic cystitis. How supplied: Contact supplier.

TREXALL Teva

℞

ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity. Diabetes. Peptic ulcer. Ulcerative colitis. Infection. Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated. Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, non-absorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin). Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome). How supplied: Tabs–30 Soln (2mL, 4mL, 8mL, 10mL)–10 (single-use vials) Pwd (1 gram)–1 (single-use vial)

Vinblastine for injection

℞

Bedford

Contraindications: Significant granulocytopenia (unless result of disease being treated). Bacterial infections (treat first). Warnings/Precautions: For IV use only; fatal if given intrathecally. Hepatic impairment. Avoid in elderly with cachexia or ulcerated skin; or in patients with malignant-cell infiltration of the bone marrow. Pre-existing pulmonary dysfunction. Progressive dyspnea requiring chronic therapy (do not re-administer). Ischemic cardiac disease. Bone marrow suppression; monitor WBC before and during treatment. Avoid contamination of the eyes or injecting into an extremity with poor circulation (thrombosis possible). Avoid extravasation. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May be potentiated by CYP3A inhibitors (eg, erythromycin). Antagonizes phenytoin. Adverse reactions: Leukopenia, alopecia, GI upset, paresthesias, malaise, pain; dyspnea, severe bronchospasm. How supplied: Pwd–10 Soln–1

BRAND NAME The main name under which the product and all other dosage forms in the monograph are marketed.

LEGAL CATEGORY Federal schedule. The laws governing the prescribing/dispensing of products vary from state to state.

PHARMACOLOGIC CLASS The chemical/therapeutic class of the drug is listed in italics.

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HEAD AND NECK CANCER Head And Neck Cancer Treatment Regimens (Part 1 Of 3) Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Squamous Cell Cancers*

Primary Systemic Therapy + Concurrent Radiotherapy1 REGIMEN

DOSING

Cisplatin (preferred)2,3

Days 1, 22 and 43: Cisplatin 100mg/m2 IV + concurrent radiotherapy 2Gy/day to a total of 70Gy.

Cetuximab4

Day 1: Cetuximab 400mg/m2 loading dose over 2 hours, 1 week before radiotherapy, plus Day 7: Begin radiotherapy with 7 weekly infusions of cetuximab 250mg/m2.

Carboplatin + infusional 5-FU5,6

Days 1–4: 5-FU 600mg/m2/day as continuous IV infusion + carboplatin 70mg/m2/day IV bolus. Repeat every 3 weeks for 3 cycles (given concurrently with radiotherapy).

5-FU + hydroxyurea7

Day 1: Hydroxyurea 1,000mg PO every 12 hours (11 doses/cycle) and 5-FU 400mg/m2/day continuous IV infusion, plus radiotherapy: 70Gy, delivered in 35 fractions; 1 fraction delivered daily Monday–Friday. Concurrent radiotherapy and chemotherapy every other week for total treatment duration of 13 weeks.

Cisplatin + paclitaxel7

Day 1: Paclitaxel 30mg/m2 IV (begin on Monday), plus Day 2: Cisplatin 20mg/m2 IV (every Tuesday). Repeat cycle every week for 7 cycles, plus radiotherapy: 70Gy, delivered in 35 fractions; 1 fraction delivered daily Monday–Friday.

Cisplatin + infusional 5-FU8

Day 1: Cisplatin 60mg/m2 over 15 minutes; plus Days 1–5: 5-FU 800mg/m2 by continuous infusion; plus Days 1–5: Radiotherapy: 2Gy repeated every other week for 7 cycles.

Carboplatin/paclitaxel9

Day 1: Paclitaxel 40–45mg/m2/week and carboplatin 100mg/m2/week; prior to radiotherapy: 70.2Gy at 1.8Gy/fraction/day for 5 days/week.

Weekly cisplatin10,11

Day 1–28: Cisplatin 40mg/mg2 IV over 30 minutes weekly; plus Days 1–38: Radiotherapy (5 fractions/week): 1.8Gy single dose (up to total dose of 50.4Gy); plus Days 22–38: Boost radiotherapy: 1.5Gy/day (up to 19.5Gy) in addition to regular dose. Booster doses to be given at least 6-hours after regular dose (total tumor dose of 69.9Gy.) Or Day 1–28: Cisplatin 40mg/mg2 IV weekly; plus Days 1–40: Radiotherapy: five fractions of 1.8Gy/week (up to total dose of 54Gy); plus Days 25–40: Boost radiotherapy: 1.5Gy/day (up to 19.5Gy) in addition to regular dose. Booster doses to be given at least 6-hours after regular dose.

Primary Chemotherapy With Postoperative Chemoradiation1 Cisplatin12–15

Days 1, 22 and 43: Cisplatin 100mg/m2 IV + radiotherapy.

Induction Chemotherapy†/Sequential chemotherapy1‡ Docetaxel + cisplatin + 5-FU16-18

Day 1: Docetaxel 75mg/m2 IV + cisplatin 75mg/m2 IV, plus Days 1–5: 5-FU 750mg/m2 continuous IV infusion. Repeat every 3 weeks for 4 cycles.

Paclitaxel + cisplatin+ infusional 5-FU19

Day 1: Paclitaxel 175mg/m2 over 3 hours Day 2: Cisplatin 100mg/m2; plus Day 2–6: 5-FU 500mg/m2 continuous infusion Repeat every 3 weeks for 3 cycles.§ continued

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HEAD AND NECK CANCER Head And Neck Cancer Treatment Regimens Nasopharynx Cancer

Chemoradiation Followed by Adjuvant Chemotherapy1 REGIMEN

DOSING

Cisplatin + radiotherapy + cisplatin + 5-FU20-22

Cycles 1–3 Day 1: Cisplatin 100mg/m2 IV; plus radiotherapy. Repeat cycle every 3 weeks; followed by Cycles 4–6 Days 1–4: Cisplatin 80mg/m2/day + 5-FU 1,000mg/m2/day IV over 96 hours. Repeat cycle every 4 weeks for 3 cycles.

Carboplatin + radiotherapy + carboplatin + 5-FU23

Cycles 1–3 Day 1: Carboplatin AUC 6 IV; plus radiotherapy: 200cGy/fraction w/ five daily fractions/week (to a total dose of 6600–7000cGy). Repeat every 3 weeks for 3 cycles; followed by Cycles 4–6 Days 1–4: Carboplatin AUC 5 IV + 5-FU 1,000mg/m2/day IV over 96 hours. Repeat cycle every 3 weeks.

Induction Chemotherapy†/Sequential Chemotherapy1|| Docetaxel + cisplatin + 5-FU24

Day 1: Docetaxel 70mg/m2 IV over 1 hour and cisplatin 75mg/m2 IV over 3 hours; followed by Days 1–4: 5-FU 1,000mg/m2 IV over 96 hours. Repeat every week for 3 cycles; followed by Cisplatinw 100mg/m2; plus radiotherapy: 5 daily fractions of 1.8 or 2Gy/day (total dose of 68.4Gy) Repeat every 3 weeks.

Cisplatin + 5-FU17,25

Day 1: Cisplatin 100mg/m2/day IV. Days 1–4: 5-FU 1,000mg/m2/day continuous IV infusion. Repeat cycle every 3 weeks for a minimum of 6 cycles.

Cisplatin + epirubicin + paclitaxel

This regimen was included in the NCCN guidelines but no reference was provided to indicate appropriate dosage.

Principles of Systemic Therapy • The choice of chemotherapy should be individualized based on patient characteristics (performance status, goals of therapy). • Unless otherwise specified, regimens listed below can be used for either nasopharyngeal or non-nasopharyngeal cancer. 1

Combination Therapy for Recurrent, Unresectable, or Metastatic Disease (incurable)1 Cisplatin or carboplatin + 5-FU + cetuximab26 (non-nasopharyngeal)

Day 1: Cisplatin 100mg/m2 IV or carboplatin AUC=5mg/mL/min 1 hour IV infusion, plus Day 1: Cetuximab 400mg/m2 IV over 2 hours (initial dose), followed by 250mg/m2 IV over 1 hour once weekly. Days 1–4: 5-FU 1,000mg/m2/day. Repeat cycle every 3 weeks for a maximum of 6 cycles.

Carboplatin + docetaxel27

Day 1: Docetaxel 65mg/m2 IV over 1 hour; followed immediately by carboplatin AUC=6 IV. Repeat cycle every 3 weeks.

Cisplatin + paclitaxel25

Day 1: Cisplatin 75mg/m2/day IV + paclitaxel 175mg/m2 IV over 3 hours. Repeat cycle every 3 weeks for a minimum of 6 cycles.

Cisplatin + cetuximab28 (for non-nasopharyngeal disease)

Day 1: Cetuximab 400mg/m2 IV for one cycle, then cetuximab 250mg/m2 IV for subsequent cycles. Repeat once weekly, plus Day 1: Cisplatin 100mg/m2 IV. Repeat every 4 weeks

Cisplatin + 5-FU25,29

Day 1: Cisplatin 100mg/m2/day IV. Days 1–4: 5-FU 1,000mg/m2/day continuous IV infusion. Repeat cycle every 3 weeks for a minimum of 6 cycles.

Carboplatin + cetuximab30

Day 1: Cetuximab initial dose of 400mg/m2 IV over 2 hours; followed by weekly doses of cetuximab 250mg/m2 IV over 1 hour; followed by carboplatin AUC=5 IV. Repeat every 3 weeks for a maximum of 8 cycles.

Gemcitabine + vinorelbine31

Day 1 and 8: Vinorelbine 25mg/m2 IV; followed by gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat every 3 weeks.

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HEAD AND NECK CANCER REGIMEN

DOSING

Single Agents for Recurrent, Unresectable, or Metastatic Disease (incurable)1 Cisplatin28,32

Day 1: Cisplatin 100mg/m2 IV over 15–20 minutes. Repeat every 3–4 weeks.

Carboplatin33

Day 1: 25mg/m2 daily followed by radiotherapy: 5 daily fractions of 1.8 or 2Gy.

Paclitaxel34

Day 1: Paclitaxel 80mg/m2 IV over 1 hour. Repeat every 6 weeks.

Docetaxel35,36

Day 1: Docetaxel 40–100mg/m2 IV over 1 hour. Repeat every 3 weeks.

5-FU32

Days 1–4: 5-FU 1,000mg/m2 IV over 24 hours. Repeat every 3 weeks.

Methotrexate29,37

Day 1: Methotrexate 40mg/m2 IV weekly.

Cetuximab38 (non-nasopharyngeal)

Day 1: Cetuximab 400mg/m2 over 2 hours as a loading dose (including a 20mg test dose); followed by cetuximab 250mg/m2 IV over 1 hour weekly. Repeat at least every 6 weeks.

Ifosfamide39

Days 1–3: Ifosfamide 3g/m2 IV daily; plus mesna 600mg/m2 PO daily. Repeat every 3 weeks.

Bleomycin40,41

Days 1–21: Bleomycin 10mg IV bolus twice weekly on Tuesday and Thursday (60mg/six fractions); followed by radiotherapy: 25Gy split into two courses, with each course given in 10 fractions over 2 weeks, with a 2 week split (total dose of 50Gy/20 fractions). OR Days 1–35: Bleomycin 15mg IM twice a week (total dose 150mg); followed by radiotherapy: 70Gy

Gemcitabine42 (nasopharyngeal)

Days 1, 8, 15: Gemcitabine 1,000mg/m2 IV over 30 minutes. Repeat every 4 weeks.

Capecitabine43

Days 1–14: Capecitabine 1,250mg/m2 PO; followed by a 1-week rest period. Repeat every 3 weeks for at least two cycles.

Vinorelbine44,45 (non-nasopharyngeal)

Day 1: Vinorelbine 30mg/m2/week IV (over a short duration, on an out-patient basis)

* † ‡ §

Includes lip, oral cavity, oropharynx, hypopharynx, glottic larynx, supraglottic larynx, ethmoid sinus, maxillary sinus, occult primary. Induction chemotherapy should only be done in a tertiary setting. Following induction, agents to be used with concurrent chemoradiation typically include weekly carboplatin or cetuximab.46-48 Patients with complete partial response of greater than 80% in primary tumor received additional chemoradiation therapy (i.e., cisplatin 100mg/m2 on days 1, 22, and 43 plus 70Gy). Radiotherapy was administered in 35 fractions of 2Gy each over a 7-week period. || Following induction, agents to be used with concurrent chemoradiation typically include weekly cisplatin21 or carboplatin.46

References 1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™. Bladder Cancer. v 1.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf. Accessed April 10, 2014. 2. Adelstein DJ, Li Y, Adams GL, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol. 2003; 21(1):92–98. 3. Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91–11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013;31:845–852. 4. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomized trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11:21–28. 5. Denis F, Garaud P, Bardet E, et al. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 2004;22:69–76.

6. Bourhis J, Sire C, Graff P, et al. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol. 2012;13:145–153. 7. Garden AS, Harris J, Vokes EE, et al. Preliminary results of Radiation Therapy Oncology Group 97-03: A randomized phase II trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004;22(14):2856–2864. 8. Taylor 5, Murthy A, Vannetzel J, et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994;12:385–395. 9. Suntharalingam M, Haas ML, Conley BA, et al. The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys. 2000;47:49–56. 10. Beckmann GK, Hoppe F, Pfreundner L, et al. Hyperfractionated accelerated radiotherapy in combination with weekly cisplatin for locally advanced head and neck cancer. Head Neck. 2005;27:36–43.

continued

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MASTER CANCER TREATMENT REGIMEN

HEAD AND NECK CANCER Head And Neck Cancer Treatment Regimens References (continued) 11. Medina JA, Rueda A, de Pasos AS, et al. A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas. Radiother Oncol. 2006;79:34–38. 12. Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N EngI J Med. 2004; 350:1937–1944. 13. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N EngI J Med. 2004;350: 1945–1952. 14. Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005;27:843–850. 15. Bachaud JM, Cohen-Jonathan E, Alzieu C, et al. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys. 1996 Dec 1; 36:999–1004. 16. Vermorken JB, Remenar E, van Herpen C, et al; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N EngI J Med. 2007;357(17):1695–1704. 17. Posner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N EngI J Med. 2007;357(17):1705–1715. 18. Pointreau Y, Garaud P, Chapet 5, et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J NatI Cancer Inst. 2009;101:498–506. 19. Hiff R, LOpez-Pousa A, Martinez-Trufero J, et al. Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol. 2005;23:8636–8645. 20. Al-Sarraf M, LeBlanc M, Gin PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasophanyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 1998;16:1310–1317. 21. Chan AT, Leung SF, Ngan RK, et al. Overall survival after concurrent cisplatinradiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J NatI Cancer Inst. 2005;97:536–539. 22. Lee AW, Tung SY, Chua DT, et al. Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2010;102:1188–1198. 23. Dechaphunkul T, Pruegsanusak K, Sangthawan D, et al. Concurrent chemoradiotherapy with carboplatin followed by carboplatin and 5- fluorouracil in locally advanced nasopharyngeal carcinoma. Head Neck Oncol. 2011;3:30. 24. Bae WK, Hwang JE, Shim HJ, et al. Phase II study of docetaxel, cisplatin, and 5-FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced nasopharyngeal cancer. Cancer Chemother Pharmacol. 2010;65(3):589–595. 25. Gibson MK, Li Y, Murphy B, Hussain MH, DeConti RC, Ensley J, Forastiere AA; Eastern Cooperative Oncology Group. Random- ized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2005; 23:3562–3567. 26. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–1127. 27. Samlowski WE, Moon J, Kuebler JP, et al. Evaluation of the combination of docetaxel/carboplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN): a Southwest Oncology Group Phase II study. Cancer Invest. 2007;25:182–188. 28. Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; Eastern Cooperative Oncology Group. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer:an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005;23(34):8646–8654. 29. Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus flurouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous cell carcinoma of the head and neck: A Southwest Oncology Group Study. J Clin Oncol. 1992;10:1245–1251.

30. Chan AT, Hsu MM, Goh BC, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol. 2005;23:3568–3576. 31. Chen C, Wang FH, Wang ZQ, et al. Salvage gemcitabine-vinorelbine chemotherapy in patients with metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Oral Oncol. 2012;48:1146–1151. 32. Jacobs C, Lyman G, Velez-GarcIa E, et al. A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol. 1992; 1O:257–263. 33. Jeremic B1, Shibamoto Y, Stanisavljevic B, et al. Radiation therapy alone or with concurrent low-dose daily either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck: a prospective randomized trial. Radiother Oncol. 1997 Apr;43(1):29–37. 34. Grau JJ, Caballero M, Verger E, et al. Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients. Acta Otolaryngol. 2009;129:1294–1299. 35. Catimel G, Verweij J, Mattijssen V, et al. Docetaxel (Taxotere): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. Ann Oncol. 1994;5:533–537. 36. Guardiola E, Peyrade F, Chaigneau L, et al. Results of a randomised phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer. Eur J Cancer. 2004;40:2071–2076. 37. Stewart JS, Cohen EE, Licitra L, et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected]. J Clin Oncol. 2009:27:1864–1 871. 38. Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007;25:2171–2177. 39. Martin M, Diaz-Rubio E, Gonzalez Larriba JL, et al. Ifosfamide in advanced epidermoid head and neck cancer. Cancer Chemother Pharmacol. 1993;31:340–342 40. Eschwege F, Sancho-Gamier H, Gerard JP, et al. Ten-year results of randomized trial comparing radiotherapy and concomitant bleomycin to radiotherapy alone in epidermoid carcinomas of the oropharynx: experience of the European Organization for Research and Treatment of Cancer. NCI Monogr. 1988;(6):275–278. 41. Minatel E, Gigante M, Franchin G, et al. Combined radiotherapy and bleomycin in patients with inoperable head and neck cancer with unfavourable prognostic factors and severe symptoms. Oral Oncol. 1998;34:119–122. 42. Zhang L, Zhang Y, Huang PY, et al. Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy. Cancer Chemother Pharmacol. 2008; 61:33–38. Epub 2007 Mar 20. 43. Martinez-Trufero J, Isla D, Adansa JC, et al. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment. Br J Cancer. 2010; 102:1687–1691. 44. Degardin M, Oliveira J, Geoffrois L, et al. An EORTC-ECSG phase II study of vinorelbine in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol. 1998;9:1103–1107. 45. Saxman 5, Mann B, Canfield V, et al. A phase II trial of vinorelbine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Am J Clin Oncol. 1998;21: 398–400. 46. Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, et al. Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: Randomised, non-inferiority, open trial. Eur J Cancer. 2007;43:1399–1406. 47. Haddad R, O’Neill A, Rabinowits G, et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013;14:257–264. 48. Lefebvre JL, Pointreau Y, Rolland F, et al. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol. 2013;31:853–859. (Revised 6/2014) © 2014 Haymarket Media, Inc.

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HEAD AND NECK CANCER Bleomycin (various)

℞

Cytotoxic glycopeptide antibiotic. Bleomycin 15units/vial, 30units/vial; lyophilized pwd for IM, IV, SC, or intrapleural administration after reconstitution. Indications: Palliative treatment for squamous cell carcinoma (head and neck). Adults: 0.25–0.5 units/kg IV, IM, or SC weekly or twice weekly. Renal impairment: see literature. Total doses >400 units: increased risk of pulmonary toxicity. Children: Not recommended. Warnings/Precautions: Renal impairment. Compromised pulmonary function. Monitor renal function. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: May be potentiated by nephrotoxic drugs. Adverse reactions: Erythema, rash, striae, vesiculation, hyperpigmentation, tenderness of the skin, hyperkeratosis, nail changes, alopecia, pruritus, stomatitis; pneumonitis, pulmonary fibrosis, idiosyncratic reaction (hypotension, mental confusion, fever, chills, wheezing). How supplied: Contact supplier.

ERBITUX Bristol-Myers Squibb

℞

Epidermal growth factor receptor blocker. Cetuximab 100mg/vial, 200mg/vial; soln for IV infusion; preservative-free. Indications: In combination with radiation therapy for treating locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN). In combination with platinum-based therapy with 5-fluorouracil (5-FU) for first-line treatment of recurrent locoregional disease or metastatic SCCHN. As a single agent for recurrent or metastatic SCCHN after failure of prior platinum-based therapy. Adults: Pretreat with H1 blocker. Give by IV infusion (use filter); max rate: 10mg/min. Initial dose: 400mg/m2 once over 2 hours; then 250mg/m2 once weekly over 1 hour. Combination therapy: Give initial dose 1 week prior to initiation of radiation therapy. Complete administration 1 hour prior to platinum-based therapy with 5-FU. Give subsequent weekly dose for duration of radiation therapy (6–7 weeks) or until disease progression or unacceptable toxicity. Permanently reduce infusion rate by 50% if Grade 1 or 2 and non-serious Grade 3 infusion reaction occurs; permanently discontinue if Grade 3 or 4 serious reaction occurs. Monitor patient during and for 1 hr post-infusion. Skin toxicity: see full labeling. Children: Not recommended. Warnings/Precautions: Discontinue if severe infusion reactions or interstitial lung disease occur. Monitor for infusion reactions, cardiopulmonary arrest, pulmonary toxicity, skin inflammation/infection; avoid sun, UV light. Additive cutaneous reactions with irradiation. Cardiovascular diseases (w. irradiation or

platinum-based therapy with 5-FU). Monitor electrolytes (eg, magnesium, potassium, calcium) during and after cetuximab therapy. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Increased mucositis (Grade 3–4), radiation recall syndrome, acneiform rash, cardiac events, and electrolyte disturbances with radiation and cisplatin. Adverse reactions: Cutaneous reactions (pruritus, nail changes), acneform rash, headache, diarrhea, infection, asthenia, mucositis, weight loss, xerostomia, dehydration, electrolyte abnormalities; infusion reactions (may be severe: eg, bronchospasm, dyspnea), interstitial lung disease, cardiopulmonary arrest, hypomagnesemia, fever, sepsis, kidney failure, pulmonary embolus; others (see full labeling). How supplied: Single-use vials–1

HYDREA Bristol-Myers Squibb

℞

Substituted urea. Hydroxyurea 500mg; caps. Indications: Adjunct with irradiation therapy in primary squamous cell (epidermoid) carcinomas of the head and neck, excluding the lip. Adults: See literature. 80mg/kg as single dose every 3rd day. Renal impairment: reduce dose. Children: Not recommended. Contraindications: Marked bone marrow depression. Warnings/Precautions: Previous irradiation therapy or chemotherapy. Correct anemia before starting. Monitor hematologic, renal, hepatic function before and during treatment. Marked renal dysfunction. Myeloproliferative disorders; discontinue if cutaneous vasculitic ulcerations develop and use alternative agents. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [monitor], fatal hepatotoxicity, peripheral neuropathy). Myelosuppressives potentiate antineoplastic effect. May antagonize antigout agents. Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated urease, uricase, lactate dehydrogenase. Adverse reactions: Leukopenia, anemia, erythrocytic abnormalities, thrombocytopenia, GI upset, rash, erythema, fever, CNS effects, temporary renal impairment, acute pulmonary reactions, secondary leukemias, skin cancer. Note: Wear disposable gloves when handling caps or bottle. How supplied: Caps–100

TAXOTERE Sanofi Aventis

℞

advanced squamous cell carcinoma of the head and neck. Adults: Give by IV infusion over 1hr once every 3 weeks. 75mg/m2. Premedicate with oral corticosteroid. Adjust dose based on tolerability and effect (see full labeling); allow neutrophils and platelets to recover before subsequent cycles. Children: Not established. Contraindications: Neutrophil count <1500 cells/mm3. Hypersensitivity to polysorbate 80. Warnings/Precautions: Hepatic dysfunction; bilirubin >ULN, SGOT and/or SGPT >1.5×ULN concomitant with alkaline phosphatase >2.5×ULN: not recommended. Obtain bilirubin, AST/ALT, and alkaline phosphatase values prior to each cycle. Monitor peripheral blood counts frequently (esp. neutrophils, platelets). Monitor for hypersensitivity reactions (esp. during 1st and 2nd infusions). Pre-existing effusions. Adjust dose if severe neurosensory symptoms (eg, paresthesia, dysesthesia, pain) occur; discontinue if symptoms persist. Monitor for eye disorders; discontinue if cystoid macular edema is diagnosed (consider alternative non-taxane chemotherapy). Elderly. Pregnancy (Cat.D; use adequate contraception); nursing mothers: not recommended. Interactions: May affect, or be affected by, other CYP3A4 inhibitors, inducers, or substrates (eg, ketoconazole, ritonavir). Adverse reactions: Infections, neutropenia, anemia, febrile neutropenia, hypersensitivity/ infusion site reactions, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, myalgia; cutaneous reactions (eg, erythema, edema, desquamation), acute myeloid leukemia, death (septic and nonseptic), cystoid macular edema. How supplied: Single-dose vials (1mL, 4mL, 8mL)–1 (w. diluent, supplies)

TREXALL Teva

℞

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HEAD AND NECK CANCER and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration). Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity. Diabetes. Peptic ulcer.

Ulcerative colitis. Infection. Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated. Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, non-absorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy.

Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin). Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome). How supplied: Tabs–30 Soln (2mL, 4mL, 8mL, 10mL)–10 (single-use vials) Pwd (1 gram)–1 (single-use vial)

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HEMATOLOGIC CANCER ADCETRIS Seattle Genetics

℞

CD30-directed antibody-drug conjugate. Brentuximab vedotin 50mg/vial; pwd for IV infusion after reconstitution; preservative-free. Indications: Treatment of Hodgkin lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates. Treatment of systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multiagent chemotherapy regimen. Adults: Give by IV infusion over 30 minutes. 1.8mg/kg every 3 weeks (if >100kg, calculate dose based on wt. of 100kg); continue until a max of 16 cycles, disease progression or unacceptable toxicity. Peripheral neuropathy: if Grade 2/3: withhold until resolve to ≤Grade 1, then restart with 1.2mg/kg; if Grade 4: discontinue therapy. Neutropenia: Grade 3/4: withhold until resolve to ≤Grade 2; may consider growth factor support; recurrent Grade 4: discontinue or consider reducing dose to 1.2mg/kg. Children: Not established. Contraindications: Concomitant bleomycin. Warnings/Precautions: Risk of JC virus infection. Monitor for progressive multifocal leukoencephalopathy (PML); withhold dose if suspected and discontinue if confirmed. Monitor for neuropathy and delay, change, or discontinue dose accordingly. Monitor for infusion-related reactions; permanently discontinue and treat if anaphylaxis occurs. Monitor CBCs prior to each dose and frequently for Grade 3 or 4 neutropenia; if develops, delay, reduce or discontinue dose. Increased risk of tumor lysis syndrome in rapidly proliferating tumor/high tumor burden patients; monitor closely. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: See Contraindications. Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole); monitor. Antagonized by potent CYP3A4 inducers (eg, rifampin). Adverse reactions: Neutropenia, peripheral sensory neuropathy, fatigue, GI upset, anemia, upper respiratory tract infection, pyrexia, rash, thrombocytopenia, cough; infusion reactions, Stevens-Johnson syndrome (discontinue if occurs), PML (may be fatal). How supplied: Single-use vial–1

ALKERAN GlaxoSmithKline

℞

Nitrogen mustard derivative. Melphalan 2mg; scored tabs. Indications: Palliative treatment for multiple myeloma. Adults: 6mg once daily for 2–3 weeks; stop for up to 4 weeks, maintenance 2mg per day.

Continue treatment as hematological recovery permits (esp. WBCs and platelets); for other regimens: see literature. Children: Not recommended. ℞ Also: ALKERAN FOR INJECTION Melphalan HCl 50mg/vial; pwd for IV infusion after reconstitution and dilution. Indications: Palliative treatment of multiple myeloma when oral therapy is not appropriate. Adults: Give by IV infusion over 15–20 minutes. 16mg/m2 every 2 weeks for a total of 4 doses, then at 4-week intervals. Continue treatment as hematological recovery permits. Renal insufficiency (BUN≥30mg/dL): consider reducing dose by 50%. Children: Not recommended. Contraindications: Prior resistance to melphalan. Warnings/Precautions: Prior irradiation or chemotherapy. Bone marrow suppression. Azotemia. Monitor platelets, hemoglobin, WBC and differential at start of therapy and prior to each course; discontinue if WBC <3,000cells/ µL or platelets <100,000cells/µL. Moderate to severe renal impairment. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Radiotherapy potentiates antineoplastic effect. For IV: caution with cyclosporine, cisplatin, BCNU, nalidixic acid. Adverse reactions: Bone marrow suppression, GI upset, hepatic dysfunction, anemia, blood dyscrasias, secondary malignancies (eg, nonlymphocytic leukemia), rash, alopecia, pulmonary fibrosis, interstitial pneumonitis, gonadal toxicity (amenorrhea, infertility); hypersensitivity reactions, cardiac arrest (rare). How supplied: Tabs–50 Single-use vial–1 (w. diluent)

ARRANON GlaxoSmithKline

℞

Nucleoside analogue. Nelarabine 250mg/vial; soln for IV infusion. Indications: T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) that is unresponsive or has relapsed after ≥2 chemotherapy regimens. Adults and Children: Contact manufacturer. From the pediatric trial: Patients ≤21 yrs: 650mg/m2 by IV infusion over 1 hour daily for 5 consecutive days; repeat every 21 days. From the adult trial: Patients 16–65yrs: 1500mg/m2 by IV infusion over 2 hours on days 1, 3, and 5; repeat every 21 days. The recommended duration of treatment has not been clearly established. Treatment was generally continued until there was evidence of disease progression, the patient experienced unacceptable toxicity, the patient became a candidate for bone marrow transplant,

F P O for

or the patient no longer continued to benefit from treatment. See literature. Warnings/Precautions: Discontinue if ≥ Grade 2 neurotoxicity occurs; may delay dosing if other toxicities occur (eg, hematologic toxicity). Prior or concurrent intrathecal chemotherapy or craniospinal irradiation (increased risk of neurotoxicity). Renal or hepatic impairment. Obtain CBCs, platelet counts. Monitor for signs/ symptoms of infection, tumor lysis syndrome. Ensure adequate hydration. Elderly. Pregnancy (Cat.D); use effective contraception. Nursing mothers: not recommended. Interactions: Avoid live vaccines. Concomitant adenosine deaminase inhibitors (eg, pentostatin): not recommended. Adverse reactions: Hematologic disorders (eg, anemia, neutropenia, thrombocytopenia), headache, GI upset, constipation, fatigue, somnolence, dizziness, peripheral neuropathy, seizures, respiratory disorders, pyrexia; increased transaminase levels, bilirubin; decreased potassium, albumin. How supplied: Vials–6

ARZERRA GlaxoSmithKline

℞

CD20-directed cytolytic monoclonal antibody. Ofatumumab 20mg/mL; soln for IV infusion after dilution; preservative-free. Indications: In combination with chlorambucil in previously untreated patients with chronic lymphocytic leukemia (CLL), for whom fludarabine-based therapy is considered inappropriate. CLL refractory to fludarabine and alemtuzumab. Adults: See full labeling. Premedicate with acetaminophen (oral), antihistamine (oral or IV), corticosteroid (IV). Give by IV infusion (use in-line filter; rate varies with dose and during infusion). Previously untreated: initially 300mg on Day 1, then 1 week later by 1000mg on Day 8 (Cycle 1), follow by 1000mg on Day 1 of subsequent 28-day cycles for at least 3 cycles until best response or max 12 cycles. Refractory: initially 300mg once, then 1 week later by 2000mg weekly for 7 doses, followed 4 weeks later by 2000mg every 4 weeks for 4 doses. Children: Not established. Warnings/Precautions: Increased risk of HBV reactivation. Test/treat HBV infection prior to initiating therapy. Monitor for signs of hepatitis or HBV reactivation during and for several months after therapy; discontinue if HBV reactivation occurs. Monitor CBCs at regular intervals during and after therapy, increase frequency if Grade 3/4 cytopenias develop. Monitor for new onset of or changes in neurological signs/symptoms. Increased risk of tumor lysis syndrome (TLS)

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HEMATOLOGIC CANCER in high tumor burden and/or high circulating lymphocytes; consider prophylaxis with anti-hyperuricemics and hydration beginning 12–24hrs prior to infusion. Pregnancy (Cat.C). Nursing mothers. Interactions: Avoid vaccination with live viral vaccines. Adverse reactions: Neutropenia, thrombocytopenia, anemia, pneumonia, pyrexia, cough, fatigue, dyspnea, rash, nausea, diarrhea, bronchitis, upper respiratory tract infections; infusion reactions (eg, bronchospasm; laryngeal, pulmonary, or angioedema; flushing, hyper- or hypotension, syncope, cardiac ischemia, back or abdominal pain, fever, urticaria) (interrupt, adjust infusion rate and monitor; permanently discontinue if anaphylaxis occurs), progressive multifocal leukoencephalopathy (discontinue if suspected and evaluate), infections (eg, sepsis), hepatotoxicity, TLS. How supplied: Single-use vial (5mL)–3; (50mL)–1

BEXXAR GlaxoSmithKline

℞

Radionuclide (B-lymphocyte-restricted differentiation antigen [CD20] inhibitor). Tositumomab 35mg/vial, 225mg/vial; soln; Iodine I131 tositumomab 0.61mCi/mL, 5.6mCi/mL soln; both for IV infusion after dilution; preservative-free. Indications: Non-Hodgkin’s lymphoma (CD20 antigen-expressing relapsed or refractory, low grade, follicular, transformed, or rituximabrefractory). Adults: See literature. Pretreat with acetaminophen 650mg and oral diphenhydramine 50mg and thyroid blockers; continue thyroid blockers 2 weeks after therapeutic dose. Give by IV infusion. Dosimetric step: Tositumomab 450mg over 1hr, then Iodine I131 tositumomab (containing 5mCi I131 and 35mg tositumomab) over 20 minutes. Therapeutic step (7–14 days after dosimetric step if biodistribution acceptable): tositumomab 450mg over 1hr, then calculated therapeutic dose of Iodine I131 tositumomab over 20 minutes. Reduce infusion rate by 50% if infusional toxicity occurs; stop if severe; may continue at 50% rate if severe symptoms resolve. Children: Not recommended. Contraindications: Hypersensitivity to murine proteins. Pregnancy (Cat.X). Warnings/Precautions: Use only by physicians trained in radionuclide therapy. Handle and dispose of properly. See literature on patient contact restrictions. Not for initial treatment. >25% lymphoma marrow involvement and/ or impaired bone marrow reserve, platelet count <100000cells/mm3, neutrophil count <1500cells/mm3, or intolerant to thyroid blockers: not recommended. High tumor burden. Splenomegaly. Renal impairment. Screen for human anti-mouse antibodies (increases anaphylaxis risk). Obtain CBCs and platelet counts before and for up to 12 weeks after

therapy. Monitor TSH (before and annually), serum creatinine (before). Use adequate contraception during and for 12 months after therapy. Elderly. Nursing mothers: not recommended. Interactions: Concomitant other forms of irradiation or chemotherapy: not recommended. Caution with live viral vaccines, anticoagulants, platelet aggregation inhibitors. Adverse reactions: Thrombocytopenia, neutropenia, anemia, headache, asthenia, fever, chills, pain, GI upset, cough, pneumonia, pleural effusion, dehydration, rash, infection, hemorrhage, hypersensitivity reactions (may be fatal), myelodysplastic syndrome, secondary malignancies, antibody formation. Note: For technical questions call (877) 423-9927. How supplied: Dosimetric pack (tositumomab 2 × 225mg/vial + 1 × 35mg/vial and Iodine I131 tositumomab 1 × 20mL single-use vial)–1 Therapeutic pack (tositumomab 2 × 225mg/vial + 1 × 35mg/vial and Iodine I131 tositumomab 1 or 2 × 20mL single-use vial)–1

BICNU Bristol-Myers Squibb

℞

Alkylating agent. Carmustine 100mg/vial; lyophilized pwd for IV infusion after reconstitution and dilution; preservative-free. Indications: Palliative therapy in multiple myeloma (in combination with prednisone), Hodgkin’s disease (as secondary therapy in combination with other approved drugs in patients who relapse or fail to respond to primary therapy), Non-Hodgkin’s lymphomas (as secondary therapy in combination with other approved drugs in patients who relapse or fail to respond to primary therapy). Adults: Pretreat with antiemetics. Give by slow IV infusion. Previously untreated patients as a single agent: Initially 150–200mg/m2 every 6 weeks. May give as one single dose or divided into daily injections (eg, 75–100mg/m2) on 2 consecutive days. Adjust subsequent doses based on hematologic response (see literature). In combination therapy: adjust doses accordingly (see literature). Children: Not recommended. Contraindications: Bone marrow suppression. Warnings/Precautions: Monitor blood counts weekly for > 6 weeks after a dose. Do not give repeat doses until platelets are >100,000/mm3 and leukocytes are 4000/mm3. Monitor liver and renal function. Perform pulmonary function tests prior to and during therapy. History of lung disease. Patients with baseline < 70% of the predicted Forced Vital Capacity or Carbon Monoxide Diffusing Capacity, and cumulative doses > 1400mg/m2 increase risk of pulmonary toxicity. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. Adverse reactions: Delayed myelosuppression leading to infection and bleeding, pulmonary

toxicity, delayed pulmonary fibrosis, secondary malignancies, nausea, vomiting, hepatotoxicity, nephrotoxicity, neuroretinitis, chest pain, headache, hypersensitivity, hypotension, tachycardia. Intensive flushing of the skin and suffusion of the conjunctiva related to rapid IV infusion. How supplied: Single-use vial–1 (w. 3mL sterile diluent)

Bleomycin (various)

℞

Cytotoxic glycopeptide antibiotic. Bleomycin 15units/vial, 30units/vial; lyophilized pwd for IM, IV, SC, or intrapleural administration after reconstitution. Indications: Palliative treatment for lymphomas (Hodgkin’s disease, non-Hodgkin’s lymphoma). Adults: Lymphomas: treat with ≤2 units for the first two doses, if no acute reaction occurs, follow regular dosage schedule. Non-Hodgkin’s lymphoma: 0.25–0.5 units/kg IV, IM, or SC weekly or twice weekly. Hodgkin’s disease: 0.25–0.5 units/kg IV, IM, or SC weekly or twice weekly; after a 50% response, a maintenance dose of 1 unit daily or 5 units weekly IV or IM should be given. Renal impairment: see literature. Total doses >400 units: increased risk of pulmonary toxicity. Children: Not recommended. Warnings/Precautions: Renal impairment. Compromised pulmonary function. Monitor renal function. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: May be potentiated by nephrotoxic drugs. Adverse reactions: Erythema, rash, striae, vesiculation, hyperpigmentation, tenderness of the skin, hyperkeratosis, nail changes, alopecia, pruritus, stomatitis; pneumonitis, pulmonary fibrosis, idiosyncratic reaction (hypotension, mental confusion, fever, chills, wheezing). How supplied: Contact supplier.

BOSULIF Pfizer

℞

Tyrosine kinase inhibitor. Bosutinib 100mg, 500mg; tabs. Indications: Treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy. Adults: 500mg once daily with food. Continue until disease progression or patient intolerance. Consider dose escalation to 600mg once daily in patients who do not reach complete hematological response (CHR) by Week 8 or a complete cytogenetic response (CCyR) by Week 12, who did not have Grade 3 or higher adverse reactions. Adjust dose for hematologic and non-hematologic toxicity: see full labeling. Hepatic impairment: 200mg daily. Severe renal impairment (CrCl <30mL/min): 300mg daily. Children: <18yrs: not established. Warnings/Precautions: Monitor and manage GI toxicity, fluid retention; withhold, reduce

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HEMATOLOGIC CANCER dose, or discontinue as necessary. Perform CBC weekly for first month, then monthly; hepatic enzyme tests monthly for first three months (more frequently if transaminase elevations occur); withhold, reduce dose, or discontinue as necessary. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Potentiated by concomitant strong or moderate CYP3A and/or P-gp inhibitors (eg, ritonavir, indinavir, nelfinavir, saquinavir, ketoconazole, boceprevir, telaprevir, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, conivaptan, fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprenavir, crizotinib, imatinib, verapamil, grapefruit products, ciprofloxacin); avoid. Antagonized by concomitant strong or moderate CYP3A inducers (eg, rifampin, phenytoin, carbamazepine, St. John’s Wort, rifabutin, phenobarbital, bosentan, nafcillin, efavirenz, modafinil, etravirine); avoid. Antagonized by proton pump inhibitors (eg, lansoprazole); consider shortacting antacids or H2 blockers instead; separate dosing by more than 2hrs. May potentiate drugs that are P-gp substrates (eg, digoxin). Adverse reactions: Diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, fatigue; fluid retention (monitor), hepatic toxicity. How supplied: Tabs 100mg–120; 500mg–30

BUSULFEX Otsuka

℞

Alkylating agent. Busulfan 6mg/mL; soln for IV administration after dilution. Indications: In combination with cyclophosphamide, as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia. Adults: See literature. Premedicate with phenytoin and antiemetics. Give by IV infusion over 2 hours. 0.8mg/kg of ideal body weight or actual body weight, whichever is lower, every 6 hours for 4 days (total of 16 doses). Obese: base dose on adjusted ideal body weight. Children: See literature. Warnings/Precautions: Myelosuppression. Seizure disorder. Head trauma. Renal or hepatic impairment. Obtain CBCs with differential, platelet count, liver enzymes, bilirubin during treatment and until recovery. Monitor for infection and bleeding. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Potentiated by itraconazole and acetaminophen. May be antagonized by phenytoin. Caution with potentially epileptogenic drugs. Adverse reactions: Myelosuppression (eg, granulocytopenia, thrombocytopenia, anemia),

GI upset, stomatitis, anorexia, abdominal pain, dyspepsia, fever, headache, asthenia, chills, pain, tachycardia, hypertension, edema, dyspnea, dizziness, depression, elevated creatinine, hypomagnesemia, hyperglycemia, hypokalemia, hypocalcemia, hyperbilirubinemia, insomnia, anxiety, rhinitis, rash; seizures (with higher doses), hepatic veno-occlusive disease, cardiac tamponade (in pediatric patients with thalassemia); rare: bronchopulmonary dysplasia with pulmonary fibrosis. How supplied: Single-use vials (10mL)–8

CAMPATH Genzyme

℞

Monoclonal antibody, CD52 (recombinant, humanized). Alemtuzumab 30mg/mL; soln; for IV infusion after dilution; preservative-free. Indications: B-cell chronic lymphocytic leukemia (B-CLL). Adults: Premedicate with antihistamine and acetaminophen before 1st dose, and at dose escalations. Give by IV infusion over 2 hrs. Initially 3mg per day until infusion reactions are ≤ grade 2, then increase to 10mg per day until infusion reactions are ≤ grade 2, then to maintenance 30mg/day three times per week (on alternate days); duration of therapy (including escalation): 12 weeks. Do not exceed max single dose 30mg/dose or 90mg/week. Give prophylactic antibiotics and antivirals during treatment and for at least 2 months after completion or until CD4+ counts resolve (whichever occurs later). Dose adjustments for neutropenia and thrombocytopenia: see literature. Retitrate if therapy interrupted for ≥7 days. Children: Not recommended. Warnings/Precautions: Discontinue dose for autoimmune or recurrent/persistent severe cytopenias (except lymphopenia). Withhold dose for severe cytopenias (except lymphopenia), grade 3 or 4 infusion reactions, serious infections, or during antiviral treatment for cytomegalovirus (CMV) infection or confirmed CMV viremia. Obtain CBCs, platelet counts weekly, assess CD4+ counts after treatment until recovery to ≥200cells/µL. Monitor for infusion reactions; CMV infection (continue for 2 months after therapy ends). Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Avoid live virus vaccines (after recent therapy). May interfere with tests using antibodies. Irradiate any blood products given (GVHD may occur). Adverse reactions: See literature; may be fatal. Infusion reactions, cytopenias (eg, neutropenia, lymphopenia, thrombocytopenia, anemia), infections (eg, CMV), GI upset, insomnia, anxiety; others. How supplied: Single-use vials–1, 3

F P O for

CEENU Bristol-Myers Squibb

℞

Alkylating agent. Lomustine 10mg, 40mg, 100mg; caps. Indications: Secondary therapy for Hodgkin’s disease in combination with other approved drugs in patients who relapse while being treated or who fail primary therapy. Adults and Children: Pretreat with antiemetics and give on empty stomach. Give one dose every 6 weeks. Previously untreated (as a single agent): 130mg/m2. Compromised bone marrow function: 100mg/m2. Combination with other myelosuppressive drugs: adjust doses accordingly. Subsequent doses: adjust according to hematologic response (see literature). Warnings/Precautions: Monitor blood counts weekly for ≥6 weeks after a dose; repeat courses should not be given before 6 weeks (delayed hematologic toxicity) or until platelets are >100,000/mm3 or leukocytes >4000/mm3. Monitor liver and renal function. Perform pulmonary function tests prior to and frequently during therapy; increased risk of pulmonary toxicity in patients with baseline <70% of the predicted Forced Vital Capacity or Carbon Monoxide Diffusing Capacity. Pregnancy (Cat.D). Nursing mothers: not recommended. Adverse reactions: Delayed or cumulative myelosuppression (thrombocytopenia, leukopenia) leading to infection or bleeding, pulmonary toxicity, delayed pulmonary fibrosis, secondary malignancies, liver and renal dysfunction, nausea, vomiting, stomatitis, alopecia, optic atrophy, visual disturbances, disorientation, lethargy, ataxia, dysarthria. Note: Wear gloves when handling capsules. How supplied: Caps–20 Dose pack (100mg–2 caps, 40mg–2 caps, 10mg–2 caps)–1

CERUBIDINE Bedford

℞

Anthracycline. Daunorubicin HCl 20mg/vial; lyophilized pwd for IV infusion after reconstitution; contains mannitol. Indications: In combination with other chemotherapy for remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults. Adults: Give by IV infusion. Acute nonlymphocytic leukemia (in combination with cytosine arabinoside): <60yrs: 45mg/m2 daily on days 1, 2 and 3 of the first course and on days 1, 2 of subsequent courses; ≥60yrs: 30mg/m2 daily on days 1, 2 and 3 of the first course and on days 1, 2 of subsequent courses. Acute lymphocytic

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HEMATOLOGIC CANCER leukemia (in combination with vincristine, prednisone, L-asparaginase): 45mg/m2 daily on days 1, 2 and 3. Hepatic or renal impairment: reduce dose (see literature). Children: Give by IV infusion. <2yrs or BSA<0.5m2: use weight (mg/kg) to calculate dose. 25mg/m2 on Day 1 every week (in combination with vincristine and prednisone). Warnings/Precautions: Treat if any systemic infections 1st. Pre-existing drug-induced bone marrow suppression. Cardiovascular disease, thoracic irradiation, previous doxorubicin therapy (cumulative doses >550mg/m2): increased risk of cardiotoxicity. Monitor blood counts, cardiac, hepatic and renal function prior to each treatment. Renal or hepatic impairment. Hyperuricemia; monitor blood uric acid levels and give allopurinol prophylatically. Avoid extravasation. Children. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Do not use if previously received max cumulative doxorubicin dose; or if concomitant with cyclophosphamide: increased cardiotoxicity. Concomitant myelosuppressives: consider dose reduction. Increased risk of liver toxicity with hepatotoxic agents (eg, high-dose methotrexate). Adverse reactions: Myelosuppression, cardiotoxicity, alopecia, rash, inj site reactions, GI upset, mucositis, abdominal pain, hyperuricemia; rare: anaphylaxis. How supplied: Single-dose vials–10

Cladribine (various)

℞

Chlorinated purine nucleoside analog. Cladribine 1mg/mL; soln for IV infusion after dilution; preservative-free. Indications: Active hairy cell leukemia. Adults: Give by continuous IV infusion for 7 consecutive days. 0.09mg/kg per day. Children: See full labeling. Warnings/Precautions: Delay or discontinue if neurotoxicity or renal toxicity occurs. Myelosuppression. Active infection. Renal or hepatic insufficiency. Monitor blood counts (esp. during first 4–8 weeks post-dose), renal and hepatic function. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Live attenuated vaccines: not recommended. Increased toxicity with myelosuppressive, immunosuppressive, or nephrotoxic agents. Adverse reactions: Severe myelosuppression (eg, neutropenia, anemia, thrombocytopenia), fever, infection, fatigue, nausea, rash, headache, inj site reactions, others; neurotoxicity, nephrotoxicity, tumor lysis syndrome (rare). How supplied: Contact supplier.

CLOLAR Genzyme Purine nucleoside antimetabolite. Clofarabine 1mg/mL; soln for IV infusion after dilution; preservative-free.

℞

Indications: Acute lymphoblastic leukemia (ALL) in patients 1–21 years of age after relapses from, and/or refractoriness to, at least two prior regimens. Adults: Not established. Children: Monitor blood pressure, cardiac, renal, and hepatic function before and during therapy. Give by IV infusion over 2 hours. 1–21yrs: 52mg/m2 daily for 5 consecutive days; repeat approximately every 2–6 weeks following recovery or return to baseline organ function. Provide supportive care (eg, IV fluids, antihyperuricemics, alkalinize urine, steroids, antiemetics, diuretics, albumin) throughout treatment. Renal impairment (CrCl 30–60mL/min): reduce dose by 50%. Dose modifications: see full labeling. Warnings/Precautions: Obtain CBCs and platelets daily during the 5 days of therapy, then 1–2 times weekly or as needed. Monitor for signs/symptoms of infection, tumor lysis syndrome, cytokine release (eg, tachypnea, hypotension); if cytokine release progresses to systemic inflammatory response syndrome (SIRS)/capillary leak syndrome and/or if organ dysfunction (grade 3 or 4 hepatic or renal toxicity) occurs, discontinue and treat; may restart at lower dose if organ function recovers and patient is stable. Ensure adequate hydration. Monitor for venous occlusive disease of the liver in patients who previously received hematopoietic stem cell transplant; discontinue if suspected. Pregnancy (Cat.D); use effective contraception. Nursing mothers: not recommended. Interactions: Minimize exposure to drugs with known renal toxicity during treatment. Consider avoiding concomitant drugs known to induce hepatic toxicity. Caution with drugs that affect BP or cardiac function; monitor. Adverse reactions: Nausea, vomiting, diarrhea, headache, rash, pruritus, pyrexia, fatigue, palmarplantar erythrodysesthesia syndrome, anxiety, flushing, mucosal inflammation; bone marrow suppression (eg, febrile neutropenia, anemia, leukopenia, thrombocytopenia), infections, hyperuricemia, hypotension, cardiac events, SIRS/capillary leak syndrome. How supplied: Single-use vial (20mL)–1, 4

Cyclophosphamide (various)

℞

Alkylating agent. Cyclophosphamide 25mg, 50mg; tabs. Indications: Malignant lymphomas (Stages III and IV of the Ann Arbor staging system), Hodgkin’s disease, lymphocytic lymphoma (nodular or diffuse), mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma. Multiple myeloma. Leukemias: chronic lymphocytic leukemia, chronic granulocytic leukemia (it is usually ineffective in acute blastic crisis), acute myelogenous and monocytic leukemia, acute lymphoblastic (stem-cell) leukemia in children (cyclophosphamide given during remission is effective in prolonging its duration). Mycosis fungoides (advanced disease).

Adults: Initial and maintenance: 1–5mg/kg/day. Children: See literature. ℞ Also: CYTOXAN INJECTION Bristol-Myers Squibb Cyclophosphamide 500mg, 1g, 2g; per vial; pwd for inj after reconstitution; preservative-free. Adults: Initially 40–50mg/kg IV in divided doses over 2–5 days; or 10–15mg/kg IV every 7–10 days; or 3–5mg/kg IV twice weekly. Children: See literature. Contraindications: Severe bone marrow depression. Warnings/Precautions: Leukopenia. Thrombocytopenia. Tumor cell infiltration of bone marrow. Previous X-ray therapy or cytotoxic chemotherapy. Impaired renal or hepatic function. Infections. Adrenalectomy. General anesthesia within 10 days of therapy. Monitor hematologic profile (esp. neutrophils and platelets). Obtain urine sample (monitor for hemorrhagic cystitis); maintain adequate hydration. May interfere with wound healing. Elderly. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Potentiated by phenobarbital. Potentiates other myelosuppressives, radiotherapy, succinylcholine. May potentiate doxorubicin-induced cardiotoxicity. Adverse reactions: GI upset, alopecia, leukopenia, infections, thrombocytopenia, anemia, hemorrhagic cystitis (discontinue if occurs), renal tubular necrosis, interstitial pulmonary fibrosis, gonadal toxicity (amenorrhea, infertility), anaphylactic reactions. How supplied: Tabs–contact supplier Single-use vial–1

Cytarabine Bedford

℞

Antimetabolite. Cytarabine 100mg, 500mg, 1g, 2g; per vial; lyophilized pwd for IV, intrathecal, SC inj after reconstitution. Indications: Remission induction in acute non-lymphocytic leukemia of adults and children. Acute lymphocytic leukemia. Chronic myelocytic leukemia (blast phase). Prophylaxis and treatment of meningeal leukemia (intrathecal route). Adults and Children: Induction therapy of acute non-lymphocytic leukemia: 100mg/m2 per day by continuous IV infusion (days 1–7) or 100mg/m2 IV every 12 hours (days 1–7). Acute lymphocytic leukemia and chronic myelocytic leukemia: see literature. Meningeal leukemia: Usual range: 5–75mg/m2 intrathecally; may give once daily for 4 days to once every 4 days; most frequently used dose: 30mg/m2 every 4 days until cerebrospinal fluid findings are normal. Warnings/Precautions: Do not use diluent with benzyl alcohol for intrathecal administration. Pre-existing myelosuppression. Renal or hepatic impairment. Monitor blood counts, renal, hepatic function. Neonates. Pregnancy (Cat.D); avoid use. Nursing mothers. Interactions: May antagonize gentamicin, fluorocytosine.

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HEMATOLOGIC CANCER Adverse reactions: Myelosuppression (leukopenia, thrombocytopenia, anemia), GI upset, anorexia, abdominal pain, oral ulceration, rash, fever, hepatic dysfunction, infection, bleeding; cytarabine syndrome, hyperuricemia, pancreatitis, paralysis (rare), others. How supplied: Vials (100mg, 200mg)–10 1g, 2g–1

DACOGEN Otsuka

℞

Nucleoside analogue. Decitabine 50mg/vial; lyophilized pwd for IV infusion after reconstitution and dilution. Indications: Myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all FrenchAmerican-British subtypes and Intermediate-1, Intermediate-2, and High-risk International Prognostic Scoring System groups. Adults: May premedicate with antiemetics. Treat for a minimum of 4 cycles; may take longer for a complete or partial response. Regimen 1: Give by continuous IV infusion over 3 hours. 15mg/m2 every 8 hours for 3 days; repeat every 6 weeks. Regimen 2: Give by continuous IV infusion over 1 hour. 20mg/m2 once daily for 5 days; repeat every 4 weeks. Both: dose adjustment based on hematology values: see literature. Nonhematologic toxicities (eg, serum creatinine ≥2mg/dL; SGPT, total bilirubin ≥ 2 × ULN; active or uncontrolled infection): do not restart until toxicity resolved. Children: Not recommended. Warnings/Precautions: Renal or hepatic impairment. Obtain CBC and platelet counts before each dosing cycle and as needed. Monitor hepatic function (do baseline liver chemistries and serum creatinine). Pregnancy (Cat.D); use appropriate contraception (both men and women). Nursing mothers: not recommended. Adverse reactions: Neutropenia, thrombocytopenia, anemia, leukopenia, fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, hyperglycemia. How supplied: Single-use vial–1

DEPOCYT Sigma-Tau

℞

Antimetabolite. Cytarabine 50mg/vial; liposomal suspension for intrathecal administration; preservative-free. Indications: Intrathecal treatment of lymphomatous meningitis. Adults: See literature. Give intrathecally over 1–5 minutes. Administer dexamethasone 4mg twice daily for 5 days with each cycle of treatment. Induction: 50mg every 14 days for 2 doses (weeks 1 and 3). Consolidation: 50mg every 14 days for 3 doses (weeks 5, 7 and 9) followed by 1 additional

dose at week 13. Maintenance: 50mg every 28 days for 4 doses (weeks 17, 21, 25 and 29). Reduce dose to 25mg if neurotoxicity develops and discontinue if it persists. Children: Not recommended. Contraindications: Active meningeal infection. Warnings/Precautions: Chemical arachnoiditis; reduce symptoms with dexamethasone. Previous irradiation, cytotoxic chemotherapy. Monitor blood counts and for development of neurotoxicity. Renal and hepatic impairment. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Increased risk of neurotoxicity with concomitant cranial/spinal irradiation or other intrathecal antineoplastics. Adverse reactions: See literature. Arachnoiditis, GI upset, headache, fever, neurological toxicity (myelopathy), hydrocephalus, elevated CSF protein and WBC, weakness, back pain, insomnia, blurred vision, anaphylactic reactions; others. How supplied: Single-use vials (5mL)–1

DOXIL Janssen Biotech

℞

Anthracycline. Doxorubicin HCl (liposomal) 2mg/mL; dispersion for IV infusion after dilution; preservative-free. Indications: Multiple myeloma, in combination with bortezomib, in patients not previously treated with bortezomib and who have received at least one prior therapy. Adults: Give by IV infusion at initial rate of 1mg/min; may increase rate to complete infusion over 1hr if no infusion reactions occur; may premedicate with antiemetics. 30mg/m2 on Day 4 of each cycle following bortezomib (see full labeling for bortezomib dose); may treat for up to 8 cycles. Hepatic dysfunction (serum bilirubin ≥1.2mg/dL), hand-foot syndrome, hematologic toxicity (esp. ANC, platelets), or stomatitis: reduce dose. Consider total anthracycline and anthracenedione doses and irradiation when calculating total cumulative dose. See full labeling. Children: Not established. Warnings/Precautions: Not substitutable on a mg/mg basis with other doxorubicin products. Cardiotoxicity, acute infusion-related reactions, myelosuppression may occur. Have resuscitative/ antiallergic equipment and expertise available. Hepatic impairment. Monitor blood (esp. CBC + platelets), hepatic (esp. SGOT/SGPT, alkaline phosphatase), and cardiac function (esp. myocardial biopsy). Monitor periodically for secondary oral cancers with long-term use. Avoid extravasation. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Caution with cyclosporine, phenobarbital, phenytoin, streptozocin, digoxin,

F P O for

myelosuppressants, others. Previous mediastinal irradiation, cyclophosphamide, other cardiotoxic drugs: monitor for cardiotoxicity and hepatotoxicity. Adverse reactions: Asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand and foot syndrome, rash, neutropenia, thrombocytopenia, anemia; infusion reactions, cardiovascular events (eg, cardiomyopathy, CHF, acute LV failure), recall of skin reaction from prior radiation therapy, toxoplasmosis, urine discoloration (red/orange). How supplied: Single-use vials (10mL, 25mL)–1

Doxorubicin HCl (various)

℞

Anthracycline. Doxorubicin HCl 10mg/vial, 20mg/vial, 50mg/vial; pwd for IV inj after reconstitution; contains lactose. ℞ Also: Doxorubicin HCl Solution Doxorubicin HCl 2mg/mL; soln for IV inj. Indications: Disseminated neoplasias (eg, acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin’s disease, malignant lymphoma). Adults and Children: Monotherapy: usually 60–75mg/m2 IV every 21 days. Combination therapy: usually 40–60mg/m2 IV every 21 to 28 days. Hyperbilirubinemia, inadequate bone marrow reserves: reduce dose. Contraindications: Severe myelosuppression (baseline neutrophils <1500cells/mm3) or severe hepatic impairment. Cardiac disease (eg, severe myocardial insufficiency, arrhythmias). Recent MI. Previous treatment with max cumulative doses of anthracyclines, anthracenediones. Warnings/Precautions: Pre-existing heart disease or risk thereof. Obtain baseline CBC, bilirubin, AST, creatinine, LVEF. Hepatic dysfunction. Monitor cardiac function (LVEF, ECG echocardiogram), hepatic function, CBC, uric acid levels. Avoid extravasation. Children (cardiotoxicity, impaired myocardial growth). Elderly. Pregnancy (Cat.D; use adequate contraception). Nursing mothers: not recommended. Interactions: See Contraindications. Mediastinal irradiation, cyclophosphamide, calcium channel blockers, other anthracyclines increase risk of cardiac toxicity; limit lifetime dose to 400mg/m2. Necrotizing colitis with cytarabine. May increase toxicity of cyclophosphamide, mercaptopurine. May reduce serum digoxin levels. Doxorubicin toxicity increased with high-dose IV progesterone, cyclosporine, streptozocin, and if given after paclitaxel infusion (give doxorubicin dose first). Elimination increased by phenobarbital. May decrease phenytoin levels. Recall pneumonitis with actinomycin and radiation in children. Adverse reactions: Local necrosis if extravasation occurs, myocardial toxicity

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HEMATOLOGIC CANCER (immediate or delayed), arrhythmias, leukemia, myelosuppression, hyperuricemia, urine discoloration, alopecia, hyperpigmentation, severe GI upset/ulceration, phlebosclerosis, facial flushing, fever, urticaria, peripheral neuropathy, anaphylaxis. How supplied: Contact supplier.

DTIC-DOME Bayer

℞

Alkylating agent. Dacarbazine 200mg/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol. Indications: Metastatic malignant melanoma. Second-line therapy for Hodgkin’s disease, in combination with other agents. Adults: Give by IV infusion. Malignant melanoma: 2–4.5mg/kg/day for 10 days, may repeat every 4 weeks; or 250mg/m2 daily for 5 days, may repeat every 3 weeks. Hodgkin’s disease (in combination with other drugs): 150mg/m2 daily for 5 days, may repeat every 4 weeks; or 375mg/m2 on Day 1, then repeat every 15 days. Children: Not recommended. Warnings/Precautions: Monitor CBCs, platelets; may need to discontinue or suspend therapy if hemopoietic toxicity occurs. Pregnancy (Cat.C). Nursing mothers: not recommended. Adverse reactions: Myelosuppression (eg, leukopenia, thrombocytopenia, anemia), anorexia, nausea, vomiting, flu-like syndrome, alopecia, facial flushing/paresthesia, inj site reactions, anaphylaxis; rare: hepatic necrosis, photosensitivity reactions. How supplied: Vials (20mL)–12

ERWINAZE Jazz

℞

Asparagine-specific enzyme. Asparaginase Erwinia chrysanthemi 10,000 IU; per vial; lyophilized pwd for IM inj after reconstitution. Indications: As a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coliderived asparaginase. Adults and Children: Give by IM inj (max 2mL/inj site). To substitute for a pegaspargase dose: 25,000 IU/m2 three times weekly (M/W/F) for 6 doses for each planned pegaspargase dose. To substitute for a native E. coli asparaginase dose: 25,000 IU/m2 for each scheduled native E. coli asparaginase dose within a treatment. Contraindications: History of serious pancreatitis, thrombosis, hemorrhagic events with prior L-asparaginase therapy. Warnings/Precautions: Have resuscitation equipment available and other agents necessary to treat anaphylaxis. Discontinue if serious hypersensitivity reactions occur. Monitor for pancreatitis; discontinue if severe or hemorrhagic pancreatitis manifested by abdominal pain >72hrs and amylase elevation ≥2×ULN occurs. Withhold therapy if mild pancreatitis; may resume after resolution. Monitor glucose levels at baseline

and during therapy. Discontinue if thrombotic or hemorrhagic event occurs; may resume after resolution. Pregnancy (Cat.C). Nursing mothers: not recommended. Adverse reactions: Serious hypersensitivity reactions including anaphylaxis, pancreatitis, abnormal transaminases, coagulation abnormalities including thrombosis and hemorrhage, nausea, vomiting, hyperglycemia. How supplied: Vials–5

FLUDARA Genzyme

℞

Antimetabolite. Fludarabine phosphate 50mg/vial; lyophilized pwd for IV infusion after reconstitution and dilution; preservative-free; contains mannitol. Indications: B-cell chronic lymphocytic leukemia (CLL) in patients who have not responded to or whose disease progressed during treatment with at least 1 alkylating-agent containing regimen. Adults: Give by IV infusion over 30 minutes. 25mg/m2 daily for 5 days every 28 days. Renal dysfunction (CrCl 30–70mL/min): reduce dose by 20%; CrCl <30mL/min: not recommended. Give for 3 cycles after the max response. Reduce or delay dose if toxicity occurs. Children: Not recommended. Warnings/Precautions: Myelosuppression. Evaluate and monitor for hemolysis. Monitor blood (esp CBC, platelets). Use irradiated blood products if transfusions are required. May need to prophylax for tumor lysis syndrome with large tumors. Renal insufficiency. Delay or stop therapy if neurotoxicity occurs. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Severe pulmonary toxicity with pentostatin (not recommended). Adverse reactions: Myelosuppression (severe/ cumulative), bone marrow hypoplasia, autoimmune hemolytic anemia (fatal/severe), infection, fever, chills, GI upset, malaise, fatigue, CNS effects (eg, weakness, agitation, confusion, visual disturbances, coma, peripheral neuropathy), pneumonia, pulmonary hypersensitivity (eg, dyspnea, interstitial pulmonary infiltrate), stomatitis, GI bleeding, edema, tumor lysis syndrome, rash, hemorrhagic cystitis (rare); others. How supplied: Single-dose vials–5

FOLOTYN Allos

℞

Folate analogue inhibitor. Pralatrexate 20mg/mL; soln for IV inj; preservative-free. Indications: Relapsed or refractory peripheral T-cell lymphoma. Adults: Prior to administration: mucositis should be ≤Grade 1, platelets should be ≥100,000/μL for first dose and ≥50,000/μL for subsequent doses, absolute neutrophil count should be ≥1000/ μL. Give by IV push over 3–5min. 30mg/m2 once weekly for 6 weeks in 7-week cycles; may reduce to 20mg/m2 or interrupt treatment to

manage toxicity (see literature for adjustment criteria). Continue until disease progression or unacceptable toxicity develops. Supplement with vitamin B12 (1mg IM every 8–10 weeks, starting within 10 weeks before first Folotyn dose) and folic acid (1–1.25mg orally daily, beginning 10 days before starting Folotyn and for 30 days after stopping). Children: Not recommended. Warnings/Precautions: End stage renal disease (including dialysis): avoid, unless benefit justifies potential risk for toxicity. Adjust dose to manage toxicities (eg, hematological, mucositis, hepatic impairment); see literature. Monitor CBC and for mucositis weekly. Monitor serum chemistry, renal and hepatic function before the 1st and 4th dose per cycle. Monitor for dermatological reactions; withhold dose or discontinue if severe. Renal or hepatic impairment. Pregnancy (Cat.D) (may cause fetal harm), nursing mothers: not recommended. Interactions: May be potentiated by probenecid, NSAIDs, trimethoprim/sulfamethoxazole, other renally-excreted drugs. Adverse reactions: Mucositis, thrombocytopenia, neutropenia, anemia, abnormal liver function tests, nausea, fatigue, pyrexia, dehydration, sepsis, dyspnea; dermatological reactions (eg, skin exfoliation, ulceration, toxic epidermal necrolysis), tumor lysis syndrome. How supplied: Single-use vials (1mL, 2mL)–1

GAZYVA Genentech

℞

Cytolytic monoclonal antibody (CD20-directed). Obinutuzumab 25mg/mL; soln for IV infusion after dilution; preservative-free. Indications: Treatment of patients with previously untreated chronic lymphocytic leukemia (CLL), in combination with chlorambucil. Adults: Premedicate (eg, glucocorticoid, APAP, antihistamine) before each infusion. Give by IV infusion for 6 treatment cycles (28 days duration). Cycle 1: 100mg on Day 1 at 25mg/hr over 4 hours; 900mg on Day 2 at 50mg/hr, may increase at 50mg/hr every 30mins (max 400mg/hr); 1000mg on Days 8 and 15 at 100mg/hr, may increase by 100mg/hr increments every 30mins (max 400mg/hr); Cycles 2–6: 1000mg on Day 1 at 100mg/hr, may increase by 100mg/hr increments every 30mins (max 400mg/hr). Infusion rate and premedication adjustments: see full labeling. Children: Not established. Warnings/Precautions: Risk of hepatitis B virus (HBV) reactivation; immediately discontinue and any concomitant chemotherapy if occurs. Screen for HBV infection prior to initiation; if positive evidence, monitor and consider antiviral therapy. Discontinue treatment and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressives if PML develops. Monitor closely for infusion reactions; if Grade 4: discontinue permanently; if Grade

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HEMATOLOGIC CANCER 3: interrupt until resolved; if Grade 1 or 2: interrupt or reduce the infusion rate and manage symptoms. Preexisting cardiac or pulmonary conditions: monitor more frequently during and post-infusion period for severe reactions. Risk of TLS in high tumor burden and/or high circulating lymphocyte count (>25 × 109/L): prophylaxis with antihyperuricemics and hydration. Active infection: do not administer. Monitor for bleeding; obtain blood and platelet counts frequently. Risk of neutropenia; give antimicrobial prophylaxis. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Concomitant live viral vaccines: not recommended. Consider withholding antihypertensives for 12hrs prior to, during, and for 1hr after infusion until BP is stable. Adverse reactions: Infusion reactions, neutropenia, thrombocytopenia, anemia, pyrexia, cough, musculoskeletal disorders. How supplied: Single-use vial (40mL)–1

GLEEVEC Novartis

℞

Kinase inhibitor. Imatinib (as mesylate) 100mg, 400mg; tabs. Indications: Philadelphia-chromosome (+) chronic myeloid leukemia (CML): in newlydiagnosed adults and children in chronic phase; in patients in blast crisis, accelerated phase, or chronic phase after failure of interferon-alpha therapy. Adults with relapsed or refractory Ph (+) acute lymphoblastic leukemia (ALL). Children with newly diagnosed Ph+ ALL in combination with chemotherapy. Adults with myelodysplastic/ myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene rearrangements. Adults with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unkown. Adults: Take with food and water. May disperse tab in water or apple juice and take promptly. ≥18yrs: Chronic phase CML: 400mg once daily. Accelerated phase or blast crisis: 600mg once daily. Relapsed/refractory Ph+ ALL: 600mg once daily. MDS/MPD: 400mg once daily. HES/CEL: 400mg once daily. HES/CEL w. FIP1L1-PDGFRα fusion kinase: initially 100mg once daily; may increase to 400mg once daily if insufficient response. If severe non-hematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction. Severe hepatic impairment: reduce dose by 25%. Renal or hematologic reactions: see full labeling. Potent CYP3A4 inducers (eg, rifampin): increase imatinib dose by at least 50%.

Children: Take with food and water in 1 or 2 divided doses; may disperse tab in water or apple juice and take promptly. <1yrs: not recommended. ≥1yrs: Newly diagnosed Ph+CML: 340mg/m2 per day (max 600mg). Newly diagnosed Ph+ALL: 340mg/m2 per day (max 600mg); give with chemotherapy. If severe nonhematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction. Renal or hematologic reactions: see full labeling. Potent CYP3A4 inducers (eg, phenytoin): increase imatinib dose by at least 50%; monitor closely. Warnings/Precautions: Hepatic or renal impairment. Monitor weight and for fluid retention regularly; CBCs weekly for 1st month, bi-weekly for 2nd month, then periodically (eg, every 2–3 months); liver function at baseline then monthly or as needed; GI symptoms at baseline. Cardiovascular disease or risk factors; monitor. Immunosuppression from long-term use. Monitor for tumor lysis syndrome; correct clinically significant dehydration and treat high uric acid levels before initiating therapy. Monitor growth in children. Possible cardiogenic shock/LV dysfunction in conditions with high eosinophil levels (eg, HES/CEL, MDS/MPD, ASM); consider concomitant systemic steroid prophylaxis (1–2mg/kg) for 1 or 2 wks if abnormal ECG or serum troponin. Monitor TSH levels in thyroidectomy patients undergoing levothyroxine replacement. Pregnancy (Cat.D); avoid. Use highly effective contraception during treatment. Nursing mothers: not recommended. Interactions: Avoid grapefruit juice. Potentiated by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin). May potentiate drugs metabolized by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain statins, sirolimus, tacrolimus), CYP2D6, or CYP2C9 (use heparin instead of warfarin). Adverse reactions: Edema (may be severe), nausea, vomiting, musculoskeletal pain, diarrhea, muscle cramps, rash (may be severe; eg, erythema multiforme, Stevens-Johnson syndrome), fatigue, abdominal pain, dizziness, blurred vision, somnolence, fever, headache, cough, arthralgia/myalgia, dyspnea, hypokalemia, night sweats, anorexia, pruritus, hemorrhage, anemia, neutropenia, thrombocytopenia, weight gain, renal or hepatotoxicity, immunosuppression, hypothyroidism; rare: severe CHF, LV dysfunction. Testing considerations: BCR-Abl t(9;22) in Ph+ CML patients How supplied: 100mg–90; 400mg–30

F P O for

HYDREA Bristol-Myers Squibb

℞

Substituted urea. Hydroxyurea 500mg; caps. Indications: Resistant chronic myelocytic leukemia. Adults: See literature. 20–30mg/kg/day as single dose. Renal impairment: reduce dose. Children: Not recommended. Contraindications: Marked bone marrow depression. Warnings/Precautions: Previous irradiation therapy or chemotherapy. Correct anemia before starting. Monitor hematologic, renal, hepatic function before and during treatment. Marked renal dysfunction. Myeloproliferative disorders; discontinue if cutaneous vasculitic ulcerations develop and use alternative agents. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [monitor], fatal hepatotoxicity, peripheral neuropathy). Myelosuppressives potentiate antineoplastic effect. May antagonize antigout agents. Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated urease, uricase, lactate dehydrogenase. Adverse reactions: Leukopenia, anemia, erythrocytic abnormalities, thrombocytopenia, GI upset, rash, erythema, fever, CNS effects, temporary renal impairment, acute pulmonary reactions, secondary leukemias, skin cancer. Note: Wear disposable gloves when handling caps or bottle. How supplied: Caps–100

ICLUSIG ARIAD

℞

Kinase inhibitor. Ponatinib 15mg, 45mg; tabs; contains lactose. Indications: Treatment of adults with T315Ipositive chronic, accelerated, or blast phase chronic myeloid leukemia (CML) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Treatment of adults with chronic, accelerated, or blast phase CML or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated. Adults: Swallow whole. ≥18yrs: initially 45mg once daily; consider reducing dose in chronic and accelerated phase CML if major cytogenic response achieved. Consider discontinuing if no response occurred by 3 months. Concomitant strong CYP3A inhibitors: reduce to 30mg once daily. Dose modification for hematologic and nonhematologic toxicity: see full labeling. Children: <18yrs: not established. Warnings/Precautions: Risk of vascular occlusion (eg, arterial and venous thrombosis,

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HEMATOLOGIC CANCER fatal MI, stroke, stenosis of arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures) in patients with or without CV risk factors (including ≤50yrs old, or increasing age, history of ischemia, HTN, diabetes, hyperlipidemia); monitor and interrupt or discontinue if occurs. Monitor for signs/symptoms of heart failure; interrupt or consider discontinuing if develops or worsens. Monitor hepatic function at baseline, then at least monthly or as needed; interrupt, reduce or discontinue as clinically indicated. Moderate-tosevere hepatic impairment: not recommended. Monitor and manage BP elevations; interrupt, reduce dose or discontinue if not controlled. Risk of pancreatitis; check serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated; do not restart until complete resolution and lipase levels <1.5×ULN. Monitor for neuropathy; consider interrupting and evaluate if suspected. Conduct eye exams at baseline and periodically during treatment. Interrupt therapy and evaluate for serious/severe hemorrhage or cardiac arrhythmias. Monitor for fluid retention; interrupt, reduce, or discontinue as indicated. Obtain CBCs every 2 weeks for the first 3 months, then monthly or as indicated. Tumor lysis syndrome; ensure adequate hydration and treat uric levels prior to therapy. Compromised wound healing (withhold for 1 week prior to major surgery) and GI perforation. Elderly. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Potentiated by strong CYP3A inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole); see Adult dose. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, rifampin, phenytoin, St. John’s Wort), or drugs that elevate gastric pH (eg, PPIs, H2 blockers, antacids). Caution with concomitant P-gp and ABCG2 substrates. Adverse reactions: Hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, pyrexia, anemia, thrombocytopenia, leukopenia, neutropenia, lymphopenia; vascular occlusion, heart failure, hepatotoxicity, ocular toxicities, hemorrhage, myelosuppression. How supplied: Tabs 15mg–60, 180; 45mg–30, 90

IDAMYCIN Pfizer

℞

Anthracycline. Idarubicin HCl 20mg/vial; lyophilized pwd for IV infusion after reconstitution. ℞ Also: IDAMYCIN PFS Idarubicin 1mg/mL; soln for IV infusion; preservative-free. Indications: Acute myeloid leukemia. Adults: Give by slow IV infusion (over 10–15 minutes). 12mg/m2 daily for 3 days (in combination with cytarabine). May give 2nd course

if needed; if toxicity develops after 1st course, delay until resolved; reduce dose by 25%. Hepatic and renal impairment: consider reduce dose. Children: Not recommended. Warnings/Precautions: Pre-existing bone marrow suppression. Cardiovascular disease. Thoracic irradiation. Previous anthracycline therapy at high cumulative doses. Renal or hepatic impairment. Monitor CBCs, cardiac, renal and hepatic function prior to and during treatment. Avoid extravasation. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Adverse reactions: Myelosuppression, GI upset, mucositis, abdominal pain, alopecia, rash, inj site reactions, hepatotoxicity, renal toxicity, cardiotoxicity (eg, CHF, arrhythmias, chest pain, MI, asymptomatic declines in LVEF), hyperuricemia. How supplied: Single-dose vials–1 PFS: Single-dose vials (5mL, 10mL, 20mL)–1

IMBRUVICA

℞

Pharmacyclics and Janssen Biotech

Bruton’s tyrosine kinase (BTK) inhibitor. Ibrutinib 140mg; caps. Indications: Mantle cell lymphoma (MCL) in patients who have received at least one prior therapy. Chronic lymphocytic leukemia (CLL) in patients who have received at least one prior therapy. Adults: Swallow whole with water. MCL: 560mg once daily. CLL: 420mg once daily. Concomitant moderate CYP3A inhibitors: 140mg once daily. Dose modifications for toxicities: see full labeling. Children: Not established. Warnings/Precautions: Risk of hemorrhage; consider the benefit/risk of withholding treatment for 3–7 days pre-and post-surgery. Monitor for fever and infections; evaluate promptly if occurs. Monitor for myelosuppression; obtain CBCs monthly. Risk of second primary malignancies (eg, skin cancer or other carcinomas). Hepatic or renal impairment. Monitor creatinine levels periodically. Maintain adequate hydration. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Concomitant strong CYP3A inhibitors taken chronically (eg, ritonavir, indinavir, nelfinavir, saquinavir, boceprevir, telaprevir, nefazodone): not recommended; for shortterm (≤7days) use of strong CYP3A inhibitors (eg, ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin); consider interrupting ibrutinib therapy. If concomitant moderate CYP3A inhibitors must be used (eg, fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprevir, crizotinib, imatinib, verapamil, ciprofloxacin): reduce ibrutinib dose (see Adults). Avoid grapefruit and Seville oranges during treatment. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, rifampin, phenytoin, St. John’s Wort); consider alternatives.

Increased risk of hemorrhage with concomitant antiplatelets or anticoagulants. Adverse reactions: Thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory tract infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting, decreased appetite, pyrexia, arthralgia, stomatitis, sinusitis, dizziness. How supplied: Caps–90, 120

INTRON A Merck

℞

Interferon alfa-2b, recombinant; 10 million, 18 million, or 50 million IU per vial; pwd; for inj after reconstitution/dilution; preservative-free. ℞ Also: INTRON A SOLN Interferon alfa-2b, recombinant; 10 million IU, 18 million IU, 25 million IU; per vial; for inj; contains m-cresol. Indications: Hairy cell leukemia. Initial treatment of clinically aggressive follicular Non-Hodgkin’s lymphoma in conjunction with anthracyclinecontaining combination chemotherapy. Adults: Use SC route if platelets <50,000/mm3. Hairy cell leukemia: 2 million IU/m2 IM or SC 3 times a week for up to 6 months. Follicular lymphoma: 5 million IU SC 3 times a week for up to 18 months in conjunction with anthracyclinecontaining chemotherapy regimen and following completion of the chemotherapy regimen. See literature for appropriate preparation and route and for dose adjustments. Children: Not recommended. Contraindications: Hepatitis: decompensated liver disease. Autoimmune disorders. Warnings/Precautions: May cause or exacerbate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders: monitor closely, discontinue if they worsen. Severe psychiatric disorders (esp. depression). Cardiovascular or pulmonary disease. Severe myelosuppression. Uncontrolled thyroid abnormalities. Diabetes. Coagulation disorders. Maintain adequate hydration. Monitor blood, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Psoriasis. Renal dysfunction. Transplant recipients. Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Caution with myelosuppressives, and drugs that can exacerbate depression. May potentiate theophylline (may double its levels). Adverse reactions: Flu-like symptoms (fever, headache, myalgia, fatigue); hepatic, hematologic, respiratory, skin, genitourinary system, CNS, cardiovascular, endocrine (esp thyroid), GI, or visual disorders; colitis, hypertriglyceridemia, pancreatitis, infections, injection site reactions; others (see literature). How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial–1; Soln (vials): 10million IU/vial–6 (kit w. supplies); Soln (multidose vials): 18million, 25million IU/vial–1

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HEMATOLOGIC CANCER ISTODAX Celgene

℞

Histone deacetylase inhibitor. Romidepsin 10mg/vial; pwd for IV infusion after reconstitution and dilution; contains povidone. Indications: Cutaneous T-cell lymphoma in patients who have received at least one prior systemic therapy. Peripheral T-cell lymphoma in patients who have received at least one prior therapy. Adults: ≥18yrs: Give by IV infusion over 4hrs. 14mg/m2 on days 1, 8, and 15 of a 28-day cycle; repeat cycle every 28 days; continue as tolerated and as beneficial. May interrupt, reduce dose to 10mg/m2, or discontinue based on toxicities (see full labeling). Children: <18yrs: not established. Warnings/Precautions: Correct electrolyte imbalances (esp. K+, Mg++) before starting. Monitor ECG and electrolytes in congenital long QT syndrome, significant cardiovascular disease. Advanced stage disease and/or high tumor syndrome: monitor closely for tumor lysis syndrome. Moderate to severe hepatic impairment. End-stage renal disease. Monitor CBC with differential. Pregnancy (Cat.D; may cause fetal harm). Nursing mothers: not recommended. Interactions: Caution with other drugs that can cause QT prolongation (monitor). Monitor PT/INR with warfarin. Potentiated by drugs that inhibit P-glycoprotein and CYP3A4; avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, clarithromycin, nefazodone). Caution with moderate CYP3A4 inhibitors. Avoid concomitant rifampin. May be antagonized by other strong CYP3A4 inducers (eg, dexamethasone, carbamazepine, phenytoin, phenobarbital, rifabutin, rifapentine, St. John’s Wort); avoid when possible. Adverse reactions: Nausea, vomiting, fatigue, infections, anorexia, anemia, thrombocytopenia, ECG T-wave changes, neutropenia, lymphopenia; tumor lysis syndrome. How supplied: Kit–1 (single-use vial + diluent and supplies)

JAKAFI Incyte

℞

Kinase inhibitor. Ruxolitinib 5mg, 10mg, 15mg, 20mg, 25mg; tabs. Indications: Treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. Adults: Doses may be given by NG tube if unable to swallow tabs. Platelets >200×109/L: initially 20mg twice daily. Platelets 100–200×109/L: initially 15mg twice daily. Platelets 50–<100×109/L:

initially 5mg twice daily. May increase doses by 5mg twice daily to a max of 25mg twice daily; do not increase during the first 4wks of therapy and not more frequently than every 2wks. Discontinue treatment after 6mos if no reduction in spleen size or symptom improvement. Interrupt treatment if platelets <50×109/L. May restart after recovery of platelets (see full labeling for max allowable restarting doses). Consider dose reductions if platelets decrease but remain ≥50×109/L (see full labeling). Dose modifications for patients starting treatment with platelets 50–<100×109/L: see full labeling. Concomitant strong CYP3A4 inhibitors: initially 10mg twice daily if platelets ≥100×109/L; if platelets <100×109/L: avoid. Moderate or severe renal impairment (CrCl 15–59mL/min) and platelets between 100–150×109/L: initially 10mg twice daily. ESRD (CrCl <15mL/min) on dialysis with platelets between 100–200×109/L: 15mg after dialysis session; if with platelets >200×109/L: 20mg after dialysis session. ESRD not requiring dialysis, moderate or severe renal impairment with platelets <100×109/L: avoid. Hepatic impairment with platelets between 100–150×109/L: initially 10mg twice daily; if platelets <100×109/L: avoid. Children: Not established. Warnings/Precautions: Monitor for thrombocytopenia, anemia, neutropenia; withhold or reduce dose if occur. Obtain CBC and platelets before initiating therapy, every 2–4 weeks until doses are stabilized, and then as clinically indicated. Risk of serious bacterial, mycobacterial, fungal, and viral infections; evaluate and treat if signs/symptoms occur. Confirm resolution of active infections before starting. Renal or hepatic impairment. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Potentiated by strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and mild or moderate CYP3A4 inhibitors (eg, erythromycin). Antagonized by CYP3A4 inducers (eg, rifampin). Adverse reactions: Thrombocytopenia, anemia, neutropenia, bruising, dizziness, headache, UTIs, weight gain, flatulence, progressive multifocal leukoencephalopathy (discontinue if occurs), herpes zoster. How supplied: Tabs–60

KYPROLIS Onyx Proteasome inhibitor. Carfilzomib 60mg/vial; lyophilized pwd for IV inj after reconstitution; preservative-free. Indications: Treatment of patients with multiple myeloma who have received at least

F P O for

℞

two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. Adults: See literature. Premedicate with dexamethasone prior to all Cycle 1 doses, during 1st dose escalation and if infusion reactions occur. Give by IV over 2–10 minutes, on two consecutive days each week for 3 weeks (Days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest period (Days 17–28). In Cycle 1: 20mg/m2 per each dose, if tolerated increase to 27mg/m2 starting in Cycle 2 and subsequent cycles; continue until disease progression or unacceptable toxicity occurs. On dialysis: give dose after session. Toxicity dose modification: see literature. Children: Not established. Warnings/Precautions: Risk of cardiac complications (eg, CHF, MI, pulmonary edema); monitor and manage promptly if occurs. Pulmonary hypertension; if suspected, withold therapy until resolved; may consider restarting after reevaluate. Monitor for dyspnea or tumor lysis syndrome, and manage promptly if occurs; interrupt therapy until resolved. Maintain adequate hydration. Monitor platelets frequently during therapy. Hepatic impairment (monitor enzymes). Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Adverse reactions: Fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, pyrexia; cardiac events, pulmonary HTN, infusion reactions, tumor lysis syndrome, hepatic toxicity/failure. How supplied: Single use vial–1

LEUKERAN GlaxoSmithKline

℞

Alkylating agent. Chlorambucil 2mg; tabs. Indications: Palliative treatment of chronic lymphatic (lymphocytic) leukemia and malignant lymphomas (including lymphosarcoma, giant follicular lymphoma, and Hodgkin’s disease). Adults: See literature. 0.1–0.2mg/kg per day for 3–6 weeks. Reduce dose if leukocyte or platelet counts fall below normal values and discontinue if more severe depression occurs. Do not give full dose within 4 weeks of radio- or chemotherapy. Children: Not recommended. Warnings/Precautions: Compromised bone marrow function. History of seizure disorder or head trauma. Monitor blood weekly (during first 3–6 weeks, do WBC count 3–4 days after each weekly CBC). Discontinue if skin reactions occur. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Avoid live vaccines. Myelosuppressives, radiotherapy potentiate antineoplastic effect. Caution with drugs that lower seizure threshold.

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HEMATOLOGIC CANCER Adverse reactions: Bone marrow suppression, seizures, fever, rash, hypersensitivity, urticaria, azoospermia, amenorrhea, sterility, hepato- and pulmonary toxicity, secondary malignancies, GI upset. How supplied: Tabs–50

MARQIBO Spectrum

℞

Vinca alkaloid. Vincristine sulfate liposome injection; after preparation, each vial contains 0.16mg/mL; for IV infusion. Indications: Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or has progressed following ≥2 anti-leukemia therapies. Adults: 2.25mg/m2 IV over 1hr once every 7 days. Dose modifications for peripheral neuropathy: see full labeling. Children: Not established. Contraindications: Demyelinating conditions, including Charcot-Marie-Tooth syndrome. Intrathecal administration (death has occurred). Warnings/Precautions: For IV use only; fatal if given by other routes. Discontinue and treat if extravasation is suspected. Preexisting neuromuscular disorders. Monitor for symptoms of neuropathy before and during therapy; if occurs or worsens, delay, reduce or discontinue dose. Monitor CBCs prior to each dose; if Grade 3 or 4 myelosuppression develops, consider dose modification or reduction. Monitor for tumor lysis syndrome; manage if occurs. Institute a prophylactic bowel regimen to mitigate potential constipation, bowel obstruction, and/or paralytic ileus; consider dietary fiber intake, hydration, stool softeners. Monitor liver function tests; if hepatotoxicity occurs, reduce or interrupt dosing. Elderly. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Drugs known to interact with non-liposomal vincristine sulfate (eg, phenytoin: increased seizure risk). Avoid concomitant strong CYP3A inhibitors (eg, ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin) or strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s Wort). Avoid concomitant potent P-gp inhibitors or inducers. Adverse reactions: Constipation, nausea, pyrexia, fatigue (may be severe; adjust dose or discontinue), peripheral neuropathy, febrile neutropenia, diarrhea, anemia, decreased appetite, insomnia. How supplied: Kit–1, 3 (vials + supplies)

MATULANE Sigma-Tau

℞

Alkylating agent. Procarbazine (as HCl) 50mg; caps. Indications: Stage III and IV Hodgkin’s disease as part of the MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) regimen. Adults: Initially 2–4mg/kg per day for the first week, then 4–6mg/kg per day until max response

is obtained or until WBCs <4,000cells/mm3 or platelets <100,000cells/mm3. Maintain at 1–2mg/kg per day once max response attained. In MOPP regimen: 100mg/m2 daily for 14 days. Children: Individualize. Initially 50mg/m2 per day for the first week, then 100mg/m2 per day until max response is obtained or leukopenia or thrombocytopenia occurs. Maintain at 50mg/m2 per day once max response attained. Contraindications: Inadequate marrow reserve. Warnings/Precautions: Discontinue if CNS effects (eg, paresthesias, neuropathies, confusion), leukopenia, thrombocytopenia, hypersensitivity reactions, stomatitis, diarrhea, hemorrhage or bleeding tendencies occur. Hepatic or renal impairment. Obtain baseline CBCs with differential, hemoglobin, hematocrit, reticulocytes, platelets prior to therapy, then monitor at least every 3–4 days. Do renal and hepatic function tests before starting therapy, then repeated weekly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Avoid sympathomimetics, tricyclic antidepressants (eg, amitriptyline, imipramine), foods with high tyramine content (eg, wine, yogurt, ripe cheese, bananas). CNS depression with barbiturates, antihistamines, narcotics, hypotensive agents, phenothiazines. Disulfiramlike reactions with alcohol. Separate radiation or other myelosuppressives by at least 1 month (allow for bone marrow recovery). Adverse reactions: Leukopenia, anemia, thrombopenia, GI upset, bleeding tendencies, CNS effects, dysphagia, anorexia, abdominal pain, hypotension, tachycardia, syncope, cough, alopecia, dermatitis, pain, others. How supplied: Caps–100

Mitoxantrone HCl (various)

℞

Topoisomerase II inhibitor. Mitoxantrone (as HCl) 2mg/mL; soln for IV infusion after dilution; preservative-free. Indications: Acute nonlymphocytic leukemia (ANLL) in combination with other approved drugs. Adults: Give by IV infusion. See full labeling for cytarabine dose. Induction therapy: 12mg/m2 daily on Days 1–3 + cytarabine on days 1–7; if 2nd induction course needed, give for 2 days + cytarabine for 5 days using same daily dosage levels. Consolidation therapy: 12mg/m2 on Days 1–2 + cytarabine on Days 1–5 for 2 courses (1st course given 6 weeks after the final induction course and the 2nd course given 4 weeks after the 1st course). Children: Not established. Warnings/Precautions: Risk of myelosuppression esp. in high doses (>14mg/m2 daily for 3 days); do not administer if baseline neutrophil count <1500 cell/mm3, except in ANLL. Increased risk of cardiotoxicity with pre-existing cardiovascular disease, prior radiotherapy to mediastinal/ pericardial area, or previous anthracycline therapy. Assess cardiac history, physical exam, ECG, and LVEF prior to therapy. Increased risk of secondary acute myeloid leukemia. Hepatic impairment.

Monitor CBCs, platelets, liver function tests prior to each course. Monitor for signs of infection. Avoid extravasation. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Caution with concomitant cardiotoxic drugs. Adverse reactions: Myelosuppression, nausea, vomiting, infection, fever, fatigue, alopecia, dyspnea, hypersensitivity reactions, bluishgreen urine, sclera discoloration, hyperuricemia (monitor), menstrual disorders, amenorrhea, interstitial pneumonitis; cardiotoxicity (eg, CHF). How supplied: Contact supplier.

MUSTARGEN Recordati

℞

Nitrogen mustard. Mechlorethamine HCl 10mg/vial; pwd for IV or intracavitary inj after reconstitution. Indications: Palliative treatment of Hodgkin’s disease (stages III and IV), lymphosarcoma, chronic myelocytic or chronic lymphocytic leukemia, polycythemia vera, mycosis fungoides. Palliative treatment of metastatic carcinoma resulting in effusion. Adults: By IV infusion, per therapeutic course: 0.4mg/kg (lean body weight) as single dose or in divided doses of 0.1–0.2mg/kg per day. See literature for intracavitary (eg, intrapleural) administration. Do not exceed recommended dose. Repeat course only after hematological recovery (eg, every 3 weeks). Children: See literature. Contraindications: Infectious diseases. Warnings/Precautions: Drug is highly toxic; verify potential benefits outweigh risks; avoid inadvertent contact with powder or vapor. Do not use if foci of acute and chronic suppurative inflammation are present. Ensure adequate hydration. Avoid extravasation. Chronic lymphatic leukemia. Bone marrow suppression. Previous X-ray, cytotoxic chemotherapy. Infection. Hemorrhagic tendency. Monitor renal, hepatic and bone marrow function. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Adverse reactions: Bone marrow suppression, hyperheparinemia, GI upset (may be severe), anorexia, weakness, thrombosis, thrombophlebitis, hypersensitivity, jaundice, alopecia, vertigo, auditory disturbances, hemolytic anemia, skin reactions, infection, amyloidosis, hyperuricemia, gonad damage. How supplied: Vials–4

MYLERAN GlaxoSmithKline

℞

Alkylating agent. Busulfan 2mg; tabs. Indications: Palliative treatment of chronic myelogenous leukemia. Adults: Remission induction: 4–8mg/day or 60micrograms/kg or 1.8mg/m2, daily. Reserve doses >4mg/day for severe cases. Reduce dose or discontinue at first sign of reduced bone marrow reserve. Discontinue before leukocyte count normalizes; see literature. Normal leukocyte counts usually achieved in 12–20 weeks. If

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HEMATOLOGIC CANCER remission <3 months, maintenance therapy of 1–3mg/day may be advisable. Children: Remission induction: 60micrograms/kg or 1.8mg/m2, daily. Reduce dose or discontinue at first sign of reduced bone marrow reserve. Discontinue before leukocyte count normalizes. Normal leukocyte counts usually achieved in 12–20 weeks. See literature. Warnings/Precautions: Confirm diagnosis. Monitor hepatic and bone marrow function. Obtain CBCs and differential weekly; monitor for anemia. Previously compromised bone marrow (irradiation, chemotherapy). Seizure disorder or risk. Head trauma. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Myelosuppression increased with other myelosuppressives. Increased pulmonary toxicity with other cytotoxic drugs. Potentiated by itraconazole, cyclophosphamide (see literature). May be antagonized by phenytoin. Hepatotoxicity possible with long-term continuous thioguanine therapy. Caution with drugs that lower seizure threshold. Adverse reactions: See literature. Bone marrow suppression (eg, pancytopenia, anemia, leukopenia, thrombocytopenia, aplastic anemia), pulmonary toxicity, cellular dysplasia, malignant tumors, acute leukemias, cardiac tamponade (esp. in thalassemia), hyperpigmentation, adrenal insufficiency, seizures, hepatic veno-occlusive disease, infection (eg, pneumonia, sepsis), mucositis, myasthenia gravis, gonadal suppression, rash; rare: cataracts, bronchopulmonary dysplasia (discontinue if occurs). How supplied: Tabs–25

ONCASPAR Sigma-Tau

℞

Enzyme. Pegaspargase 750 IU/mL; soln for IV or IM inj; preservative-free. Indications: First-line acute lymphoblastic leukemia (including patients with asparaginase hypersensitivity). Adults and Children: Give by IV inj over 1–2 hours or by IM inj (max 2mL/inj site). 2500 IU/m2 no more frequently than every 14 days. Contraindications: History of pancreatitis, serious hemorrhage, or thrombosis with prior L-asparaginase therapy. Warnings/Precautions: Have resuscitation equipment available and observe patient for 1 hour post-dose. Monitor coagulation parameters. Discontinue if serious allergic reactions, thrombotic events, or pancreatitis occurs. Pregnancy (Cat.C). Nursing mothers: not recommended. Adverse reactions: Allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, CNS thrombosis, coagulopathy, hyperbilirubinemia, elevated transaminases. How supplied: Single-use vial (5mL)–1

ONTAK Eisai

℞

Interleukin 2-diphtheria toxin fusion protein. Denileukin diftitox 150mcg/mL; soln for IV infusion after thawing and dilution. Indications: Persistent or recurrent cutaneous T-cell lymphoma in which malignant cells express the CD25 component of the IL-2 receptor. Adults: Premedicate with an antihistamine or acetaminophen prior to each infusion. Give by IV infusion over 30–60 minutes. 9 or 18mcg/kg per day for 5 consecutive days every 21 days for 8 cycles. Children: Not recommended. Warnings/Precautions: Ensure CD25 expression before starting therapy. Have resuscitative equipment available during administration. Permanently discontinue if serious infusion reactions occur. Monitor for signs/symptoms of capillary leak syndrome (hypotension, edema, hypoalbuminemia) and weight gain. Monitor serum albumin levels prior to each treatment course; withhold treatment if serum albumin <3g/dL. Pregnancy (Cat.C). Nursing mothers: not recommended. Adverse reactions: Fever, fatigue, rigors, GI upset, headache, edema, cough, dyspnea, pruritus, rash, hypotension, back pain, myalgia, chest pain, tachycardia, hypoalbuminemia, asthenia, elevated transaminases; capillary leak syndrome (may be fatal), serious infusion reactions, visual impairment (monitor). Testing considerations: CD25 expression How supplied: Single-use vials (2mL)–6

Pamidronate disodium

Injection (various)

℞

Bisphosphonate. Pamidronate disodium 30mg, 90mg; per vial; pwd for IV infusion after reconstitution; contains mannitol. Indications: Osteolytic lesions of multiple myeloma. Adults: Give by IV infusion. 90mg infused over 4hrs once monthly. Max single dose: 90mg. Children: Not recommended. Warnings/Precautions: Severe renal impairment in patients with bone metastases: not recommended. Renal or hepatic insufficiency. Check serum creatinine before each dose: withhold until serum creatinine is within 10% of baseline if serum creatinine increases 0.5mg/dL from normal pre-treatment levels, or by 1mg/dL from an abnormal pre-treatment level. Monitor electrolytes (esp. calcium, magnesium, phosphate, potassium), CBC/differential, hematocrit/hemoglobin. Preexisting blood disorders (eg, anemia, leukopenia, thrombocytopenia); monitor closely for first 2 weeks after treatment. Avoid dental surgery (do preventative dental work before therapy). Evaluate if thigh or groin pain develops and consider discontinuing if

F P O for

atypical femur fracture is suspected. Pregnancy (Cat.D): not recommended. Nursing mothers. Interactions: Caution with other nephrotoxic drugs (eg, thalidomide). Adverse reactions: Infusion-site reactions, fever, headache, dizziness, paresthesia, increased sweating, GI upset, anemia, fatigue, musculoskeletal pain (may be severe), electrolyte disturbances, hypertension, dyspnea, renal toxicity; jaw osteonecrosis, atypical subtrochanteric and diaphyseal femoral fractures. How supplied: Contact supplier.

Pentostatin Bedford

℞

Antimetabolite. Pentostatin 10mg/vial; lyophilized pwd for IV inj after reconstitution; contains mannitol. Indications: Active hairy cell leukemia. Adults: Ensure adequate hydration. Give as IV bolus or infuse over 20–30 minutes after dilution. 4mg/m2 every other week. Reevaluate after 6 months; discontinue if complete or partial response not achieved; max duration of therapy 12 months. Withhold dose if ANC <200 cells/mm3; may resume when resolved. Children: Not recommended. Warnings/Precautions: Active infections; treat prior to initiating therapy. Withhold or discontinue therapy if severe rash or neurotoxicity develops. Renal impairment. Monitor and obtain CBCs, liver, and renal function before and during therapy. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Concomitant fludarabine: not recommended. Potentiates vidarabine. Acute pulmonary toxicity and hypotension with carmustine, etoposide, and high dose cyclophosphamide (see literature). Adverse reactions: GI upset, fever, rash, fatigue, leukopenia, pruritus, cough, myalgia, chills, headache, abdominal pain, anorexia, asthenia, stomatitis, rhinitis, dyspnea, anemia, pain, sweating, infections, thrombocytopenia. How supplied: Single-dose vials–1

POMALYST Celgene

℞

Immunomodulator. Pomalidomide 1mg, 2mg, 3mg, 4mg; capsules. Indications: Multiple myeloma, in patients who have received at least two prior therapies (including lenalidomide and bortezomib), and have shown disease progression on or within 60 days of completion of the last therapy. Clinical benefit, such as improvement in survival or symptoms, has not been verified. Adults: Swallow whole; may be taken with water. Take without food. 4mg once daily on Days 1–21 of repeated 28-day cycles until disease progression;

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HEMATOLOGIC CANCER may give with dexamethasone. Dose modification for hematologic and other Grade 3/4 toxicities: see full labeling. Children: <18yrs: not established. Contraindications: Pregnancy (Cat.X): avoid during and for at least 4 weeks after completing therapy. Warnings/Precautions: Females of reproductive potential must commit either to abstain from heterosexual sex or to use two methods of reliable contraception, beginning 4 weeks prior to initiating, during therapy, dose interruptions and for 4 weeks after discontinuation. Obtain two negative pregnancy tests prior to initiating therapy: perform first test within 10–14 days, and second test within 24 hours prior to prescribing, and then weekly during first month, then monthly thereafter in women with regular menstrual cycles or every 2 weeks if irregular cycles. Males: must use latex or synthetic condom during therapy and up to 28 days after discontinuing, even after successful vasectomy; do not donate sperm. Patients must not donate blood during therapy and for 1 month after discontinuation. Venous thromboembolism; consider anticoagulation prophylaxis. Monitor for hematologic toxicities (esp. neutropenia); obtain CBCs weekly for first 8 weeks and monthly thereafter; may need dose interruption and/or modification. Renal impairment (serum creatinine >3mg/dL) or hepatic impairment (serum bilirubin >2mg/dL and AST/ALT >3x ULN): avoid. Risk of hypersensitivity or second primary malignancies. Nursing mothers: not recommended. Interactions: May be potentiated by strong CYP1A2, CYP3A (eg, ketoconazole), or P-gp inhibitors; avoid. May be antagonized by strong CYP1A2, CYP3A (eg, rifampin), or P-gp inducers; avoid. Smoking may reduce efficacy. Adverse reactions: Fatigue, asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, pyrexia; venous thromboembolism, dizziness, confusion, neuropathy, pneumonia, thrombocytopenia. Note: Available only through Pomalyst REMS program. How supplied: Caps–21, 100

PURINETHOL Teva

℞

Antimetabolite. Mercaptopurine (6-MP) 50mg; scored tabs. Indications: Maintenance therapy of acute lymphatic leukemia as part of a combination regimen. Adults and Children: 1.5–2.5mg/kg per day as a single dose. Concomitant allopurinol: reduce dose of mercaptopurine to 1/3–1/4 of the usual dose. TPMT-deficient, renal or hepatic impairment: reduce dose, see literature. Contraindications: Prior resistance to mercaptopurine. Warnings/Precautions: Not effective in CNS leukemia, acute myelogenous leukemia, chronic

lymphocytic leukemia, the lymphomas (including Hodgkin’s disease), or solid tumors. Renal impairment. Monitor liver function tests weekly at start of therapy, then monthly thereafter; discontinue if hepatotoxicity occurs. Preexisting liver disease (monitor more frequently). Obtain CBCs with differential, hemoglobin, hematocrit, platelets; discontinue if severe bone marrow suppression occurs. Thiopurine-Smethyltransferase (TPMT) deficient: increased risk of myelosuppression, consider genotypic/ phenotypic testing. Pregnancy (Cat.D); esp. 1st trimester, nursing mothers: not recommended. Interactions: Increased risk of bone marrow suppression with allopurinol, aminosalicylate derivatives (eg, olsalazine, mesalazine, sulphasalazine), trimethoprim-sulfamethoxazole. Antagonizes warfarin. Caution with concomitant hepatotoxic agents. Adverse reactions: Myelosuppression, hyperuricemia/hyperuricosuria, GI upset, intestinal ulceration, rash, hyperpigmentation, alopecia, oligospermia; hepatotoxicity, infection, immunosuppression. How supplied: Tabs–60

REVLIMID Celgene

cycles 2–4, and then monthly thereafter. Renal impairment (monitor). Monitor for tumor lysis syndrome in those with high tumor burden. Monitor liver enzymes; discontinue if elevation occurs. Monitor for second primary malignancies. Maximum 1 month per ℞. Nursing mothers: not recommended. Interactions: Monitor digoxin. Concomitant warfarin; monitor PT, INR. May increase risk of thrombosis with erythropoietic agents or estrogen containing therapies. Adverse reactions: Birth defects, thrombocytopenia, neutropenia, GI upset, pruritus, rash, fatigue, arthralgia, pyrexia, back pain, cough, dizziness, headache, dyspnea, blurred vision, muscle cramp; thrombosis/ embolism, allergic reactions (discontinue if occurs; do not resume), tumor flare reaction (monitor; esp. in treating MCL), hepatotoxicity. Note: Available only through RevAssist program. Report any suspected fetal exposure to the FDA at (800) FDA-1088 and Celgene at (888) 423-5436. How supplied: Caps 2.5mg, 5mg, 10mg–28, 100; 15mg, 20mg, 25mg–21, 100

RITUXAN Genentech ℞

Immunomodulator. Lenalidomide 2.5mg, 5mg, 10mg, 15mg, 20mg, 25mg; caps. Indications: In combination with dexamethasone for treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. Treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. Adults: Do not break, chew, or open caps. Swallow whole with water. ≥18yrs: initially 25mg once daily on Days 1–21 of each 28-day cycle. Renal impairment: Moderate (CrCL 30–60mL/min): 10mg per day. Severe (CrCL <30mL/min without dialysis): 15mg every 48 hrs. ESRD (CrCL <30mL/min with dialysis): 5mg once daily; administer after dialysis (on dialysis days). Dose adjustments if thrombocytopenia or neutropenia develops: see full labeling. Children: <18yrs: not established. Contraindications: Pregnancy (Cat.X). Women who may become pregnant. Warnings/Precautions: Must register patient in RevAssist program; patient must understand toxicity with fetal exposure. Counsel patient on need for contraception; female: use 2 forms of contraception 1 month before, during, and 1 month after therapy; male: use condom during and 1 month after therapy; obtain 2 negative pregnancy tests (one within 10–14 days, and then another within 24 hours prior to starting therapy), repeat at least weekly for 1st month then every 4 weeks; get informed consent. Monitor for signs/symptoms of thromboembolic events. For MM: obtain CBCs every 2 weeks for first 3 months, then monthly. For MCL: obtain CBCs weekly for the first cycle, every 2 weeks during

℞

CD20-directed cytolytic monoclonal antibody. Rituximab 10mg/mL; soln for IV infusion; preservative-free. Indications: Relapsed or refractory, low-grade or follicular, CD20(+), B-cell non-Hodgkin’s lymphoma (NHL). Previously untreated follcular, CD20(+), B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to Rituxan in combination with chemotherapy, as singleagent maintenance therapy. Non-progressing (including stable disease), low-grade, CD20(+), B-cell NHL as a single agent after first-line CVP chemotherapy. Previously untreated diffuse large B-cell, CD20(+) NHL (DLBCL) in combination with CHOP or other anthracycline-based chemotherapy regimens. CD20(+) chronic lymphocytic leukemia (CLL) in combination with fludarabine and cyclophosphamide. Limitation of use: not recommended for use in patients with severe, active infections. Adults: Give by IV infusion. Premedicate with an antihistamine and acetaminophen prior to each infusion. First infusion: initially at a rate of 50mg/hr; may increase infusion rate in 50mg/hr increments every 30 mins. Subsequent infusions: initially at a rate of 100mg/hr; may increase infusion rate in 100mg/hr increments every 30 mins. Both: max 400mg/hr if infusion reactions do not occur. Previously untreated follicular NHL and DLBCL patients: if no Grade 3 or 4 infusion related adverse events during Cycle 1, a 90-minute infusion may be given in Cycle 2 with a glucocorticoid-containing chemotherapy regimen (see full labeling). NHL: 375mg/m2 once weekly for 4 or 8 doses. Retreatment therapy: 375mg/m2 once weekly for 4 doses. Previously untreated, follicular, CD20(+), B-cell NHL: 375mg/m2 on

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HEMATOLOGIC CANCER Day 1 of each cycle of CVP chemotherapy for up to 8 doses. In patients with complete or partial response, initiate Rituxan maintenance 8 weeks following completion of Rituxan in combination with chemotherapy. Administer Rituxan as a single-agent every 8 weeks for 12 doses. Low-grade, CD20(+), B-cell NHL after CVP chemotherapy: 375mg/m2 once weekly for 4 doses every 6 months for up to 16 doses. Diffuse large B-cell NHL: 375mg/m2 on Day 1 of each cycle for up to 8 infusions. CLL: 375mg/m2 the day prior to FC chemotherapy, then 500mg/m2 on Day 1 of cycles 2–6 (every 28 days). Give PCP and antiherpetic viral prophylaxis during and up to 12 months after CLL therapy. As a component of Zevalin regimen: see full labeling. Children: Not established. Warnings/Precautions: Discontinue if severe infusion or mucocutaneous reactions occur (eg, urticaria, hypotension, angioedema, hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, MI, ventricular fibrillation, cardiogenic shock, paraneoplastic pemphigus, StevensJohnson syndrome, lichenoid or vesiculobullous dermatitis, toxic epidermal necrolysis). Increased risk of HBV reactivation. Test/treat HBV infection prior to initiating therapy. Monitor for signs of hepatitis or HBV reactivation during and for several months after therapy; discontinue if HBV reactivation occurs. Tumor lysis syndrome (esp. with high tumor burden); monitor for renal toxicity, fluid balance, electrolyte abnormalities (correct if occurs); discontinue if SCr rises or oliguria occurs. Monitor for new-onset neurologic manifestations; discontinue if progressive multifocal leukoencephalopathy (PML) develops. Discontinue and treat if serious infections (eg, bacterial, fungal, viral) occur. Pre-existing cardiovascular disease; monitor during and after treatment. Monitor CBCs, platelet counts during treatment, then periodically. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Live virus vaccines: not recommended. Renal toxicity with cisplatin. Adverse reactions: Fever, chills, rigors, nausea, vomiting, diarrhea, asthenia, fatigue, headache, throat irritation, flushing, rash, pruritus, urticaria, angioedema, cough, rhinitis, bronchospasm, dizziness, myalgia, arthralgia, hypotension, hypertension, chest tightness; myelosuppression (eg, lymphopenia, neutropenia, leukopenia, anemia, thrombocytopenia), infusion reactions (may be fatal), mucocutaneous reactions (may be fatal), PML, serious infections, tumor lysis syndrome, renal toxicity, bowel obstruction/perforation, HBV reactivation with fulminant hepatitis, cardiac arrhythmias (discontinue if serious). Testing considerations: FCGR3A genotype testing How supplied: Single-use vial (10mL, 50mL)–1

SPRYCEL Bristol-Myers Squibb

℞

Tyrosine kinase inhibitor. Dasatinib 20mg, 50mg, 70mg, 80mg, 100mg, 140mg; tabs. Indications: Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib. Philadelphia chromosomepositive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. Adults: Swallow whole. ≥18yrs: Chronic phase CML: 100mg once daily. Doses of up to 140mg once daily have been used. Accelerated phase CML, myeloid or lymphoid blast CML, Ph+ ALL: 140mg once daily. Doses of up to 180mg once daily have been used. Concomitant CYP3A4 inhibitors (see Interactions): consider reducing dose. Concomitant CYP3A4 inducers (see Interactions): consider increasing dose. See literature for dose adjustments with toxicity. Children: <18yrs: not established. Warnings/Precautions: History of QT prolongation. Proarrhythmic conditions. Cumulative high-dose anthracycline therapy. Monitor for signs/symptoms of cardiac dysfunction; treat appropriately if occur. Hypokalemia, hypomagnesemia; correct electrolyte imbalances before starting therapy. Monitor for pleural effusions. Increased risk of pulmonary arterial hypertension (PAH); evaluate for signs/symptoms of underlying cardiopulmonary disease before and during treatment; permanently discontinue if occurs. Obtain CBCs weekly for the first 2 months, then monthly thereafter. Hepatic impairment. Pregnancy (Cat.D; use adequate contraception); nursing mothers: not recommended. Interactions: Avoid potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, ritonavir, atazanavir, indinavir, nefazodone, nelfinavir, saquinavir, telithromycin, voriconazole), grapefruit juice. May be antagonized by CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital); St. John’s wort: not recommended. Separate dosing of antacids by at least 2hrs; H2 blockers, proton pump inhibitors: not recommended. May potentiate drugs metabolized by CYP3A4 (eg, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, ergot alkaloids). Caution with concomitant anticoagulants or drugs that inhibit platelet function. Caution with anti-arrhythmics or other drugs that may lead to QT prolongation. Adverse reactions: Myelosuppression (eg, severe thrombocytopenia, neutropenia, anemia), fluid retention (eg, ascites, edema, pleural and pericardial effusions), diarrhea,

F P O for

headache, dyspnea, musculoskeletal pain, rash, fatigue, severe hemorrhage (eg, CNS, GI); QT prolongation; cardiac events (eg, cardiomyopathy, CHF, fatal MI, left ventricular dysfunction); PAH. How supplied: Tabs 20mg, 50mg, 70mg–60; 80mg, 100mg, 140mg–30

SYNRIBO Teva

℞

Protein synthesis inhibitor. Omacetaxine mepesuccinate 3.5mg/vial; lyophilized powder for SC injection after reconstitution; contains mannitol; preservative-free. Indications: Treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/ or intolerance to two or more tyrosine kinase inhibitors (TKI). Adults: Induction: 1.25mg/m2 by SC injection twice daily for 14 consecutive days every 28 days, over a 28-day cycle. Repeat cycles every 28 days until hematologic response achieved. Maintenance: 1.25mg/m2 by SC injection twice daily for 7 consecutive days every 28 days, over a 28-day cycle, as long as clinically beneficial. Dose adjustments and modifications: see full labeling. Children: Not established. Warnings/Precautions: Risk of myelosuppression (thrombocytopenia, neutropenia, anemia), hemorrhage (cerebral, GI). Monitor CBCs with platelets weekly during induction, initial maintenance cycles, and every 2 weeks during later cycles. Monitor glucose levels (esp. in diabetics). Avoid in poorly controlled diabetes until glycemic control is established. Elderly. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Avoid concomitant anticoagulants, aspirin, NSAIDs if platelets <50,000/microliters; may increase risk of bleeding. Adverse reactions: Thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, lymphopenia; bleeding, hyperglycemia. How supplied: Single-use vial–1

TABLOID GlaxoSmithKline

℞

Antimetabolite. Thioguanine 40mg; tabs; scored. Indications: Remission induction and remission consolidation treatment of acute nonlymphocytic leukemias. Treatment of the chronic phase of chronic myelogenous leukemia (see literature). Adults and Children: See literature. Initially, 2mg/kg per day. If, after 4 weeks, with no improvement, no leukocyte or platelet depression, may increase to 3mg/kg per day. Total daily dose may be given at one time. Contraindications: Allergy to mercaptopurine. Warnings/Precautions: Not recommended for maintenance therapy or long-term continuous

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HEMATOLOGIC CANCER treatments; increased risk of liver toxicity (discontinue if occurs). Pre-existing liver disease. Monitor liver function tests weekly at start of therapy, then monthly thereafter. Thiopurine methyltransferase (TPMT) enzyme deficiency (may need to reduce dose to avoid severe bone marrow suppression); consider testing for TPMT deficiency. Obtain hemoglobin, hematocrit, WBCs with differential, platelets frequently during therapy. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Avoid live vaccines (if immunocompromised). Caution with drugs that inhibit TPMT (eg, olsalazine, mesalazine, or sulphasalazine). Adverse reactions: Myelosuppression, hyperuricemia, GI upset, anorexia, stomatitis, hepatotoxicity, elevated liver enzymes, jaundice (discontinue if occurs). How supplied: Tabs–25

TARGRETIN Eisai

℞

Retinoid. Bexarotene 75mg; caps. Indications: Cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. Adults: Take with food. Initially 300mg/m2 once daily; may increase after 8 weeks to 400mg/m2 once daily if no tumor response and if well tolerated; monitor carefully. If toxicity occurs, reduce to 200mg/m2 then 100mg/m2 once daily, or suspend therapy. Children: Not recommended. Contraindications: Pregnancy (Cat.X). Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Pancreatitis or risk of pancreatitis (eg, history of pancreatitis, uncontrolled hyperlipidemia, excess alcohol consumption, uncontrolled diabetes, biliary tract disease, drugs that can cause pancreatitis). Counsel patients monthly about need for contraception. Women of childbearing potential: obtain reliable negative pregnancy test within 1 week of start; repeat monthly. Start therapy on 2nd or 3rd day of normal menstrual period. Use two effective forms of contraception 1 month prior to, during, and for 1 month after therapy. Max 1 month/℞. Men with partners who are or may become pregnant: use condoms during and for at least 1 month after therapy. Monitor lipids before treatment, weekly until stable, then every 8 weeks; try to keep triglycerides <400mg/dL; treat hyperlipidemia, or reduce or suspend bexarotene if needed. Hepatic or renal insufficiency. Monitor liver function at baseline, 1, 2, and 4 weeks after start, then (if stable) at least every 8 weeks during therapy; consider suspending or discontinuing treatment if SGOT/AST, SGPT/ALT, or bilirubin >3×ULN occurs. Monitor WBC with differential and thyroid function at baseline and during treatment; treat hypothyroidism if needed. Avoid sun and UV light. Nursing mothers: not recommended. Interactions: Concomitant gemfibrozil: not recommended. Levels may be increased by CYP3A4 inhibitors (eg, ketoconazole, itraconazole,

erythromycin, grapefruit juice). Levels may be reduced by CYP3A4 inducers (eg, rifampin, phenobarbital, phenytoin). May potentiate antihyperglycemics (eg, insulin, sulfonylureas, thiazolidinediones); monitor. May potentiate or be potentiated by protein-bound drugs. May antagonize tamoxifen, hormonal contraceptives, other CYP3A4 substrates. Limit Vit. A supplements to avoid toxicity. May increase CA125 assay values. Adverse reactions: Lipid abnormalities, headache, hypothyroidism, asthenia, leukopenia, anemia, rash, GI disturbances, peripheral edema, dry skin, exfoliative dermatitis, alopecia, insomnia, fatigue, abnormal liver function tests, pancreatitis, pruritus, photosensitivity. How supplied: Caps–100

TARGRETIN GEL Eisai

℞

Retinoid. Bexarotene 1%; gel. Indications: Cutaneous lesions in patients with CTCL (Stage IA and IB) who have refractory or persistent disease after other therapies or who have not tolerated other therapies. Adults: Apply once every other day for the 1st week; then increase frequency at weekly intervals to once daily, then twice daily, then 3 times daily, then 4 times daily based on lesion tolerance. Usual dosing frequency: 2–4 times daily; may reduce if application site toxicity occurs. Allow gel to dry. Do not occlude. Children: Not recommended. Contraindications: Pregnancy (Cat.X). Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Counsel patients monthly about need for contraception. Women of childbearing potential: obtain reliable negative pregnancy test within 1 week of start; repeat monthly. Start therapy on 2nd or 3rd day of normal menstrual period. Use two effective forms of contraception 1 month prior to, during, and for 1 month after therapy. Max 1 month/℞. Men with partners who are or may become pregnant: use condoms during and for at least 1 month after therapy. Hepatic or renal insufficiency. Discontinue temporarily if severe irritation occurs. Avoid sun, UV light, and mucosal membranes. Nursing mothers: not recommended. Interactions: Avoid concomitant products that contain DEET. May be potentiated by CYP3A4 inhibitors (eg, ketoconazole, itraconazole, erythromycin, grapefruit juice). Caution with gemfibrozil. Limit Vit. A supplements to avoid toxicity. Adverse reactions: Application site reactions (eg, rash, pruritus, skin disorders, pain, contact dermatitis). How supplied: Gel–60g

TASIGNA Novartis

℞

Kinase inhibitor. Nilotinib (as HCl monohydrate) 150mg, 200mg; caps; contains lactose. Indications: Newly diagnosed adults with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. Chronic and accelerated phase Ph+ CML in adults resistant or intolerant to imatinib.

Adults: Take on an empty stomach. Swallow whole with water; if unable, may disperse capsule contents in 1 tsp of applesauce, then take immediately (within 15 mins). Newly diagnosed Ph+ CML: 300mg every 12hrs. Hepatic impairment (mild, moderate, severe): initially 200mg twice daily, followed by dose increase to 300mg twice daily if tolerated. Resistant or intolerant Ph+ CML: 400mg every 12hrs. Hepatic impairment (mild or moderate): initially 300mg twice daily, followed by dose increase to 400mg twice daily if tolerated; severe: initially 200mg twice daily, followed by sequential dose increase to 300mg twice daily, and then 400mg twice daily if tolerated. May give concomitant hematopoietic growth factors, hydroxyurea, or anagrelide if clinically indicated. See full labeling for dose adjustments in QT prolongation, hematological and non-hematological toxicities, concomitant strong CYP3A4 inhibitors and inducers. Children: Not established. Contraindications: Hypokalemia. Hypomagnesemia. Long QT syndrome. Warnings/Precautions: Prolongs QT interval, sudden deaths have been reported; correct electrolyte abnormalities before starting; monitor. Monitor ECG at baseline, after 7 days, then periodically and after dose changes. Hereditary galactose intolerance, severe lactase deficiency, glucose-galactose malabsorption: not recommended. Hepatic impairment. History of pancreatitis. Cardiovascular disorders. Monitor for myelosuppression; withhold or reduce dose if occurs; perform CBCs every 2 weeks for 1st 2 months then once monthly. Monitor serum lipase, liver function monthly. Total gastrectomy (monitor frequently); consider dose increase or alternative therapy. Tumor lysis syndrome possible; maintain adequate hydration, correct uric acid levels prior to initiating therapy. Pregnancy (Cat.D) (use adequate contraception), nursing mothers: not recommended. Interactions: Avoid concomitant food (for at least 2hrs before and 1hr after dose), antiarrhythmics (eg, amiodarone, disopyramide, procainamide, quinidine, sotalol), or other drugs that may prolong QT interval (eg, chloroquine, haloperidol, methadone, moxifloxacin, pimozide). Avoid strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), grapefruit; if necessary, interrupt therapy or consider dose reduction of nilotinib; if unavoidable, monitor closely for QT prolongation. Avoid strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s wort. May affect, or be affected by, other drugs metabolized by CYP3A4, 2B6, 2C8, 2C9, 2D6, UGT1A1, P-glycoprotein. Concomitant proton pump inhibitors: not recommended. Administer H2-blockers at least 10hrs before or 2hrs after nilotinib dose. Separate dosing of antacids by at least 2hrs of nilotinib dose. Adverse reactions: Rash, pruritus, nausea, fatigue, headache, myalgia, nasopharyngitis, constipation, diarrhea, abdominal pain, vomiting, arthralgia,

76 CANCER THERAPY ADVISOR | FALL 2014 | CancerTherapyAdvisor.com

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8/25/14 4:44 PM

Start with TREANDA® (bendamustine HCI) for Injection for established front-line CLL therapy

TREANDA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). Efficacy relative to first-line therapies other than chlorambucil has not been established. Important Safety Information Contraindication: TREANDA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine. Myelosuppression: TREANDA caused severe myelosuppression (Grade 3-4) in 98% of patients in the two NHL studies. Three patients (2%) died from myelosuppression-related adverse reactions. If myelosuppression occurs, monitor leukocytes, platelets, hemoglobin (Hgb), and neutrophils frequently. Myelosuppression may require dose delays and/or subsequent dose reductions if recovery to the recommended values has not occurred by the first day of the next scheduled cycle. Infections: Infection, including pneumonia, sepsis, septic shock, and death have occurred. Patients with myelosuppression following treatment with TREANDA are more susceptible to infections. Anaphylaxis and Infusion Reactions: Infusion reactions to TREANDA have occurred commonly in clinical trials. Symptoms include fever, chills, pruritus, and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe (Grade 3-4) reactions. Ask patients about symptoms suggestive of infusion reactions after their first cycle of therapy. Consider measures to prevent severe reactions, including antihistamines, antipyretics, and corticosteroids in subsequent cycles in patients who have experienced Grade 1 or 2 infusion reactions. Tumor Lysis Syndrome: Tumor lysis syndrome associated with TREANDA treatment has occurred. The onset tends to be within the first treatment cycle of TREANDA and, without intervention, may lead to acute renal failure and death. Preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium and uric acid levels. There may be an increased risk of severe skin toxicity when TREANDA and allopurinol are administered concomitantly. ©2014 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved. TRE-40315 January 2014.

727-37345

DIGITAL

Skin Reactions: Skin reactions have been reported with TREANDA treatment and include rash, toxic skin reactions, and bullous exanthema. In a study of TREANDA (90 mg/m2) in combination with rituximab, one case of toxic epidermal necrolysis (TEN) occurred. TEN has been reported for rituximab. Cases of Stevens-Johnson syndrome (SJS) and TEN, some fatal, have been reported when TREANDA was administered concomitantly with allopurinol and other medications known to cause these syndromes. Where skin reactions occur, they may be progressive and increase in severity with further treatment. Monitor patients with skin reactions closely. If skin reactions are severe or progressive, withhold or discontinue TREANDA. Other Malignancies: There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with TREANDA, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia, and bronchial carcinoma. The association with TREANDA therapy has not been determined. Extravasation Injury: TREANDA extravasations have been reported in postmarketing resulting in hospitalizations from erythema, marked swelling, and pain. Ensure good venous access prior to starting TREANDA infusion and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of TREANDA. Embryo-fetal Toxicity: TREANDA can cause fetal harm when administered to a pregnant woman. Women should be advised to avoid becoming pregnant while using TREANDA. Most Common Adverse Reactions: The most common non-hematologic adverse reactions for CLL (frequency ≥15%) are pyrexia, nausea, and vomiting. The most common hematologic abnormalities (frequency ≥15%) are anemia, thrombocytopenia, neutropenia, lymphopenia, and leukopenia.

Please see accompanying brief summary of Full Prescribing Information on following pages. Learn more at TREANDAHCP.com.

Job Number: 20391 Revision No: 0 Date: 01/08/14

Start with TREANDA® (bendamustine HCI) for Injection for established front-line CLL therapy

727-37345

DIGITAL

Please see accompanying brief summary of Full Prescribing Information on following pages. Learn more at TREANDAHCP.com.

Job Number: 20391 Revision No: 0 Date: 01/08/14

Brief Summary of Prescribing Information for Chronic Lymphocytic Leukemia 1 INDICATIONS AND USAGE TREANDA® is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). Efficacy relative to first line therapies other than chlorambucil has not been established. 2 DOSAGE AND ADMINISTRATION 2.1 Dosing Instructions for CLL Recommended Dosage: The recommended dose is 100 mg/m2 administered intravenously over 30 minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles. Dose Delays, Dose Modifications and Reinitiation of Therapy for CLL: TREANDA administration should be delayed in the event of Grade 4 hematologic toxicity or clinically significant ≥ Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to ≤ Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) ≥ 1 x 109/L, platelets ≥ 75 x 109/L], TREANDA can be reinitiated at the discretion of the treating physician. In addition, dose reduction may be warranted. [See Warnings and Precautions (5.1)] Dose modifications for hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 25 mg/m2 on Days 1 and 2 of each cycle. Dose modifications for non-hematologic toxicity: for clinically significant Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle. Dose re-escalation in subsequent cycles may be considered at the discretion of the treating physician. 2.3 Reconstitution/Preparation for Intravenous Administration Aseptically reconstitute each TREANDA vial as follows: • 25 mg TREANDA vial: Add 5 mL of only Sterile Water for Injection, USP. • 100 mg TREANDA vial: Add 20 mL of only Sterile Water for Injection, USP. Shake well to yield a clear, colorless to a pale yellow solution with a bendamustine HCl concentration of 5 mg/mL. The lyophilized powder should completely dissolve in 5 minutes. If particulate matter is observed, the reconstituted product should not be used. Aseptically withdraw the volume needed for the required dose (based on 5 mg/mL concentration) and immediately transfer to a 500 mL infusion bag of 0.9% Sodium Chloride Injection, USP (normal saline). As an alternative to 0.9% Sodium Chloride Injection, USP (normal saline), a 500 mL infusion bag of 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, may be considered. The resulting final concentration of bendamustine HCl in the infusion bag should be within 0.2–0.6 mg/mL. The reconstituted solution must be transferred to the infusion bag within 30 minutes of reconstitution. After transferring, thoroughly mix the contents of the infusion bag. The admixture should be a clear and colorless to slightly yellow solution. Use Sterile Water for Injection, USP, for reconstitution and then either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, for dilution, as outlined above. No other diluents have been shown to be compatible. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Any unused solution should be discarded according to institutional procedures for antineoplastics. 2.4 Admixture Stability TREANDA contains no antimicrobial preservative. The admixture should be prepared as close as possible to the time of patient administration. Once diluted with either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, the final admixture is stable for 24 hours when stored refrigerated (2-8°C or 36-47°F) or for 3 hours when stored at room temperature (15-30°C or 59-86°F) and room light. Administration of TREANDA must be completed within this period. 3 DOSAGE FORMS AND STRENGTHS TREANDA for Injection single-use vial containing either 25 mg or 100 mg of bendamustine HCl as white to off-white lyophilized powder. 4 CONTRAINDICATIONS TREANDA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine. [See Warnings and Precautions (5.3)] 5 WARNINGS AND PRECAUTIONS 5.1 Myelosuppression TREANDA caused severe myelosuppression (Grade 3-4) in 98% of patients in the two NHL studies. Three patients (2%) died from myelosuppressionrelated adverse reactions; one each from neutropenic sepsis, diffuse alveolar hemorrhage with Grade 3 thrombocytopenia, and pneumonia from an opportunistic infection (CMV). In the event of treatment-related myelosuppression, monitor leukocytes, platelets, hemoglobin (Hgb), and neutrophils frequently. In the clinical trials, blood counts were monitored every week initially. Hematologic nadirs were observed predominantly in the third week of therapy. Myelosuppression may require dose delays and/or subsequent dose reductions if recovery to the recommended values has not occurred by the first day of the next scheduled cycle. Prior to the initiation of the next cycle of therapy, the ANC should be ≥ 1 x 109/L and the platelet count should be ≥ 75 x 109/L. [See Dosage and Administration (2.1)]

727-37345 Pg3 PRINT

5.2 Infections Infection, including pneumonia, sepsis, septic shock, and death have occurred in adult and pediatric patients in clinical trials and in postmarketing reports. Patients with myelosuppression following treatment with TREANDA are more susceptible to infections. Advise patients with myelosuppression following TREANDA treatment to contact a physician if they have symptoms or signs of infection. 5.3 Anaphylaxis and Infusion Reactions Infusion reactions to TREANDA have occurred commonly in clinical trials. Symptoms include fever, chills, pruritus and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe reactions. Ask patients about symptoms suggestive of infusion reactions after their first cycle of therapy. Patients who experience Grade 3 or worse allergic-type reactions should not be rechallenged. Consider measures to prevent severe reactions, including antihistamines, antipyretics and corticosteroids in subsequent cycles in patients who have experienced Grade 1 or 2 infusion reactions. Discontinue TREANDA for patients with Grade 4 infusion reactions. Consider discontinuation for Grade 3 infusion reactions as clinically appropriate considering individual benefits, risks, and supportive care. 5.4 Tumor Lysis Syndrome Tumor lysis syndrome associated with TREANDA treatment has occurred in patients in clinical trials and in postmarketing reports. The onset tends to be within the first treatment cycle of TREANDA and, without intervention, may lead to acute renal failure and death. Preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium and uric acid levels. Allopurinol has also been used during the beginning of TREANDA therapy. However, there may be an increased risk of severe skin toxicity when TREANDA and allopurinol are administered concomitantly [see Warnings and Precautions (5.5)]. 5.5 Skin Reactions Skin reactions have been reported with TREANDA treatment in clinical trials and postmarketing safety reports, including rash, toxic skin reactions and bullous exanthema. Some events occurred when TREANDA was given in combination with other anticancer agents. In a study of TREANDA (90 mg/m2) in combination with rituximab, one case of toxic epidermal necrolysis (TEN) occurred. TEN has been reported for rituximab (see rituximab package insert). Cases of Stevens-Johnson syndrome (SJS) and TEN, some fatal, have been reported when TREANDA was administered concomitantly with allopurinol and other medications known to cause these syndromes. The relationship to TREANDA cannot be determined. Where skin reactions occur, they may be progressive and increase in severity with further treatment. Monitor patients with skin reactions closely. If skin reactions are severe or progressive, withhold or discontinue TREANDA. 5.6 Other Malignancies There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with TREANDA, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia and bronchial carcinoma. The association with TREANDA therapy has not been determined. 5.7 Extravasation Injury TREANDA extravasations have been reported in postmarketing resulting in hospitalizations from erythema, marked swelling, and pain. Assure good venous access prior to starting TREANDA infusion and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of TREANDA. 5.8 Embryo-fetal toxicity TREANDA can cause fetal harm when administered to a pregnant woman. Single intraperitoneal doses of bendamustine in mice and rats administered during organogenesis caused an increase in resorptions, skeletal and visceral malformations, and decreased fetal body weights. 6 ADVERSE REACTIONS The following serious adverse reactions have been associated with TREANDA in clinical trials and are discussed in greater detail in other sections [See Warnings and Precautions] of the label: Myelosuppression (5.1); Infections (5.2); Infusion Reactions and Anaphylaxis (5.3); Tumor Lysis Syndrome (5.4); Skin Reactions (5.5); Other Malignancies (5.6). The data described below reflect exposure to TREANDA in 153 patients who participated in an actively-controlled trial for the treatment of CLL. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. 6.1 Clinical Trials Experience in CLL The data described below reflect exposure to TREANDA in 153 patients with CLL studied in an active-controlled, randomized trial.The population was 45-77 years of age, 63% male, 100% white, and were treatment naïve. All patients started the study at a dose of 100 mg/m2 intravenously over 30 minutes on Days 1 and 2 every 28 days. Adverse reactions were reported according to NCI CTC v.2.0. Non-hematologic adverse reactions (any grade) in the TREANDA group that occurred with a frequency greater than 15% were pyrexia (24%), nausea (20%), and vomiting (16%). Other adverse

Job Number: 20294 Revision No: 0 Date: 10/31/13

reactions seen frequently in one or more studies included asthenia, fatigue, malaise, and weakness; dry mouth; somnolence; cough; constipation; headache; mucosal inflammation and stomatitis. Worsening hypertension was reported in 4 patients treated with TREANDA in the CLL trial and in none treated with chlorambucil. Three of these 4 adverse reactions were described as a hypertensive crisis and were managed with oral medications and resolved. The most frequent adverse reactions leading to study withdrawal for patients receiving TREANDA were hypersensitivity (2%) and pyrexia (1%). Table 1 contains the treatment emergent adverse reactions, regardless of attribution, that were reported in ≥ 5% of patients in either treatment group in the randomized CLL clinical study. Table 1: Non-Hematologic Adverse Reactions Occurring in Randomized CLL Clinical Study in at Least 5% of Patients Number (%) of patients TREANDA (N=153) System organ class Preferred term Total number of patients with at least 1 adverse reaction Gastrointestinal disorders Nausea Vomiting Diarrhea General disorders and administration site conditions Pyrexia Fatigue Asthenia Chills Immune system disorders Hypersensitivity Infections and infestations Nasopharyngitis Infection Herpes Simplex Investigations Weight decreased Metabolism and nutrition disorders Hyperuricemia Respiratory, thoracic and mediastinal disorders Cough Skin and subcutaneous tissue disorders Rash Pruritus

Chlorambucil (N=143)

All Grades

Grade 3/4

All Grades

Grade 3/4

121 (79)

52 (34)

96 (67)

25 (17)

31 (20) 24 (16) 14 (9)

1 (<1) 1 (<1) 2 (1)

21 (15) 9 (6) 5 (3)

1 (<1) 0 0

36 (24) 14 (9) 13 (8) 9 (6)

6 (4) 2 (1) 0 0

8 (6) 8 (6) 6 (4) 1 (<1)

2 (1) 0 0 0

7 (5)

2 (1)

3 (2)

10 (7) 9 (6) 5 (3)

0 3 (2) 0

12 (8) 1 (<1) 7 (5)

0 1 (<1) 0

11 (7)

5 (3)

11 (7)

3 (2)

2 (1)

6 (4)

1 (<1)

7 (5)

1 (<1)

12 (8) 8 (5)

4 (3) 0

7 (5) 2 (1)

3 (2) 0

The Grade 3 and 4 hematology laboratory test values by treatment group in the randomized CLL clinical study are described in Table 2. These findings confirm the myelosuppressive effects seen in patients treated with TREANDA. Red blood cell transfusions were administered to 20% of patients receiving TREANDA compared with 6% of patients receiving chlorambucil. Table 2: Incidence of Hematology Laboratory Abnormalities in Patients Who Received TREANDA or Chlorambucil in the Randomized CLL Clinical Study TREANDA N=150

Chlorambucil N=141

Laboratory Abnormality

All Grades n (%)

Grade 3/4 n (%)

All Grades n (%)

Grade 3/4 n (%)

Hemoglobin Decreased

134 (89)

20 (13)

115 (82)

12 (9)

Platelets Decreased

116 (77)

16 (11)

110 (78)

14 (10)

Leukocytes Decreased

92 (61)

42 (28)

26 (18)

4 (3)

Lymphocytes Decreased

102 (68)

70 (47)

27 (19)

6 (4)

Neutrophils Decreased

113 (75)

65 (43)

86 (61)

30 (21)

727-37345 Pg4 PRINT

In the CLL trial, 34% of patients had bilirubin elevations, some without associated significant elevations in AST and ALT. Grade 3 or 4 increased bilirubin occurred in 3% of patients. Increases in AST and ALT of Grade 3 or 4 were limited to 1% and 3% of patients, respectively. Patients treated with TREANDA may also have changes in their creatinine levels. If abnormalities are detected, monitoring of these parameters should be continued to ensure that further deterioration does not occur. 6.3 Postmarketing Experience The following adverse reactions have been identified during post-approval use of TREANDA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: anaphylaxis; and injection or infusion site reactions including phlebitis, pruritus, irritation, pain, and swelling; pneumocystis jiroveci pneumonia and pneumonitis. Skin reactions including SJS and TEN have occurred when TREANDA was administered concomitantly with allopurinol and other medications known to cause these syndromes. [See Warnings and Precautions (5.5)] 10 OVERDOSAGE The intravenous LD50 of bendamustine HCl is 240 mg/m2 in the mouse and rat. Toxicities included sedation, tremor, ataxia, convulsions and respiratory distress. Across all clinical experience, the reported maximum single dose received was 280 mg/m2. Three of four patients treated at this dose showed ECG changes considered dose-limiting at 7 and 21 days post-dosing. These changes included QT prolongation (one patient), sinus tachycardia (one patient), ST and T wave deviations (two patients), and left anterior fascicular block (one patient). Cardiac enzymes and ejection fractions remained normal in all patients. No specific antidote for TREANDA overdose is known. Management of overdosage should include general supportive measures, including monitoring of hematologic parameters and ECGs. 15 REFERENCES 1. OSHA Hazardous Drugs. OSHA. [Accessed on June 19, 2013, from http://www.osha.gov/SLTC/hazardousdrugs/index.html] 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 Safe Handling and Disposal As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of solutions prepared from TREANDA. The use of gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. If a solution of TREANDA contacts the skin, wash the skin immediately and thoroughly with soap and water. If TREANDA contacts the mucous membranes, flush thoroughly with water. TREANDA is an antineoplastic product. Follow special handling and disposal procedures1. 16.2 How Supplied TREANDA (bendamustine hydrochloride) for Injection is supplied in individual cartons as follows: NDC 63459-390-08 TREANDA (bendamustine hydrochloride) for Injection, 25 mg in 8 mL amber single-use vial and NDC 63459-391-20 TREANDA (bendamustine hydrochloride) for Injection, 100 mg in 20 mL amber single-use vial. 16.3 Storage TREANDA may be stored up to 25°C (77°F) with excursions permitted up to 30°C (86°F) (see USP Controlled Room Temperature). Retain in original package until time of use to protect from light.

Distributed By: Teva Pharmaceuticals USA, Inc. North Wales, PA 19454 TREANDA is a trademark of Cephalon, Inc. or its affiliates. ©2008-2013 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd or its affiliates. All rights reserved. (Label Code: 00016287.06) 8/2013 TRE-40156 This brief summary is based on TRE-008 TREANDA full Prescribing Information.

Job Number: 20294 Revision No: 0 Date: 10/31/13

MASTER DRUG MONOGRAPHS

HEMATOLOGIC CANCER pyrexia, upper respiratory tract infection, back pain, cough, asthenia, pneumonia, febrile neutropenia, leukopenia, intracranial hemorrhage, reversible myelosuppression (thrombocytopenia, neutropenia, anemia); QT prolongation, elevated serum lipase, electrolyte disturbances (hypophosphatemia, hypo- and hyperkalemia, hypocalcemia, hyponatremia), sudden death, hepatotoxicity. Testing considerations: BCR-Abl t(9;22) How supplied: Blister pack (28 caps)–1, 4

THALOMID Celgene

℞

Immunomodulator. Thalidomide 50mg, 100mg, 150mg, 200mg; caps. Indications: Newly diagnosed multiple myeloma in combination with dexamethasone. Treatment, suppression and prevention of cutaneous manifestations of erythema nodosum leprosum (ENL). Adults: Take at bedtime, at least 1 hour after evening meal. Multiple myeloma: 200mg once daily in combination with dexamethasone in 28-day treatment cycles. ENL: initially 100–300mg/day; <50kg: start with lower dose; continue until signs/symptoms of active reaction have subsided (usually at least 2 weeks), then taper off in 50mg decrements every 2–4 weeks. Severe ENL: may start at higher doses; max 400mg/day. Moderate to severe neuritis with severe ENL: give concomitant corticosteroids (see literature). Children: Not recommended. Contraindications: Pregnancy (Cat.X). Nursing mothers. Women who may become pregnant. Warnings/Precautions: Must register patient in STEPS program; patient must understand toxicity with fetal exposure. Counsel patient on need for contraception; female: use 2 forms of contraception 1 month before, during, and 1 month after therapy; male: use condom during and 1 month after therapy; obtain negative pregnancy test within 24 hours prior to starting treatment; repeat at least weekly for 1st month then every 4 weeks; get informed consent. Monitor for signs/ symptoms of thromboembolic events, neuropathy, bradycardia, orthostatic hypotension. Discontinue if pregnancy or severe skin rash occurs. History of seizure. Avoid contact with non-intact capsule or powder content. Maximum 1 month per ℞. Interactions: Increased sedative effect with barbiturates, alcohol, chlorpromazine, reserpine. Caution with drugs associated with peripheral neuropathy. Avoid drugs (eg, rifampin, carbamazepine, St. John’s wort) that decrease effectiveness of hormonal contraceptives. Adverse reactions: Birth defects, skin rash (eg, Stevens-Johnson Syndrome, toxic epidermal necrolysis), bradycardia, peripheral neuropathy, seizures, drowsiness, dizziness, orthostatic hypotension, neutropenia, increased HIV viral

load, constipation, confusion, hypocalcemia, edema, dyspnea, thrombosis/embolism. Note: Available only through STEPS program. Suspected fetal exposure must be reported to the FDA at (800) FDA-1088 and Celgene at (888) 423-5436. How supplied: Caps–28

TREANDA Teva

℞

Alkylating agent. Bendamustine HCl 25mg, 100mg; per vial; lyophilized pwd for IV infusion after reconstitution and dilution; contains mannitol; preservative-free. Indications: Chronic lymphocytic leukemia (CLL). Indolent B-cell non-Hodgkin’s lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab or a rituximab–containing regimen. Adults: CLL: Give by IV infusion over 30 minutes. 100mg/m2 on Days 1 and 2 of a 28-day cycle, up to 6 cycles. Hematologic toxicity (≥Grade 3): reduce dose to 50mg/m2 on Days 1 and 2 of each cycle; if toxicity recurs, reduce dose to 25mg/m2 on Days 1 and 2. Non-hematologic toxicity (clinically significant ≥Grade 3): reduce dose to 50mg/m2 on Days 1 and 2 of each cycle. Subsequent cycles: may consider dose re-escalation. NHL: Give by IV infusion over 60 minutes. 120mg/m2 on Days 1 and 2 of a 21-day cycle, up to 8 cycles. Hematologic toxicity (Grade 4) or non-hematologic toxicity (≥Grade 3): reduce dose to 90mg/m2 on Days 1 and 2 of each cycle; if toxicity recurs, reduce dose to 60mg/m2 on Days 1 and 2. Both: May give allopurinol prophylactically for those at high risk of tumor lysis syndrome. Delay treatment for Grade 4 hematologic toxicity or clinically significant ≥Grade 2 non-hematologic toxicity. Severe renal impairment (CrCl <40mL/min) or moderate to severe hepatic impairment: not recommended. Children: Not recommended. Warnings/Precautions: Myelosuppression; monitor leukocytes, platelets, hemoglobin, neutrophils closely; restart treatment based on ANC and platelet count recovery. Renal or hepatic impairment. Monitor for infection, infusion or skin reactions, tumor lysis syndrome. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: May be potentiated or antagonized by CYP1A2 inhibitors, inducers. Adverse reactions: Lymphopenia, anemia, thrombocytopenia, leukopenia, neutropenia, pyrexia, nausea, vomiting, asthenia, fatigue, malaise, dry mouth, somnolence, cough, constipation, headache, mucosal inflammation, stomatitis, increased bilirubin, increased AST or ALT; infection, infusion reactions (discontinue if severe), tumor lysis syndrome, skin reactions (if severe or progressive, withhold dose or discontinue), other

F P O for

malignancies (eg, myelodysplastic syndrome, acute myeloid leukemia). How supplied: Single-use vial (25mg/8mL, 100mg/20mL)–1

TREXALL Teva

℞

Folic acid antagonist. Methotrexate sodium 5mg, 7.5mg, 10mg, 15mg; scored tabs. ℞ Also: Methotrexate injection Bedford Methotrexate 25mg/mL; soln for IV, IM, intraarterial, or intrathecal administration after dilution; preservative-free. ℞ Also: Methotrexate for injection Bedford Methotrexate 1g/vial; pwd for IV, IM, intra-arterial, or intrathecal administration after dilution; preservative-free. Indications: Prophylaxis and treatment of meningeal leukemia. Advanced mycosis fungoids (cutaneous T cell lymphoma). Advanced nonHodgkin’s lymphomas. Adults: See literature. Tablet form is often preferred when low doses are being administered. Leukemia: Induction: 3.3mg/m2 + prednisone, given daily; maintenance: give twice weekly either orally or by IM inj for a total weekly dose of 30mg/m2; or 2.5mg/kg IV every 14 days. Meningeal leukemia (treatment): 12mg/m2 intrathecally (max 15mg) at intervals of 2–5 days; see literature for prophylaxis treatment. Burkitt’s tumor (stage I–II): 10–25mg per day orally for 4–8 days. Lymphosarcomas (stage III): 0.625–2.5mg/kg daily. Mycosis fungoides (cutaneous T cell lymphoma): 5–50mg once weekly. Children: See literature. Contraindications: Pregnancy (Cat.X). Nursing mothers. Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration). Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity. Diabetes. Peptic ulcer. Ulcerative colitis. Infection. Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated. Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin,

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HEMATOLOGIC CANCER sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, nonabsorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin). Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome). How supplied: Tabs–30 Soln (2mL, 4mL, 8mL, 10mL)–10 (single-use vials) Pwd (1 gram)–1 (single-use vial)

TRISENOX Teva

℞

Antineoplastic. Arsenic trioxide 1mg/mL; soln for IV inj after dilution; preservative-free. Indications: Induction of remission and consolidation in acute promyelocytic leukemia (APL) refractory to or relapsed from retinoid and anthracycline chemotherapy, and whose APL has the t(15;17) translocation or PML/RAR-alpha gene expression. Adults: Give by IV infusion over 1–2 hours; may extend infusion up to 4 hours if acute vasomotor symptoms occur. Induction: 0.15mg/kg per day until bone marrow remission; max 60 doses. Consolidation treatment (begin 3–6 weeks after completion of induction therapy): 0.15mg/kg per day for 25 doses for up to 5 weeks. Children: See literature. <5yrs: not recommended. 5–16yrs: doses of 0.15mg/kg per day have been used. Warnings/Precautions: Renal or hepatic dysfunction. History of torsades de pointes. Preexisting QT interval prolongation. CHF. Monitor hematology, renal function, and electrolytes at least twice weekly, perform ECG at baseline then weekly (hospitalize if cardiac irregularities develop); unstable patients: monitor more frequently. Correct electrolyte imbalances before starting therapy (maintain K+ above 4mEq/dL and Mg++ above 1.8mg/dL). Pregnancy: (Cat.D), nursing mothers: not recommended. Interactions: Caution with drugs that can cause QT prolongation (discontinue these before starting therapy, if possible) or electrolyte imbalances. Adverse reactions: Leukocytosis, GI upset, fatigue, edema, hyperglycemia, cough, rash, headache, dizziness, paresthesia, arthralgia, renal failure, electrolyte disorders (eg,hypokalemia, hypomagnesemia), abnormal LFTs; APL differentiation syndrome (eg, fever, dyspnea, weight gain, pulmonary infiltrates, pericardial effusion; give high-dose IV steroids at 1st sign), hyperleukocytosis, QT interval prolongation/heart block, atrial dysrhythmias, tachycardia, others (see literature). How supplied: Single-use amps (10mL)–10

UVADEX Therakos

℞

Photoactive agent. Methoxsalen 20mcg/mL; sterile soln. Indications: Extracorporeal administration with the UVAR Photopheresis System in the palliative treatment of skin manifestations of cutaneous T-cell lymphoma that is unresponsive to other forms of treatment. Adults: Consult UVAR Photopheresis System Operator’s Manual before administering. Give on two consecutive days every 4 weeks for minimum of 7 treatment cycles (6 months). 200mcg per photopheresis treatment. Accelerated treatment schedule: see literature. Children: Not recommended. Contraindications: Idiosyncratic reactions to psoralen compounds. History of light sensitive disease. Lupus erythematosus. Porphyria cutanea tarda. Erythropoietic protoporphyria. Variegate porphyria. Xeroderma pigmentosum. Albinism. Aphakia. Warnings/Precautions: Exposure to sun or UV light may cause actinic degeneration, skin burning, cataracts; wear UVA-absorbing, wrap-around sunglasses and cover exposed skin (or use sunblock: SPF ≥15) for 24hrs after treatment. Basal cell carcinomas (monitor and treat if occur). Pregnancy (Cat.D); nursing mothers: not recommended. Interactions: Increased photosensitivity with anthralin, coal tar, griseofulvin, phenothiazines, nalidixic acid, halogenated salicylanilides, sulfonamides, tetracyclines, thiazides, organic staining dyes. Adverse reactions: Hypotension secondary to changes in extracorporeal volume. How supplied: Vials (10mL)–12

VALCHLOR Actelion

℞

Nitrogen mustard. Mechlorethamine 0.016%; topical gel; contains propylene glycol, isopropyl alcohol. Indications: Treatment of Stage IA and IB mycosis fungoides-type cutaneous T-cell lymphoma in patients who have received prior skin-directed therapy. Adults: Apply a thin film once daily to affected areas of the skin. Apply to completely dry skin ≥4 hours before or 30 minutes after showering or washing. Allow treated areas to completely dry for 5–10 minutes after applying. Wash hands thoroughly after application. Discontinue if any grade of skin ulceration, blistering, or moderatelyto-severe, or severe dermatitis occur; restart at reduced frequency of once every 3 days upon improvement; if reintroduction is tolerated for at least 1 week, can increase to every other day for 1 week and then once daily if tolerated. Children: Not established. Warnings/Precautions: Mucosal (oral, nasal) or eye exposure; blindness and severe irreversible anterior eye injury may occur; immediately irrigate for ≥15 minutes with copious amounts of water. Secondary exposure; avoid direct skin contact with patient. Risk of dermatitis (eg, face, genitalia, anus, and intertriginous skin); monitor for

redness, swelling, inflammation, itchiness, blisters, ulceration, and secondary skin infections. Monitor for nonmelanoma skin cancer during and after treatment. Flammable (avoid fire and flame until gel has dried). Pregnancy (Category D); may cause fetal harm. Nursing mothers: not recommended. Adverse reactions: Dermatitis, pruritus, bacterial skin infection, skin ulceration or blistering, hyperpigmentation. How supplied: Gel–60g

VELCADE Millennium

℞

Proteasome inhibitor. Bortezomib 3.5mg/vial; pwd for IV or SC inj after reconstitution; contains mannitol. Indications: Multiple myeloma. Mantle cell lymphoma in patients who have received at least one prior therapy. Adults: Give as a 3–5 second IV bolus inj or as SC inj into thigh or abdomen (rotate sites). Previously untreated multiple myeloma: Treat for nine 6-week cycles in combination with oral melphalan and oral prednisone. Cycles 1–4: 1.3mg/m2 twice weekly (days 1, 4, 8, 11, 22, 25, 29, 32); Cycles 5–9: 1.3mg/m2 once weekly (days 1, 8, 22, 29). Relapsed multiple myeloma or mantle cell lymphoma: Standard schedule: 1.3mg/m2 twice weekly for 2 weeks (days 1, 4, 8, 11) then 10 day rest period (days 12–21); Extended therapy (if using >8 cycles): may use standard schedule, or maintenance schedule: 1.3mg/m2 once weekly for 4 weeks (days 1, 8, 15, 22) then 13 day rest period (days 23–35). Allow at least 72 hours between consecutive doses. Adjust dose if toxicity develops: see literature. SC inj may be considered for patients with pre-existing or at high-risk of peripheral neuropathy. Moderate-to-severe hepatic impairment: reduce to 0.7mg/m2 in 1st cycle; may consider dose increase to 1mg/m2 or decrease to 0.5mg/m2 in subsequent cycles based on tolerance. Children: Not established. Contraindications: Boron or mannitol sensitivity. Intrathecal administration. Warnings/Precautions: Hepatic impairment. Pre-existing severe neuropathy; treat only after careful risk-benefit assessment. Monitor for development or worsening of peripheral neuropathy; consider dose or schedule adjustment. Diabetes. History of syncope. Avoid dehydration; give fluids and electrolytes. Heart disease (monitor for CHF). Monitor CBC and platelets and for toxicities. High tumor burden (monitor for tumor lysis syndrome). Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Concomitant strong CYP3A4 inducers (eg, rifampin): not recommended; efficacy may be reduced. Avoid St. John’s Wort. Potentiated by ketoconazole, other potent CYP3A inhibitors. Increased risk of peripheral neuropathy with other agents that can cause neuropathy (eg, amiodarone, antivirals, isoniazid, metronidazole, statins, nitrofurantoin, or previous neurotoxic agents). Caution with hypotensives and hypoglycemics. Adverse reactions: Asthenia, GI upset, peripheral neuropathy, decreased appetite, thrombocytopenia,

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HEMATOLOGIC CANCER anemia, orthostatic hypotension, pyrexia, headache, insomnia, psychiatric disorders, arthralgia, neutropenia, hypercalcemia, pain, edema, paresthesia, dysesthesia, dyspnea, cough, pruritus, dizziness, blurred vision, pneumonia, CHF, decreased LVEF, herpes reactivation, hepatotoxicity; rare: pulmonary disorders, reversible posterior leukoencephalopathy syndrome (discontinue if occurs). How supplied: Single-dose vial–1

VESANOID Roche

℞

Retinoid. Tretinoin 10mg; soft gelatin caps; contain parabens. Indications: Induction of remission in patients with acute promyelocytic leukemia (APL), FrenchAmerican-British (FAB) classification M3 (including the M3 variant), characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene who are refractory to, or who have relapsed from, anthracycline chemotherapy, or for whom anthracycline-based chemotherapy is contraindicated. Adults: Use only for induction of remission. 45mg/m2 per day in two divided doses until complete remission is documented. Discontinue 30 days after complete remission or after 90 days of treatment, whichever occurs first. Children: See literature. Warnings/Precautions: Confirm APL diagnosis. Monitor for Retinoic Acid-APL (RA-APL) syndrome, leukocytosis, pseudotumor cerebri, or respiratory compromise. Consider temporarily interrupting therapy if moderate to severe RA-APL syndrome develops. Monitor blood counts, coagulation profile, lipids, liver function; consider temporary withdrawal if tests >5×ULN. Pregnancy (Cat.D); obtain negative pregnancy test 1 week before starting treatment, counsel patient about need to use 2 effective methods of contraception during, and 1 month after therapy. Nursing mothers: not recommended. Interactions: Do not administer with Vitamin A. May be potentiated or antagonized by CYP450 enzyme inducers or inhibitors. Caution with antifibrinolytic agents; and other agents known to cause pseudotumor cerebri/intracranial hypertension. Adverse reactions: Headache, fever, skin/ mucous membrane dryness, bone pain, GI upset, rash, mucositis, pruritus, increased sweating, visual disturbances, alopecia; RA-APL syndrome, leukocytosis, pseudotumor cerebri, hypercholesterolemia/hypertriglyceridemia, others. How supplied: Caps–100

VIDAZA Celgene

℞

Cytidine analogue. Azacitidine 100mg/vial; pwd for SC inj after reconstitution or IV inj after reconstitution and dilution; contains mannitol; preservative-free.

Indications: Myelodysplastic syndromes (refractory anemias, chronic myelomonocytic leukemia). Adults: Premedicate for nausea & vomiting. Initially 75mg/m2 SC (doses >4mL divide equally into 2 syringes and inject into 2 separate sites) or IV (infuse over 10–40 minutes, must complete within 1 hour of reconstitution) daily for 7 days; repeat cycle every 4 weeks. May increase to 100mg/m2 after 2 cycles if no response and no toxicity. Treat for at least 4–6 cycles. Adjust subsequent doses on blood counts and toxicities (eg, neutropenia, thrombocytopenia, decreased serum bicarbonate). Children: Not recommended. Contraindications: Advanced malignant hepatic tumors. Warnings/Precautions: Renal or hepatic impairment. High tumor burden. Obtain CBC counts before each dosing cycle and as needed. Monitor serum bicarbonate and renal and hepatic function (do baseline liver chemistries and serum creatinine). Elderly. Pregnancy (Cat.D); use appropriate contraception (both men and women). Nursing mothers: not recommended. Adverse reactions: GI upset, blood dyscrasias (esp. anemia, thrombocytopenia, neutropenia, leukopenia), fever, fatigue, inj site reactions, constipation, ecchymosis, petechiae, rigors, dyspnea, arthralgia, headache, anorexia, renal failure/tubular acidosis, hypokalemia, hepatic coma, others (see literature). How supplied: Single-use vial–1

Vinblastine for injection

℞

Bedford

F P O for

Children: See literature. IV use only. Hodgkin’s disease: initially 6mg/m2. Adjust dose according to hematologic tolerance. Contraindications: Significant granulocytopenia (unless result of disease being treated). Bacterial infections (treat first). Warnings/Precautions: For IV use only; fatal if given intrathecally. Hepatic impairment. Avoid in elderly with cachexia or ulcerated skin; or in patients with malignant-cell infiltration of the bone marrow. Pre-existing pulmonary dysfunction. Progressive dyspnea requiring chronic therapy (do not re-administer). Ischemic cardiac disease. Bone marrow suppression; monitor WBC before and during treatment. Avoid contamination of the eyes or injecting into an extremity with poor circulation (thrombosis possible). Avoid extravasation. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May be potentiated by CYP3A inhibitors (eg, erythromycin). Antagonizes phenytoin. Adverse reactions: Leukopenia, alopecia, GI upset, paresthesias, malaise, pain; dyspnea, severe bronchospasm. How supplied: Pwd–10 Soln–1

VINCASAR PFS Teva

℞

Antimicrotubule agent. Vincristine sulfate 1mg/mL; soln for IV inj; contains mannitol; preservative-free. Indications: Acute leukemia. In combination with other chemotherapeutic agents for Hodgkin’s disease, non-Hodgkin’s malignant lymphomas (lymphocytic, mixed-cell, histiocytic, undifferentiated, nodular, diffuse types). Adults: Usual dose: 1.4mg/m2 IV once weekly. Serum bilirubin >3mg/100mL: reduce dose by 50%. Children: ≤10kg: initially 0.05mg/kg IV once weekly. >10kg: usual dose: 2mg/m2 IV once weekly. Contraindications: Demyelinating form of Charcot-Marie-Tooth syndrome. Warnings/Precautions: For IV use only; fatal if given intrathecally. Hepatic dysfunction. Pre-existing neuromuscular disease. Obtain CBCs, platelets before each dose, then periodically. Monitor serum uric acid levels during first 3–4 weeks of treatment. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Concomitant radiotherapy through ports that include the liver: not recommended. Potentiated by CYP3A4 enzyme inhibitors (eg, itraconazole). Antagonizes phenytoin. Caution with other neurotoxic or platinum-containing agents. Separate L-asparaginase dose by 12–24hrs (administer after vincristine). Consider

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HEMATOLOGIC CANCER discontinuing drugs that cause urinary retention for the first few days following therapy. Adverse reactions: GI upset, paralytic ileus (esp. in children; discontinue temporarily if occurs), polyuria, dysuria, urinary retention, hypertension, hypotension, neuromuscular effects, dyspnea, bronchospasm, alopecia, rash, fever, headache, hypersensitivity reactions, acute uric acid nephropathy. How supplied: Single-use vials (1mL, 2mL)–1

VUMON Bristol-Myers Squibb

℞

Topoisomerase inhibitor. Teniposide 10mg/mL; soln for IV infusion after dilution; contains benzyl alcohol, Cremophor EL (polyoxyethylated castor oil), dehydrated alcohol. Indications: Refractory childhood acute lymphoblastic leukemia. Adults and Children: See literature. Give as slow IV infusion (at least 30–60 minutes). Patients failing induction therapy with a cytarabine-containing regimen: 165mg/m2 + cytarabine twice weekly for 8 to 9 doses. Refractory to vincristine/prednisone-containing regimen: 250mg/m2 + vincristine weekly for 4 to 8 weeks + oral prednisone for 28 days. Warnings/Precautions: Severe myelosuppression. Monitor for hypersensitivity reactions following infusion; have epinephrine available. Risk of hypotension with rapid IV administration. Hepatic dysfunction. Monitor and obtain CBCs with differential, hemoglobin, platelets, renal and hepatic functions before, during, and after therapy. Down syndrome (use reduced dose). Monitor children with hypoalbuminemia. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Potentiated by tolbutamide, sodium salicylate, and sulfamethizole. Concomitant vincristine sulfate may cause neuropathy. Concomitant antiemetics in patients given high doses of teniposide may increase risk of CNS depression, hypotension. Adverse reactions: Myelosuppression (leukopenia, neutropenia, thrombocytopenia, anemia), mucositis, GI upset, infection, alopecia, bleeding, rash, fever, hypotension, CNS depression, hypersensitivity reactions (may be fatal). How supplied: Ampules (5mL)–1

ZEVALIN Spectrum

℞

Radionuclide (B-lymphocyte-restricted differentiation antigen [CD20] inhibitor). Ibritumomab tiuxetan 3.2mg/2mL; soln for IV inj; contains albumin; preservative-free. Indications: B-cell non-Hodgkin’s lymphoma (relapsed or refractory, low grade or follicular). Previously untreated follicular non-Hodgkin’s lymphoma in patients who achieve a partial or complete response to first-line chemotherapy. Adults: See literature. Prepare In-111 Zevalin and Y-90 Zevalin as directed. Initiate Zevalin therapy after recovery of platelets to ≥150000/mm3

at least 6 weeks, but no more than 12 weeks, after the last dose of first-line chemotherapy. Administered in two steps. Step 1: Single infusion of rituximab followed by a fixed dose of 5mCi (1.6mg total antibody dose) of In-111 Zevalin given as a 10-minute IV push. Step 2 (7–9 days after Step 1): Second rituximab infusion followed by 0.4mCi/kg of Y-90 Zevalin given as a 10-minute IV push; if platelet count 100000–149000cells/mm3, reduce dose to 0.3 mCi/kg. Do not treat if platelets <100000cells/mm3. Max Y-90 Zevalin dose: 32mCi. Children: Not recommended. Contraindications: Hypersensitivity to murine proteins. Warnings/Precautions: See literature. Use only if trained in radionuclide therapy. Do not treat patients with altered biodistribution. ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve (eg, prior myeloablative therapies, platelet count <100000cells/mm3, neutrophil count <1500cells/mm3), or history of failed stem cell collection: not recommended. Monitor for cytopenias and complications (eg, febrile neutropenia, hemorrhage) for up to 3 months after treatment. Obtain CBCs, platelets weekly until levels recover. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Caution with anticoagulants, platelet aggregation inhibitors, or live viral vaccines. Separate growth factor treatment by 2 weeks before and after Zevalin therapy. Adverse reactions: Neutropenia, leukopenia, thrombocytopenia, anemia, infections, asthenia, musculoskeletal symptoms, GI upset, abdominal pain, fatigue, nasopharyngitis, cough, dizziness, hemorrhage, altered biodistribution; infusion reactions, severe cutaneous/mucocutaneous reactions: both may be fatal, discontinue if occurs; leukemia and myelodysplastic syndrome. Note: Indium-11 chloride sterile solution must be ordered separately at the time the In-11 Zevalin kit is ordered. Yttrium-90 chloride sterile solution will be shipped directly upon placement of order for Y-90 Zevalin kit. How supplied: In-111 Zevalin kit (ibritumomab tiuxetan 3.2mg/2mL vial + sodium acetate vial + formulation buffer vial + empty reaction vial)–1 Y-90 Zevalin kit (ibritumomab tiuxetan 3.2mg/2mL vial + sodium acetate vial + formulation buffer vial + empty reaction vial)–1

ZOLINZA Merck

℞

Histone deacetylase inhibitor. Vorinostat 100mg; caps. Indications: Refractory cutaneous T-cell lymphoma. Adults: Take with food. Swallow whole. 400mg once daily. If not tolerated, may reduce to 300mg once daily, then to 300mg once daily 5 days/week if needed. Continue until disease progression or not tolerated. Children: <18yrs: not recommended. Warnings/Precautions: Renal or hepatic impairment. Monitor for DVT, pulmonary

embolism. Correct electrolyte disturbances before starting therapy. Maintain adequate hydration. Diabetes. Monitor CBC, platelets, blood glucose, serum creatinine, electrolytes (esp. potassium, calcium, magnesium) every 2 weeks for 1st 2 months, then monthly. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Increased risk of thrombocytopenia and GI bleed with other HDAC inhibitors (eg, valproic acid). Concomitant warfarin: monitor PT, INR. Adverse reactions: GI upset, fatigue, chills; thrombocytopenia, anemia (may need to modify dose or discontinue); anorexia, dysgeusia, pulmonary embolism, DVT, hyperglycemia. How supplied: Caps–120

ZOMETA Novartis

℞

Bisphosphonate. Zoledronic acid 4mg/5mL concentrated soln for IV infusion after dilution; 4mg/100mL ready-to-use soln for IV infusion. Indications: Adjunct in multiple myeloma and bone metastases of solid tumors. Limitation of use: not established for use in hyperparathyroidism or nontumor-related hypercalcemia. Adults: Give by IV infusion over at least 15 minutes. CrCl >60mL/min: 4mg; CrCl 50–60mL/min: 3.5mg; CrCl 40–49mL/min: 3.3mg; CrCl 30–39mL/min: 3mg; CrCl <30mL/min: see full labeling; all: every 3–4 weeks (give oral multivitamin supplement with calcium 500mg + Vit. D 400 IU daily). Children: Not recommended. Warnings/Precautions: Not recommended for use in patients with bone metastases with severe renal impairment. Renal or hepatic insufficiency. Check serum creatinine before each dose: withhold until serum creatinine is within 10% of baseline if serum creatinine increases by 0.5 mg/dL from a normal pre-treatment level, or by 1 mg/dL from an abnormal pre-treatment level, within 2 weeks of next dose. Assure adequate hydration when treating hypercalcemia of malignancy. Correct hypocalcemia before initiating treatment; supplement with calcium and vitamin D. Closely monitor electrolytes (esp. calcium, magnesium, phosphate), CBC/differential, hematocrit, hemoglobin. Evaluate if thigh or groin pain develops and consider discontinuing if atypical femur fracture is suspected. Aspirin-sensitive asthma. Avoid dental surgery (do preventative dental work before therapy). Elderly. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Avoid concomitant other bisphosphonates. Additive hypocalcemic effect with aminoglycosides, loop diuretics. Caution with other nephrotoxic drugs (eg, thalidomide). Adverse reactions: Nausea, fatigue, anemia, musculoskeletal pain (discontinue if severe), constipation, fever, vomiting, dyspnea, flu-like syndrome, electrolyte disturbances, hypotension, CNS effects, rigors, headache, paresthesia, renal toxicity; jaw osteonecrosis, atypical subtrochanteric, diaphyseal femoral fractures, severe hypocalcemia. How supplied: Single-use vial, ready-to-use bottle–1

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LUNG CANCER ABRAXANE Celgene

℞

Taxane antimicrotubule. Paclitaxel [bound to albumin (human)] 100mg/vial; pwd for IV infusion after reconstitution; solvent-free. Indications: First-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy. Adults: Do not treat if neutrophil count <1,500 cells/mm3 or platelets <100,000 cells/mm3. In combination with carboplatin: 100mg/m2 IV over 30 minutes on Days 1, 8, and 15 of each 21-day cycle. Dose reductions for hematologic and neurologic adverse reactions, hepatic impairment: see full labeling. Avoid extravasation. Children: Not evaluated. Contraindications: Baseline neutrophil count <1,500 cells/mm3. Prior severe hypersensitivity reaction (do not rechallenge). Warnings/Precautions: Do not substitute for, or with, other paclitaxel products (due to formulation differences). Do frequent complete blood cell counts. Monitor for sensory neuropathy, sepsis, or pneumonitis. Hepatic or renal dysfunction. Contains human albumin; remote risk of viral transmission. Use appropriate contraception (men and women). Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May potentiate or be potentiated by CYP2C8 and/or CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, efavirenz, nevirapine) and/or inhibitors (eg, ketoconazole, other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, nelfinavir). Adverse reactions: Bone marrow suppression (eg, neutropenia, anemia), infections, alopecia, sensory neuropathy (may require dose reduction or interruption), peripheral neuropathy, GI upset, mucositis, fatigue/asthenia, myalgia/arthralgia, abnormal ECG; alkaline phosphatase or AST elevation; dyspnea, edema, hypotension, rash (may be serious); rare: thrombotic events. How supplied: Single-use vial–1

ALIMTA Lilly

℞

Antifolate. Pemetrexed 100mg/vial, 500mg/vial; pwd for IV inj after reconstitution and dilution; preservative-free. Indications: Locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC): in combination with cisplatin as initial treatment, or as maintenance in patients whose disease has not progressed after 4 cycles of

platinum-based 1st-line chemotherapy; or as a single agent after prior chemotherapy. Malignant pleural mesothelioma (MPM): in combination with cisplatin in patients whose disease is either unresectable or who are otherwise not candidates for curative surgery. Limitations of use: not for the treatment of squamous cell NSCLC. Adults: See full labeling. 500mg/m2 by IV infusion over 10 mins on Day 1 of each 21-day cycle. Adjust dose if toxicity (esp. myelosuppression) develops. Combination therapy: Give cisplatin beginning 30 mins after pemetrexed infusion. Supplement with oral folic acid and intramuscular vitamin B12 prior to initiating pemetrexed and continue during treatment. Pretreat with corticosteroid the day before, the day of, and day after pemetrexed. Children: Not recommended. Warnings/Precautions: See full labeling. Renal impairment (CrCl <45mL/min): not recommended. Discontinue if Grade 3 or 4 neurotoxicity occurs, or if any Grade 3 or 4 toxicity occurs after two dose reductions. Do not start a treatment cycle unless ANC is ≥1500cells/mm3, platelets ≥100,000cells/mm3 and CrCl ≥45mL/min. Hepatic impairment. Monitor CBCs, platelets, renal and hepatic function. Clinically significant third space fluid: consider draining effusion first. Pregnancy (Cat.D); avoid, use effective contraception. Nursing mothers: not recommended. Interactions: May be potentiated by nephrotoxic agents, drugs eliminated by renal tubular secretion (eg, probenecid). Concomitant NSAIDs: use caution in patients with mild to moderate renal insufficiency (esp. ibuprofen). Adverse reactions: Fatigue, nausea, anorexia, vomiting, stomatitis, pharyngitis, constipation, fever, infection with neutropenia, rash, desquamation, neutropenia, leukopenia, anemia, thrombocytopenia, elevated creatinine, chest pain, neuropathy; rare: renal failure. Testing considerations: TS (thymidylate synthase) expression for response and toxicity How supplied: Single-use vial–1

AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free. Indications: First-line treatment of unresectable, locally advanced, recurrent or metastatic nonsquamous, non-small cell lung cancer (NSCLC), in combination with carboplatin and paclitaxel. Adults: Give by IV infusion after chemotherapy. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses

over 30 mins. 15mg/kg once every 3 weeks with carboplatin/paclitaxel. Children: Not established. Warnings/Precautions: Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). History of hemoptysis of ≥ ½-teaspoon of red blood: do not administer. Discontinue if GI perforation, wound healing complications, serious hemorrhage, severe arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, non-GI fistula formation, or reversible posterior leukoencephalopathy syndrome occurs; suspend therapy if severe hypertension, moderate to severe proteinuria, or severe infusion reaction occurs. Cardiovascular disease. Diabetes. Renal or hepatic impairment. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis. Elderly. Increases risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy (Cat.C). Nursing mothers: not recommended. Adverse reactions: Epistaxis, headache, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome, infusion reactions, ovarian failure. How supplied: Single-use vial–1

Bleomycin (various)

℞

Cytotoxic glycopeptide antibiotic. Bleomycin 15units/vial, 30units/vial; lyophilized pwd for IM, IV, SC, or intrapleural administration after reconstitution. Indications: Sclerosing agent for the treatment of malignant pleural effusion and prevention of recurrent pleural effusions. Adults: 60 units as a single dose bolus intrapleural injection. Renal impairment: see literature. Children: Not recommended. Warnings/Precautions: Renal impairment. Compromised pulmonary function. Monitor renal function. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: May be potentiated by nephrotoxic drugs. Adverse reactions: Erythema, rash, striae, vesiculation, hyperpigmentation, tenderness of the skin, hyperkeratosis, nail changes, alopecia, pruritus, stomatitis; pneumonitis, pulmonary fibrosis, idiosyncratic reaction (hypotension, mental confusion, fever, chills, wheezing). How supplied: Contact supplier.

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LUNG CANCER Doxorubicin HCl (various)

℞

Anthracycline. Doxorubicin HCl 10mg/vial, 20mg/vial, 50mg/vial; pwd for IV inj after reconstitution; contains lactose. ℞ Also: Doxorubicin HCl Solution Doxorubicin HCl 2mg/mL; soln for IV inj. Indications: Disseminated neoplasias (eg, bronchogenic carcinoma). Adults and Children: Monotherapy: usually 60–75mg/m2 IV every 21 days. Combination therapy: usually 40–60mg/m2 IV every 21 to 28 days. Hyperbilirubinemia, inadequate bone marrow reserves: reduce dose. Contraindications: Severe myelosuppression (baseline neutrophils <1500cells/mm3) or severe hepatic impairment. Cardiac disease (eg, severe myocardial insufficiency, arrhythmias). Recent MI. Previous treatment with max cumulative doses of anthracyclines, anthracenediones. Warnings/Precautions: Pre-existing heart disease or risk thereof. Obtain baseline CBC, bilirubin, AST, creatinine, LVEF. Hepatic dysfunction. Monitor cardiac function (LVEF, ECG echocardiogram), hepatic function, CBC, uric acid levels. Avoid extravasation. Children (cardiotoxicity, impaired myocardial growth). Elderly. Pregnancy (Cat.D; use adequate contraception). Nursing mothers: not recommended. Interactions: See Contraindications. Mediastinal irradiation, cyclophosphamide, calcium channel blockers, other anthracyclines increase risk of cardiac toxicity; limit lifetime dose to 400mg/m2. Necrotizing colitis with cytarabine. May increase toxicity of cyclophosphamide, mercaptopurine. May reduce serum digoxin levels. Doxorubicin toxicity increased with high-dose IV progesterone, cyclosporine, streptozocin, and if given after paclitaxel infusion (give doxorubicin dose first). Elimination increased by phenobarbital. May decrease phenytoin levels. Recall pneumonitis with actinomycin and radiation in children. Adverse reactions: Local necrosis if extravasation occurs, myocardial toxicity (immediate or delayed), arrhythmias, leukemia, myelosuppression, hyperuricemia, urine discoloration, alopecia, hyperpigmentation, severe GI upset/ulceration, phlebosclerosis, facial flushing, fever, urticaria, peripheral neuropathy, anaphylaxis. How supplied: Contact supplier.

ETOPOPHOS Bristol-Myers Squibb

℞

Topoisomerase inhibitor. Etoposide (as phosphate) 100mg/vial; pwd for IV infusion after reconstitution and dilution. Indications: Small cell lung cancer. Adults: See literature. Give by IV infusion over 5 to 210 minutes; use doses equivalent to those used for VePesid (eg, 35mg/m2 per day for 4 days to 50mg/m2 per day for 5 days). Repeat course every 3 to 4 weeks after recovery (esp myelosuppression). Toxicity unknown at doses

>175mg/m2 per day. Renal impairment (CrCl ≤50mL/min): reduce dose (see literature). Consider dose reduction with existing myelosuppression due to previous radiation or chemotherapy. Children: Not recommended. Warnings/Precautions: Monitor blood (esp. CBCs/differential, platelets, hemoglobin) before each cycle and during therapy; renal function. Withhold dose if platelet count <50,000/mm3 or ANC <500/mm3. Hypoalbuminemia. Elderly. Pregnancy (Cat.D); nursing mothers: not recommended. Interactions: Caution with levamisole, others that inhibit phosphatase activity. May be potentiated by cyclosporine. Additive toxicity with radiation, other cytotoxic therapies. Adverse reactions: Hypersensitivity/ infusion reactions (eg, fever/chills, hypotension, bronchospasm), GI upset, mucositis, myelosuppression (esp. neutropenia, thrombocytopenia; may be fatal), asthenia, alopecia, fever, infections, peripheral neurotoxicity; rare: acute leukemia; others. How supplied: Single-dose vials–1

Etoposide (various)

℞

Topoisomerase inhibitor. Etoposide 50mg; caps; contain parabens. Indications: Small cell lung cancer. Adults: Round dose to nearest 50mg increment. Range: 70mg/m2 per day for 4 days to 100mg/m2 per day for 5 days. Repeat course every 3 to 4 weeks after recovery (esp myelosuppression). Renal impairment (CrCl ≤50mL/min): reduce dose (see literature). Consider dose reduction with existing myelosuppression due to previous radiation or chemotherapy. Children: Not recommended. Warnings/Precautions: Monitor blood (esp CBC/differential, platelets, hemoglobin) before each cycle and during therapy; renal function. Withhold dose if platelet count <50,000/mm3 or ANC <500/mm3. Hypoalbuminemia. Elderly. Pregnancy (Cat.D); nursing mothers: not recommended. Interactions: Potentiated by cyclosporine. Additive toxicity with radiation, other cytotoxic therapies. Adverse reactions: GI upset, mucositis, myelosuppression (esp. neutropenia, thrombocytopenia; may be fatal), alopecia, fever, infections, peripheral neurotoxicity; hypersensitivity reactions, acute leukemia (rare); others. How supplied: Contact supplier.

GEMZAR Lilly

℞

Antimetabolite. Gemcitabine HCl 200mg, 1g; per vial; pwd for IV infusion after reconstitution; contains mannitol. Indications: First-line treatment of inoperable, locally advanced (Stage IIIA or IIIB), or metastatic

(Stage IV) non-small cell lung cancer (NSCLC) (in combination with cisplatin). Adults: Infuse over 30 minutes (increased toxicity if infusion goes beyond 60 minutes). 4-week schedule: 1000mg/m2 on Days 1, 8, and 15 of each 28 day cycle; or 3-week schedule: 1250mg/m2 on Days 1 and 8 of each 21 day cycle. Adjust dose based on toxicity (see literature). Children: Not recommended. Warnings/Precautions: Not for use in combination with radiation therapy. Discontinue immediately if severe lung toxicity, hemolytic uremic syndrome, or capillary leak syndrome occurs. Renal or hepatic impairment. Evaluate renal and hepatic function prior to therapy, then periodically thereafter. Discontinue if severe liver injury develops. Monitor for myelosuppression; obtain CBCs, platelets prior to each dose. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: See Warnings/Precautions. Concomitant radiation therapy: may cause severe radiation toxicity. Adverse reactions: Myelosuppression, nausea, vomiting, elevated transaminases, proteinuria, hematuria, rash, pruritus, dyspnea, edema, flulike symptoms, infection, alopecia, neurotoxicity, others; rare: renal or liver failure, hemolytic uremic syndrom, capillary leak syndrome. Testing considerations: ERCC1 overexpression for response and prognosis; RRM1 How supplied: Single-use vials–1

GILOTRIF Boehringer Ingelheim

℞

Tyrosine kinase inhibitor. Afatinib 20mg, 30mg, 40mg; tabs. Indications: First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitutions as detected by an FDAapproved test. Limitations of use: safety and efficacy of Gilotrif have not been established in patients whose tumors have other EGFR mutations. Adults: Take on an empty stomach at least 1 hour before or 2 hours after a meal. 40mg once daily until disease progression or not tolerated. Concomitant P-gp inhibitors: reduce afatinib daily dose by 10mg if not tolerated; resume previous dose after discontinuing the P-gp inhibitor. Concomitant P-gp inducers: increase afatinib by 10mg as tolerated; resume previous dose 2–3 days after discontinuing the P-gp inducer. Dose modification: see full labeling. Children: Not established. Warnings/Precautions: Permanently discontinue for life-threatening bullous, blistering, or exfoliative skin lesions, confirmed interstitial lung disease, severe drug-induced hepatic impairment, persistent ulcerative keratitis, symptomatic left ventricular dysfunction, or severe/intolerable adverse reactions (at dose 20mg/day). Withhold for severe or prolonged

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LUNG CANCER diarrhea Grade ≥2 lasting for ≥2 consecutive days while taking antidiarrheal, prolonged cutaneous reaction Grade ≥2 (lasting >7 days) or intolerable, renal dysfunction Grade ≥2, or worsening liver function. History of keratitis, ulcerative keratitis, or severe dry eye. Monitor closely in moderate-to-severe renal impairment or severe hepatic impairment; adjust dose if not tolerated. Embryofetal toxicity: females of reproductive potential should use highly effective contraception during treatment and for at least 2 weeks after last afatinib dose. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Potentiated by P-gp inhibitors (eg, ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, amiodarone). Antagonized by P-gp inducer (eg, rifampicin, carbamazepine, phenytoin, phenobarbital, St. John’s wort). Adverse reactions: Diarrhea, rash/dermatitis acneiform, stomatitis, paronychia, dry skin, decreased appetite, pruritus. How supplied: Tabs–30

HYCAMTIN GlaxoSmithKline

℞

Topoisomerase inhibitor. Topotecan (as HCl) 4mg/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol; preservative-free. Indications: Small cell lung cancer sensitive disease after failure of 1st line chemotherapy. Adults: Confirm baseline neutrophils >1,500cells/mm3 and platelets >100,000cells/mm3 prior to 1st course of therapy. Give by IV infusion over 30 minutes. 1.5mg/m2 daily for 5 consecutive days starting on Day 1 of a 21-day cycle. Dose adjustments, renal impairment: see literature. Children: Not recommended. ℞ Also: HYCAMTIN CAPSULES Topotecan (as HCl) 0.25mg, 1mg; caps. Indications: Relapsed small cell lung cancer with prior complete or partial response and at least 45 days from the end of 1st line chemotherapy. Adults: Confirm baseline neutrophils >1,500cells/mm3 and platelets >100,000cells/mm3 prior to 1st course of therapy. Swallow whole. 2.3mg/m2/day once daily for 5 consecutive days; repeat every 21 days. Dose adjustments, renal impairment: see literature. Children: Not recommended. Contraindications: Severe bone marrow depression. Pregnancy (Cat.D). Nursing mothers. Warnings/Precautions: Monitor peripheral blood cell counts during therapy; hold subsequent doses until neutrophils >1,000cells/mm3, platelets >100,000cells/mm3, and hemoglobin ≥9g/dL. History of interstitial lung disease, pulmonary fibrosis, lung cancer, thoracic exposure to radiation, use of pneumotoxic drugs and/or colony stimulating factors: increased risk of interstitial lung disease; monitor, discontinue if occurs. Moderate to severe renal impairment.

Caps: severe diarrhea; may need to reduce dose. IV: avoid extravasation. Elderly. Interactions: Myelosuppression potentiated with platinum agents. IV: Neutropenia potentiated by G-CSF. Caps: Avoid concomitant P-glycoprotein inhibitors (eg, cyclosporine A, elacridar, ketoconazole, ritonavir, saquinavir). Adverse reactions: See literature. Neutropenia, leukopenia, thrombocytopenia, anemia, GI upset, anorexia, abdominal pain, stomatitis, headache, dyspnea, cough, pyrexia, alopecia, fatigue; infection, sepsis, interstitial lung disease, neutropenic colitis (may be fatal). How supplied: Single-use vials–1, 5 Caps–10

MUSTARGEN Recordati

℞

Nitrogen mustard. Mechlorethamine HCl 10mg/vial; pwd for IV or intracavitary inj after reconstitution. Indications: Palliative treatment of bronchogenic carcinoma. Adults: By IV infusion, per therapeutic course: 0.4mg/kg (lean body weight) as single dose or in divided doses of 0.1–0.2mg/kg per day. See literature for intracavitary (eg, intrapleural) administration. Do not exceed recommended dose. Repeat course only after hematological recovery (eg, every 3 weeks). Children: See literature. Contraindications: Infectious diseases. Warnings/Precautions: Drug is highly toxic; verify potential benefits outweigh risks; avoid inadvertent contact with powder or vapor. Do not use if foci of acute and chronic suppurative inflammation are present. Ensure adequate hydration. Avoid extravasation. Chronic lymphatic leukemia. Bone marrow suppression. Previous X-ray, cytotoxic chemotherapy. Infection. Hemorrhagic tendency. Monitor renal, hepatic and bone marrow function. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Adverse reactions: Bone marrow suppression, hyperheparinemia, GI upset (may be severe), anorexia, weakness, thrombosis, thrombophlebitis, hypersensitivity, jaundice, alopecia, vertigo, auditory disturbances, hemolytic anemia, skin reactions, infection, amyloidosis, hyperuricemia, gonad damage. How supplied: Vials–4

NAVELBINE Pierre Fabre

℞

Antimicrotubule agent. Vinorelbine (as tartrate) 10mg/mL; soln for IV inj after dilution; preservative-free. Indications: First-line treatment of ambulatory patients with unresectable, advanced non-small cell lung cancer (NSCLC), as a single agent or in combination with cisplatin. In Stage III NSCLC, use in combination with cisplatin. Adults: See literature. Give by IV inj over 6–10 minutes. Monotherapy: 30mg/m2 once weekly.

Combination therapy: 25mg/m2 once weekly with cisplatin given every 4 weeks; or 30mg/m2 once weekly with cisplatin given on Days 1 and 29, then every 6 weeks. Dose adjustment for toxicities, hepatic impairment: see literature. Children: Not recommended. Contraindications: Pretreatment granulocyte counts <1000 cells/mm3. Warnings/Precautions: IV use only; fatal if given intrathecally. Discontinue if neurotoxicity ≥grade 2. Pre-existing pulmonary dysfunction or neuropathy. Prior irradiation or chemotherapy. Cardiovascular disease. Monitor for myelosuppression, infection, and/or fever; obtain CBCs with differentials prior to each dose. Avoid contamination of the eyes or injecting into an extremity with poor circulation (thrombosis possible). Hepatic injury or impairment. Avoid extravasation. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May be potentiated by CYP3A inhibitors. Acute pulmonary reactions possible with mitomycin. Increased risk of granulocytopenia with cisplatin. May increase risk of neurotoxicity with paclitaxel. Prior or concomitant radiation therapy; may result in radiosensitizing effects. Adverse reactions: Myelosuppression (esp. granulocytopenia), inj site reactions, elevated liver enzymes, chest pain, fatigue, GI upset, alopecia, jaw pain, myalgia, arthralgia, rash, severe constipation, paralytic ileus, intestinal obstruction, necrosis, and/or perforation; dyspnea, severe bronchospasm. How supplied: Single-use vial (1mL, 5mL)–1

PHOTOFRIN Pinnacle Biologics

℞

Photosensitizing agent. Porfimer (as sodium) 75mg/vial; pwd for IV inj after reconstitution; preservative-free. Indications: Reduction of obstruction and palliation in patients with completely or partially obstructing endobronchial non-small-cell lung cancer (NSCLC). Treatment of microinvasive endobronchial NSCLC in patients for whom surgery and radiotherapy is not indicated. Adults: See literature. Give by slow IV inj over 3–5 minutes. 2mg/kg then illumination with laser light 40–50 hours following injection. 2nd course may be given at a minimum of 30 days after initial therapy; max 3 courses (separated by ≥30 days). Children: Not recommended. Contraindications: Porphyria. Existing tracheoesophageal or bronchoesophageal fistula. Tumors eroding into a major blood vessel. Emergency treatment of patients with severe acute respiratory distress caused by an obstructing endobronchial lesion. Esophageal or gastric varices. Esophageal ulcers >1cm in diameter. Warnings/Precautions: Avoid direct sunlight or bright indoor light; wear dark sunglasses when outdoors. Increased risk of fatal massive

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LUNG CANCER hemoptysis with large, centrally located tumors, cavitating tumors, extensive tumor extrinsic to the bronchus. Caution with endobronchial tumors in locations where treatment-induced inflammation could obstruct airway. Avoid extravasation. Pregnancy (Cat.C; use adequate contraception), nursing mothers: not recommended. Interactions: Increased risk of photosensitivity reactions with other photosensitizing agents (eg, tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics, griseofulvin, fluoroquinolones). May be antagonized by dimethyl sulfoxide, β-carotene, ethanol, formate, mannitol, allopurinol, calcium channel blockers, prostaglandin synthesis inhibitors, drugs that decreased clotting, vasoconstriction or platelet aggregation (eg, thromboxane A2 inhibitors), glucocorticoid hormones. Separate radiotherapy by 2–4 weeks. Adverse reactions: Photosensitivity reactions (eg, erythema, swelling, itching, burning sensation, feeling hot, blisters), fluid imbalance, chest pain, fever, pain, abdominal pain, GI upset, constipation, mucositis, ocular sensitivity, dyspnea, pleural effusion, anemia, fistula formation, fatal massive hemoptysis, others. How supplied: Vial–1

TARCEVA Genentech

℞

Human epidermal growth factor receptor type 1/ epidermal growth factor receptor tyrosine kinase inhibitor. Erlotinib (as HCl) 25mg, 100mg, 150mg; tabs. Indications: Maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. Treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. Adults: Take on empty stomach. 150mg once daily. Use until disease progression or unacceptable toxicity occurs. Diarrhea unresponsive to loperamide, severe skin reactions, strong CYP3A4 inhibitors (see Interactions), hepatic impairment: reduce in 50mg decrements. CYP3A4 inducers (see Interactions): consider increased dose (see literature). Children: Not recommended. Warnings/Precautions: Discontinue if interstitial lung disease, hepatic failure, or GI perforation occurs; interrupt or discontinue therapy in patients with dehydration at risk for renal failure, or with severe bullous, blistering or exfoliative skin conditions, or with acute/ worsening ocular disorders. Hepatic impairment. Monitor liver function tests periodically; if tests worsen, consider withholding or reducing dose; interrupt or discontinue therapy if severe changes (eg, total bilirubin >3×ULN, and/or transaminases >5×ULN) occur. Monitor renal

function, serum electrolytes, pulmonary function, INR, prothrombin time. History of peptic ulcers or diverticular disease. Pregnancy (Cat.D); use adequate contraception (see literature). Nursing mothers: not recommended. Interactions: Potentiated by CYP3A4 inhibitors (eg, clarithromycin, ritonavir, ketoconazole). Plasma levels decreased by CYP3A4 inducers (eg, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort), proton pump inhibitors or H2 blockers, and smoking. Antagonizes midazolam. Increased risk of GI perforation with concomitant anti-angiogenic agents, steroids, NSAIDs, taxane-based chemotherapy. Monitor for bleeding with oral anticoagulants, NSAIDs. Adverse reactions: Rash, diarrhea, GI upset, anorexia, fatigue, elevated LFTs, unexplained pulmonary symptoms (eg, dyspnea, cough, fever; discontinue and follow-up if occurs), stomatitis, infection; rare: GI perforation (may be fatal), ocular disorders (eg, conjunctivitis, keratitis, corneal ulceration/perforation), MI/ischemia, hemolytic anemia, cerebrovascular accidents, interstitial lung disease; hepatic or renal failure and hepatorenal syndrome (may be fatal); bullous, blistering and exfoliative skin conditions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis). Testing considerations: K-RAS mutation analysis, EGFR amplification analysis How supplied: Tabs–30

TAXOL Bristol-Myers Squibb

℞

Antimicrotubule agent. Paclitaxel 6mg/mL; soln for IV infusion after dilution; contains Cremophor EL (polyoxyethylated castor oil), dehydrated alcohol. Indications: First-line treatment of non-small cell lung cancer in combination with cisplatin in patients who are not candidates for potentially curative surgery and/or radiation therapy. Adults: See literature. Premedicate with corticosteroids, diphenhydramine, H2 antagonists. 135mg/m2 IV over 24 hours + cisplatin every 3 weeks. Hepatic impairment or neutropenia: see literature for dose modifications. Do not treat if neutrophil count <1,500cells/mm3 or platelets <100,000cells/mm3. Children: Not recommended. Contraindications: Baseline neutrophil count <1,500cells/mm3. Warnings/Precautions: Do frequent peripheral blood cell counts. Hepatic dysfunction. Conduction abnormalities: monitor cardiac function. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: May potentiate or be potentiated by CYP2C8 or CYP3A4 substrates, inducers and/or inhibitors. Potentiated by cisplatin. May potentiate doxorubicin. Adverse reactions: Bone marrow suppression (eg, neutropenia, leukopenia, thrombocytopenia,

anemia), inj site reactions, infections, hypotension, bradycardia, hypersensitivity reactions (if severe, do not rechallenge), peripheral neuropathy, myalgia, arthralgia, GI upset, mucositis, alopecia, abnormal ECG, elevated liver enzymes. How supplied: Multidose vial (5mL, 16.7mL, 50mL)–1

TAXOTERE Sanofi Aventis

℞

Antimicrotubule agent. Docetaxel 20mg/mL; soln for IV infusion after dilution; contains polysorbate 80; diluent contains alcohol. Indications: Locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy. In combination with cisplatin: initial treatment of unresectable, locally advanced or metastatic non-small cell lung cancer without previous chemotherapy. Adults: Give by IV infusion over 1hr once every 3 weeks. NSCL after platinum therapy failure: 75mg/m2. Chemotherapy-naïve NSCLC: 75mg/m2 followed by cisplatin (see full labeling). Premedicate with oral corticosteroid. Adjust dose based on tolerability and effect (see full labeling); allow neutrophils and platelets to recover before subsequent cycles. Children: Not established. Contraindications: Neutrophil count <1500 cells/mm3. Hypersensitivity to polysorbate 80. Warnings/Precautions: Hepatic dysfunction; bilirubin >ULN, SGOT and/or SGPT >1.5×ULN concomitant with alkaline phosphatase >2.5×ULN: not recommended. Obtain bilirubin, AST/ALT, and alkaline phosphatase values prior to each cycle. Monitor peripheral blood counts frequently (esp. neutrophils, platelets). Monitor for hypersensitivity reactions (esp. during 1st and 2nd infusions). Pre-existing effusions. Adjust dose if severe neurosensory symptoms (eg, paresthesia, dysesthesia, pain) occur; discontinue if symptoms persist. Monitor for eye disorders; discontinue if cystoid macular edema is diagnosed (consider alternative non-taxane chemotherapy). Elderly. Pregnancy (Cat.D; use adequate contraception); nursing mothers: not recommended. Interactions: May affect, or be affected by, other CYP3A4 inhibitors, inducers, or substrates (eg, ketoconazole, ritonavir). Adverse reactions: Infections, neutropenia, anemia, febrile neutropenia, hypersensitivity/ infusion site reactions, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, myalgia; cutaneous reactions (eg, erythema, edema, desquamation), acute myeloid leukemia, death (septic and nonseptic), cystoid macular edema. How supplied: Single-dose vials (1mL, 4mL, 8mL)–1 (w. diluent, supplies)

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LUNG CANCER TOPOSAR Teva

℞

Topoisomerase inhibitor. Etoposide 20mg/mL; soln for IV infusion; contains dehydrated alcohol 33.2%, polysorbate 80. Indications: First-line treatment of small cell lung cancer. Adults: Give by slow IV infusion over 30–60mins. Range 35mg/m2 per day for 4 days to 50mg/m2 per day for 5 days. Repeat course every 3 to 4 weeks after recovery from any toxicity. Renal impairment (CrCl 15–50mL/min): reduce dose to 75%; (CrCl <15mL/min): see literature. Consider dose reduction with existing myelosuppression due to previous radiation or chemotherapy. Children: Not recommended. Warnings/Precautions: Monitor for myelosuppression; obtain CBCs with differential, platelets, hemoglobin at baseline, prior to each subsequent dose, during and after therapy. Withhold dose if platelet count <50,000/mm3 or ANC <500/mm3. Renal impairment. Hypoalbuminemia. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Potentiated by cyclosporine. Additive toxicity with radiation, other cytotoxic therapies. Adverse reactions: Hypersensitivity/ infusion reactions (eg, fever/chills, hypotension, bronchospasm), GI upset, anorexia, mucositis, myelosuppression (esp neutropenia, thrombocytopenia; may be fatal), alopecia, fever, infections, peripheral neurotoxicity; rare: acute leukemia; others. How supplied: Multi-dose vials (5mL, 25mL, 50mL)–1

TREXALL Teva

℞

Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity. Diabetes. Peptic ulcer. Ulcerative colitis. Infection. Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated. Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, non-absorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin). Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome). How supplied: Tabs–30 Soln (2mL, 4mL, 8mL, 10mL)–10 (single-use vials) Pwd (1 gram)–1 (single-use vial)

XALKORI Pfizer

℞

Tyrosine kinase inhibitor. Crizotinib 200mg, 250mg; hard gel caps. Indications: Treatment of metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. Adults: Swallow whole. 250mg twice daily until disease progression or intolerance. Dose modification and/or dose reduction to 200mg twice daily may be required based on Grade 3 or 4 severity, then to 250mg once daily, or permanently discontinue if intolerable. Severe renal impairment (CrCl <30mL/min) not requiring dialysis: 250mg once daily. Dose reduction for hematologic and non-hematologic toxicities: see full labeling. Children: Not established. Warnings/Precautions: Confirm ALK-positive NSCLC with an FDA-approved test before treating. Monitor ALT and total bilirubin every 2 weeks during first 2 months, then monthly, and more frequently for elevated transaminases; temporarily suspend, reduce dose, or permanently discontinue as clinically indicated.

Monitor CBCs with differential monthly and more frequently if Grade 3 or 4 abnormalities, fever or infection occurs. Risk of severe pneumonitis: monitor for pulmonary symptoms; permanently discontinue if occurs. Congenital long QT syndrome; avoid. History of or predisposition for QTc prolongation (eg, CHF, bradyarrhythmias, electrolyte abnormalities, concomitant drugs that prolong QT interval): consider monitoring ECG, electrolytes periodically. Torsade de pointes, ventricular tachycardia, serious arrhythmia: permanently discontinue if QTc >500ms or ≥60ms change from baseline. Monitor hr and BP regularly; discontinue if life-threatening bradycardia occurs. Hepatic impairment. Severe renal impairment. Pregnancy (Cat.D); avoid. Use adequate contraception during therapy and at least 90 days after completion. Nursing mothers: not recommended. Interactions: Avoid concomitant strong CYP3A inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), grapefruit juice, or strong CYP3A inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John’s Wort). Avoid concomitant CYP3A substrates with narrow therapeutic indices (eg, alfentanil, cyclosporine, ergots, fentanyl, pimozide, quinidine, sirolimus, tacrolimus). Avoid concomitant agents known to cause bradycardia (eg, beta-blockers, nondihydropyridine calcium channel blockers, clonidine, digoxin). Caution with moderate CYP3A inhibitors. Dose reduction may be needed with coadministered drugs metabolized by CYP3A. Adverse reactions: Vision disorder, nausea, diarrhea, vomiting, constipation, edema, fatigue, Grade 3–4 events: ALT increased, neutropenia; elevated total bilirubin, pneumonitis (may be fatal), QT prolongation, bradycardia, hepatotoxicity (may be fatal). How supplied: Caps–60

ADVERSE REACTIONS Those adverse reactions listed within product monographs represent the potential for adverse effects based upon the active ingredient(s) and/or the drug class. It is not meant to be an inclusive list of responses.

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SARCOMA DOXIL Janssen Biotech

℞

Anthracycline. Doxorubicin HCl (liposomal) 2mg/mL; dispersion for IV infusion after dilution; preservative-free. Indications: AIDS-related Kaposi’s sarcoma refractory to combination chemotherapy. Adults: Give by IV infusion at initial rate of 1mg/min; may increase rate to complete infusion over 1hr if no infusion reactions occur; may premedicate with antiemetics. 20mg/m2 once every 3 weeks. Hepatic dysfunction (serum bilirubin ≥1.2mg/dL), hand-foot syndrome, hematologic toxicity (esp. ANC, platelets), or stomatitis: reduce dose. Consider total anthracycline and anthracenedione doses and irradiation when calculating total cumulative dose. See full labeling. Children: Not established. Warnings/Precautions: Not substitutable on a mg/mg basis with other doxorubicin products. Cardiotoxicity, acute infusion-related reactions, myelosuppression may occur. Have resuscitative/ antiallergic equipment and expertise available. Hepatic impairment. Monitor blood (esp. CBC + platelets), hepatic (esp. SGOT/SGPT, alkaline phosphatase), and cardiac function (esp. myocardial biopsy). Monitor periodically for secondary oral cancers with long-term use. Avoid extravasation. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Caution with cyclosporine, phenobarbital, phenytoin, streptozocin, digoxin, myelosuppressants, others. Previous mediastinal irradiation, cyclophosphamide, other cardiotoxic drugs: monitor for cardiotoxicity and hepatotoxicity. Adverse reactions: Asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand and foot syndrome, rash, neutropenia, thrombocytopenia, anemia; infusion reactions, cardiovascular events (eg, cardiomyopathy, CHF, acute LV failure), recall of skin reaction from prior radiation therapy, toxoplasmosis, urine discoloration (red/orange). How supplied: Single-use vials (10mL, 25mL)–1

INTRON A Merck

℞

Warnings/Precautions: May cause or exacerbate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders: monitor closely, discontinue if they worsen. Severe psychiatric disorders (esp. depression). Cardiovascular or pulmonary disease. Severe myelosuppression. Uncontrolled thyroid abnormalities. Diabetes. Coagulation disorders. Maintain adequate hydration. Monitor blood, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Psoriasis. Renal dysfunction. Transplant recipients. Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Caution with myelosuppressives, and drugs that can exacerbate depression. May potentiate theophylline (may double its levels). Adverse reactions: Flu-like symptoms (fever, headache, myalgia, fatigue); hepatic, hematologic, respiratory, skin, genitourinary system, CNS, cardiovascular, endocrine (esp thyroid), GI, or visual disorders; colitis, hypertriglyceridemia, pancreatitis, infections, injection site reactions; others (see literature). How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial–1; Soln (vials): 10million IU/vial–6 (kit w. supplies); Soln (multidose vials): 18million, 25million IU/vial–1

PANRETIN Eisai

℞

Retinoid. Alitretinoin 0.1%; gel. Indications: Cutaneous lesions of AIDS-related Kaposi’s sarcoma (KS). Adults: Apply twice daily to lesions (avoid mucous membranes and normal skin); do not occlude; may increase to 3-4 times daily as tolerated. Reduce frequency or suspend treatment if local toxicity occurs. Children: Not recommended. Warnings/Precautions: Not for use when systemic KS therapy required. Avoid sun, UV light. Flammable. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Increases DEET toxicity (avoid). Adverse reactions: Photosensitivity, rash, pruritus, pain, exfoliative dermatitis, paresthesia, edema. How supplied: Gel–60g

TAXOL Bristol-Myers Squibb

℞

Antimicrotubule agent. Paclitaxel 6mg/mL; soln for IV infusion after dilution; contains Cremophor EL (polyoxyethylated castor oil), dehydrated alcohol. Indications: Second-line treatment of AIDSrelated Kaposi’s sarcoma. Adults: See literature. Premedicate with corticosteroids, diphenhydramine, H2 antagonists. 135mg/m2 IV over 3 hours every 3 weeks; or 100mg/m2 IV over 3 hours every 2 weeks. Hepatic impairment or neutropenia: see literature for dose modifications. Do not treat if neutrophil count <1,000cells/mm3 or platelets <100,000cells/mm3. Children: Not recommended. Contraindications: Baseline neutrophil count <1,000cells/mm3.

Warnings/Precautions: Do frequent peripheral blood cell counts. Hepatic dysfunction. Conduction abnormalities: monitor cardiac function. Avoid extravasation. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: May potentiate or be potentiated by CYP2C8 or CYP3A4 substrates, inducers and/or inhibitors. Potentiated by cisplatin. May potentiate doxorubicin. Adverse reactions: Bone marrow suppression (eg, neutropenia, leukopenia, thrombocytopenia, anemia), inj site reactions, infections, hypotension, bradycardia, hypersensitivity reactions (if severe, do not rechallenge), peripheral neuropathy, myalgia, arthralgia, GI upset, mucositis, alopecia, abnormal ECG, elevated liver enzymes. How supplied: Multidose vial (5mL, 16.7mL, 50mL)–1

Vinblastine for injection

℞

Bedford

Antimicrotubule agent. Vinblastine (as sulfate) 10mg/vial; lyophilized pwd for IV inj or infusion after reconstitution. ℞ Also: Vinblastine injection Fresenius Kabi Vinblastine (as sulfate) 1mg/mL; soln for IV inj or infusion; contains benzyl alcohol. Indications: Frequently responsive: palliative treatment of Kaposi’s sarcoma. Adults: See literature. Give by IV once weekly. 1st dose: 3.7mg/m2 as a single dose, continue to increase dose by increments (2nd dose: 5.5mg/m2, 3rd dose: 7.4mg/m2, 4th dose: 9.25mg/m2, 5th dose: 11.1mg/m2, max dose: 18.5mg/m2) until WBC 3,000cells/mm3 reached, stop at this dose, then administer a dose one increment smaller at weekly intervals for maintenance. Usual weekly dosage: 5.5–7.4mg/m2. Do not give the next dose, even if 7 days have elapsed, unless WBC ≥4,000cells/mm3. If oncolytic effect occurs before leukopenia, do not increase the size of subsequent doses. Hepatic impairment: reduce dose by 50% if serum bilirubin >3mg/100mL. Children: Not recommended. Contraindications: Significant granulocytopenia (unless result of disease being treated). Bacterial infections (treat first). Warnings/Precautions: For IV use only; fatal if given intrathecally. Hepatic impairment. Avoid in elderly with cachexia or ulcerated skin; or in patients with malignant-cell infiltration of the bone marrow. Pre-existing pulmonary dysfunction. Progressive dyspnea requiring chronic therapy (do not re-administer). Ischemic cardiac disease. Bone marrow suppression; monitor WBC before and during treatment. Avoid contamination of the eyes or injecting into an extremity with poor circulation (thrombosis possible). Avoid extravasation. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May be potentiated by CYP3A inhibitors (eg, erythromycin). Antagonizes phenytoin. Adverse reactions: Leukopenia, alopecia, GI upset, paresthesias, malaise, pain; dyspnea, severe bronchospasm. How supplied: Pwd–10; Soln–1

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MASTER CANCER TREATMENT REGIMEN

SKIN CANCER Melanoma Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Systemic Therapy Options For Advanced Or Metastatic Melanoma1

Preferred Regimens (Consider Clinical Trial) REGIMEN

DOSING

Ipilimumab2–6*†

Day 1: Ipilimumab 3mg/kg IV once. Repeat cycle every 3 weeks for 4 cycles.

Vemurafenib7,9‡

Vemurafenib 960mg PO twice daily.

Dabrafenib

Dabrafenib 150mg PO twice daily.

10‡§

Dabrafenib + trametinib

Dabrafenib 150mg PO twice daily; plus trametinib 2 mg PO once daily.

High-dose IL-2

Days 1–5: IL-2 22mcg/kg (360,000 IU/kg), 33mcg/kg (540,000 IU/kg), 36mcg/kg (600,000 IU/kg), or 44mcg/kg (720,000mcg/kg) IV every 8 hours for up to 14 consecutive doses as clinically tolerated.**

11‡||

12–15¶#

Other Active Regimens Trametinib16‡††

Trametinib 2mg PO once daily.

Imatinib

Imatinib 400mg PO twice daily.

Dacarbazine18,19

Day 1: Dacarbazine 2–4.5mg/kg/day IV for 10 days. Repeat cycle every 4 weeks. OR Days 1–5: Dacarbazine 250mg/m2/day IV. Repeat cycle every 3 weeks.

Temozolomide20

Days 1–5: Temozolomide 200mg/m2/day PO for 5 days. Repeat cycle every 4 weeks.

Albumin-bound paclitaxel21,22

Nab-paclitaxel 100mg/m2 (in previously treated patients) or 150mg/m2 (in chemotherapy-naive patients) IV. Repeat every week for 3–4 cycles.

Dacarbazine + cisplatin + vinblastine23–25

Days 1 and 22: Dacarbazine 800mg/m2 IV, plus Days 1–4 and 22–25: Cisplatin 20mg/m2 IV + vinblastine 2mg/m2 IV. Repeat cycle every 3 weeks for 2 cycles. OR Day 1: Dacarbazine 800mg/m2 IV, plus Days 1–4: Cisplatin 20mg/m2 IV + vinblastine 1.2mg/m2 IV. Repeat cycle every 3 weeks for max 4 cycles. OR Day 1: Dacarbazine 800mg/m2 IV, plus Days 1–4: Cisplatin 20mg/m2 IV + vinblastine 1.6mg/m2 IV; plus IL-2 9 × 106 IU/m2 IV over 4 days and IFN-alpha 5 × 106 U/m2 SQ daily for 5 days. Repeat cycle every 3 weeks for max 6 cycles.

17‡‡

Dacarbazine + paclitaxel + cisplatin26 Day 1: Dacarbazine 800mg/m2 IV, plus Days 1–4: Cisplatin 20mg/m2 IV, plus Days 1 and 8: Paclitaxel 100mg/m2 IV. Low-dose interleukin-2 (IL-2) + Days 1–5: IL-2 1 million IU/m2/day SQ, plus granulocyte macrophage-stimulating Days 1–14: GM-CSF 125mcg/m2/day SQ. factor (GM-CSF)27 Repeat cycle every 4 weeks for 12 cycles. Paclitaxel + carboplatin28

Days 1, 8, and 15: Paclitaxel 100mg/m2 IV + carboplatin AUC=2 IV. Repeat cycle every 4 weeks until disease progression. continued

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MASTER CANCER TREATMENT REGIMEN

SKIN CANCER Melanoma Treatment Regimens Other Active Regimens (continued) REGIMEN

DOSING

Paclitaxel + carboplatin ± sorafenib29–31

Day 1: Carboplatin AUC=6 IV + paclitaxel 225mg/m2 IV, followed by Days 2–19: Sorafenib 400mg orally twice daily. Repeat cycle every 3 weeks.

* Ipilimumab has the potential for significant immune-mediated complications. Participation in the risk evaluation and mitigation strategy (REMS) program and/or experience in use of the drug as well as resources to follow the patient closely are essential. Ipilimumab should be used with extreme caution, if at all, in patients with serious underlying autoimmune disorders. † Re-induction with ipilimumab may be considered for select patients who experienced no significant systemic toxicity during prior ipilimumab therapy and who relapse after initial clinical response or progress after stable disease >3 months. ‡ Vemurafenib, dabrafenib, and trametinib are recommended only for patients with V600 mutation of the BRAF gene documented by an FDA-approved or Clinical Laboratory Improvement Amendments (CLIA)-approved facility. § Dabrafenib administration can be associated with significant episodic and recurrent fevers that should be managed by discontinuation of dabrafenib and institution of anti-pyretics such as acetaminophen and/or NSAIDs. Dabrafenib is associated with keratoacanthoma/low grade squamous carcinomas and little if any significant photosensitivity. Regular dermatologic evaluation and referral to a dermatologist is recommended. Patients should also be educated to report the development of other adverse reactions such as joint pain and swelling. || The combination of dabrafenib with trametinib was associated with improved progression-free survival (PFS) compared to dabrafenib monotherapy in a phase I/Il trial; however, improvement in overall survival has not been demonstrated. Combination therapy may be associated with less cutaneous toxicity than monotherapy. ¶ High-dose IL-2 should not be used for patients with inadequate organ reserve, poor performance status, or untreated or active brain metastases. For patients with small brain metastases and without significant peritumoral edema, IL-2 therapy may be considered (category 2B). # Administration of multiagent regimens and high-dose lL-2 is complex and associated with significant toxicities. Therapy should be restricted to an institution with medical staff experienced in the administration and management of these regimens. ** In the clinical trial setting, a second identical treatment cycle was scheduled after 6 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients for up to five courses [two cycles/course]. †† Single-agent trametinib is not indicated for the treatment of patients who have experienced progression of disease on prior BRAF inhibitor therapy. Single-agent trametinib can be used for the treatment of BRAF-mutated melanoma in patients who are intolerant to single-agent BRAF inhibitors. ‡‡ For C-KIT mutated tumors.

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Melanoma. v 3.2014. Available at: http://www.nccn.org/professionals/physician_gls/ pdf/melanoma.pdf. Accessed April 21, 2014. 2. Yervoy [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2011. 3. Margolin K, Ernstoff MS, Hamid O, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13:459–465. 4. Weber JS, Kähler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30:2691–2697. 5. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–2526. 6. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–723. 7. Chapman PB, Hauschild A, Robert C, et al; BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–2516. 8. Zelboraf. [package insert]. San Francisco, CA: Genentech; 2011. 9. Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600- mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;366:707–714. 10. Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAFmutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380:358–365. 11. Flaherty KT, Infante JR, Daud A, et al. Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations. N Eng J Med. 2012:367:1694–1703. 12. Rosenberg SA, Yang JO, Topalian SL, et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994;271: 907–913. 13. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleu kin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17:2105–2116. 14. Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000;6 Suppl 1:S11–14. 15. Smith FO, Downey SG, Klapper JA, et al. Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin Cancer Res. 2008; 14(17):5610–5618. 16. Flaherty KT, Robert C, Hersey P, et al. Improved Survial with MEK Inhibition in BRAF-mutated melanoma. N Eng J Med. 2012;367:107–114. 17. Carvajal RD, Antonescu CR, Wolchok, JD, et al. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011;395:2327–2334. 18. Serrone L, Zeuli M, Sega FM, et al. Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview. J Exp Clin Cancer Res. 2000;19:21–34.

19. Dacarbazine for injection USP [prescribing information]. Bedford, Ohio: Bedford Laboratories, 2007. 20. Middleton MR, Grob JJ, Aaronson N, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol. 2000;18:158–166. 21. Hersh EM, O’Day SJ, Ribas A, et al. A phase 2 Clinical trial of nab-Paclitaxel in previously treated and chemotherapy-naïve patients with metastatic melanoma. Cancer. 200;116:155–163. 22. Kottschade LA, Suman VJ, Amatruda T, et al. A phase II trial of nab-paclitaxel (ABI007) and carboplatin in patients with unresectable stage iv melanoma: a north central cancer treatment group study, N057E(1). Cancer. 2011;117:1704–1710. 23. Eton O, Legha SS, Bedikian AY, et al. Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial. J Clin Oncol. 2002; 20:2045–2052. 24. Atkins MB, Hsu J, Lee S, et al; Eastern Cooperative Oncology Group. Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b with cisplatin, vinblastine, and dacarbazine alone in patients with metastatic malignant melanoma (E3695): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2008;26:5748–5754. 25. Legha SS, Ring S, Eton 0, et al. Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma. J Clin Oncol. 1998;16:1752–1759. 26. Papadopoulos NE, Bedikian A, Ring S, et al. Phase I/II study of a cisplatintaxol-dacarbazine regimen in metastatic melanoma. Am J Clin Oncol. 2009;32(5):509–514. 27. O’Day SJ, Boasburg PD, Piro L et al. Maintenance biotherapy for metastatic melanoma with interleukin-2 and granulocyte macrophage-colony stimulating factor improves survival for patients responding to induction concurrent biochemotherapy. Clin Cancer Res. 2002;8:2775–2781. 28. Rao RD, Holtan SG, Ingle JN, et al. Combination of paclitaxel and carboplatin as second-line therapy for patients with metastatic melanoma. Cancer. 2006;106:375–382. 29. Hauschild A, Agarwala SS, Trefzer U, et al. Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma. J Clin Oncol. 2009;27:2823–2823. 30. Flaherty KT, Lee SJ, Schuchter LM, et al. Final results of E2603: a double-blind, randomized phase III trials comparing carboplatin (C), paclitaxel (P) with or without sorafenib (S) in metastatic melanoma [abstract]. J Clin Oncol. 2010:28(suppl):8511. 31. Agarwala SS, Keilholz U, Hogg D, et al. Randomized phase Ill study of paclitaxel plus carboplatin with or without sorafenib as second-line treatment in patients with advanced melanoma. J Clin Oncol. 2007;25(18_suppl):8510. (Revised 5/2014) © 2014 Haymarket Media, Inc.

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MASTER DRUG MONOGRAPHS

SKIN CANCER DTIC-DOME Bayer

℞

EFUDEX Valeant

℞

Antimetabolite. Fluorouracil 2%, 5%; soln. ℞ Also: EFUDEX CREAM Fluorouracil 5%. Indications: Multiple actinic or solar keratoses. Superficial basal cell carcinoma when conventional therapy is impractical (5% only); see literature. Adults: Keratoses: Apply twice daily until erosion occurs (usually 2–4 wks). Basal cell carcinoma (5% only): Apply twice daily, usually for 3–6 weeks (obliteration may take 10–12 weeks). Children: Not recommended. Contraindications: Dihydropyrimidine dehydrogenase (DPD) deficiency. Pregnancy (Cat.X). Warnings/Precautions: Apply cautiously near eyes, nose, mouth. Avoid mucous membranes, occlusion, ulcerated/inflamed skin, exposure to UV light. Wash hands after application if fingers were used. Notify patients of expected skin reaction. Biopsy unresponsive lesions. Nursing mothers: not recommended. Adverse reactions: Pain or burning at application site, pruritus, irritation, hyperpigmentation. How supplied: Soln–10mL (w. drop dispenser); Crm–25g

ERIVEDGE Genentech

℞

Hedgehog pathway inhibitor. Vismodegib 150mg; caps. Indications: Treatment of adults with metastatic basal cell carcinoma, or locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation.

Adults: Swallow whole. 150mg once daily, until disease progression or unacceptable toxicity. Children: Not established. Warnings/Precautions: Risk of embryo-fetal death and severe birth defects in pregnant women. Verify pregnancy status prior to initiation of therapy. Counsel patients (males and females) on the need for contraception during and after treatment. Advise patients not to donate blood or blood products while on therapy and for at least 7 months after last dose. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: May be potentiated by P-gp inhibitors (eg, clarithromycin, erythromycin, azithromycin). May be antagonized by drugs that affect gastric pH (eg, proton pump inhibitors, H2-receptor antagonists, antacids). Adverse reactions: Muscle spasms, alopecia, dysgeusia, weight loss, fatigue, GI upset, decreased appetite, constipation, arthralgias, ageusia. Note: Report immediately exposure to Erivedge during pregnancy by contacting the Genentech Adverse Event Line at (888) 835-2555. How supplied: Caps–28

GLEEVEC Novartis

℞

Kinase inhibitor. Imatinib (as mesylate) 100mg, 400mg; tabs. Indications: Adults with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown. Adults with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP). Adults: Take with food and water. May disperse tab in water or apple juice and take promptly. ≥18yrs: ASM without D816V c-Kit mutation or status unknown: 400mg once daily. ASM associated with eosinophilia: initially 100mg once daily; may increase to 400mg once daily if insufficient response. If severe non-hematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction. Severe hepatic impairment: reduce dose by 25%. Renal or hematologic reactions: see full labeling. Potent CYP3A4 inducers (eg, rifampin): increase imatinib dose by at least 50%. Children: Not recommended. Warnings/Precautions: Hepatic or renal impairment. Monitor weight and for fluid retention regularly; CBCs weekly for 1st month, bi-weekly for 2nd month, then periodically (eg, every 2–3 months); liver function at baseline then monthly or as needed; GI symptoms at baseline. Cardiovascular disease or risk factors; monitor. Immunosuppression from long-term use. Monitor for tumor lysis syndrome; correct clinically significant dehydration and treat high uric acid levels before initiating therapy. Monitor growth in children. Possible cardiogenic shock/LV dysfunction in conditions with high eosinophil levels (eg, HES/CEL, MDS/MPD, ASM); consider concomitant systemic steroid prophylaxis (1–2mg/kg) for 1 or 2 wks if abnormal ECG or serum troponin. Monitor TSH levels in thyroidectomy patients undergoing levothyroxine

replacement. Pregnancy (Cat.D); avoid. Use highly effective contraception during treatment. Nursing mothers: not recommended. Interactions: Avoid grapefruit juice. Potentiated by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin). May potentiate drugs metabolized by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain statins, sirolimus, tacrolimus), CYP2D6, or CYP2C9 (use heparin instead of warfarin). Adverse reactions: Edema (may be severe), nausea, vomiting, musculoskeletal pain, diarrhea, muscle cramps, rash (may be severe; eg, erythema multiforme, Stevens-Johnson syndrome), fatigue, abdominal pain, dizziness, blurred vision, somnolence, fever, headache, cough, arthralgia/myalgia, dyspnea, hypokalemia, night sweats, anorexia, pruritus, hemorrhage, anemia, neutropenia, thrombocytopenia, weight gain, renal or hepatotoxicity, immunosuppression, hypothyroidism; rare: severe CHF, LV dysfunction. How supplied: 100mg–90; 400mg–30

HYDREA Bristol-Myers Squibb

℞

Substituted urea. Hydroxyurea 500mg; caps. Indications: Melanoma. Adults: See literature. Intermittant therapy for solid tumors: 80mg/kg as single dose every 3rd day. Continuous therapy for solid tumors: 20–30mg/kg/day as single dose. Renal impairment: reduce dose. Children: Not recommended. Contraindications: Marked bone marrow depression. Warnings/Precautions: Previous irradiation therapy or chemotherapy. Correct anemia before starting. Monitor hematologic, renal, hepatic function before and during treatment. Marked renal dysfunction. Myeloproliferative disorders; discontinue if cutaneous vasculitic ulcerations develop and use alternative agents. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [monitor], fatal hepatotoxicity, peripheral neuropathy). Myelosuppressives potentiate antineoplastic effect. May antagonize antigout agents. Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated urease, uricase, lactate dehydrogenase. Adverse reactions: Leukopenia, anemia, erythrocytic abnormalities, thrombocytopenia, GI upset, rash, erythema, fever, CNS effects, temporary renal impairment, acute pulmonary reactions, secondary leukemias, skin cancer. Note: Wear disposable gloves when handling caps or bottle. How supplied: Caps–100

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MASTER DRUG MONOGRAPHS

SKIN CANCER INTRON A Merck

℞

Interferon alfa-2b, recombinant; 10 million, 18 million, or 50 million IU per vial; pwd; for inj after reconstitution/dilution; preservative-free. ℞ Also: INTRON A SOLN Interferon alfa-2b, recombinant; 10 million IU, 18 million IU, 25 million IU; per vial; for inj; contains m-cresol. Indications: Malignant melanoma. Adults: Induction: 20million IU/m2 IV over 20 mins, 5 consecutive days per week, for 4 weeks. Maintenance: 10 million IU/m2 SC 3 times per week for 48 weeks. See literature for appropriate preparation and route and for dose adjustments. Children: Not recommended. Contraindications: Hepatitis: decompensated liver disease. Autoimmune disorders. Warnings/Precautions: May cause or exacerbate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders: monitor closely, discontinue if they worsen. Severe psychiatric disorders (esp. depression). Cardiovascular or pulmonary disease. Severe myelosuppression. Uncontrolled thyroid abnormalities. Diabetes. Coagulation disorders. Maintain adequate hydration. Monitor blood, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Psoriasis. Renal dysfunction. Transplant recipients. Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Caution with myelosuppressives, and drugs that can exacerbate depression. May potentiate theophylline (may double its levels). Adverse reactions: Flu-like symptoms (fever, headache, myalgia, fatigue); hepatic, hematologic, respiratory, skin, genitourinary system, CNS, cardiovascular, endocrine (esp thyroid), GI, or visual disorders; colitis, hypertriglyceridemia, pancreatitis, infections, injection site reactions; others (see literature). How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial–1; Soln (vials): 10million IU/vial–6 (kit w. supplies); Soln (multidose vials): 18million, 25million IU/vial–1

MEKINIST GlaxoSmithKline

℞

Kinase inhibitor. Trametinib 0.5mg, 1mg, 2mg; tabs. Indications: As monotherapy or in combination with dabrafenib for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDAapproved test. Limitation of use: as a single agent is not indicated for the treatment of patients who have received prior BRAF-inhibitor therapy. Adults: Confirm presence of BRAF V600E or V600K mutation prior to initiation. Take at least 1hr before or 2hrs after a meal. Monotherapy or in combination with dabrafenib: 2mg once daily; continue until disease progression or unacceptable toxicity occurs. In combination therapy: take at

same time each day either with the AM or PM dose of dabrafenib. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: See full labeling for dabrafenib prior to starting combination therapy. Risk of cardiomyopathy; assess LVEF prior to initiation, after one month, and then at every 2–3 month intervals during treatment; withhold if absolute LVEF decreases by 10% from pretreatment values and is less than the lower limit of normal; permanently discontinue if symptomatic cardiomyopathy or persistent asymptomatic LVEF dysfunction is unresolved within 4 weeks. Perform eye exam at any time for visual disturbances and compare to baseline. Retinal pigment epithelial detachment; withhold if diagnosed; if resolved within 3 weeks, may resume at reduced dose. Withhold if new or progressive pulmonary symptoms or findings develop. Permanently discontinue if retinal vein occlusion, interstitial lung disease, or pneumonitis occurs. Monitor for skin toxicities and secondary infections. Embryofetal toxicity. Females of reproductive potential should use highly effective contraception during and for 4 months after treatment. Pregnancy (Cat.D). Nursing mothers: not recommended. Adverse reactions: Rash, diarrhea, lymphedema; combination with dabrafenib: pyrexia, chills, fatigue, rash, nausea, vomiting, constipation, abdominal pain, peripheral edema, cough, headache, arthralgia, night sweats, decreased appetite, myalgia; hemorrhage, thromboembolic events. How supplied: Tabs–30

PROLEUKIN Prometheus

℞

output is reduced, systolic BP <90mmHg, CHF, cardiac ischemia or arrhythmias occur; or if moderate-to-severe lethargy or somnolence (continuing may result in coma) develops. Evaluate and treat CNS metastases; obtain negative scan before starting treatment. Do thallium stress test; monitor vital signs, weight, fluid intake and output daily. Correct hypovolemia or fluid accumulations if occur. Obtain CBCs, differential and platelets, blood chemistries (electrolytes, renal and hepatic function tests), chest X-rays, serum creatinine (should be ≤1.5mg/dL before starting therapy), pulmonary function tests, arterial blood gases. Monitor for capillary leak syndrome, mental status changes, thyroid changes, diabetes onset. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Psychotropics may increase CNS toxicity. Increased toxicity with other nephrotoxic, hepatotoxic, myelotoxic, or cardiotoxic drugs. Hypersensitivity reactions with other antineoplastics. Myocardial injury and rhabdomyolysis risk increased with interferonalfa. Antagonized by glucocorticoids (avoid). β-blockers and other antihypertensives may potentiate hypotension. Delayed reactions to iodinated contrast media. May increase risk of allograft rejection. Adverse reactions: Hypotension, GI upset, oliguria, flu-like syndrome, respiratory disorders (eg, dyspnea), CNS effects (eg, confusion, somnolence), rash, metabolic and nutritional disorders (eg, bilirubinemia, increased creatinine), hyperglycemia, thyroid disorder, thrombocytopenia, anemia, impaired neutrophil function, capillary leak syndrome, cardiotoxicity, exacerbation of autoimmune and inflammatory disease, eosinophilia, possible antibody formation; others. How supplied: Single-use vials–1

SYLATRON Merck

℞

Alpha interferon. Peginterferon alfa-2b 296mcg, 444mcg, 888mcg; per vial; pwd for SC inj after reconstitution. Indications: Adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy. Adults: ≥18yrs: Give by SC inj. Rotate inj sites. Premedicate with acetaminophen. 6mcg/kg/ week for 8 doses, followed by 3mcg/kg/week for up to 5 years. Withhold dose if ANC <0.5×109/L, platelets <50×109/L, ECOG PS ≥2, or for non-hematologic toxicity ≥ Grade 3. Resume at reduced dose (see literature) when: ANC ≥0.5×109/L, platelets ≥50×109/L, ECOG PS 0–1, and non-hematologic toxicity has completely resolved or improved to Grade 1. Children: <18yrs: not established. Contraindications: Anaphylaxis to peginterferon alfa-2b or interferon alfa-2b. Autoimmune hepatitis. Hepatic decompensation (Child-Pugh score >6 [Class B and C]).

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SKIN CANCER Warnings/Precautions: Increased risk of depression and other neuropsychiatric disorders. Permanently discontinue for: persistent severe or worsening neuropsychiatric disorders (eg, depression, psychosis, encephalopathy); new onset ventricular arrhythmia or cardiovascular decompensation; new or worsening retinopathy; severe (Grade 3) hepatic injury or hepatic decompensation; hypothyroidism, hyperthyroidism, or diabetes mellitus that cannot be effectively managed; or if unable to tolerate a dose of 1mcg/kg/week. Monitor for signs/symptoms of depression/psychosis every 3 weeks during first 8 weeks, then every 6 months, continue for at least 6 months after last dose. Perform eye exam in patients with retinopathy and those with vision changes during therapy. Monitor hepatic function with serum bilirubin, ALT/AST, alkaline phosphate, and LDH at 2 and 8 weeks, and 2 and 3 months following initiation, then every 6 months. Obtain TSH levels within 4 weeks prior to initiation, at 3 and 6 months following initiation, then every 6 months. Moderate-to-severe renal impairment (monitor). Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Therapeutic effect of drugs metabolized by CYP2C9 or CYP2D6 may be altered. Adverse reactions: Fatigue, increased ALT/AST, pyrexia, headache, anorexia, myalgia, nausea, chills, inj site reactions; neuropsychiatric disorders. How supplied: Single-use vial–1, 4 (w. diluent)

TAFINLAR GlaxoSmithKline

℞

Kinase inhibitor. Dabrafenib 50mg, 75mg; caps. Indications: As monotherapy for the treatment of unresectable or metastatic melanoma with BRAF V600E mutation, as detected by an FDA-approved test. In combination with trametinib for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test. Limitation of use: not indicated for the treatment of wild-type BRAF melanoma. Adults: Confirm presence of BRAF V600E or V600K mutation prior to initiation. Swallow whole. Take at least 1hr before or 2hrs after a meal. Monotherapy or in combination with trametinib: 150mg twice daily (about 12hrs apart); continue until disease progression or unacceptable toxicity occurs. Dose modifications or reductions: see full labeling. Children: Not established. Warnings/Precautions: See full labeling for trametinib prior to starting combination therapy. Increased incidence of new primary cutaneous malignancies; perform skin evaluation prior to initiation, every 2 months during therapy, and up to 6 months after discontinuation. Withhold if fever ≥101.3°F or any serious febrile drug reaction occurs and evaluate for infection; prophylaxis with antipyretics may be needed when resuming. Pre-existing diabetes or hyperglycemia; monitor serum glucose levels. Monitor for visual signs/ symptoms of uveitis. Closely monitor patients

with G6PD deficiency for signs of hemolytic anemia. Males (risk of infertility). Embryo-fetal toxicity. Females of reproductive potential should use highly effective non-hormonal contraception during and for 4 weeks after treatment. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Concomitant strong inhibitors (eg, ketoconazole, nefazodone, clarithromycin, gemfibrozil) or inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, St John’s wort) of CYP3A4 or CYP2C8: not recommended; if unavoidable, monitor closely. Drugs that affect gastric pH (eg, PPIs, H2-blockers, antacids) may decrease dabrafenib exposure. May antagonize effects of CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP2C19, UGT, transporters, or other substrates (eg, midazolam, warfarin, dexamethasone, hormonal contraceptives). Adverse reactions: Hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, palmarplantar erythrodysesthesia syndrome; combination with trametinib: chills, fatigue, rash, nausea, vomiting, diarrhea, constipation, abdominal pain, peripheral edema, cough, night sweats, decreased appetite, myalgia; hemorrhage, thromboembolic events. How supplied: Caps–120

YERVOY Bristol-Myers Squibb

℞

Cytotoxic T-lymphocyte antigen 4 (CTLA-4)blocking antibody. Ipilimumab 5mg/mL; soln for IV infusion; preservative-free. Indications: Treatment of unresectable or metastatic melanoma. Adults: Give by IV infusion over 90 mins. 3mg/kg every 3 weeks for a total of 4 doses. Withhold dose for moderate immune-mediated reactions or symptomatic endocrinopathy. Complete/partial resolution of adverse reaction and receiving <7.5mg prednisone or equivalent per day: may resume treatment. Permanently discontinue and initiate systemic high-dose corticosteroids for severe adverse reactions. Children: Not established. Warnings/Precautions: Permanently discontinue if: persistent moderate adverse reactions or inability to reduce corticosteroid dose to 7.5mg prednisone or equivalent per day; failure to complete full treatment course within 16 weeks from first dose; severe or life-threatening reactions, including: 1) colitis with abdominal pain, fever, ileus, or peritoneal signs; increase in stool frequency and incontinence, need for IV hydration for >24hrs, GI hemorrhage/perforation; 2) AST or ALT >5X ULN or total bilirubin >3X ULN; 3) Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; 4) severe motor or sensory neuropathy, GuillainBarre syndrome, or myasthenia gravis; 5) severe immune-mediated reactions involving any organ system; 6) immune-mediated ocular disease that is unresponsive to topical immunosuppressive therapy. Monitor for enterocolitis, dermatitis, neuropathy, endocrinopathy; perform LFTs and

thyroid tests at baseline and before each dose. Moderate or severe hepatic impairment. Pregnancy (Cat.C). Nursing mothers: not recommended. Adverse reactions: Fatigue, diarrhea, pruritus, rash, colitis; immune-mediated adverse reactions (may be severe and fatal). How supplied: Single-use vial (50mg, 200mg)–1

ZELBORAF Genentech

℞

Kinase inhibitor. Vemurafenib 240mg; tabs. Indications: Treatment of unresectable or metastatic melanoma with BRAFV600E mutation as detected by an FDA-approved test. Limitation of use: not for treatment of wild-type BRAF melanoma. Adults: Swallow whole with water. Take in the AM and PM (approx. 12hrs apart). ≥18yrs: 960mg twice daily; until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions or QTc prolongation: see full labeling. Dose reductions <480mg twice daily: not recommended. Children: <18yrs: not established. Warnings/Precautions: Confirm BRAFV600E mutation-positive melanoma with FDA-approved test before treating. Risk of cutaneous squamous cell carcinoma (cuSCC): ≥65yrs, prior skin cancer, chronic sun exposure; if occurs, do excision and continue without dose adjustment. Do dermatologic evaluation before therapy, every 2 months during, and consider monitoring 6 months after. Monitor for signs/symptoms of new non-cutaneous SCC and other malignancies. Long QT syndrome or QTc >500ms, uncorrectable electrolyte abnormalities, or concomitant drugs that prolong the QT interval: not recommended. Monitor electrolytes before therapy and after dose adjustments. Monitor ECG prior to initiation, at Day 15 of treatment, monthly during the 1st 3 months, then every 3 months thereafter, or more as needed. If QTc >500ms, interrupt therapy, correct electrolytes, and control cardiac risk factors. Severe hepatic or renal impairment. Monitor liver enzymes, bilirubin before therapy and monthly, or as needed. Monitor for ophthalmologic reactions routinely. Avoid sun exposure. Pregnancy (Cat.D); avoid. Use adequate contraception during therapy and for at least 2 months after. Nursing mothers: not recommended. Interactions: Avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir) or strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital); consider alternatives. Concomitant CYP1A2 substrates with narrow therapeutic indices: not recommended; if unavoidable, consider dose reduction of substrates and monitor. Increased transaminase and bilirubin with concomitant ipilimumab. Adverse reactions: Arthralgia, rash, alopecia, fatigue, photosensitivity, nausea, pruritus, skin papilloma; severe hypersensitivity or dermatologic reactions (discontinue if occurs), prolonged QTc, uveitis, other malignancies. How supplied: Tabs–120

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ASSOCIATED HEMATOLOGICAL DISORDERS Anemias

ANADROL-50 Meda

CIII

Androgen. Oxymetholone 50mg; scored tabs. Indications: Anemia caused by deficient red cell production. Acquired aplastic anemia, congenital anemia, myelofibrosis, and hypoplastic anemias due to myelotoxic drugs. Adults and Children: Individualized. 1–5mg/kg per day for at least 3–6 months; may attempt to lower dose or discontinue after remission. Congenital aplastic anemia: may need continued maintenance dose. Contraindications: Male breast or prostate carcinoma. Breast cancer in females with hypercalcemia. Nephrosis or the nephrotic phase of nephritis. Severe hepatic dysfunction. Pregnancy (Cat.X). Warnings/Precautions: Not a replacement for other supportive treatments (eg, transfusion; iron, folic acid, Vit. B12, Vit. B6 replacement). Discontinue if jaundice, abnormal liver function, hypercalcemia, or edema occurs. Cardiac, hepatic, or renal dysfunction. Monitor hepatic function, blood, and bone age. Elderly. Young children. Nursing mothers: not recommended. Interactions: May potentiate oral anticoagulants. May alter insulin needs. Adverse reactions: Peliosis hepatis, premature epiphyseal closure in adolescents, edema, hepatic carcinoma, prostatic hypertrophy or carcinoma, gynecomastia, priapism, oligospermia, nausea, jaundice, hirsutism, virilization, male pattern baldness, acne, polycythemia, headache, CNS excitation, insomnia, altered libido, fluid and electrolyte disturbances, suppression of clotting factors, increased serum cholesterol. How supplied: Tabs–100

ARANESP Amgen

℞

Erythropoiesis stimulating protein. Darbepoetin alfa 25mcg/mL, 40mcg/mL, 60mcg/mL, 100mcg/mL, 150mcg/0.75mL, 200mcg/mL, 300mcg/mL, 500mcg/mL; for IV or SC inj; preservative-free; contains albumin (human) or polysorbate 80. ℞ Also: ARANESP SINGLEJECT Darbepoetin alfa 25mcg/0.42mL, 40mcg/0.4mL, 60mcg/0.3mL, 100mcg/0.5mL, 150mcg/0.3mL, 200mcg/0.4mL, 300mcg/0.6mL, 500mcg/mL; per prefilled syringe; for IV or SC inj; preservative-free; contains albumin (human) or polysorbate 80. Indications: Anemia of chronic renal failure (CRF), including patients on and not on dialysis. Chemotherapy-induced anemia in patients with non-myeloid malignancies. Adults: CRF (not currently on epoetin alfa): initially 0.45mcg/kg SC or IV once weekly; alternatively for CRF (not on dialysis): 0.75mcg/kg SC once

every 2 weeks. Cancer: initially 2.25mcg/kg SC once weekly or 500mcg SC once every 3 weeks. Discontinue after completion of chemotherapy course. Adjust dose to maintain hemoglobin level (target 10–12g/dL; max 12g/dL) sufficient to avoid red blood cell transfusion; see literature. Converting from epoetin alfa, and for dose adjustment: see literature. Children: Not recommended. Contraindications: Uncontrolled hypertension. Do not use in patients with pure red cell aplasia due to erythropoietin antibodies. Warnings/Precautions: See literature. Evaluate serum iron, ferritin, transferrin saturation before and during therapy; most patients will need iron supplementation. Monitor hemoglobin weekly for 4 weeks after start and dose changes, until stabilized, then periodically; reduce dose if hemoglobin increases >1g/dL in any 2-week period; withhold dose if hemoglobin exceeds 12g/dL. Monitor BP (reduce or withhold dose if hypertension occurs), folate, Vit. B12, renal function, electrolytes, fluid balance, and for premonitory neurological symptoms. Seizure, cardiovascular, or hematologic disorders. Infection, inflammation, malignancy, occult blood loss, severe albumin toxicity, bone marrow fibrosis may reduce effectiveness; consider other etiologies in treatment failures. Adjust dialysis ℞ as needed. Latex allergy. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Infection, hyper- or hypotension, myalgia, headache, GI upset, dyspnea, edema, arthralgia, limb or back pain, arrhythmia/cardiac arrest, cough, fatigue, chest pain, dizziness, pruritus, clotted vascular access, CHF, flu-like symptoms, local reactions, asthenia, seizure, iron deficiency. Increased risk of death, cardiovascular or thrombotic events if hemoglobin >12g/dL. May stimulate tumor growth, shorten time to tumor progression or overall survival if hemoglobin ≥12g/dL. Cancer patients also: pneumonia, dehydration. How supplied: Single-dose vials (25, 40, 60, 100, 150mcg)–4; Single-dose vial (200, 300mcg)–1; Single-dose prefilled syringes (25, 40, 60, 100, 150mcg)–4; Single-dose prefilled syringes (200, 300, 500mcg)–1

ATGAM Pfizer

℞

Immune globulin. Lymphocyte immune globulin, anti-thymocyte globulin [equine] 50mg/mL; soln for IV infusion after dilution. Indications: Treatment of moderate to severe aplastic anemia in patients who are unsuitable for bone marrow transplantation. Adults: Perform intradermal test dose before initiating therapy (see literature). Do not dilute in dextrose injection or highly acidic infusion solutions. Give by IV infusion over >4hrs. 10–20mg/kg daily for 8–14 days. Additional alternate-day therapy up to a total of 21 doses can

be administered. May need prophylactic platelet transfusions to maintain platelets. Children: Limited experience (see literature). Warnings/Precautions: To be administered by physicians with experience in immunosuppressive therapy and in facilities equipped with adequate lab and supportive medical resources. Discontinue if symptoms of anaphylaxis develop. Contains human plasma; monitor for possible infection transmission. Monitor for leukopenia, thrombocytopenia, or infection esp. with concomitant corticosteroids and antimetabolites. Pregnancy (Cat.C): not recommended. Nursing mothers. Interactions: Previously masked reactions may occur when corticosteroids and other immunosuppressant doses are reduced. Adverse reactions: Fever, skin reactions, chills, arthralgia, headache, myalgia, GI upset, chest pain, phlebitis, diaphoresis, joint stiffness, edema, muscle ache, vomiting, agitation/ lethargy, listlessness, light-headedness, seizures, bradycardia, myocarditis, cardiac irregularity, hepatosplenomegaly, possible encephalitis or post viral encephalopathy, hypotension, CHF, hypertension, burning soles/palms, foot sole pain, lymphadenopathy, post-cervical lymphadenopathy, tender lymph nodes, bilateral pleural effusion, respiratory distress, anaphylactic reaction, proteinuria, abnormal LFTs and renal function, serum sickness. How supplied: Ampules (5mL)–5

BIFERA Meda

OTC

Iron (as polysaccharide iron complex [PIC] 22mg + heme iron polypeptide [HIP] as Proferrin bovine source 6mg) 28mg; gluten-free tabs. Indications: Iron supplement. Iron deficiency. Adults: 1 tab once daily. Children: Not recommended. Contraindications: Hemochromatosis. Hemosiderosis. Warnings/Precautions: May mask pernicious anemia. Monitor hemoglobin, hematocrit, ferritin levels periodically. Pregnancy. Nursing mothers. Adverse reactions: Allergic sensitization. How supplied: Tabs–30

BIFERARx Meda

℞

Iron (as polysaccharide iron complex [PIC] 22mg + heme iron polypeptide [HIP] as Proferrin bovine source 6mg) 28mg, folic acid 1mg, Vit. B12 25mcg; tabs. Indications: Iron supplement. Iron deficiency. Adults: 1 tab once daily. Children: Not recommended. Contraindications: Hemochromatosis. Hemosiderosis. Warnings/Precautions: May mask pernicious anemia. Monitor hemoglobin, hematocrit, ferritin levels periodically. Pregnancy. Nursing mothers. Adverse reactions: Allergic sensitization. How supplied: Tabs–90

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ASSOCIATED HEMATOLOGICAL DISORDERS Cyanocobalamin injection

℞

(various)

Vitamin. Cyanocobalamin 1000mcg/mL; soln for IM or SC inj; contains benzyl alcohol. Indications: Vit. B12 deficiencies due to malabsorption. Pernicious anemia. Vit. B12 absorption test (Schilling test). Adults: Give by IM or deep SC inj. Pernicious anemia: 100mcg daily for 6–7 days; then 100mcg every other day for 7 doses; then every 3–4 days for 2–3 weeks; then 100mcg monthly for life. Deficiencies due to malabsorption: if severe, may need to treat like pernicious anemia; use oral preparations for chronic treatment. Schilling test: 1000mcg. Children: See literature. Contraindications: Sensitivity to cobalt. Warnings/Precautions: Hereditary optic nerve atrophy (Leber’s disease). Severe megaloblastic anemia (intense treatment may lead to hypokalemia and death). Monitor potassium for first 48 hours; replace if needed. Obtain hematocrit, reticulocyte count, Vit. B12, folate, and iron levels before and during treatment. Reevaluate periodically. Premature infants. Renal impairment (possible aluminum toxicity). Folic acid use may mask B12 deficiency. Pregnancy (Cat.C). Interactions: Antibiotics, methotrexate, pyrimethamine interfere with Vit. B12 diagnostic tests. Colchicine, para-aminosalicylic acid, heavy alcohol intake for >2 weeks may produce malabsorption of Vit. B12. Adverse reactions: Pulmonary edema, CHF, vascular thrombosis, polycythemia vera, transient diarrhea, itching, transitory exanthema; anaphylactic shock (may be fatal; do test dose if hypersensitivity suspected). How supplied: Contact suppliers.

DEXFERRUM American Regent

℞

Hematinic. Iron (as dextran complex) 50mg/mL; soln for IV inj. Indications: Iron deficiency where oral therapy is unsatisfactory or impossible. Adults and Children: <4months: not recommended. Give by IV inj. Administer 0.5mL test dose first; if no signs/symptoms of anaphylactic-type reactions, may give full therapeutic dose. ≥4months: Iron deficiency anemia: determine total dose based on hemoglobin and body weight (see literature). Iron replacement for blood loss: Replacement iron (in mg) = blood loss (in mL) × hematocrit. Max daily doses: <5kg: 0.5mL (25mg), <10kg: 1mL (50mg), ≥10kg: 2mL (100mg). Contraindications: Anemia not associated with iron deficiency.

Warnings/Precautions: Monitor for signs/ symptoms of anaphylactic-type reactions, esp. in patients with history of allergies, asthma; have epinephrine available. Hepatic impairment. Avoid during acute phase of infectious kidney disease. Cardiovascular disease. Avoid large IV doses: higher incidence of adverse events. Iron overload more likely with hemoglobinopathies or refractory anemias. Rheumatoid arthritis. Neonates. Pregnancy (Cat.C). Nursing mothers. Interactions: Concomitant ACE inhibitors may increase the risk for anaphylactic-type reactions. May falsely elevate serum bilirubin and decrease serum calcium. Adverse reactions: See literature. Anaphylactic reactions (may be fatal, even in patients who tolerated test dose), cardiovascular events, pruritus, GI upset, arthralgia, arthritis, inj site reactions, others. How supplied: Single-dose vials (1mL, 2mL)–10

DROXIA Bristol-Myers Squibb

℞

Substituted urea. Hydroxyurea 200mg, 300mg, 400mg; caps. Indications: To reduce the frequency of painful crises and to reduce the need for blood transfusions in adults with sickle cell anemia with recurrent moderate-to-severe painful crises. Adults: Base dose on ideal or actual weight, whichever is less. Initially 15mg/kg/day as a single dose. May increase dose by 5mg/kg/day every 12 weeks to maximum tolerated dose or 35mg/kg/day achieved; do not increase dose if blood counts are between acceptable range and toxic. If blood counts toxic, discontinue until hematologic recovery, see literature for dosage adjustments. Renal impairment (CrCl <60mL/min or ESRD): initially 7.5mg/kg per day; give dose following dialysis. Children: Not recommended. Warnings/Precautions: Markedly depressed bone marrow function: not recommended. Monitor hematologic, renal, and liver function before and during therapy. Renal dysfunction. Macrocytosis may mask folic acid deficiency; prophylactic folic acid is recommended. Myeloproliferative disorders; discontinue if cutaneous vasculitic ulcerations develop. Pregnancy (Cat.D); avoid use. Nursing mother: not recommended. Interactions: Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [monitor], fatal hepatotoxicity, peripheral neuropathy). May antagonize antigout agents. Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated urease, uricase, lactate dehydrogenase.

Adverse reactions: Neutropenia, thrombocytopenia, anemia, low reticulocyte count, hair loss, rash, fever, GI upset, weight gain, bleeding, parvovirus B-19 infection, melanonychia, erythema, CNS effects, temporary renal impairment, acute pulmonary reactions, secondary leukemias, skin cancer. Note: Wear disposable gloves when handling caps or bottle. How supplied: Caps–60

EPOGEN Amgen

℞

Erythropoietin (human, recombinant). Epoetin alfa 2000 Units, 3000 Units, 4000 Units, 10000 Units, 40000 Units; per mL; soln for IV or SC inj; contains albumin (human); preservativefree. ℞ Also: EPOGEN MULTIDOSE Epoetin alfa 10000 Units, 20000 Units; per mL; soln for IV or SC inj; contains albumin (human) and benzyl alcohol. Indications: Anemia in chronic renal failure (CRF). Anemia related to zidovudine in HIVinfected patients. Chemotherapy-induced anemia in patients with non-myeloid malignancies (serum erythropoietin ≤200 mUnits/mL). To reduce need for allogeneic blood transfusions in anemic (hemoglobin >10 to ≤13g/dL) patients scheduled for elective, noncardiac, nonvascular surgery. Adults: Individualize (see literature for titration). CRF: initially 50–100 Units/kg 3 times per week IV (dialysis or non dialysis) or SC (non dialysis); usual max (non dialysis) 150 Units/kg 3 times per week; (dialysis) 200 Units/kg 3 times per week; target hemoglobin 10–12g/dL. Zidovudine-treated HIV patients: if serum erythropoietin ≤500 mUnits/mL and zidovudine dose ≤4.2 g/wk: initially 100 Units/kg IV or SC 3 times per week for 8 weeks; usual max 300 Units/kg 3 times per week. Chemotherapyinduced: initially 150 Units/kg SC 3 times per week; may increase to 300 Units/kg 3 times per week after 8 weeks. Or, initially 40000 Units SC once weekly; may increase to 60000 Units once weekly after 4 weeks. Discontinue after completion of chemotherapy course. Surgery: If ≥21 days until surgery: 600 Units/kg once weekly SC at 21, 14 and 7 days before surgery, and a 4th dose on day of surgery. If <21 days until surgery: 300 Units/kg per day SC for 10 days before, on day of, and for 4 days after surgery. All: adjust dose to maintain the lowest hemoglobin level (target max 12g/dL) sufficient to avoid red blood cell transfusion; see literature. Children: Individualize (see literature for monitoring). CRF (dialysis): <1 month: not

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ASSOCIATED HEMATOLOGICAL DISORDERS recommended. ≥1 month of age: initially 50 Units/kg three times per week IV or SC. Target hemoglobin: 10–12g/dL. Chemotherapy-induced: ≥5yrs: 600 Units/kg IV weekly (max 40,000 Units); may increase to 900 Units/kg IV weekly (max 60,000 Units) after 4 weeks. Discontinue after completion of chemotherapy course. Other uses: see literature. Contraindications: Uncontrolled hypertension. Warnings/Precautions: See literature. Evaluate serum iron, ferritin, transferrin saturation before therapy; all patients will need iron supplementation. Monitor hemoglobin (measure twice weekly for 2–6 weeks after any dosage adjustment; reduce dose if hemoglobin increases >1g/dL in any 2-week period; withhold dose if hemoglobin exceeds 12g/dL), blood pressure, renal function, iron levels, clotting times, serum chemistry, CBC, and for premonitory neurological symptoms. Seizure disorders. Cardiovascular or hematologic disorders. Hypertension (esp. in renal failure). Porphyria. Concurrent infection, inflammation, increased zidovudine dose, or other factors may reduce effectiveness. Perisurgery: consider DVT prophylaxis. Consider other etiologies in treatment failures. Adjust anticoagulant dose in dialysis patients. Menses may resume. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Iron deficiency, hypertension, headache, arthralgia, GI disturbances, edema, local reaction, rash, paresthesia, dizziness, clotted vascular access (A-V shunt), pyrexia, respiratory congestion, seizures. Increased risk of death, cardiovascular or thrombotic events if hemoglobin >12g/dL. May stimulate tumor growth, shorten time to tumor progression or overall survival if hemoglobin ≥12g/dL. Children: also abdominal pain, upper respiratory infection, cough, pharyngitis, constipation. How supplied: Single-use 1mL vials (all)–10; Multidose 2mL vials (10000 Units/mL)–10; Multidose 1mL vials (20000 Units/mL)–10

FEOSOL Meda

OTC

Iron 65mg (as sulfate 200mg); tabs. OTC Also: FEOSOL CAPLETS Iron 50mg (as carbonyl). OTC Also: FEOSOL ELIXIR Iron 44mg/5mL (as sulfate 220mg/5mL); alcohol 5%. Indications: Iron deficiency and iron deficiency anemia. Adults: 1 tab or 1 caplet or 5mL daily. Children: Individualize. May mix with water or fruit juice. Contraindications: Hemochromatosis. Hemosiderosis. Warnings/Precautions: Monitor hemoglobin, hematocrit, reticulocyte count periodically. Elderly. Interactions: Inhibits tetracycline absorption.

Adverse reactions: Nausea, abdominal discomfort and pain, constipation, diarrhea, masks occult bleeding, black stools, tooth discoloration (elixir). How supplied: Tabs, caplets–30, 60; Elixir–16oz

FER-IN-SOL DROPS

OTC

Mead Johnson Iron 15mg/1mL (as sulfate 75mg/1mL); contains sulfites, alcohol; gluten-free. Indications: Iron deficiency and iron deficiency anemias. Adults and Children: May give directly into the mouth or mix with formula, fruit juice, cereal or other foods. <4yrs: 1mL daily. ≥4yrs: not recommended. Contraindications: Hemochromatosis. Hemosiderosis. Warnings/Precautions: Monitor hemoglobin, hematocrit, reticulocyte count periodically. Elderly. Interactions: Inhibits tetracycline absorption. Adverse reactions: Nausea, abdominal discomfort and pain, constipation, masks occult bleeding, black stools, stains teeth and dentures. How supplied: Drops–50mL (w. calibrated dropper)

FERAHEME AMAG

℞

Hematinic. Elemental iron 30mg/mL (as ferumoxytol 510mg/17mL); colloidal iron for IV inj; contains mannitol 44mg/mL; preservativefree. Indications: Iron deficiency anemia in adult patients with chronic kidney disease. Adults: Give undiluted by IV injection at a rate up to 1mL/sec (30mg/sec). Initially 510mg, then an additional dose 3–8 days later. May repeat in persistent or recurrent iron deficiency anemia. Hemodialysis: give at least 1 hour after starting hemodialysis and after BP is stable. Children: Not recommended. Warnings/Precautions: Iron overload: do not administer. Monitor for severe hypotension, and for hypersensitivity for at least 30 minutes after each injection. Evaluate hemoglobin, ferritin, iron, transferrin saturation at least 1 month after 2nd injection. Have equipment/personnel available to treat hypersensitivity reactions. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: May reduce absorption of concomitantly administered oral iron preparations. May transiently (up to 3 months) affect diagnostic ability of MRI (see literature). Adverse reactions: Diarrhea, nausea, hypotension (may be significant), dizziness, constipation, peripheral edema; infusion reactions, anaphylactoid reactions (may be fatal), other hypersensitivity reactions (eg, rash, pruritus, urticaria, wheeze). How supplied: Single-use vials (17mL)–1, 10

FERGON Bayer Consumer

OTC

Iron 27mg (as gluconate 240mg); tabs. Indications: Iron deficiency anemias. Adults: 1 tab daily. Children: Not recommended. Contraindications: Hemochromatosis. Hemosiderosis. Warnings/Precautions: Monitor hemoglobin, hematocrit, reticulocyte count periodically. Elderly. Interactions: Inhibits tetracycline absorption. Adverse reactions: Nausea, abdominal discomfort and pain, constipation, diarrhea, masks occult bleeding, black stools. How supplied: Tabs–100

FERO-FOLIC-500 Abbott

℞

Iron (as sulfate) 105mg, folic acid 0.8mg, Vit.C 500mg; sust rel tabs. Indications: Iron deficiency and prophylaxis of folic acid deficiency. Pregnancy. Adults: 1 tab daily on an empty stomach. Children: Not recommended. Contraindications: Hemochromatosis. Hemosiderosis. Pernicious anemia. Warnings/Precautions: May mask pernicious anemia. Monitor hemoglobin, hematocrit, reticulocyte count periodically. Elderly. Interactions: Inhibits tetracycline absorption. Aluminum- or magnesium-containing antacids inhibit iron absorption. Adverse reactions: Nausea, abdominal discomfort and pain, constipation, diarrhea, masks occult bleeding, black stools. How supplied: Tabs–30

FERRALET 90 Mission

℞

Iron (as carbonyl) 90mg, folic acid 1mg, Vit.B12 12mcg, Vit.C 120mg, docusate sodium 50mg; tabs; contains tartrazine. Indications: Iron deficiency anemia. Adults: Swallow whole. Take 2hrs after meals. 1 tab once daily. Children: Not recommended. Contraindications: Hemolytic anemia. Hemochromatosis. Hemosiderosis. Warnings/Precautions: May mask pernicious anemia. Monitor hemoglobin, hematocrit, reticulocyte count periodically. Elderly. Interactions: Inhibits tetracycline, fluoroquinolone absorption. Aluminum- or magnesium-containing antacids inhibit iron absorption. Adverse reactions: GI upset or irritation, constipation, dark stools, allergic sensitization. How supplied: Tabs–90

FERRETTS Pharmics

OTC

Iron 106mg (as fumarate); scored tabs; phosphorus- and gluten-free. Indications: Iron deficiency and iron deficiency anemia.

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ASSOCIATED HEMATOLOGICAL DISORDERS Adults: 1 tablet daily. Children: Not recommended. Contraindications: Hemochromatosis. Hemosiderosis. Warnings/Precautions: Monitor hemoglobin, hematocrit, reticulocyte count periodically. Elderly. Interactions: Inhibits tetracycline absorption. Adverse reactions: GI upset, abdominal discomfort, constipation, masks occult bleeding, black stools. How supplied: Tabs–60

FERRLECIT Sanofi Aventis

℞

Hematinic. Iron (as sodium ferric gluconate complex in sucrose) 12.5mg/mL; soln for IV inj or infusion; contains benzyl alcohol. Indications: Iron deficiency anemia in patients on chronic hemodialysis receiving epoetin therapy. Adults: Give by IV infusion (diluted) or slow IV inj (undiluted). 125mg infused over 1 hour or by slow IV inj (at a rate of up to 12.5mg/min). Minimum cumulative dose: 1g given over 8 sequential dialysis sessions; usual max: 125mg/dose. Children: <6 yrs: not recommended. Give by IV infusion (diluted) over 1 hour. ≥6yrs: 1.5mg/kg per dose at 8 sequential dialysis sessions; max: 125mg/dose. Contraindications: Anemias not caused by iron deficiency. Iron overload. Neonates. Warnings/Precautions: Hemoglobinopathies. Refractory anemias. Pregnancy (Cat.B). Nursing mothers. Interactions: May reduce absorption of concomitant oral iron preparations. Adverse reactions: Hypotension, hypertension, GI upset, chest pain, back pain, abdominal pain, pruritus, inj site reaction, headache, dizziness, syncope, fatigue, fever, cramps, dyspnea, tachycardia; rare: hypersensitivity reactions. How supplied: Ampules (5mL)–10

FERRO-SEQUELS IVC

OTC

Iron (as fumarate) 50mg; timed-rel caplets; contains docusate sodium. Indications: Iron deficiency and iron deficiency anemias. Adults: 1 caplet daily or as needed. Children: Not recommended. Contraindications: Hemochromatosis. Hemosiderosis. Warnings/Precautions: Monitor hemoglobin, hematocrit, reticulocyte count periodically. Elderly. Interactions: Inhibits tetracycline absorption. Adverse reactions: Nausea, abdominal discomfort and pain, constipation, diarrhea, masks occult bleeding, black stools. How supplied: Caplets–100

Folic acid (various)

℞

Hematinic. Folic acid 1mg; tabs. ℞ Also: Folic acid injection Folic acid 5mg/mL; soln for IV, IM or SC inj; contains benzyl alcohol and aluminum. Indications: Megaloblastic anemias of folic acid deficiency. Anemias of nutritional origin, pregnancy, infancy or childhood. Adults and Children: Usual dose: up to 1mg daily; may need higher dose if resistant disease. Maintenance: infants: 0.1mg/day; <4yrs: 0.3mg/day; ≥4yrs: 0.4mg/day. Pregnant or lactating: 0.8mg/day. Alcoholism, hemolytic anemia, anticonvulsant therapy or chronic infection: may require higher dose. Warnings/Precautions: Use injectable form if disease is severe or GI absorption impaired. Rule out or treat vitamin B12 deficiency prior to treatment. May obscure diagnosis of pernicious anemia. Pregnancy (Cat.A). Interactions: May antagonize phenytoin. False low serum and red cell folate levels may occur with antibiotics (eg, tetracycline). Adverse reactions: Allergic sensitization. How supplied: Contact supplier.

ICAR-C Hawthorn

OTC

Iron (as carbonyl) 100mg, Vit. C 250mg; tabs. ℞ Also: ICAR-C PLUS Iron (as carbonyl) 100mg, Vit. B12 25mcg, folic acid 1mg, Vit. C 250mg; tabs. OTC Also: ICAR PEDIATRIC SUSP Iron (as carbonyl) 15mg/1.25mL; grape flavor; sugar- and alcohol-free. Indications: Iron deficiency and iron deficiency anemia. Adults: 1 tab once daily. Children: Use Ped Susp. 15mg (of iron) once daily. Contraindications: Hemochromatosis. Hemosiderosis. Warnings/Precautions: Folic acid may mask pernicious anemia. Monitor hemoglobin, hematocrit, reticulocyte count periodically. Elderly. Interactions: Inhibits tetracycline absorption. Aluminum- or magnesium-containing antacids inhibit iron absorption. Adverse reactions: Nausea, abdominal discomfort and pain, constipation, diarrhea, masks occult bleeding, black stools. How supplied: Tabs–100 Ped Susp–4oz (w. dosing syringe)

INFED Actavis

℞

Hematinic. Iron (as dextran complex) 50mg/mL; soln for IV or IM inj. Indications: Iron deficiency where oral therapy is unsatisfactory or impossible. Adults and Children: Give by IV or by deep IM (into upper outer quadrant of buttock only) inj. Administer 0.5mL test dose first; if no signs/

symptoms of anaphylactic-type reactions, may give full therapeutic dose. Iron deficiency anemia: determine total dose based on hemoglobin and body weight (see literature). Iron replacement for blood loss: Replacement iron (in mg) = blood loss (in mL) × hematocrit. Max daily doses: <5kg: 0.5mL (25mg), <10kg: 1mL (50mg), ≥10kg: 2mL (100mg). Contraindications: Anemias not associated with iron deficiency. Warnings/Precautions: Monitor for signs/ symptoms of anaphylactic-type reactions, esp. in patients with history of drug allergies, asthma; have epinephrine available. Avoid large IV doses: higher incidence of adverse events. Severe hepatic impairment. Avoid during acute phase of infectious kidney disease. Dialysis. Cardiovascular disease. May reactivate quiescent rheumatoid arthritis. Neonates (avoid during first 4 months). Pregnancy (Cat.C). Nursing mothers. Interactions: Concomitant ACE inhibitors may increase the risk for anaphylactic-type reactions. May falsely elevate serum bilirubin or decrease serum calcium levels. Adverse reactions: See literature. Anaphylactic reactions (may be fatal; even if test dose was tolerated), cardiovascular events, pruritus, GI upset, arthralgia, arthritis, inj site reactions, others; possible IM inj site tumors, sepsis in neonates. How supplied: Vials (2mL)–10

INJECTAFER American Regent

℞

Hematinic. Iron (as ferric carboxymaltose) 50mg/mL; soln for IV inj or infusion; preservativefree. Indications: Iron deficiency anemia in adults who have intolerance or insufficient response to oral iron; or have non-dialysis-dependent chronic kidney disease. Adults: Give by slow IV push (undiluted) at rate of approx. 100mg (2mL)/min; or by IV infusion (diluted) administered over at least 15 mins. When giving via IV infusion, dilute to concentration not less than 2mg iron/mL. Give in 2 doses separated by ≥7 days. <50kg: 15mg/kg/dose. ≥50kg: 750mg/dose. Total cumulative dose per course: max 1500mg. May repeat treatment if condition reoccurs. Children: Not established. Warnings/Precautions: Have epinephrine inj (1:1000) available. Monitor for serious hypersensitivity reactions during and after administration for ≥30 mins and until clinically stable. Monitor for signs/symptoms of hypertension after each administration. Avoid extravasation. Pregnancy (Cat.C). Nursing mothers. Interactions: Lab assays may result in overestimating serum iron and transferrin bound iron within 24hrs after administration. Adverse reactions: Nausea, hypertension, flushing, hypophosphatemia, dizziness; rare: hypersensitivity reactions. How supplied: Single-use vial (15mL)–1, 2

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ASSOCIATED HEMATOLOGICAL DISORDERS Leucovorin Teva

℞

Folic acid derivative. Leucovorin calcium 100mg/vial, 350mg/vial; lyophilized pwd for IV or IM inj after reconstitution; preservative-free. Indications: Megalobastic anemia due to folic acid deficiency when oral therapy is not feasible. Adults: Up to 1mg daily. Children: See literature. Contraindications: Pernicious anemia and other megaloblastic anemias due to Vit. B12 deficiency. Warnings/Precautions: Do not administer intrathecally. CNS metastases. Monitor CBCs with differential, platelets, electrolytes, liver function tests prior to each treatment, then periodically. Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers. Interactions: Potentiates toxicity of 5-fluorouracil; use lower 5-fluorouracil dose. May antagonize phenobarbital, phenytoin, and primidone. Caution with trimethoprimsulfamethoxazole. Adverse reactions: Leukopenia, thrombocytopenia, infection, GI upset, stomatitis, constipation, lethargy, malaise, fatigue, alopecia, dermatitis, anorexia; seizures, syncope. How supplied: Single-use vials–1

LUPRON DEPOT 3.75mg

℞

AbbVie

GnRH analogue. Leuprolide acetate 3.75mg; depot susp for IM inj; preservative-free. Indications: Presurgical treatment of patients with anemia due to uterine leiomyomata (fibroids), with iron therapy if iron therapy alone is inadequate. Adults: ≥18 years: 3.75mg IM once per month for up to 3 months. Children: <18 years: not applicable. Also: LUPRON DEPOT-3 MONTH 11.25mg ℞ Leuprolide acetate 11.25mg; depot susp for IM inj; preservative-free. Adults: ≥18 years: 11.25mg IM once every 3 months (1 injection). Do not split doses. Children: <18 years: not applicable. Contraindications: Undiagnosed abnormal vaginal bleeding. Pregnancy (Cat.X). Nursing mothers. Warnings/Precautions: Exclude pregnancy before starting; use nonhormonal contraception during therapy; discontinue if pregnancy occurs. Risk factors for decreased bone mineral density (eg, chronic alcohol, tobacco, anticonvulsants, corticosteroids). Missing successive doses may cause breakthrough bleeding or ovulation. Elderly. Adverse reactions: Hot flashes, headache, vaginitis, depression, emotional lability, pain, decreased libido, breast changes, amenorrhea, mastodynia, joint disorder, asthenia, GI upset, edema, bone density loss, local reactions, acne, memory disorders, others; rarely: anaphylaxis,

asthma, increased serum transaminases or lipids. How supplied: Kit–1 (single-dose syringe w. diluent, supplies)

NASCOBAL Strativa

℞

Cyanocobalamin 500mcg/0.1mL; soln for nasal spray; contains benzalkonium chloride. Indications: Maintenance of normal hematologic status in pernicious anemia patients who are in remission after intramuscular Vit. B12 therapy and who have no nervous system involvement. Supplementation for other Vit. B12 deficiencies. Adults: Hematological parameters must be within normal range before beginning therapy. Allow at least 1 hour before or after hot foods or liquids. Initial dose: One spray (500mcg) in one nostril once per week. Monitor response, may increase dose if serum B12 levels decline. Children: Not recommended. Warnings/Precautions: Confirm diagnosis. May need supplemental folate. Leber’s disease. Defer dose if nasal congestion, rhinitis, or upper respiratory infections occur. Reevaluate if low levels of Vit. B12 persist despite treatment. Do not use for Schilling Test. Infection, uremia, bone marrow suppressants, and iron or folic acid deficiency may reduce response. May unmask polycythemia vera. Monitor B12 blood levels 1 month after starting therapy, 1 month after any dose increase, and regularly at 3–6 month intervals. Monitor serum potassium, platelet counts. Pregnancy (Cat.C). Interactions: Antibiotics, methotrexate, pyrimethamine may interfere with lab tests. Colchicine, chronic heavy alcohol use may impair Vit. B12 absorption. Adverse reactions: Headache, nausea, rhinitis. How supplied: Nasal spray (1.3mL)–1 (4 doses)

NULECIT Actavis

℞

Hematinic. Iron (as sodium ferric gluconate complex in sucrose) 12.5mg/mL; soln for IV inj or infusion; contains benzyl alcohol. Indications: Iron deficiency anemia in patients on chronic hemodialysis receiving epoetin therapy. Adults: Give by IV infusion (diluted) or slow IV inj (undiluted). 125mg infused over 1 hour or by slow IV inj (at a rate of up to 12.5mg/min). Minimum cumulative dose: 1g given over 8 sequential dialysis sessions; usual max: 125mg/dose. Children: <6yrs: not recommended. Give by IV infusion (diluted) over 1 hour. ≥6yrs: 1.5mg/kg per dose at 8 sequential dialysis sessions; max: 125mg/dose. Contraindications: Anemias not caused by iron deficiency. Iron overload. Warnings/Precautions: Hemoglobinopathies. Refractory anemias. Avoid in neonates. Pregnancy (Cat.B). Nursing mothers.

Interactions: May reduce absorption of concomitant oral iron preparations. Adverse reactions: Hypotension, hypertension, GI upset, chest pain, back pain, abdominal pain, pruritus, inj site reaction, cramps, headache, dizziness, syncope, fatigue, fever, dyspnea, tachycardia; rare: hypersensitivity reactions. How supplied: Vials (5mL)–10

PROCRIT Janssen Biotech

℞

Erythropoietin (human, recombinant). Epoetin alfa 2000 Units, 3000 Units, 4000 Units, 10000 Units, 40000 Units; per mL; soln for IV or SC inj; contains albumin (human); preservativefree. ℞ Also: PROCRIT MULTIDOSE Epoetin alfa 10000 Units, 20000 Units; per mL; soln for IV or SC inj; contains albumin (human) and benzyl alcohol. Indications: Anemia in chronic renal failure (CRF). Anemia related to zidovudine in HIVinfected patients. Chemotherapy-induced anemia in patients with non-myeloid malignancies (serum erythropoietin ≤200 mUnits/mL). To reduce need for allogeneic blood transfusions in anemic (hemoglobin >10 to ≤13g/dL) patients scheduled for elective, noncardiac, nonvascular surgery. Adults: Individualize (see literature for titration). CRF: initially 50–100 Units/kg 3 times per week IV (dialysis or non dialysis) or SC (non dialysis); usual max (non dialysis) 150 Units/kg 3 times per week; (dialysis) 200 Units/kg 3 times per week; target hemoglobin: 10–12g/dL. Zidovudinetreated HIV patients: if serum erythropoietin ≤500 mUnits/mL and zidovudine dose ≤4.2g/wk: initially 100 Units/kg IV or SC 3 times per week for 8 weeks; usual max 300 Units/kg 3 times per week. Chemotherapy-induced: initially 150 Units/kg SC 3 times per week; may increase to 300 Units/kg 3 times per week after 8 weeks. Or, initially 40000 Units SC once weekly; may increase to 60000 Units once weekly after 4 weeks. Discontinue after completion of chemotherapy course. Surgery: If ≥21 days until surgery: 600 Units/kg once weekly SC at 21, 14 and 7 days before surgery, and a 4th dose on day of surgery. If <21 days until surgery: 300 Units/kg per day SC for 10 days before, on day of, and for 4 days after surgery. All: adjust dose to maintain the lowest hemoglobin level (target max 12g/dL) sufficient to avoid red blood cell transfusion; see literature. Children: Individualize (see literature for monitoring). CRF (dialysis): <1 month: not recommended. ≥1 month of age: initially 50 Units/kg three times per week IV or SC. Target hemoglobin: 10–12g/dL. Chemotherapy-induced: ≥5yrs: 600 Units/kg IV weekly (max 40,000 Units); may increase to 900 Units/kg IV weekly (max 60,000 Units) after 4 weeks. Discontinue after completion of chemotherapy course. Other uses: see literature. Contraindications: Uncontrolled hypertension.

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ASSOCIATED HEMATOLOGICAL DISORDERS Warnings/Precautions: See literature. Evaluate serum iron, ferritin, transferrin saturation before therapy; all patients will need iron supplementation. Monitor hemoglobin (measure twice weekly for 2–6 weeks after any dosage adjustment; reduce dose if hemoglobin increases >1g/dL in any 2-week period; withhold dose if hemoglobin exceeds 12g/dL), blood pressure, renal function, iron levels, clotting times, serum chemistry, CBC, and for premonitory neurological symptoms. Seizure disorders. Cardiovascular or hematologic disorders. Hypertension (esp. in renal failure). Porphyria. Concurrent infection, inflammation, increased zidovudine dose, or other factors may reduce effectiveness. Perisurgery: consider DVT prophylaxis. Consider other etiologies in treatment failures. Adjust anticoagulant dose in dialysis patients. Menses may resume. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Iron deficiency, hypertension, headache, arthralgia, GI disturbances, edema, local reaction, rash, paresthesia, dizziness, clotted vascular access (A-V shunt), pyrexia, respiratory congestion, seizures. Increased risk of death, cardiovascular or thrombotic events if hemoglobin >12g/dL. May stimulate tumor growth, shorten time to tumor progression or overall survival if hemoglobin ≥12g/dL. Children: also abdominal pain, upper respiratory infection, cough, pharyngitis, constipation. How supplied: Single-use 1mL vials (2000 Units/mL, 3000 Units/mL, 4000 Units/mL, 10000 Units/mL)–6, 25; Single-use 1mL vials (40000 Units/mL)–4; Multidose 2mL vials (10000 Units/mL)–4, 6; Multidose 1mL vials (20000 Units/mL)–4, 6

REVLIMID Celgene

℞

Immunomodulator. Lenalidomide 2.5mg, 5mg, 10mg, 15mg, 20mg, 25mg; caps. Indications: Transfusion-dependent anemia due to Low- or Intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality. Adults: Do not break, chew, or open caps. Swallow whole with water. ≥18yrs: initially 10mg per day; adjust dose based on response. Renal impairment: Moderate (CrCL 30–60mL/min): 5mg per day. Severe (CrCL <30mL/min without dialysis): 2.5mg per day. ESRD (CrCL <30mL/min with dialysis): 2.5mg once daily; administer after dialysis (on dialysis days). Dose adjustments if thrombocytopenia or neutropenia develops: see full labeling. Children: <18yrs: not established. Contraindications: Pregnancy (Cat.X). Women who may become pregnant. Warnings/Precautions: Must register patient in RevAssist program; patient must understand toxicity with fetal exposure. Counsel patient on need for contraception; female: use 2 forms of contraception 1 month before, during, and 1

month after therapy; male: use condom during and 1 month after therapy; obtain 2 negative pregnancy tests (one within 10–14 days, and then another within 24 hours prior to starting therapy), repeat at least weekly for 1st month then every 4 weeks; get informed consent. Monitor for signs/symptoms of thromboembolic events. Obtain CBCs weekly for first 8 weeks, then monthly. Renal impairment (monitor). Monitor for tumor lysis syndrome in those with high tumor burden. Monitor liver enzymes; discontinue if elevation occurs. Maximum 1 month per ℞. Nursing mothers: not recommended. Interactions: Monitor digoxin. Concomitant warfarin; monitor PT, INR. May increase risk of thrombosis with erythropoietic agents or estrogen containing therapies. Adverse reactions: Birth defects, thrombocytopenia, neutropenia, GI upset, pruritus, rash, fatigue, arthralgia, pyrexia, back pain, cough, dizziness, headache, dyspnea, blurred vision, muscle cramp; thrombosis/ embolism, allergic reactions (discontinue if occurs; do not resume), tumor flare reaction (monitor; esp. in treating MCL), hepatotoxicity. Note: Available only through RevAssist program. Report any suspected fetal exposure to the FDA at (800) FDA-1088 and Celgene at (888) 423-5436. How supplied: Caps 2.5mg, 5mg, 10mg–28, 100; 15mg, 20mg, 25mg–21, 100

SLOW FE Novartis Consumer

OTC

Iron 50mg (as sulfate 160mg); sust-rel tabs. Indications: Iron deficiency and iron deficiency anemias. Adults: Swallow whole. 1–2 tabs daily; max 4 daily. Children: Swallow whole. <6 yrs: not recommended. ≥6 yrs: 1 tab daily. OTC Also: SLOW FE PLUS FOLIC ACID Iron, elemental 50mg (as ferrous sulfate 160mg), folic acid 0.4mg; sust-rel tabs. Adults: Swallow whole. 1–2 tabs daily. Children: Not recommended. Contraindications: Hemochromatosis. Hemosiderosis. Warnings/Precautions: Hepatitis. Pancreatitis. Peptic ulcer or GI inflammation. Achlorhydria. Monitor hematocrit. Folic acid may mask pernicious anemia. Repeated blood transfusions. Elderly. Interactions: Inhibits tetracycline absorption. Adverse reactions: Nausea, abdominal discomfort and pain, constipation, diarrhea, masks occult bleeding, black stools. How supplied: Slow Fe–30, 60, 90; Plus folic acid–20

SOLIRIS Alexion Complement inhibitor. Eculizumab 10mg/mL; soln for IV infusion after dilution; preservativefree.

℞

Indications: Treatment of paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. Treatment of atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. Limitation of use: not for treating Shiga toxin E. coli-related HUS. Adults: Give by IV infusion over 35 mins; monitor for ≥1hr after completion. ≥18yrs: PNH: initially 600mg weekly for the first 4 weeks, followed by 900mg for the fifth dose 1 week later, then 900mg every 2 weeks thereafter. aHUS: initially 900mg weekly for the first 4 weeks, followed by 1200mg for the fifth dose 1 week later, then 1200mg every 2 weeks thereafter. Supplemental dosing after PE/PI: see full labeling. Children: <18yrs: PNH: not established. aHUS: Give by IV infusion over 1–4hrs via gravity feed, syringe-type pump, or infusion pump; monitor for ≥1hr after completion. 5–<10kg: induction: 300mg weekly for 1 dose; maintenance: 300mg at Week 2, then 300mg every 3 weeks; 10–<20kg: induction: 600mg weekly for 1 dose; maintenance: 300mg at Week 2, then 300mg every 2 weeks; 20–<30kg: induction: 600mg weekly for 2 doses; maintenance: 600mg at Week 3, then 600mg every 2 weeks; 30–<40kg: induction: 600mg weekly for 2 doses; maintenance: 900mg at Week 3, then 900mg every 2 weeks; ≥40kg: induction: 900mg weekly for 4 doses; maintenance: 1200mg at Week 5, then 1200mg every 2 weeks. Supplemental dosing after PE/PI: see full labeling. Contraindications: Unresolved serious Neisseria meningitidis infection. Individuals not vaccinated against Neisseria meningitidis. Warnings/Precautions: Increased risk of meningococcal infection. Give meningococcal vaccine at least 2 weeks prior to treatment. Monitor for early signs of meningococcal infection; evaluate and treat if an infection develops. Discontinue eculizumab if undergoing treatment for meningococcal infections. Administering eculizumab treatment with any other systemic infection (eg, S. pneumoniae, H. influenza). PNH: risk of hemolysis after treatment discontinuation; monitor for at least 8 weeks. aHUS: risk of thrombotic microangiopathy (TMA) after treatment discontinuation; monitor for at least 12 weeks; if TMA occurs, consider reinitiating eculizumab, plasma therapy [plasmapheresis, plasma exchange, or fresh frozen plasma infusion (PE/PI)], or appropriate organ-specific supportive measures. Monitor platelets, serum LDH, and creatinine during and after therapy. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Headache, nasopharyngitis, back pain, nausea, diarrhea, vomiting, abdominal pain, hypertension, upper respiratory tract infection, anemia, cough, peripheral edema, UTI, pyrexia; meningococcal infection (may be fatal), hypersensitivity reactions. How supplied: Single-use vials (30mL)–1

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ASSOCIATED HEMATOLOGICAL DISORDERS TRINSICON UCB

℞

Iron (as fumarate) 110mg, Vit. B12 15micrograms, folic acid 0.5mg, Vit. C 75mg, liver-stomach concentrate 240mg; caps. Indications: Megaloblastic anemias. Iron deficiency anemia. Adults: 1 cap twice daily. Children: <10yrs: not recommended. Contraindications: Hemochromatosis. Hemosiderosis. Warnings/Precautions: For pernicious anemia, parenteral cyanocobalamin is preferred. Resistance to exogenous intrinsic factor may develop. Folic acid may mask pernicious anemia. Monitor blood parameters. Hepatitis. Pancreatitis. Peptic ulcer or GI inflammation. Achlorhydria. Repeated blood transfusions. Pregnancy (Cat.C). Nursing mothers. Elderly. Interactions: Inhibits tetracycline absorption. Adverse reactions: Nausea, abdominal discomfort and pain, constipation, diarrhea, masks occult bleeding, black stools, rash. How supplied: Caps–60, 100

VENOFER American Regent

℞

Hematinic. Iron (as sucrose) 20mg/mL; soln for IV inj or infusion; preservative-free. Indications: Iron deficiency anemia in chronic kidney disease. Adults: Give by slow IV inj (undiluted) or infusion (diluted). Usual total cumulative dose: 1000mg. Hemodialysis dependent: 100mg slow IV inj over 2–5 dmins or infuse 100mg over at least 15 mins per consecutive session. Non-dialysis dependent: 200mg slow IV inj over 2–5 dmins on 5 different occasions within a 14-day period; limited experience with IV infusion (see full labeling). Peritoneal dialysis dependent: Two infusions of 300mg over 1.5hrs 14 days apart, then one 400mg infusion over 2.5hrs 14 days later. Children: Not recommended. Contraindications: Anemia not caused by iron deficiency. Iron overload. Warnings/Precautions: Withhold therapy if tissue iron overload suspected. Monitor hemoglobin, hematocrit, serum ferritin, transferrin saturation; obtain serum iron values 48 hours after dosing. Pregnancy (Cat.B). Nursing mothers. Interactions: May reduce absorption of concomitant oral iron preparations. Adverse reactions: Hypotension (esp. by IV infusion), hypertension, muscle cramps, GI upset, headache, dizziness, chest pain, graft complications, dysgeusia, pruritus, edema, constipation; rare: hypersensitivity reactions (may be severe). How supplied: Single-dose vials (100mg/5mL)–1, 10, 25; 200mg/10mL–1, 5,10

Bleeding disorders

ADVATE Baxter

℞

Clotting factor. Antihemophilic Factor VIII (recombinant) 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU, 3000 IU; per vial; pwd for IV inj after reconstitution; albumin- and preservative-free. Indications: In patients with Hemophilia A: to control and prevent hemorrhagic episodes, for perioperative management, and routine prophylaxis to prevent or reduce the frequency of hemorrhagic episodes. Adults and Children: Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Infuse over ≤5 minutes (max infusion rate 10mL/min); monitor pulse; if increased significantly, reduce infusion rate or hold. Hemorrhage: Mild: obtain 20–40% FVIII increase; give every 12–24hrs for 1–3 days until resolved. Moderate: obtain 30–60% FVIII increase; give every 12–24hrs for 3 days or until pain or disability resolved. Major: obtain 60–100% FVIII increase; give every 8–24hrs until resolved. Perioperative: Minor: obtain 60–100% FVIII increase; give single bolus infusion within 1 hour of surgery, then every 12–24hrs as needed to control bleeding; Major: pre- and Post-op: obtain 80–120% FVIII increase; give pre-op and maintenance bolus infusion, then repeat every 8–24hrs based on healing. Routine prophylaxis: give 20–40 IU/kg every other day (3–4 times weekly). Or, alternatively, an every 3rd day dosing regimen may be followed. Adjust based on response. Contraindications: Mouse or hamster protein sensitivity. Warnings/Precautions: Not for von Willebrand’s disease. Confirm Factor VIII deficiency prior to treatment. Monitor for development of Factor VIII inhibitors. Labor & delivery. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Headache, arthralgia, pyrexia, cough, nasopharyngitis, pharyngolaryngeal pain; antibody formation, hypersensitivity reactions. How supplied: Single-dose vial–1 (w. diluent, Baxject II needleless transfer device)

ALPHANATE Grifols Biologicals

℞

Clotting factor. Antihemophilic Factor VIII/von Willebrand Factor Complex (human) 250 IU, 500 IU, 1000 IU, 1500 IU; per vial; lyophilized pwd for IV inj after reconstitution; contains albumin. Indications: Prevention and control of bleeding in Hemophilia A or acquired Factor VIII deficiency. Surgical and/or invasive procedures in von Willebrand disease (VWD) when desmopressin is ineffective or contraindicated. Adults: Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Individualize. Give by IV inj; max infusion rate

≤10mL/min. Hemorrhage: Minor: 15 FVIII IU/kg twice daily for 1–2 days. Moderate: 25 FVIII IU/kg twice daily for 2–7 days. Severe: 40–50 FVIII IU/kg twice daily for at least 3–5 days, then 25 FVIII IU/kg twice daily until healed (up to 10 days). Surgery: 40–50 FVIII IU/kg prior to surgery then 25–50 FVIII IU/kg twice daily for 7–10 days or until healed. Von Willebrand: pre-op dose: 60 VWF:RCof IU/kg, then 40–60 VWF:RCof IU/kg every 8–12hrs if needed; may reduce dose after 3rd post-op day; treat until healed. Others: see literature. Children: Give by IV inj; max infusion rate ≤10mL/min. Von Willebrand: initially 75 VWF:RCof IU/kg, then 50–75 VWF:RCof IU/kg every 8–12hrs if needed; may reduce dose after 3rd post-op day; treat until healed. Warnings/Precautions: Not for those with severe VWD undergoing major surgery. Contains human plasma; monitor for possible infection transmission. Blood groups A, B or AB; large and/or frequent dosing may result in hemolytic anemia. Monitor for development of Factor VIII inhibitors. Pregnancy (Cat.C). Adverse reactions: Urticaria, fever, chills, GI upset, headache, somnolence, lethargy, inj site reactions, pruritus, pharyngitis, paresthesia, facial edema, rash; antibody formation, infection, thromboembolic events (in VWD patients), hemolytic anemia (rare). Note: Report all infections suspected to be transmitted by Alphanate to (888) GRIFOLS. How supplied: Single-dose vial–1 (w. diluent, supplies)

ALPHANINE SD Grifols Biologicals ℞ Clotting factor. Coagulation Factor IX (human) 250 IU, 500 IU, 1000 IU, 1500 IU; per vial; lyophilized concentrate for IV infusion after reconstitution; contains non-therapeutic Factor II, Factor VII, Factor X. Indications: Prevention and control of bleeding in Hemophilia B. Adults: Dosage Required (IU) = Body Weight (kg) × Desired Factor IX increase × 1 IU/kg. Individualize. Max infusion rate: 10mL/min. Mild hemorrhage: increase FIX 20–30% (20–30 IU/kg twice daily) for 1–2 days or until resolved. Moderate hemorrhage: increase FIX 25–50% (25–50 IU/kg twice daily) for 2–7 days. Major hemorrhage: increase FIX 50% (30–50 IU/kg twice daily) for 3–5 days then maintain at 20% (20 IU/kg twice daily) for up to 10 days. Surgery: Pre-op: increase FIX 50–100% (50–100 IU/kg twice daily), then maintain at 50–100% for 7–10 days or until healed. Children: See literature. Warnings/Precautions: Not for treating Factor II, VII, or X deficiencies; Hemophilia A with Factor VIII inhibitors, or reversal of coumarin-induced hemorrhage. Contains human plasma; monitor for transmission of infectious diseases. Previously untreated

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ASSOCIATED HEMATOLOGICAL DISORDERS patients: closely monitor for signs of anaphylaxis between days 10 and 20 of exposure. Immune tolerance induction. Major deletion mutations in Factor IX gene. Liver disease. Surgery. Pregnancy (Cat.C). Adverse reactions: Chills, nausea, inj site reactions; hypersensitivity reactions, thrombosis, disseminated intravascular coagulation. Note: Report all infections suspected to be transmitted by AlphaNine SD to (888) 675-2762. How supplied: Single-use vials–1 (w. diluent, supplies)

AMICAR TABLETS Clover

℞

Hemostatic (plasmin and plasminogen activator inhibitor). Aminocaproic acid 500mg, 1000mg; scored tabs. ℞ Also: AMICAR ORAL SOLUTION Aminocaproic acid 250mg/mL; raspberry-flavor. Indications: Bleeding associated with fibrinolysis. Adults: Initially 5g during 1st hour, then 1g/hour for 8 hours or until bleeding is controlled. Children: Not recommended. ℞ Also: Aminocaproic Acid Injection (various) Aminocaproic acid 250mg/mL; soln for IV infusion after dilution; contains benzyl alcohol. Adults: 4–5g (in 250mL of diluent) by IV infusion during the 1st hour, then 1g/hour (in 50mL of diluent) for 8 hours or until bleeding is controlled. Children: Not recommended. Contraindications: Active intravascular clotting process. Disseminated intravascular coagulation without concomitant heparin. Warnings/Precautions: Upper urinary tract bleeding: not recommended. Cardiac, hepatic or renal disease. Risk of myopathy with longterm use; monitor creatine phosphokinase (CPK); discontinue if CPK rises. Avoid rapid IV administration. Neonates. Pregnancy (Cat.C). Nursing mothers. Interactions: Avoid concomitant Factor IX complex or Anti-inhibitor Coagulant concentrates; may increase thrombosis risk. Adverse reactions: Inj site reactions, bradycardia, hypotension, GI upset, edema, headache, malaise, CNS effects, thrombosis, others; rare: myopathy. How supplied: Tabs–100; Oral soln–473mL; Inj–contact supplier

BEBULIN VH Baxter

℞

Clotting factor. Coagulation Factor IX Complex (human) 500–700 IU; per vial; freeze-dried concentrate for IV infusion after reconstitution; contains Factors II, VII, X and heparin. Indications: Prevention and control of bleeding in Hemophilia B. Adults and Children: Dosage Required (IU) = Body Weight (kg) × Desired Factor IX increase × 1.2 IU/kg. Max infusion rate: 2mL/min. Bleeding:

minor: 20% increase (25–35 IU/kg) for 1 dose. Moderate: 40% increase (40–55 IU/kg) once, give 2nd dose after 24hrs (continue until resolved). Major: ≥60% increase (60–70 IU/kg) once daily for 2–3 days or until healed. Surgery: Give loading dose 1hr prior to surgery. May repeat dose every 12hrs initially then every 24hrs in late post-op period. Minor: Initially 40–60% (50–60 IU/kg), then 20–40% (25–55 IU/kg) for 1–2 weeks. Major: Initially ≥60% increase (70–95 IU/kg) then 20–60% (35–75 IU/kg) for 1–2 weeks, then 20% (25–35 IU/kg) until healed. Prophylaxis: 20–30 IU/kg 1–2 times weekly. Warnings/Precautions: Not for treating factor deficiencies other than Factor IX deficiency. Contains human plasma; monitor for possible infection transmission. Thromboembolic disorders; risk increased during post-op period; avoid FIX increases >60%; monitor for thrombosis, disseminated intravascular coagulation (DIC). Surgery. Pregnancy (Cat.C). Adverse reactions: Hypersensitivity reactions, thrombosis, DIC. Note: Report all infections suspected to be transmitted by Bebulin VH to (800) 423-2862. How supplied: Single-use vials–1 (w. diluent, needles)

BENEFIX Pfizer

℞

Clotting factor. Coagulation Factor IX (recombinant) 250 IU, 500 IU, 1000 IU, 2000 IU; per vial; lyophilized pwd for IV infusion after reconstitution; preservative-free. Indications: Prevention and control of bleeding in hemophilia B. Peri-operative management in patients with hemophilia B. Adults: Dosage Required (IU) = Body Weight (kg) × Desired Factor IX increase × 1.3 IU/kg. Give by IV infusion over several minutes. If inhibitor present or low Factor IX recovery, may need higher doses. Minor hemorrhage: 20–30% increase every 12–24hrs for 1–2 days. Moderate: 25–50% increase every 12–24hrs for 2–7 days until resolved. Major: 50–100% increase every 12–24 hrs for 7–10 days. Children: <15yrs: See literature. Dose (IU)= body weight (kg) × % FIX increase × 1.4 IU/kg. Contraindications: Hamster protein hypersensitivity. Warnings/Precautions: Not for Hemophilia A with FVIII inhibitors or other factor deficiencies, reversal of coumarin-induced anticoagulation or for low levels of liver-dependant coagulation factors. Fibrinolysis, disseminated intravascular coagulation (DIC), liver disease, neonates, or during post-op period; increased risk of thromboembolic events. Monitor for Factor IX inhibitors and deletion mutations of Factor IX gene; increased risk of anaphylaxis. Immune tolerance induction. Latex allergy. Pregnancy (Cat.C). Adverse reactions: Headache, fever, chills, flushing, GI upset, lethargy, taste perversion,

hypoxia, inj site reactions, dizziness, allergic rhinitis; hypersensitivity reactions, inhibitor development, thrombosis. How supplied: Single-use vials–1 (w. diluent, supplies)

CARIMUNE NF CSL Behring

℞

Immune globulin. Immune globulin (human) 3g, 6g, 12g; per vial; pwd for IV infusion after reconstitution; contains sucrose and NaCl; preservative-free. Indications: Immune thrombocytopenic purpura (ITP). Adults and Children: Induction: give by IV infusion at a rate of 0.5mg/kg/min for first 30mins, if tolerated may increase to 1mg/kg/min up to max 3mg/kg/min in a stepwise manner. 0.4g/kg on 2–5 consecutive days. Use of 6% immunoglobulin solution is recommended. Acute childhood ITP: discontinue therapy after second day of 5 day course if platelet count response to first two doses is 30–50000/μL. Maintenance: If platelet count falls to <30000/μL and/or clinically significant bleed: give 0.4g/kg as a single infusion, may increase to 0.8–1g/kg as single infusion if inadequate response. Risk of renal dysfunction/ failure or thrombosis: max infusion rate <2mg/kg/min. Contraindications: IgA-deficiency with antibodies against IgA. Previous severe reaction to human immune globulin. Warnings/Precautions: Advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, cardiovascular risk factors: increased risk of thrombosis. Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Pre-existing renal insufficiency, diabetes, >65yrs, hypovolemia, sepsis, paraproteinemia: increased risk of renal dysfunction or acute renal failure. Correct volume depletion; assess renal function, BUN, serum creatinine, urine output before and during therapy; discontinue if renal function deteriorates. Monitor for aseptic meningitis, hemolysis and delayed hemolytic anemia. Monitor for pulmonary dysfunction; perform test for anti-neutrophil antibodies if transfusion-related acute lung injury (TRALI) suspected. Contains human plasma; monitor for possible infection transmission. Have epinephrine inj available. Elderly. Pregnancy (Cat.C). Interactions: Concomitant nephrotoxic drugs: increased risk of renal toxicity. May affect response to live virus vaccines. Adverse reactions: Headache, arthralgia, myalgia, transient skin reactions, infusion reactions (eg, flushing, chills, fever), renal toxicities; aseptic meningitis syndrome (esp. high dose 2g/kg), TRALI, thrombosis. How supplied: Single-use vial–1

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ASSOCIATED HEMATOLOGICAL DISORDERS CORIFACT CSL Behring

℞

Clotting factor. Factor XIII concentrate (human); 1000–1600 units; per vial; powder for IV injection after reconstitution; preservative -free. Indications: Routine prophylactic treatment and peri-operative management of surgical bleeding in patients with congenital Factor XIII (FXIII) deficiency. Adults and Children: Give by slow IV injection at a rate of ≤4mL/min. Initially 40units/kg. Adjust ±5units/kg to maintain 5–20% trough FXIII activity levels using Berichrom Activity Assay: One trough level of <5%: increase by 5units/kg; trough level of 5–20%: no change; two trough levels of >20%: decrease by 5units/kg; one trough level of >25%: decrease by 5units/kg. Routine prophylaxis: give every 28 days. Peri-operative management: individualized based on patient’s FXIII activity level, surgery type, and clinical response; dose adjustment: see full labeling. Warnings/Precautions: Contains human plasma; monitor for possible infection transmission. Long-term therapy: consider appropriate vaccination (hepatitis A and B virus). Monitor FXIII activity levels during and after surgery. Monitor for development of inhibitory antibodies, thromboembolic events. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Joint inflammation, hypersensitivity, rash, pruritus, erythema, hematoma, arthralgia, headache, elevated thrombin-antithrombin levels, increased blood lactate dehydrogenase; acute ischemia, neutralizing antibodies. How supplied: Single-use vial–1

CYKLOKAPRON Pfizer

℞

Plasminogen activation inhibitor. Tranexamic acid 100mg/mL; soln for IV inj. Indications: Short-term use in hemophilia to reduce or prevent hemorrhage, and reduce the need for replacement therapy during and following tooth extraction. Adults and Children: Give by IV inj. Max injection rate: 1mL/min. Pre-extraction: 10mg/kg; Post-op: 10mg/kg 3–4 times daily for 2–8 days. Renal impairment: serum creatinine 1.36–2.83mg/dL: 10mg/kg twice daily; 2.83–5.66mg/dL: 10mg/kg once daily; >5.66mg/dL: 10mg/kg every 48hrs or 5mg/kg every 24 hours. Contraindications: Acquired defective color vision. Subarachnoid hemorrhage. Active intravascular clotting. Warnings/Precautions: Therapy longer than several days: do ophthalmologic exam (before and during); discontinue if visual changes occur. Renal insufficiency; reduce dose. History of thromboembolic disease. Disseminated intravascular coagulation. Upper urinary tract bleeding. Pregnancy (Cat.B). Nursing mothers.

Interactions: Avoid concomitant Factor IX complex concentrates or Anti-inhibitor Coagulant concentrates; increased risk of thrombosis. Do not mix with solutions containing penicillin. Adverse reactions: GI upset, giddiness, hypotension, visual abnormalities; rare: thromboembolic events. How supplied: Amps (10mL)–10

DDAVP INJECTION

℞

Sanofi Aventis

Antidiuretic hormone. Desmopressin acetate 4mcg/mL; soln for inj or IV infusion after dilution. Indications: To maintain hemostasis or to stop bleeding in Hemophilia A and mild-to-moderate Type 1 von Willebrand’s disease (VWD), each with >5% Factor VIII activity. Adults and Children: <3 months: not recommended. ≥3 months: 0.3micrograms/kg IV over 15–30 minutes. Pre-op: give 30 minutes before scheduled procedure. May repeat dose based on clinical response. Repeated administration before 48hrs associated with tachyphylaxis. Contraindications: Moderate to severe renal impairment (CrCl <50mL/min). Hyponatremia, or history of. Warnings/Precautions: Not for treating Hemophilia A with Factor VIII coagulant activity levels ≤5%, Hemophilia B, in patients with FVIII antibodies, or for Type IIB VWD, or severe Type 1 VWD and evidence of abnormal molecular form of FVIII antigen. Monitor fluid intake, urine volume plasma osmolality. Fluid/electrolyte imbalance (eg, cystic fibrosis). Adjust fluid intake downward (esp in children and elderly) to decrease risk of water intoxication, hyponatremia. Habitual or psychogenic polydipsia. Coronary artery insufficiency. Hypertension. Predisposition to thrombosis. Pregnancy (Cat.B). Nursing mothers. Interactions: Caution with other pressor agents, drugs that may increase the risk of water intoxication with hyponatremia (eg, tricyclic antidepressants, SSRIs, chlorpromazine, opiates, NSAIDs, lamotrigine, carbamazepine). Possible convulsions with oxybutynin, imipramine. Adverse reactions: Headache, nausea, flushing, abdominal cramps, vulval pain, inj site reaction, water intoxication, hyponatremia, rare: changes in BP, severe allergic reactions, thrombotic events (inj). How supplied: Amp (1mL)–10; Multi-dose vial (10mL)–1

ETHAMOLIN QOL Medical

℞

Sclerosing agent. Ethanolamine oleate 50mg/mL; soln for IV inj; contains benzyl alcohol 2%. Indications: For the treatment of esophageal varices that have recently bled, to prevent rebleeding. Adults: Usual IV dose: 1.5–5mL per varix. Max dose per treatment session: 20mL. Child Class C or concomitant cardiopulmonary disease:

give less than the recommended max dose. To obliterate the varix, may give injections at the time of the acute bleeding episode and then after one week, six weeks, three months, and six months as indicated. Children: Not recommended. Warnings/Precautions: Should be performed by physician familiar with technique. Submucosal inj: not recommended. Cardiorespiratory disease; monitor. Child Class C (more likely to develop esophageal ulceration). Elderly, critically ill (increased risk of fatal aspiration pneumonia). Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Pleural effusion/ infiltration, esophageal ulcer, pyrexia, retrosternal pain, esophageal stricture, pneumonia, rare: anaphylactic reaction (may be fatal), acute renal failure. How supplied: Ampules (2mL)–10

FEIBA Baxter

℞

Clotting factor. Anti-inhibitor Coagulant Complex (AICC) 500 units, 1000 units, 2500 units; per vial; lyophilized pwd for IV infusion after reconstitution; contains Factors II, IX, X (non-activated); Factor VII (activated); Factor VIII inhibitor bypassing activity; Prothrombin Complex Factors; heparin-free. Indications: To control and prevent bleeding episodes, perioperative management, or as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in Hemophilia A and B with inhibitors (see full labeling). Not for treating bleeding episodes due to coagulation factor deficiencies in the absence of inhibitors to factor VIII or IX. Adults and Children: Infusion rate: ≤2units/kg/ min. Joint hemorrhage: 50–100units/kg every 12hrs until improved. Mucous membrane bleeding: 50–100units/kg every 6hrs for at least 1 day or until resolved. Soft tissue hemorrhage: 100units/kg every 12hrs until resolved. Other severe hemorrhage (eg, CNS bleeds): 100units/kg every 6–12hrs until resolved. Preoperative: 50–100units/kg once immediately prior to surgery. Postoperative: 50–100units/kg every 6–12hrs until resolved and healed. Routine prophylaxis: 85units/kg every other day. All: Max 200units/kg per day (100units/kg per dose). Contraindications: Hypersensitivity to factors of the kinin generating system. Disseminated intravascular coagulation (DIC). Acute thrombosis or embolism (including myocardial infarction). Warnings/Precautions: Increased risk of thromboembolic events esp. after high-doses (>200units/kg/day) and/or in patients with thrombotic risk factors (eg, DIC, atherosclerosis, crush injury, septicemia, concomitant recombinant factor VIIa). Monitor patients receiving doses >100units/kg for DIC development, acute coronary ischemia, and signs/symptoms of other thromboembolic

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ASSOCIATED HEMATOLOGICAL DISORDERS events; discontinue if occurs and treat. Discontinue if hypersensitivity reactions occur. Contains human plasma; monitor for possible infection transmission. Elderly. Neonates. Pregnancy (Cat.C). Nursing mothers. Interactions: Separate systemic antifibrinolytics by 12hrs. Adverse reactions: Anemia, diarrhea, hemarthrosis, hep B surface antibody positive, nausea, vomiting; hypersensitivity, thromboembolic events (eg, stroke, DVT, PE). Note: Report all infections suspected to be transmitted by Feiba to (800) 423-2862. How supplied: Single-dose vials–1 (w. diluent, transfer device)

GAMUNEX-C Grifols Biologicals

℞

Immune globulin. Immune Globulin (human) 1g/10mL, 2.5g/25mL, 5g/50mL, 10g/100mL, 20g/200mL; soln for IV or SC infusion; preservative- and sucrose-free. Indications: Idiopathic thrombocytopenic purpura (ITP). Adults and Children: Give by IV infusion at a rate of 1mg/kg/min for first 30mins, if tolerated may increase to max 8mg/kg/min. 1g/kg once daily given on 2 consecutive days or 0.4g/kg once daily given on 5 consecutive days. If adequate response after first 1g/kg dose, may withhold second dose. Risk of renal dysfunction or thrombosis: give at minimum practicable infusion rate (<8mg/kg/min). Expanded fluid volumes: high dose regimen not recommended. Contraindications: IgA deficiency with antibodies against IgA. Previous severe reaction to human immune globulin. Warnings/Precautions: Advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, cardiovascular risk factors: increased risk of thrombosis. Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Preexisting renal insufficiency, diabetes, >65yrs, hypovolemia, sepsis, paraproteinemia: increased risk of renal dysfunction or acute renal failure. Correct volume depletion; assess renal function, BUN, serum creatinine, urine output before and during therapy; discontinue if renal function deteriorates. Monitor for aseptic meningitis, hemolysis, hemolytic anemia. Monitor for pulmonary dysfunction; perform test for antineutrophil antibodies if transfusion-related acute lung injury (TRALI) suspected. Contains human plasma; monitor for possible infection

transmission. Have epinephrine inj available. Pregnancy (Cat.C). Nursing mothers: not evaluated. Interactions: May affect response to live virus vaccines. Concomitant nephrotoxic drugs: increased risk of acute renal failure. May cause false positive direct or indirect Coombs’ test. Adverse reactions: Headache, vomiting, fever, nausea, back pain, rash; renal dysfunction (may be fatal), hypersensitivity reactions; rare: hemolytic anemia, aseptic meningitis syndrome (esp. high dose of 2g/kg and/or rapid infusion), TRALI, thrombosis, hyperproteinemia. Note: Report all infections suspected to be transmitted by Gamunex-C to (800) 520-2807. How supplied: Vials–1

HELIXATE FS CSL Behring

℞

Clotting factor. Antihemophilic Factor VIII (recombinant) 250 IU, 500 IU, 1000 IU; per bottle; dried concentrate for IV infusion after reconstitution; contains sucrose; preservativefree. Indications: Prevention and control of hemorrhagic episodes or in order to perform emergency or elective surgery in Hemophilia A patients. Adults and Children: Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Individualize. Infuse over 5–10minutes if tolerated. Minor hemorrhage: 10–20 IU/kg; may repeat dose if needed. Moderate/major hemorrhage or minor surgery: 15–30 IU/kg; may repeat 1 dose at 12–24hrs if needed. Major/life-threatening hemorrhage, fractures or head trauma: initially 40–50 IU/kg, then 20–25 IU/kg every 8–12hrs. Major surgery: pre-op dose: 50 IU/kg (verify ∼100% activity prior to surgery); may repeat after 6–12hrs initially, and for 10–14 days until completely healed. Contraindications: Mouse or hamster protein sensitivity. Warnings/Precautions: Not for treating von Willebrand’s disease. Confirm Factor VIII deficiency prior to treatment. Monitor for development of Factor VIII inhibitors. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Inj site reactions, dizziness, rash, dysgeusia, increased BP, pruritus, depersonalization, GI upset, rhinitis; antibody formation, hypersensitivity reactions. How supplied: Single-use bottle–1 (w. diluent)

HEMOFIL M Baxter

℞

Clotting factor. Antihemophilic Factor VIII (human) 220–400 IU, 401–800 IU, 801–1700 IU, 1701–2000 IU; per bottle; dried concentrate for IV infusion after reconstitution; contains albumin.

Indications: Prevention and control of hemorrhagic episodes in Hemophilia A. Adults and Children: Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Individualize. Infuse at rate of up to 10mL/min. Monitor pulse rate; if increased significantly, reduce infusion rate or hold. Hemorrhage: Mild: obtain 20–40% FVIII increase; give every 12–24hrs for 1–3 days until resolved. Moderate: obtain 30–60% FVIII increase; give every 12–24hrs for 3 days or until pain or disability resolved. Life-threatening: obtain 60–100% FVIII increase; give every 8–24hrs until resolved. Surgery: Minor: obtain 60–80% FVIII increase; give single infusion plus oral antifibrinolytic therapy within 1 hour; Major: pre- and Post-op: obtain 80–100% FVIII increase; repeat every 8–24hrs based on healing. Contraindications: Mouse protein sensitivity. Warnings/Precautions: Not for von Willebrand’s disease. Confirm Factor VIII deficiency prior to treatment. Contains human plasma; monitor for possible infection transmission. Monitor for development of Factor VIII inhibitors. Latex allergy. Pregnancy (Cat.C). Adverse reactions: Allergic reactions, nausea, fever, chills, urticaria, antibody formation. Note: Report all infections suspected to be transmitted by Hemofil M to (800) 423-2862. How supplied: Single-dose bottle–1 (w. diluent, needles)

HUMATE-P CSL Behring

℞

Clotting factors. Antihemophilic Factor VIII/Von Willebrand Factor Complex (human) 250 IU FVIII + 600 IU VWF, 500 IU FVIII + 1200 IU VWF, 1000 IU FVIII + 2400 IU VWF; per vial; lyophilized pwd for IV infusion after reconstitution; contains albumin. Indications: Treatment and prevention of bleeding in adults with Hemophilia A. Treatment of spontaneous and trauma-induced bleeding, and prevention of excessive bleeding during and after surgery in adults and children with von Willebrand disease (VWD). Adults: Max injection rate: 4mL/min. Hemophilia A: Minor bleed: 15 IU FVIII/kg (obtain 30% FVIII increase) once; if needed, may give ½ dose once or twice daily for 1–2 days. Moderate bleed: initially 25 IU FVIII/kg (obtain 50% FVIII increase), then 15 IU FVIII/kg (maintain 30% FVIII increase) every 8–12hrs for 1–2 days, then repeat dose for 1–2 times daily for a total of 7 days or until healed. Severe bleed: initially 40–50 IU FVIII/kg, then 20–25 IU FVIII/kg every 8hrs (maintain 80–100% FVIII increase) for 7 days, then repeat dose for 1–2 times daily for additional

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ASSOCIATED HEMATOLOGICAL DISORDERS 7 days (maintain 30–50% FVIII increase). VWD: Type 1 (Mild): major bleed: initially 40–60 IU/kg, then 40–50 IU/kg every 8–12hrs for 3 days, then once daily for a total of 7 days. Type 1 (Moderate or severe): minor bleed: 40–50 IU/kg for 1–2 doses; major bleed: initially 50–75 IU/kg, then 40–60 IU/kg every 8–12hrs for 3 days, then once daily for a total of 7 days. Types 2 and 3: minor bleed: 40–50 IU/kg for 1–2 doses; major bleed: initially 60–80 IU/kg, then 40–60 IU/kg every 8–12hrs for 3 days, then once daily for a total of 7 days. For dosing in surgery: see literature. Children: Max injection rate: 4mL/min. VWD: Type 1 (Mild): major bleed: initially 40–60 IU/kg, then 40–50 IU/kg every 8–12hrs for 3 days, then once daily for a total of 7 days. Type 1 (Moderate or severe): minor bleed: 40–50 IU/kg for 1–2 doses; major bleed: initially 50–75 IU/kg, then 40–60 IU/kg every 8–12hrs for 3 days, then once daily for a total of 7 days. Types 2 and 3: minor bleed: 40–50 IU/kg for 1–2 doses; major bleed: initially 60–80 IU/kg, then 40–60 IU/kg every 8–12hrs for 3 days, then once daily for a total of 7 days. For dosing in surgery: see literature. Contraindications: Previous anaphylactic or severe systemic response to antihemophilic factor or von Willebrand factor preparations. Warnings/Precautions: Confirm Factor VIII or von Willebrand factor deficiency prior to treatment. Increased risk of thromboembolic events in VWD. Contains human plasma; monitor for possible infection transmission. Large or frequent doses: monitor hematocrit for signs of hemolytic anemia. Monitor for development of inhibitors. Pregnancy (Cat.C). Adverse reactions: Allergic reaction, GI upset, inj site reactions, mild vasodilation, pruritus, paresthesia, peripheral edema, antibody formation; anaphylaxis, thrombosis. Note: Report all infections suspected to be transmitted by Humate-P to (800) 504–5434. How supplied: Single-use vials–1 (w. diluent, supplies)

KCENTRA CSL Behring

℞

Clotting factor. Prothrombin complex concentrate (human) 500 units, 1000 units; per vial; lyophilized pwd for IV infusion after reconstitution; contains non-activated coagulation Factors II, VII, IX, X, antithrombotic Proteins C and S; also, heparin, human albumin, antithrombin III; preservative-free; latex-free. Indications: Urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA) therapy in adults with acute major bleeding or need for an urgent surgery/ invasive procedure. Adults: See full labeling. Administer concomitant Vitamin K. Individualize dosing based on patient’s baseline INR and weight. Potency (units) is defined by Factor IX content. Give by IV Infusion at a rate of 0.12mL/kg/min (∼3 units/kg/min); max rate of 8.4mL/min (∼210 units/min). ≤100kg: Pre-treatment INR: (2–<4):

25 units of Factor IX/kg; max 2500 units; (4–6): 35 units of Factor IX/kg; max 3500 units; (>6): 50 units of Factor IX/kg; max 5000 units. >100kg: do not exceed max dose. Repeat dosing: not recommended. Children: Not established. Contraindications: Severe hypersensitivity to heparin, Factors II, VII, IX, X, Proteins C and S, antithrombin III, human albumin. Disseminated intravascular coagulation (DIC). Known heparininduced thrombocytopenia (HIT). Warnings/Precautions: Risk of arterial and venous thromboembolic complications (may be fatal). History of thromboembolic events within the previous 3 months. Monitor for signs/ symptoms of thromboembolic events during and after infusion. Discontinue immediately if hypersensitivity reactions occur. Measure INR before, during, and after each treatment. Contains human plasma; monitor for possible infection transmission. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Headache, nausea, vomiting, hypotension, anemia; hypersensitivity, thromboembolic events (eg, stroke, PE, DVT). Note: Report all infections suspected to be transmitted by Kcentra to (866) 915-6958. How supplied: Kit (500 units, 1000 units)–1 (single-use vial + diluent, supplies)

KOATE-DVI Grifols Biologicals

℞

Clotting factor. Antihemophilic Factor VIII (human) 250 IU, 500 IU, 1000 IU; per bottle; dried concentrate for IV infusion after reconstitution; contains albumin. Indications: Prevention and control of hemorrhagic episodes or in order to perform emergency or elective surgery in Hemophilia A patients. Adults: Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Individualize. Infuse over 5–10 minutes if tolerated. Use filter needle. Hemorrhage: Mild: 10 IU/kg as single dose. Moderate: 15–25 IU/kg, then 10–15 IU/kg every 8–12hrs if needed. Severe: initially 40–50 IU/kg, then 20–25 IU/kg every 8–12hrs. Major surgery: pre-op dose: 50 IU/kg, then verify Factor VIII level achieved prior to surgery; may repeat every 6–12hrs initially and for 10–14 days until healing complete. Children: Not recommended. Warnings/Precautions: Not for von Willebrand’s disease. Confirm Factor VIII deficiency prior to treatment. Contains human plasma; monitor for possible infection transmission. Large or frequent doses: monitor hematocrit for signs of progressive anemia. Monitor for development of Factor VIII inhibitors. Pregnancy (Cat.C). Adverse reactions: Allergic reactions, tingling sensations, blurred vision, headache, GI upset, jittery feeling, antibody formation. How supplied: Single-dose bottle–1 (w. diluent)

KOGENATE FS Bayer

℞

Clotting factor. Antihemophilic Factor VIII (recombinant) 250 IU, 500 IU, 1000 IU, 2000 IU, 3000 IU; per vial; lyophilized pwd for IV infusion after reconstitution; contains sucrose; preservative-free. Indications: Prevention and control of hemorrhagic episodes in Hemophilia A. Surgical prophylaxis in Hemophilia A. Routine prophylaxis to reduce frequency of hemorrhagic episodes and joint damage in children with Hemophilia A with no pre-existing joint damage. Adults and Children: Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Individualize. Infuse over 1–15mins if tolerated. Minor hemorrhage: 10–20 IU/kg; may repeat dose if needed. Moderate hemorrhage or minor surgery: 15–30 IU/kg; may repeat dose every 12–24hrs until resolved. Major hemorrhage, fractures or head trauma: initially 40–50 IU/kg, then 20–25 IU/kg every 8–12hrs until resolved. Major surgery: Pre-op: 50 IU/kg (verify 100% activity prior to surgery); repeat if needed after 6–12hrs initially, and for 10–14 days until completely healed. Routine prophylaxis in children: 25 IU/kg every other day. Contraindications: Mouse or hamster protein sensitivity. Warnings/Precautions: Not for von Willebrand’s disease. Confirm Factor VIII deficiency prior to treatment. Monitor for development of Factor VIII inhibitors. Labor & delivery. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Inj site reactions, dizziness, rash, BP increase, pruritus, hypersensitivity reactions, antibody formation, central venous line-associated infections. How supplied: Kit–1 (vial w. diluent and BIO-SET system)

MONARC-M Baxter

℞

Clotting factor. Antihemophilic Factor VIII (human) 220–400 activity units, 401–800 activity units, 801–1700 activity units, 1701–2000 activity units; per bottle; dried concentrate for IV infusion after reconstitution; contains albumin. Indications: Prevention and control of hemorrhagic episodes in Hemophilia A. Adults and Children: Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Infuse at rate of up to 10mL/min. Monitor pulse rate; if increased significantly, reduce infusion rate or hold. Hemorrhage: Mild: obtain 20–40% FVIII increase; give every 12–24hrs for 1–3 days until resolved. Moderate: obtain 30–60% FVIII increase; give every 12–24hrs for 3 days or until pain or disability resolved. Lifethreatening: obtain 60–100% FVIII increase; give every 8–24hrs until resolved. Surgery: Minor: obtain 60–80% FVIII increase; give single infusion plus oral antifibrinolytic therapy within

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ASSOCIATED HEMATOLOGICAL DISORDERS 1 hour; Major: pre- and Post-op: obtain 80–100% FVIII increase; repeat every 8–24hrs based on healing. Contraindications: Mouse protein sensitivity. Warnings/Precautions: Not for von Willebrand’s disease. Confirm Factor VIII deficiency prior to treatment. Contains human plasma; monitor for possible infection transmission. Monitor for development of Factor VIII inhibitors. Latex allergy. Pregnancy (Cat.C). Adverse reactions: Allergic reactions, nausea, fever, chills, urticaria, antibody formation. Note: Report all infections suspected to be transmitted by Monarc-M to (800) 423-2862. How supplied: Single-dose bottle–1 (w. diluent, needles)

MONOCLATE-P CSL Behring

℞

Clotting factor. Antihemophilic Factor VIII:C (human) 250 IU, 500IU, 1000 IU, 1500 IU; per vial; lyophilized concentrate for IV infusion after reconstitution; contains albumin. Indications: Treatment and surgical prophylaxis for Hemophilia A. Adults and Children: Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Individualize. Infusion rate: 2mL/min if tolerated. Mild hemorrhages: single infusion to attain 30% FVIII increase. Moderate hemorrhage or minor surgery: initially 15–25 IU/kg, then 10–15 IU/kg every 8–12hrs if needed. Severe hemorrhage: initially 40–50 IU/kg, then 20–25 IU/kg every 8–12hrs. Major surgery: give first dose 1 hour pre-op to attain 80–100% FVIII increase, then give a ½ dose 5 hours after first dose; maintain daily at ≥30% FVIII increase for 10–14 days post-op. Contraindications: Mouse protein sensitivity. Warnings/Precautions: Not for von Willebrand’s disease. Confirm Factor VIII deficiency prior to treatment. Contains human plasma; monitor for possible infection transmission. Large or frequent dosing: monitor hematocrit for signs of progressive anemia. Monitor for development of Factor VIII inhibitors. Pregnancy (Cat.C). Adverse reactions: Allergic reactions, chills, GI upset, inj site reactions, antibody formation. Note: Report any infections suspected to be transmitted by Monoclate-P to (800) 504-5434. How supplied: Single-dose vial–1 (w. diluent, supplies)

MONONINE CSL Behring

℞

Clotting factor. Coagulation Factor IX (human) 500 IU, 1000 IU; per vial; lyophilized pwd for IV infusion after reconstitution. Indications: Prevention and control of bleeding in Hemophilia B. Adults and Children: Dosage Required (IU) = Body Weight (kg) × Desired Factor IX increase × 1 IU/kg. Individualize. Infuse at a rate of 2mL/min.

Minor spontaneous hemorrhage, prophylaxis: increase FIX 15–25%; give up to 20–30 IU/kg once; may repeat in 24hrs if needed. Major trauma, surgery: increase FIX 25–50%; give up to 75 IU/kg every 18–30hrs for up to 10 days; adjust based on FIX levels. FIX inhibitors: may use higher doses. Contraindications: Mouse protein sensitivity. Warnings/Precautions: Not for Hemophilia A or other factor deficiencies, reversal of coumarin-induced anticoagulation or for bleeding due to low levels of liver-dependant coagulation factors. Fibrinolysis, disseminated intravascular coagulation (DIC), liver disease, neonates, or during post-op period; increased risk of thromboembolic events. Immune tolerance induction. Contains human plasma; monitor for possible infection transmission. Monitor for Factor IX inhibitors and deletion mutations of Factor IX gene; increased risk of hypersensitivity reactions. Pregnancy (Cat.C). Adverse reactions: Headache, fever, chills, flushing, GI upset, tingling, lethargy, inj site reaction, elevated ALT, inhibitor development; hypersensitivity reactions, thrombosis. Note: Report all infections suspected to be transmitted by Mononine to (800) 504-5434. How supplied: Single-dose vial–1 (w. diluent, supplies)

NEUMEGA Pfizer

℞

Thrombopoietic growth factor (Interleukin-11). Oprelvekin 5mg/vial; lyophilized pwd for SC inj after reconstitution; preservative-free. Indications: Prevention of severe thrombocytopenia. To reduce platelet transfusions following myelosuppressive chemotherapy in adults with non-myeloid malignancies who are at high risk of severe thrombocytopenia. Adults: Initiate 6–24hrs after chemotherapy completion. Give by SC inj into abdomen, thigh, or hip; also upper arm if not self-injecting. 50micrograms/kg once daily until post-nadir platelet count is ≥50,000/microliter; max 21 days. Discontinue ≥2days prior to next chemotherapy cycle. Severe renal impairment: CrCl <30mL/min: 25micrograms/kg. May give for ≤6 cycles following chemotherapy. Children: Not recommended. Warnings/Precautions: Not for use after myeloablative chemotherapy. Monitor fluid balance and electrolytes; increased risk of serious fluid retention with CHF, renal impairment, chronic diuretic or aggressive hydration therapy. Consider draining pre-existing fluid collections (eg, pericardial effusion, ascites). Obtain CBCs before and during therapy; monitor platelet counts. Pre-existing papilledema or tumors involving the CNS. History of stroke, transient ischemic attack, or atrial arrhythmias. Effectiveness unknown with chemotherapy regimens >5 days duration or with regimens associated with delayed myelosuppression (eg,

nitrosoureas, mitomycin-C). Pregnancy (Cat.C). Nursing mothers: not recommended. Adverse reactions: Edema, dyspnea, tachycardia, conjunctival injection, palpitations, atrial arrhythmias, pleural effusions, neutropenic fever, syncope, atrial fibrillation, fever, pneumonia, CHF, pulmonary edema, dilutional anemia, blurred vision, paresthesia, dehydration, skin discoloration, exfoliative dermatitis, eye hemorrhage, stroke, papilledema, hypersensitivity reactions (permanently discontinue if occur). How supplied: Single-use vials–7 (w. diluent)

NITROPRESS Hospira

℞

Vasodilator. Sodium nitroprusside 25mg/mL; soln for IV infusion after dilution. Indications: To produce controlled hypotension to reduce surgical bleeding. Adults and Children: Use infusion pump only. Monitor BP closely. Initially 0.3microgram/kg/ min; may increase infusion rate every few minutes until desired effect; max 10microgram/kg/min and no more than 10 minutes. Titrate infusion rate (see literature). Contraindications: Compensatory hypertension due to aortic coarctation or arteriovenous shunting. Inadequate cerebral circulation or moribund patients requiring emergency surgery. Congenital (Lebers) optic atrophy. Tobacco amblyopia. Acute CHF associated with reduced peripheral vascular resistance. Warnings/Precautions: Use only when available equipment and personnel allow BP to be continuously monitored. Cyanide toxicity possible (esp. at infusion rates >2micrograms/kg/min); monitor acid-base disturbances and venous oxygen concentration. Elevated intracranial pressure. Correct pre-existing anemia and hypovolemia, esp. during anesthesia. Poor surigical risk. Hepatic impairment. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Hypotensive effect potentiated by ganglionic blocking agents, negative inotropic agents, and inhaled anesthetics. Adverse reactions: Excessive hypotension, cyanide toxicity, methemoglobinemia, abdominal pain, apprehension, diaphoresis, dizziness, headache, muscle twitch, nausea, palpitations, restlessness, rash, hypothyroidism, ileus, flushing, infusion site reactions. How supplied: Single-dose vials (2mL)–100

NOVOSEVEN RT Novo Nordisk

℞

Clotting factors. Recombinant Coagulation Factor VIIa (rFVIIa) Room Temperature Stable 1mg, 2mg, 5mg, 8mg; per vial; lyophilized pwd for IV inj after reconstitution; preservative-free. Indications: Treatment of bleeding and for surgical prophylaxis in Hemophilia A and B with inhibitors to Factors VIII and IX, in acquired hemophilia, and in congenital FVII deficiency. Adults and Children: Give by IV bolus. Individualize; base treatment schedule on

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ASSOCIATED HEMATOLOGICAL DISORDERS hemostasis. Hemophilia A and B with inhibitors: Bleeding: 90micrograms/kg every 2hrs; posthemostatic dosing: continue at 3–6hrs intervals for severe bleeds; caution with prolonged dosing. Surgery: initially 90micrograms/kg prior to surgery, repeat at 2hr intervals during surgery; minor (post-surgical dosing): every 2hrs for 1st 48hrs, then every 2–6hrs until healed; major (post-surgical dosing): every 2hrs for 5 days, then every 4hrs until healed. Congenital Factor VII deficiency: 15–30micrograms/kg every 4–6hrs until hemostasis acheived. Acquired hemophilia: 70–90micrograms/kg every 2–3hrs until hemostasis acheived. Warnings/Precautions: Increased risk of arterial thromboembolic adverse events when administered outside the current approved indications. Disseminated intravascular coagulation, advanced atherosclerotic disease, crush injury, septicemia, history of cardiovascular disease, hepatic disease, post-op immobilization, elderly, neonates; increased risk of thrombotic events. Monitor for signs/symptoms of coagulation activation or thrombosis; discontinue or reduce dose if occur. Monitor prothrombin time and FVII coagulant activity before and after dosing in FVII deficiency. Monitor for antibody formation. Mouse, hamster, or bovine protein hypersensitivity. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Avoid concomitant activated or non-activated prothrombin complex concentrates; may increase risk of thrombotic events. Do not mix with infusion solutions. Adverse reactions: Pyrexia, hemorrhage, inj site reactions, arthralgia, headache, hypertension,

angina, hypotension, GI upset, pain, edema, rash; thrombosis, increased levels of fibrin degradation products, disseminated intravascular coagulation, elevated D-dimer and AT-III levels, thrombophlebitis. How supplied: Single-dose vials–1 (with diluent)

NPLATE Amgen

℞

Thrombopoietin receptor agonist. Romiplostim (recombinant) 250mcg, 500mcg; per vial; lyophilized pwd for SC inj after reconstitution; contains sucrose and mannitol; preservative-free. Indications: Thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Adults: Give by SC inj. To reduce risk of bleeding: use lowest effective dose to achieve and maintain platelets ≥50×109/L. ≥18yrs: initially: 1mcg/kg weekly; may increase by 1mcg/kg if platelets <50×109/L; max: 10mcg/kg weekly. May reduce by 1mcg/kg if platelets >200×109/L for 2 consecutive weeks. Do not dose if platelets >400×109/L; resume Nplate at a dose reduced by 1mcg/kg when platelets fall to <200×109/L. Discontinue if platelets have not increased after 4 weeks at max dose. Children: <18yrs: not recommended. Warnings/Precautions: Not for normalization of platelet counts or to treat thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP. Risk of bone marrow fibrosis with cytopenias. Worsened thrombocytopenia after discontinuation. Monitor

CBCs, platelets, and peripheral blood smears before and weekly during dose adjustments then monthly after achieving stable dose; and weekly for 2 weeks after discontinuation of therapy. Monitor after initial response for formation of neutralizing antibodies. Risk of hematologic malignancies (esp. myelodysplastic syndrome). Renal or hepatic impairment. Elderly. Pregnancy (Cat.C). Nursing mothers. Interactions: May increase bleeding risk with anticoagulants or antiplatelet agents. Adverse reactions: Arthralgia, dizziness, insomnia, myalgia, pain in extremity, abdominal pain, shoulder pain, dyspepsia, paresthesia, headaches; bone marrow reticulin deposition, worsening thrombocytopenia, risk of bleeding, thrombotic/thromboembolic complications, antibody formation. How supplied: Single-use vial–1

PRIVIGEN CSL Behring

℞

Immune globulin. Immune globulin (human) 0.1g/mL; soln for IV infusion; contains L-proline; sucrose-, preservative-, and latex-free. Indications: Chronic immune thrombocytopenic purpura (ITP). Adults and Children: <15yrs: not established. ≥15yrs: Give by IV infusion at an initial rate of 0.5mg/kg/min, if tolerated may increase to 4mg/kg/min. Renal dysfunction, thrombosis risk: give at the minimum infusion rate practicable. Usual dose: 1g/kg once daily for 2 consecutive days for a total dose of 2g/kg. Increased risk of thrombosis, hemolysis, acute renal injury, or volume overload: consider carefully the relative

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ASSOCIATED HEMATOLOGICAL DISORDERS risks and benefits before prescribing high dose regimen (2g/kg). Contraindications: IgA-deficiency with antibodies against IgA and history of hypersensitivity. Hyperprolinemia. Previous severe reaction to human immune globulin. Warnings/Precautions: Advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, cardiovascular risk factors: increased risk of thrombosis. Monitor for signs/symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Pre-existing renal insufficiency, diabetes, >65yrs, obese, hypovolemia: increased risk of renal dysfunction and acute renal failure. Correct volume depletion; assess renal function, BUN, serum creatinine, urine output before and during therapy; discontinue if renal function deteriorates. Monitor for aseptic meningitis, hemolysis, delayed hemolytic anemia, transfusion-related acute lung injury (eg, respiratory distress, pulmonary edema, hypoxemia). Antibody formation. Risk of transmission of viral diseases. Have epinephrine inj available. Elderly. Pregnancy (Cat.C). Nursing mothers. Interactions: Concomitant nephrotoxic drugs: increased risk of renal toxicity. May affect response to live virus vaccines. May interfere with serological test interpretation. Adverse reactions: Headache, elevated body temperature, positive direct antiglobulin test, anemia, nausea, epistaxis, vomiting, hematocrit decreased, increase in blood bilirubin, blood total bilirubin and blood lactate dehydrogenase; hyperproteinemia, increased serum viscosity, hyponatremia; rare: aseptic meningitis syndrome (esp. high dose of 2g/kg), hemolysis, TRALI, thrombosis. How supplied: Single-use vial (50mL, 100mL, 200mL, 400mL)–1

PROFILNINE SD Grifols Biologicals ℞ Clotting factor. Coagulation Factor IX complex (human) 500 IU, 1000 IU, 1500 IU; per vial; lyophilized concentrate for IV infusion after reconstitution; contains Factor X, Factor II, Factor VII; preservative-free. Indications: Prevention and control of bleeding in Hemophilia B. Adults: Dosage Required (IU) = Body Weight (kg) × Desired Factor IX increase × 1 IU/kg. Individualize. Max infusion rate: 10mL/min. Mild to moderate hemorrhage: give single dose to increase Factor IX 20–30%. Serious hemorrhage: give daily infusions to increase Factor IX 30–50%. Surgery: increase Factor IX by 30–50% for at least 1 week Post-op. Dental extraction: increase Factor IX to 50% immediately prior to procedure; may give additional doses if bleeding recurs. Children: See literature.

Warnings/Precautions: Not for treating Factor VII deficiency. Contains human plasma; monitor for possible infection transmission. Liver disease, prolonged treatment duration or if undergoing surgery: increased risk of disseminated intravascular coagulation (DIC) and thrombosis. Pregnancy (Cat.C). Adverse reactions: Urticaria, fever, chills, GI upset, headache, somnolence, lethargy, flushing, tingling; hypersensitivity reactions, thrombosis, DIC. Note: Report all infections suspected to be transmitted by Profilnine SD to (888) 675-2762. How supplied: Single-use vials–1 (w. diluent, supplies)

PROMACTA GlaxoSmithKline

℞

Thrombopoietin receptor agonist. Eltrombopag (as olamine) 25mg, 50mg; tabs. Indications: Thrombocytopenia due to chronic immune (idiopathic) thrombocytopenic purpura (ITP) in adults who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Adults: Take on empty stomach. Initially 50mg once daily. Moderate to severe hepatic impairment or East Asian ancestry: initially 25mg once daily. Titrate to maintain platelet count ≥50×109/L; max 75mg once daily. Adjust dose based on platelet count: see literature. Children: Not recommended. Warnings/Precautions: Monitor CBC, platelet count, and peripheral blood smears for cytopenias and abnormal morphologies; discontinue if no increase in platelet count occurs after 4 weeks at max dose, or if excessive increase in platelet count occurs (eg, >400×109/L), or if evidence of bone marrow fibrosis occurs (eg, cytopenias, nucleated RBCs). Monitor liver function closely before, during, and after treatment (see literature); discontinue if ALT >3×ULN and is progressive or persistent for ≥4 weeks, or if it occurs with evidence of hepatic injury; reinitiation of therapy: not recommended; if restarted, use lower dose and monitor carefully. Do baseline eye exam; monitor for cataracts. Thromboembolism risk factors. Myelodysplastic syndromes. Renal impairment. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Do not take within 4 hours of food/drugs containing polyvalent cations (eg, Fe+2, Ca+2, Al+3, Mg+2, Se+2, Zn+2). May potentiate substrates of organic anion transporter polypeptide 1B1 (eg, benzylpenicillin, most statins, methotrexate, nateglinide, repaglinide, rifampin); monitor and consider reducing their doses. May be potentiated by strong inhibitors of CYP1A2 (eg, ciprofloxacin, fluvoxamine) or CYP2C8 (eg, gemfibrozil, trimethoprim), and with moderate or strong inhibitors of UGT1A1 or UGT1A3. Adverse reactions: Nausea, vomiting, menorrhagia, myalgia, paresthesia, cataract, ecchymosis, thrombocytopenia, increased ALT/AST, conjunctival hemorrhage, increased

risk of hematologic malignancies; thrombotic events with excessive increases in platelet counts; worsened thrombocytopenia after discontinuation. Note: Physicians, pharmacies, and patients must enroll in Promacta Cares program. Register pregnant patients taking eltrombopag by calling (888) 825-5249. How supplied: Tabs–30

RECOMBINATE Baxter

℞

Clotting factor. Antihemophilic Factor VIII (recombinant) 250 IU, 500 IU, 1000 IU; per bottle; lyophilized pwd for IV infusion after reconstitution; contains albumin; preservative-free. Indications: Prevention and control of hemorrhagic episodes and perioperative management in Hemophilia A. Adults and Children: Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Infuse at rate of up to 10mL/min. Monitor pulse rate; if increased significantly, reduce infusion rate or hold. Hemorrhage: Mild: obtain 20–40% FVIII increase; give every 12–24hrs for 1–3 days until resolved. Moderate: obtain 30–60% FVIII increase; give every 12–24hrs for 3 days or until pain or disability resolved. Life-threatening: obtain 60–100% FVIII increase; give every 8–24hrs until resolved. Surgery: Minor: obtain 60–80% FVIII increase; give single infusion plus oral antifibrinolytic therapy within 1 hour; Major: pre- and Post-op: obtain 80–100% FVIII increase; repeat every 8–24hrs based on healing. Contraindications: Mouse, hamster, or bovine protein sensitivity. Warnings/Precautions: Not for von Willebrand’s disease. Confirm Factor VIII deficiency prior to treatment. Monitor for development of Factor VIII inhibitors. Latex allergy. Pregnancy (Cat.C). Adverse reactions: Allergic reactions, nausea, fever, chills, urticaria, antibody formation. How supplied: Single-dose bottle–1 (w. diluent)

RECOTHROM ZymoGenetics

℞

Topical hemostatic. Thrombin [recombinant] 5000 IU, 20000 IU; per vial; pwd for topical use after reconstitution; preservative-free. Indications: Aid to hemostasis for minor bleeding/oozing from capillaries and venules when standard surgical techniques are inadequate or ineffective. May use with absorbable gelatin sponge. Adults: Apply directly to bleeding area, or soak into absorbable gelatin sponge and apply in a single layer. Children: Not recommended. Contraindications: Not for direct injection into circulatory system. Not for treatment of massive

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ASSOCIATED HEMATOLOGICAL DISORDERS Adults: See full labeling. 250 IU (50mcg) per kg by IV only at rate of 2mL per 15–60 secs. Children: Not recommended. Contraindications: Rho (D) positive patients. IgA deficiency. Warnings/Precautions: Monitor patients 20 mins after administration. Pregnancy (Cat.C). Interactions: Do not give live vaccines within 3 months. Adverse reactions: Local or infusion reactions, fever, chills, headache; see full labeling. How supplied: Single-dose prefilled syringes–1, 10

or brisk arterial bleeding. Hypersensitivity to hamster proteins. Warnings/Precautions: Avoid systemic absorption (thrombosis may occur). Hypersensitivity to snake proteins. Pregnancy (Cat.C). Adverse reactions: Incision site complication, infection, pain, bleeding, nausea/vomiting, cardiac events, thromboembolic events. How supplied: Single-use vial (5000 IU, 20000 IU)–1 (w. diluent, supplies) 20000 IU Recothrom kit (co-packaged with ZymoGenetics Spray Applicator Kit)–1

REFACTO Pfizer

℞

Clotting factor. Antihemophilic Factor VIII (recombinant) 250 IU, 500 IU, 1000 IU, 2000 IU; per vial; lyophilized pwd for IV infusion after reconstitution; preservative-free. Indications: Prevention and control of hemorrhagic episodes and for surgical prophylaxis in Hemophilia A. Short-term routine prophylaxis to reduce frequency of spontaneous bleeding episodes. Adults and Children: Dosage Required (IU) = Body Weight (kg) × Desired % Factor VIII Increase × 0.5. Individualize. Infuse at rate comfortable to patient. Minor hemorrhage: obtain 20–40% FVIII increase; give every 12–24hrs for at least 1 day until resolved. Moderate hemorrhage and tooth extraction: obtain 30–60% FVIII increase; give every 12–24hrs for 3–4 days until adequate hemostasis; for tooth extraction: a single infusion plus oral antifibrinolytic therapy within 1hr may be sufficient. Major hemorrhage: obtain 60–100% FVIII increase; give every 8–24hrs until resolved; or, for surgery, until local hemostasis achieved. Prophylaxis: give ≥2 times weekly; children may need shorter dosage intervals or higher doses. Contraindications: Mouse or hamster protein sensitivity. Warnings/Precautions: Not for von Willebrand’s disease. Confirm Factor VIII deficiency prior to treatment. Monitor for development of Factor VIII inhibitors. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Allergic reactions, headache, fever, chills, flushing, nausea, vomiting, lethargy, pruritus, antibody formation. How supplied: Single-use vial–1 (w. diluent, supplies)

RHOPHYLAC CSL Behring Rho (D) immune globulin human 1500 IU (300mcg)/2mL; syringe; for IV or IM inj; preservative- and latex-free; contains albumin (human); solvent/detergent treated. Indications: Raising platelet counts in Rho (D) positive non-splenectomized patients with chronic immune thrombocytopenic purpura (ITP).

℞

RIASTAP CSL Behring

℞

Hemostatic. Fibrinogen concentrate (human) 900–1300mg; per vial; lyophilized pwd for IV inj after reconstitution; contains albumin; preservative-free. Indications: Acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. Adults and Children: See literature. Give by slow IV inj at rate not exceeding 5mL/min. Individualize. Calculate dose when baseline fibrinogen level is known: Dose (mg/kg body wt) = [Target level (mg/dL)–measured level (mg/dL)]/1.7 (mg/dL per mg/kg body wt). When baseline fibrinogen level is not known: 70mg/kg. Monitor fibrinogen level during therapy. Maintain target fibrinogen level of 100mg/dL until hemostatis is obtained. Warnings/Precautions: Not for use in dysfibrinogenemia. Monitor for allergic or hypersensitivity reactions; discontinue if occur. Risk of thrombosis (monitor). Contains human plasma; monitor for possible infection transmission. Labor & delivery. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Fever, headache, chills, nausea, vomiting; thrombotic episodes (eg, pulmonary embolism, MI, DVT), anaphylactic reactions. How supplied: Single-use vial–1

RIXUBIS Baxter

℞

Clotting factor. Coagulation Factor IX (recombinant) 250 IU, 500 IU, 1000 IU, 2000 IU, 3000 IU; per vial; lyophilized pwd for IV infusion after reconstitution; preservative-free. Indications: Prevention and control of bleeding in hemophilia B. Perioperative management in hemophilia B. Routine prophylaxis to prevent or reduce the frequency of bleeding in hemophilia B. Adults: Initial dose = body weight (kg) × desired FIX increase (% or IU/dL) × reciprocal of observed recovery (IU/dL per IU/kg). Incremental recovery in previously treated patients (PTPs): Dose (IU) = body weight (kg) × desired FIX increase (% or IU/dL) × 1.1 dL/kg. Individualize. Give by IV bolus infusion only. Max infusion rate 10mL/min. Control/prevention of bleeding: Minor: 20–30%

required every 12–24hrs for at least 1 day until healing achieved. Moderate: 25–50% required every 12–24hrs for 2–7 days until bleeding stops and healing achieved. Major: 50–100% required every 12–24hrs for 7–10 days until bleeding stops and healing achieved. Peri-op management: Minor surgery: 30–60% required every 24hrs for at least 1 day until healing achieved. Major surgery: 80–100% required every 8–24hrs for 7–10 days until bleeding stops and healing achieved. Routine prophylaxis in PTPs: 40–60 IU/kg twice weekly; titration may be necessary based on patient’s age, bleeding pattern, physical activity. Children: Not established. Contraindications: Hamster protein hypersensitivity. Disseminated intravascular coagulation (DIC). Signs of fibrinolysis. Warnings/Precautions: Not for induction of immune tolerance in patients with hemophilia B; risk of nephrotic syndrome. Evaluate regularly for development of Factor IX inhibitors; measure Factor IX inhibitor concentration if expected activity plasma levels are not attained, or if bleeding is not controlled with an expected dose. Potential risk for thromboembolic complications; monitor for signs of thrombotic and consumptive coagulopathy, in patients with liver disease, signs of fibrinolysis, peri- and post-operatively, or at risk for thrombotic events or DIC. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Dysgeusia, extremity pain, positive test for furin antibody; hypersensitivity reactions (discontinue if occur). How supplied: Single-use vials–1 (w. diluent, supplies)

STIMATE CSL Behring

℞

Antidiuretic hormone. Desmopressin acetate 150mcg/spray; soln for nasal spray. Indications: To maintain hemostasis or to stop bleeding in Hemophilia A and mild-to-moderate Type I von Willebrand Disease (VWD), each with Factor VIII levels >5%. Adults and Children: <11months: not recommended. Give test dose prior to initiating therapy. >11months: <50kg: 1 spray in one nostril (150mcg). ≥50kg: 1 spray per nostril (300mcg). May repeat dose based on clinical response. Pre-op: give 2hrs prior to procedure. Repeated administration before 48 hrs associated with tachyphylaxis. Warnings/Precautions: Not for treating Type IIb VWD, or severe VWD with abnormal molecular form of Factor VIII antigen. Adjust fluid intake downward (esp in children and elderly) to reduce risk of water intoxication, hyponatremia. Monitor fluid intake, plasma osmolality. Fluid and electrolyte imbalances (eg, cystic fibrosis). Coronary artery disease. Hypertension. Predisposition to thrombosis. Unreliable absorption if altered nasal mucosa (eg, scarring, edema); discontinue until resolved. Pregnancy (Cat.B). Nursing mothers.

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ASSOCIATED HEMATOLOGICAL DISORDERS Interactions: Caution with other pressor agents (monitor). Adverse reactions: Headache, nausea, abdominal cramps, vulval pain, facial flushing, local reactions, sore throat, water intoxication, hyponatremia; rare: BP changes, severe allergic reactions, thrombotic events. How supplied: Spray Pump–2.5mL (25 sprays)

THROMBIN-JMI King

℞

Topical hemostatic. Thrombin [bovine origin] 5000 IU, 20000 IU; per vial; pwd for topical use after reconstitution; preservative-free. Indications: Aid to hemostasis for oozing blood and minor bleeding from accessible capillaries and small venules. Adjunct for surgical hemostasis with absorbable gelatin sponge. Adults: For topical use only. See literature. Profuse bleeding (eg, abraided surfaces of liver or spleen): 1000IU/mL. General use (eg, plastic surgery, dental extractions, skin grafting): 100IU/mL. May dilute to prepare intermediate strengths, if needed. Oozing surfaces: may use dry form. Children: Not recommended. Warnings/Precautions: Not for injection or use in large blood vessels. Antibody formation: do not re-expose, abnormalities in hemostasis (eg, severe bleeding or thrombosis) more likely with repeated use. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Hypersensitivity reactions, antibody formation. How supplied: Vials–1 (w. diluent) Pump Spray Kit (20000 IU)–1 (w. diluent) Syringe Spray Kit (20000 IU)–1 (w. diluent) Epistaxis Kit (5000 IU)–1 (w. diluent)

WILATE Octapharma

℞

Coagulation factor complex. Von Willebrand Factor/Factor VIII Complex (human); 450 IU VWF:RCo and 450 IU FVIII activities per 5mL; 900 IU VWF:RCo and 900 IU FVIII activities per 10mL; pwd; for IV injection after reconstitution; preservative-free; solvent-detergent treated. Indications: Bleeding episodes (spontaneous and trauma induced) in patients with severe von Willebrand disease, and patients with mild to moderate von Willebrand disease for whom desmopressin is ineffective or contraindicated. Adults and Children: <5yrs: contact manufacturer. Give by IV injection at 2–4mL/min. ≥5yrs: Minor bleed: 20–40 IU/kg once, then 20–30 IU/kg every 12–24 hours. Major bleed: 40–60 IU/kg once, then 20–40 IU/kg every 12–24 hours. Monitor and adjust according to VWF:RCo and FVIII activity, and location of bleed; usual treatment duration is 3 days (minor hemorrhage) and 5–7 days (major hemorrhage). See literature for activity level goals. Warnings/Precautions: Not for prophylaxis of spontaneous bleeding, prevention of surgical bleeding, or hemophilia A. Treatment should be supervised by physician trained in coagulopathies. Risk of thrombotic events with sustained excessive

FVIII levels; monitor. Ineffectiveness may indicate antibody formation; discontinue if confirmed. Risk of transmission of blood-borne diseases; consider vaccination against hepatitis A and B. Monitor pulse during injection; slow or stop infusion if marked increase in heart rate occurs. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Urticaria, dizziness, hypersensitivity reactions, antibody formation. How supplied: Kit–1 (w. diluent, supplies)

WINRHO SDF

℞

Emergent BioSolutions Rho(D) immune globulin intravenous human 600IU (120mcg), 1500IU (300mcg), 2500IU (500mcg), 5000IU (1000mcg), 15000IU (3000mcg); per vial; lyophilized pwd or soln; for IV or IM inj after reconstitution; preservative-free. Indications: Treatment of non-splenectomized, Rho(D) positive children with acute immune thrombocytopenic purpura (ITP); adults and children with chronic ITP and ITP secondary to HIV infection; in clinical situations requiring an increase in platelet count to prevent excessive hemorrhage. Adults and Children: Give by IV inj only. Confirm Rho(D) positive prior to treatment. Initially: 250 IU/kg as single dose or 2 divided doses on separate days; if Hgb <10g/dL, reduce to 125–200 IU/kg. Maintenance: 125–300 IU/kg; Hbg >10g/dL: 250–300 IU/kg; Hgb 8–10g/dL: 125–200 IU/kg; Hgb <8g/dL: use with caution. Base frequency and dose on clinical response. Contraindications: IgA deficiency. Allergy to blood products. Treatment of immune globulin deficiency syndromes. Warnings/Precautions: Not for use in Rho(D) negative or splenectomized patients; monitor for intravascular hemolysis, anemia, renal insufficiency; hemoglobin <10g/dL decrease dose, if <8g/dL use extreme caution. Pregnancy (Cat.C). Interactions: Do not give live vaccines within 3 months. Adverse reactions: Headache, chills, fever, local or infusion reactions; see literature. Note: Report all infections suspected to be transmitted by WinRho SDF to (800) 423-2090. How supplied: Single-dose vials (pwd) 600IU, 1500IU, 5000IU–1 (w. diluent) Single-dose vials (soln) 600IU, 1500IU, 2500IU, 5000IU, 15000IU–1

XYNTHA Pfizer

℞

Clotting factor. Antihemophilic Factor (recombinant): nominally 250 IU, 500 IU, 1000 IU, or 2000 IU per vial; pwd for IV infusion after reconstitution; plasma/albumin-free; preservative-free; contains polysorbate 80. Actual factor VIII activity noted on each vial. Indications: In Hemophilia A: to control bleeding episodes, and for surgical prophylaxis.

Adults: Individualize and titrate. Give by IV infusion over several minutes. One IU of factor VIII per kg raises the plasma factor VIII activity by about 2 IU/dL. Minor bleeds: factor VIII level required is 20–40 IU/dL or % of normal, repeat infusion every 12–24 hours as needed for at least 1 day, until resolution. Moderate bleeds: 30–60 IU/dL or % of normal; repeat infusion every 12–24 hours for 3–4 days or until hemostasis. Major bleeds: 60–100 IU/dL or % of normal, repeat infusion every 8–24 hours until resolution. Minor surgical procedures: 30–60 IU/dL or % of normal, repeat infusion every 12–24 hours for 3–4 days or until hemostasis. Major surgery: 60–100 IU/dL or % of normal; repeat infusion every 8–24 hours until hemostasis and wound healing occurs. Children: Consult manufacturer (limited pharmacokinetic data available; studies are ongoing). Warnings/Precautions: Monitor for development of Factor VIII inhibitors; may need dose adjustment. Pregnancy (Cat.C). Labor & delivery. Nursing mothers. Adverse reactions: Hypersensitivity reactions/ anaphylaxis, pyrexia, headache, GI upset, asthenia. How supplied: Kit–1 (w. diluent, supplies)

Immune-mediated blood disorders

BAYRHO-D FULL DOSE Bayer ℞ Rho(D) immune globulin human 300mcg; for IM inj; solvent/detergent treated. Indications: Preventing Rho(D) sensitization in nonsensitized Rho(D) negative or Du negative patients to the Rho(D) factor, following pregnancy or accidental transfusion. Adults: Each vial or syringe (approx. 300mcg) prevents sensitization to a volume of up to 15mL of Rh positive red blood cells. Administer IM at 28 weeks of gestation, within 72 hours of an Rh incompatible delivery, miscarriage, abortion, or transfusion accident. Children: Not recommended. ℞ Also: BAYRHO-D MINI-DOSE Rho(D) immune globulin human 50mcg; for IM inj. Indications: Prevention of Rho(D) sensitization following termination of pregnancies up to 12 weeks gestation. Adults: Each syringe (approx. 50mcg) prevents sensitization to 2.5mL of Rh positive red blood cells. Give IM up to 12 weeks’ gestation, within 3 hours of an Rh incompatible delivery, miscarriage, or abortion. Children: Not recommended. Contraindications: Rho(D) positive patients. Pregnancy (Cat.C). Warnings/Precautions: Live vaccines. Have epinephrine available. Adverse reactions: Local reactions. How supplied: Full Dose (single-dose syringes and vials)–1, 10 Mini-Dose (single-dose syringes)–10

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ASSOCIATED HEMATOLOGICAL DISORDERS HYPERRHO S/D FULL DOSE ℞

Grifols Biologicals

Immune globulin. Rho(D) immune globulin human 1500 IU; per syringe; soln for IM inj; preservativefree; latex-free. Indications: Prevention of isoimmunization in non-sensitized Rho(D) negative women during pregnancy and in appropriate obstetrical conditions, unless the fetus or father is known to be Rho(D) negative. Prevention of isoimmunization in Rho(D) negative individuals transfused with Rho(D) positive blood products. Adults: See literature. Give IM only. Pregnancy (28 weeks gestation), postpartum prophylaxis (within 72 hours), obstetric complications, invasive procedures during pregnancy: 1500IU. Incompatible transfusions (within 72 hours): volume of red blood cells transfused divided by 15mL provides the number of syringes to be administered; if the dose is a fraction, round to next higher whole number of syringes. Children: Not recommended. Also: HYPERRHO S/D MINI-DOSE ℞ Rho(D) immune globulin human; 250 IU; per syringe; soln for IM inj.; preservative-free; latexfree. Indications: Prevention of isoimmunization of Rho(D) negative women during spontaneous or induced abortion of ≤12 weeks’ gestation when mother is not sensitized to Rho(D) antigen and father is not known to be Rho(D) negative. Adults: Postabortion or miscarriage of up to 12 weeks gestation: 1 syringe IM within 3hrs of spontaneous or induced abortion or within 72hrs following termination of pregnancy. Children: Not recommended. Contraindications: Neonates. Warnings/Precautions: Contains human plasma; monitor for possible infection transmission. IgA deficiency. Pregnancy (Cat.C). Interactions: Avoid live vaccines within 3 months. Adverse reactions: Local or infusion reactions. Note: Report all infections suspected to be transmitted by HyperRHO S/D to (800) 5202807. How supplied: Full dose (Single-dose prefilled syringe)–1 Mini dose (Single-dose prefilled syringe)–10

RHOGAM Kedrion

℞

Rho(D) immune globulin human 300mcg; for IM inj. Indications: Preventing Rho(D) sensitization in nonsensitized Rho(D) negative or Du negative patients to the Rho(D) factor, following pregnancy or accidental transfusion. Adults: Each vial or syringe (approx. 300mcg) prevents sensitization to a volume of up to 15mL of Rh positive red blood cells. Administer IM at 28 weeks of gestation, within 72 hours of an Rh

incompatible delivery, miscarriage, abortion, or transfusion accident. Children: See literature. Contraindications: Rho(D) positive patients. Warnings/Precautions: Pregnancy (Cat.C). Adverse reactions: Local reactions. How supplied: Single-dose syringes–5, 25

RHOPHYLAC CSL Behring

℞

Rho (D) immune globulin human 1500 IU (300mcg)/2mL; syringe; for IV or IM inj; preservative- and latex-free; contains albumin (human); solvent/detergent treated. Indications: Suppression of Rh isoimmunization in non-sensitized Rho (D) negative women during pregnancy and in appropriate obstetrical conditions, unless the fetus or father is known to be Rho (D) negative. Suppression of Rh isoimmunization in Rho (D) negative individuals transfused with Rho (D) positive blood products. Adults: See full labeling. Pregnancy (28–30 weeks gestation), postpartum prevention (within 72hrs), obstetric complications, invasive procedures during pregnancy: 1500 IU (300mcg). Incompatible transfusions (within 72hrs): 100 IU (20mcg) per 2mL transfused blood or per 1mL erythrocyte concentrate. Children: Not recommended. Contraindications: Rho (D) positive patients. IgA deficiency. Warnings/Precautions: Monitor patients 20 mins after administration. Pregnancy (Cat.C). Interactions: Do not give live vaccines within 3 months. Adverse reactions: Local or infusion reactions, fever, chills, headache; see full labeling. How supplied: Single-dose prefilled syringes–1, 10

WINRHO SDF

℞

sampling, amniocentesis (before 34 weeks gestation), threatened abortion: 1500IU as soon as possible, repeat every 12 weeks during pregnancy. Transfusion: IV route: 3000IU (600micrograms) every 8 hours; or IM route: 6000IU (1200micrograms) every 12 hours; for both: total dose based on exposure (see literature); give within 72 hours. Children: See literature. Do not give to infant for maternal Rh incompatability. Contraindications: Rho(D) positive patients. IgA deficiency. Allergy to blood products. Treatment of immune globulin deficiency syndromes. Warnings/Precautions: Rho(D) negative patients who are Rh immunized. Thrombocytopenia. Pregnancy (Cat.C). Interactions: Do not give live vaccines within 3 months. Adverse reactions: Local or infusion reactions, fever; see literature. Note: Report all infections suspected to be transmitted by WinRho SDF to (800) 423-2090. How supplied: Single-dose vials (pwd) 600IU, 1500IU, 5000IU–1 (w. diluent) Single-dose vials (soln) 600IU, 1500IU, 2500IU, 5000IU, 15000IU–1

White blood cell disorders

GRANIX Teva

℞

Granulocyte colony stimulating factor. Tbofilgrastim 300mcg/0.5mL, 480mcg/0.8mL; soln for SC inj; preservative-free. Indications: To reduce the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. Adults: Administer the 1st dose no earlier than 24hrs following myelosuppressive chemotherapy. Do not administer within 24hrs prior to chemotherapy. Inject 5mcg/kg SC once daily until expected neutrophil nadir is passed and neutrophil count has recovered to normal range. Monitor CBC prior to chemotherapy and twice per week until recovery. Recommended inj sites: the abdomen (except for the 2-inch area around navel), the front of the middle thighs, the upper outer area of the buttocks, or the upper back portion of the upper arms; rotate inj site daily. Avoid injecting into an area that is tender, red, bruised or hard, or that has scars or stretch marks. Children: <18yrs: not established. Warnings/Precautions: Risk of splenic rupture; discontinue and evaluate if symptoms of enlarged spleen or rupture occur. Evaluate for acute respiratory distress syndrome if fever and lung infiltrates or respiratory distress develop after treatment; discontinue if acute respiratory distress syndrome is diagnosed. Permanently

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MASTER DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS discontinue if serious allergic reactions occur. Sickle cell disease: consider potential risks and benefits prior to treatment and discontinue if sickle cell crisis develops. Hepatic or moderateto-severe renal impairment. Pregnancy (Cat.C). Nursing mothers. Interactions: Caution with drugs that may potentiate release of neutrophils (eg, lithium). May cause transient positive changes in boneimaging test results. Adverse reactions: Bone pain; splenic rupture (may be fatal), acute respiratory distress syndrome, serious allergic reactions, sickle cell crisis, potential for tumor growth stimulatory effects on malignant cells. How supplied: Single-use prefilled syringe (0.5mL, 0.8mL)–1, 10 (w. safety needle guard)

LEUKINE Genzyme

℞

Granulocyte-macrophage colony stimulating factor (recombinant). Sargramostim (recombinant human granulocyte-macrophage colony stimulating factor, or rhu GM-CSF) 250mcg; per vial; pwd for SC inj or IV infusion after reconstitution; preservative-free. Indications: To speed neutrophil recovery and reduce infections after induction chemotherapy in treatment of acute myelogenous leukemia (AML) in patients >55 years of age. To mobilize hematopoietic progenitor cells into peripheral blood for collection by leukapheresis. To speed myeloid recovery in non-Hodgkin’s lymphoma, acute lymphoblastic leukemia (ALL), and Hodgkin’s disease in autologous bone marrow transplantation (BMT). To speed myeloid recovery in allogeneic BMT. Patients with BMT failure or engraftment delay. Adults: See literature for timing and duration of dosing, and for repeat courses of therapy. Individualize. Neutrophil recovery: 250mcg/ m2 per day IV over 4 hrs. Mobilization or post peripheral blood progenitor cell transplantation: 250mcg/m2 per day IV over 24 hrs or SC once daily. Myeloid recovery after BMT: 250mcg/m2 per day IV over 2 hrs. BMT failure or engraftment delay: 250mcg/m2 per day IV over 2 hrs for 14 days. Children: See literature. Contraindications: Excessive leukemic myeloid blasts in bone marrow or peripheral blood (≥10%). Allergy to GM-CMF or yeastderived products. Concomitant (within 24 hrs) chemotherapy or radiotherapy. Warnings/Precautions: Fluid retention, pleural or pericardial effusions. Pulmonary infiltrates. Respiratory disease or symptoms. Hypoxia. Reduce infusion rate by ½ if dyspnea

occurs; discontinue if dyspnea worsens. Cardiac disease. CHF. Renal or hepatic dysfunction (monitor before and every other week during therapy). Monitor CBC and differential twice weekly. Reduce dose by ½ or discontinue if absolute neutrophil count exceeds 20,000cells/mm3 or if platelet count exceeds 500,000cells/mm3. Myeloid malignancies. Monitor body weight and hydration. Pregnancy (Cat.C). Nursing mothers. Interactions: Caution with lithium, corticosteroids, others that may enhance myeloproliferative effects. May be antagonized by radiotherapy, myelotoxic drugs. Adverse reactions: Flu-like symptoms, GI disturbances, edema, dyspnea, pharyngitis, rash, joint or bone or chest pain, eye hemorrhage, hypomagnesemia, anxiety, headache, pleural +/or pericardial effusion, arthralgia, myalgia, others. How supplied: Vials–5

NEULASTA Amgen

℞

Granulocyte colony stimulating factor. Pegfilgrastim (polyethylene glycol/filgrastim conjugate) 6mg/0.6mL soln; SC inj; preservativefree. Indications: To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with clinically significant incidence of febrile neutropenia. Adults: Do not give between 14 days before and 24 hours after chemotherapy. Adolescents <45 kg: not recommended. ≥45 kg: 6mg SC once per chemotherapy cycle. Children: Not recommended. Contraindications: Do not use for peripheral blood progenitor cell (PBPC) mobilization. Hypersensitivity to E. coli-derived products. Warnings/Precautions: Monitor CBC and platelets before and during therapy. Monitor for splenomegaly/splenic rupture and for adult respiratory distress syndrome (ARDS); suspend until ARDS resolves if fever or lung infiltrates occur. Sickle cell disease (may cause sickle cell crisis). Myeloid malignancies. Myelodysplasia. Pregnancy (Cat.C). Nursing mothers. Interactions: Caution with drugs that cause delayed myelosuppression (eg, nitrosoureas, mitomycin C), or increase release of neutrophils (eg, lithium), antimetabolites (eg, 5-FU), and radiation therapy. Adverse reactions: Bone pain, anaphylaxis, ARDS; splenic rupture (rare). How supplied: Prefilled syringe–1

NEUPOGEN Amgen

℞

Granulocyte colony stimulating factor. Filgrastim 600mcg/mL prefilled syringe; for SC or IV infusion; preservative-free. ℞ Also: NEUPOGEN VIALS Filgrastim 300mcg/mL; for SC or IV infusion; preservative-free. Indications: See full labeling. To decrease incidence of infection in patients with nonmyeloid malignancies receiving certain myelosuppressive anti-cancer drugs. To reduce time to neutrophil recovery and fever duration after induction and consolidation chemotherapy treatment of adults with AML. To reduce duration of neutropenia and related sequelae in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone-marrow transplantation (BMT). To mobilize hematopoietic progenitor cells (PBPC) into peripheral blood for collection by leukapheresis. To reduce the incidence and duration of neutropenia sequelae in severe chronic neutropenia (SCN). Adults: See full labeling. Do not give for at least 24hrs before or after cytotoxic chemotherapy dose. BMT: Give 1st dose at least 24hrs after bone marrow infusion. SCN: Give on a daily basis. Children: See full labeling. Contraindications: Hypersensitivity to E. coliderived products. Warnings/Precautions: Monitor blood, including CBC and differential and platelets, before and during therapy (myelosuppressive chemotherapy: monitor twice weekly; BMT: at least 3 times weekly; SCN: twice per week during initial 4 weeks of therapy and during 2 weeks after dose adjustment). Discontinue if post nadir absolute neutrophil count (ANC) reaches 10,000/mm3 for patients receiving myelosuppressive chemotherapy; other indications: see full labeling. Monitor for splenomegaly/splenic rupture and for adult respiratory distress syndrome (ARDS); suspend until ARDS resolves if fever or lung infiltrates occur. Confirm diagnosis and do appropriate pretreatment hematological workup in SCN. Preexisting cardiac or hyperplastic skin conditions. Sickle cell disease (may cause sickle cell crisis). Avoid simultaneous chemo- and radiation therapy. Pregnancy (Cat.C). Nursing mothers. Interactions: Caution with mitomycin C, and with concomitant (same day) drugs that decrease platelets, or increase release of neutrophils (eg, lithium), or cause delayed myelosuppression, or with myelosuppressive doses of antimetabolites (eg, nitrosoureas, 5-FU). Adverse reactions: Bone pain, cutaneous vasculitis, splenomegaly, others (see literature). How supplied: Prefilled syringes (0.5mL, 0.8mL)–10; Vials (1mL, 1.6mL)–10

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Take a bite out of G-CSF acquisition costs* GRANIX is another option in short-acting G-CSF therapy TM

» GRANIX demonstrated a 71% reduction in duration of severe neutropenia (DSN) vs placebo1 – GRANIX significantly reduced DSN when compared to placebo (1.1 days vs 3.8 days; p<0.001)1 – Efficacy was evaluated in a multinational, multicenter, randomized, controlled, Phase III study of chemotherapy-naïve patients with high-risk breast cancer receiving doxorubicin (60 mg/m2 IV bolus)/docetaxel (75 mg/m2)1 *Based on wholesale acquisition cost (WAC) of all short-acting G-CSF products as of November 11, 2013. WAC represents published catalogue or list prices and may not represent actual transactional prices. Please contact your supplier for actual prices.

» Safety was evaluated in 3 Phase III clinical trials1

Indication

Important Safety Information (continued)

» GRANIX (tbo-filgrastim) Injection is a leukocyte growth factor indicated for reduction

» Use in patients with sickle cell disease: Severe and sometimes fatal sickle cell crises can occur

in the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

in patients with sickle cell disease receiving hG-CSFs. Consider the potential risks and benefits prior to the administration of GRANIX in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis.

» Potential for tumor growth stimulatory effects on malignant cells: The granulocyte colony-

Important Safety Information » Splenic rupture: Splenic rupture, including fatal cases, can occur following the administration of human granulocyte colony-stimulating factors (hG-CSFs). Discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture in patients who report upper abdominal or shoulder pain after receiving GRANIX.

» Acute respiratory distress syndrome (ARDS): ARDS can occur in patients receiving hG-CSFs. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS.

» Allergic reactions: Serious allergic reactions, including anaphylaxis, can occur in patients receiving hG-CSFs. Reactions can occur on initial exposure. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim.

stimulating factor (G-CSF) receptor, through which GRANIX acts, has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded.

» Most common treatment-emergent adverse reaction: The most common treatment-emergent adverse reaction that occurred in patients treated with GRANIX at the recommended dose with an incidence of at least 1% or greater and two times more frequent than in the placebo group was bone pain. Please see brief summary of Full Prescribing Information on adjacent page. For more information, visit GRANIXhcp.com. Reference: 1. GRANIX TM (tbo-filgrastim) Injection Prescribing Information. North Wales, PA: Teva Pharmaceuticals; 2013.

Take a bite out of G-CSF acquisition costs* GRANIX is another option in short-acting G-CSF therapy TM

» Safety was evaluated in 3 Phase III clinical trials1

Indication

Important Safety Information (continued)

» GRANIX (tbo-filgrastim) Injection is a leukocyte growth factor indicated for reduction

» Use in patients with sickle cell disease: Severe and sometimes fatal sickle cell crises can occur

in the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

» Potential for tumor growth stimulatory effects on malignant cells: The granulocyte colony-

BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR GRANIX™ (tbo-filgrastim) Injection, for subcutaneous use SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE GRANIX is indicated to reduce the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Splenic Rupture Splenic rupture, including fatal cases, can occur following administration of human granulocyte colony-stimulating factors. In patients who report upper abdominal or shoulder pain after receiving GRANIX, discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture. 5.2 Acute Respiratory Distress Syndrome (ARDS) Acute respiratory distress syndrome (ARDS) can occur in patients receiving human granulocyte colony-stimulating factors. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS. 5.3 Allergic Reactions Serious allergic reactions including anaphylaxis can occur in patients receiving human granulocyte colony-stimulating factors. Reactions can occur on initial exposure. The administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine may reduce the severity of the reactions. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim. 5.4 Use in Patients with Sickle Cell Disease Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving human granulocyte colony-stimulating factors. Consider the potential risks and benefits prior to the administration of human granulocyte colony-stimulating factors in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis. 5.5 Potential for Tumor Growth Stimulatory Effects on Malignant Cells The granulocyte colony-stimulating factor (G-CSF) receptor through which GRANIX acts has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded. 6 ADVERSE REACTIONS The following potential serious adverse reactions are discussed in greater detail in other sections of the labeling: • Splenic Rupture [see Warnings and Precautions (5.1)] • Acute Respiratory Distress Syndrome [see Warnings and Precautions (5.2)] • Serious Allergic Reactions [see Warnings and Precautions (5.3)] • Use in Patients with Sickle Cell Disease [see Warnings and Precautions (5.4)] • Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions (5.5)] The most common treatment-emergent adverse reaction that occurred at an incidence of at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group was bone pain. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. GRANIX clinical trials safety data are based upon the results of three randomized clinical trials in patients receiving myeloablative chemotherapy for breast cancer (N=348), lung cancer (N=240) and non-Hodgkin’s lymphoma (N=92). In the breast cancer study, 99% of patients were female, the median age was 50 years, and 86% of patients were Caucasian. In the lung cancer study, 80% of patients were male, the median age was 58 years, and 95% of patients were Caucasian. In the non-Hodgkin’s lymphoma study, 52% of patients were male, the median age was 55 years, and 88% of patients were Caucasian. In all three studies a placebo (Cycle 1 of the breast cancer study only) or a non-US-approved filgrastim product were used as controls. Both GRANIX and the non-US-approved filgrastim product were administered at 5 mcg/kg subcutaneously once daily beginning one day after chemotherapy for at least five days and continued to a maximum of 14 days or until an ANC of ≥10,000 x 106/L after nadir was reached.

Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group. The overall incidence of bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-US-approved filgrastim product). Leukocytosis In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed in less than 1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies. 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of antibody development in patients receiving GRANIX has not been adequately determined. 7 DRUG INTERACTIONS No formal drug interaction studies between GRANIX and other drugs have been performed. Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution. Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies of GRANIX in pregnant women. In an embryofetal developmental study, treatment of pregnant rabbits with tbo-filgrastim resulted in adverse embryofetal findings, including increased spontaneous abortion and fetal malformations at a maternally toxic dose. GRANIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In the embryofetal developmental study, pregnant rabbits were administered subcutaneous doses of tbo-filgrastim during the period of organogenesis at 1, 10 and 100 mcg/kg/day. Increased abortions were evident in rabbits treated with tbo-filgrastim at 100 mcg/kg/day. This dose was maternally toxic as demonstrated by reduced body weight. Other embryofetal findings at this dose level consisted of post-implantation loss‚ decrease in mean live litter size and fetal weight, and fetal malformations such as malformed hindlimbs and cleft palate. The dose of 100 mcg/kg/day corresponds to a systemic exposure (AUC0-24) of approximately 50-90 times the exposures observed in patients treated with the clinical tbo-filgrastim dose of 5 mcg/kg/day. 8.3 Nursing Mothers It is not known whether tbo-filgrastim is secreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GRANIX is administered to a nursing woman. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. 8.4 Pediatric Use The safety and effectiveness of GRANIX in pediatric patients have not been established. 8.5 Geriatric Use Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111 patients were 65 years of age and older. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients. 8.6 Renal Impairment The safety and efficacy of GRANIX have not been studied in patients with moderate or severe renal impairment. No dose adjustment is recommended for patients with mild renal impairment. 8.7 Hepatic Impairment The safety and efficacy of GRANIX have not been studied in patients with hepatic impairment. 10 OVERDOSAGE No case of overdose has been reported. ©2013 Cephalon, Inc., a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved. GRANIX is a trademark of Teva Pharmaceutical Industries Ltd. Manufactured by: Distributed by: Sicor Biotech UAB Teva Pharmaceuticals USA, Inc. Vilnius, Lithuania North Wales, PA 19454 U.S. License No. 1803 Product of Israel GRX-40189 January 2014 This brief summary is based on TBO-003 GRANIX full Prescribing Information.

MASTER DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS Miscellaneous hematological agents

CINRYZE ViroPharma

℞

C1 inhibitor. C1 inhibitor (human) 500 Units/vial; lyophilized pwd for IV infusion after reconstitution; preservative-free. Indications: Routine prophylaxis against angioedema attacks in adolescent and adult patients with hereditary angioedema. Adults: Give by IV infusion at a rate of 1mL/min (10mins). 1000 Units every 3–4 days. Children: Not recommended. Warnings/Precautions: Contains human plasma; monitor for possible infection transmission. Have epinephrine available to treat hypersensitivity reactions. Monitor patients with known risk factors for thrombotic events. Labor & delivery. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Upper respiratory tract infection, sinusitis, rash, headache; thrombotic events, hypersensitivity reactions (may be severe); discontinue if occurs. Note: To report infections that may have been transmitted by Cinryze, call CinryzeSolutions at (877) 945-1000. How supplied: Single-use vial–1

EXJADE Novartis

℞

Iron chelating agent. Deferasirox 125mg, 250mg, 500mg; tabs for oral susp. Indications: Chronic iron overload due to blood transfusions in patients ≥2yrs of age. Chronic iron overload in patients ≥10yrs of age with nontransfusion dependent thalassemia syndromes and with a liver iron concentration (LIC) of at least 5mg Fe per gram of dry weight and a serum ferritin >300 mcg/L. Adults and Children: Calculate dose to nearest whole tab. Take on empty stomach at least 30 mins before food. Do not chew or swallow tabs; disperse completely in water, orange juice or apple juice; drink immediately; resuspend remainder and drink. Transfusional iron overload: <2yrs: not established. ≥2yrs: initially 20mg/kg once daily; may adjust dose by 5 or 10mg/kg every 3–6 months based on serum ferritin levels or response. If inadequate control at 30mg/kg, may consider increasing up to max 40mg/kg. Adjust dose if severe skin rashes occur; consider suspending therapy if serum ferritin <500mcg/L. Non-transfusion dependent thalassemia syndromes: <10yrs: not established. ≥10yrs: 10mg/kg once daily; if baseline LIC>15mg Fe/g dw, consider increasing dose to 20mg/kg after 4 weeks. Suspend therapy if serum ferritin <300mcg/L and obtain LIC to determine whether it has fallen to <3mg Fe/g dw. After 6 months, if LIC remains >7mg Fe/g dw, increase dose to max 20mg/kg/day. If after 6 months, LIC is 3–7mg Fe/g dw, continue with max 10mg/kg/day. When LIC is <3mg Fe/g dw, interrupt treatment and continue to monitor LIC. Restart when LIC rises again to >5mg Fe/g dw. Adjustments based

on serum creatinine: see full labeling. Hepatic impairment: moderate: reduce dose by 50%; severe: avoid. Contraindications: CrCl <40mL/min or serum creatinine >2x age-appropriate ULN. Poor performance status. High risk myelodysplastic syndromes. Advanced malignancies. Platelets <50×109/L. Warnings/Precautions: May cause renal or hepatic failure, GI hemorrhage; may be fatal. Hepatic or renal impairment. Advanced disease or co-morbid conditions. Obtain baseline serum ferritin level, monitor monthly and adjust dose accordingly. Measure serum creatinine and CrCl in duplicate before starting therapy; monitor weekly during 1st month then at least monthly thereafter; more frequently if creatinine levels increase. Monitor for proteinuria monthly. Measure serum transaminases, bilirubin before initiating therapy then every 2 weeks during 1st month, then monthly. Monitor blood counts; interrupt therapy if cytopenias develop. For nontransfusion dependent thalassemia syndromes: obtain LIC by liver biopsy prior to starting therapy, monitor LIC every 6 months. Do baseline auditory and ocular exams, then every 12 months; if disturbances occur, adjust dose or suspend therapy. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Avoid aluminum-containing antacids, bile acid sequestrants (eg, cholestyramine, colesevelam, colestipol), or UGT inducers (eg, rifampicin, phenytoin, phenobarbital, ritonavir); if concomitant administration necessary consider increasing initial Exjade dose by 50% and monitor serum ferritin levels and clinical responses. Caution with drugs that have ulcerogenic or hemorrhagic potential (eg, NSAIDs, corticosteroids, oral bisphosphonates, anticoagulants) or drugs metabolized by CYP3A4 (eg, cyclosporine, simvastatin, hormonal contraceptives). Potentiates repaglinide (consider reducing repaglinide dose); monitor blood glucose levels. Caution with other CYP2C8 substrates (eg, paclitaxel). Avoid concomitant theophylline or other CYP1A2 substrates with narrow therapeutic index. Other concomitant iron chelation therapy: not recommended. Adverse reactions: GI upset, abdominal pain, elevated serum creatinine, rash; renal or hepatic impairment/failure (may be fatal), GI hemorrhage, cytopenias (eg, agranulocytosis, neutropenia, thrombocytopenia, anemia), hypersensitivity reactions, severe skin reactions (eg, Stevens-Johnson syndrome, erythema multiforme); discontinue if occurs. How supplied: Tabs–30

FERRIPROX ApoPharma

℞

Iron chelating agent. Deferiprone 500mg; scored tablets. Indications: Treatment of transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate.

Adults: Individualize. Initially 25mg/kg three times daily (total dose 75mg/kg/day). Max: 33mg/kg three times daily (total dose 99mg/kg/day). Round dose to the nearest 250mg (half-tablet). Adjust dose to individual response and therapeutic goals. Consider temporary dose interruption if serum ferritin falls consistently <500mcg/L. Children: Not recommended. Warnings/Precautions: Not established for use in treating other chronic anemias. Risk of neutropenia or fatal agranulocytosis. Measure ANC before starting therapy and monitor weekly during. Interrupt therapy if infection or neutropenia develops (ANC <1.5×109/L). If neutropenia occurs, obtain CBCs, WBCs, ANC, and platelets daily until recovery (ANC ≥1.5×109/L). History of QT prolongation (eg, those with CHF, bradycardia, diuretic use, cardiac hypertrophy, hypokalemia, hypomagnesemia). Monitor serum ALT monthly; consider interruption if persistent increase in transaminase levels. Monitor serum ferritin every 2–3 months. Monitor plasma zinc, supplement if deficient. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Avoid concomitant use with other drugs associated with neutropenia or agranulocytosis. Allow at least 4-hour interval with antacids or mineral supplements containing polyvalent cations (eg, iron, aluminum, zinc). Concomitant UGT 1A6 inhibitors: closely monitor and may need dose adjustments or interruptions. Adverse reactions: Chromaturia, GI upset, abdominal pain, increased ALT, arthralgia, neutropenia; agranulocytosis, possible Torsades de Pointes. Note: This product is available from Centric Health Resources (CHR). CHR is a specialty pharmacy specializing in orphan drugs and is the sole distributor of Ferriprox in the U.S. For more information, contact Ferriprox Total Care at (866) 758-7071. How supplied: Tabs–100

FIRAZYR Shire

℞

Bradykinin B2 receptor antagonist. Icatibant 10mg/mL; soln for SC inj; preservative-free. Indications: Treatment of acute attacks of hereditary angioedema. Adults: ≥18yrs: 30mg SC in abdominal area; may give additional doses at intervals of at least 6 hours if response inadequate or symptoms recur. Max 3 doses/24hrs. Children: <18yrs: not recommended. Warnings/Precautions: Advise patients to seek medical attention after treating laryngeal attack given the potential for airway obstruction. Elderly. Labor & delivery. Pregnancy (Cat.C). Nursing mothers. Interactions: May attenuate the antihypertensive effect of ACE inhibitors. Adverse reactions: Inj site reactions, pyrexia, transaminase increase, dizziness, rash. How supplied: Single-use prefilled syringe (3mL)–1, 3

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MASTER DRUG MONOGRAPHS

ASSOCIATED HEMATOLOGICAL DISORDERS KALBITOR Dyax

℞

Plasma kallikrein inhibitor. Ecallantide 10mg/mL; soln for SC inj; preservative-free. Indications: Treatment of acute attacks of hereditary angioedema. Adults: Give 30mg SC in three 10mg (1mL) inj into abdomen, thigh, or upper arm. May give additional 30mg within 24hrs if attack persists. Children: <12yrs: not established. Warnings/Precautions: Have medical support available to manage anaphylaxis and hereditary angioedema. Monitor closely for hypersensitivity reactions. Labor & delivery. Pregnancy (Cat.C). Nursing mothers. Adverse reactions: Headache, nausea, diarrhea, pyrexia, inj site reactions, nasopharyngitis, fatigue, upper respiratory tract infection, pruritus, upper abdominal pain; anaphylaxis, antibody formation. How supplied: Single-use vials–3

MOZOBIL Genzyme

℞

Hematopoietic stem cell mobilizer. Plerixafor 20mg/mL; soln for SC inj; preservative-free. Indications: In combination with granulocyte colony stimulating factor (G-CSF): To mobilize hematopoietic stem cells to the peripheral blood for collection and autologous transplantation in patients with non-Hodgkin’s lymphoma or multiple myeloma. Adults: Start after 4 days’ treatment with G-CSF. Give approximately 11hrs before starting apheresis. Repeat up to 4 consecutive days. Base dose on actual body weight. 0.24mg/kg SC; max 40mg/day. Renal impairment (CrCl≤50mL/min): 0.16mg/kg; max 27mg/day. Children: Not established. Warnings/Precautions: Not for use in leukemia. May cause mobilization of tumor

cells. Monitor blood and platelet counts (esp. neutrophils). Monitor for splenic rupture (eg, left upper quadrant/scapular or shoulder pain). Monitor for signs/symptoms of hypersensitivity during and after administration for at least 30mins. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: May be potentiated by drugs that reduce renal function or compete for active tubular secretion. Adverse reactions: Diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, vomiting; anaphylactic shock, hypersensitivity reactions (may be serious), tumor cell mobilization, increased circulating neutrophils, decreased platelet counts, enlarged spleen, vasovagal reaction may occur. How supplied: Single-use vials (1.2mL)–1

TOPICAL STEROID POTENCIES LOW POTENCY • Alclometasone dipropionate 0.05%:

Aclovate (crm, oint) • Fluocinolone acetonide 0.01%: Synalar (soln) • Hydrocortisone base or acetate 1%: Analpram HC 1%1 (crm); Epifoam1 (foam); Pramosone 1%1 (crm, oint, lotion); Proctocort Cream (crm); U-cort (crm) • Hydrocortisone base or acetate 1.85%: Proctocort1 (crm) • Hydrocortisone base or acetate 2%: Pediaderm HC (lotion); Scalacort (lotion) • Hydrocortisone base or acetate 2.5%: Analpram HC 2.5%1 (crm, lotion); Pramosone 2.5%1 (crm, oint, lotion) • Triamcinolone acetonide 0.025%4

INTERMEDIATE POTENCY • Betamethasone dipropionate 0.05%2 • Betamethasone valerate 0.1% • Betamethasone valerate 0.12%:

Luxiq (foam)

• Clocortolone pivalate 0.1%:

Cloderm (crm)

• Desonide 0.05%: Desonate (gel);

DesOwen (lotion, oint); Verdeso (foam)

• Desoximetasone 0.05%: Topicort-LP

(emollient crm) • Fluocinolone acetonide 0.01%: Derma-Smoothe/FS (oil); Capex (shampoo) • Fluocinolone acetonide 0.025%: Synalar (crm, oint) • Flurandrenolide 0.025%: Cordran (crm) • Flurandrenolide 0.05%: Cordran (crm); Cordran (lotion) • Fluticasone propionate 0.005%: Cutivate (oint) • Fluticasone propionate 0.05%: Cutivate (crm, lotion) • Hydrocortisone probutate 0.1%: Pandel (crm) • Hydrocortisone butyrate 0.1%: Locoid (crm, oint, soln); Locoid Lipocream (crm) • Hydrocortisone valerate 0.2% • Mometasone furoate 0.1%: Elocon (crm, lotion, oint) • Prednicarbate 0.1%: Dermatop (emollient crm, oint) • Triamcinolone acetonide 0.05%: Trianex (oint) • Triamcinolone acetonide 0.1%4 • Triamcinolone acetonide 0.2%: Kenalog (aerosol)

HIGH POTENCY • Amcinonide 0.1%5 • Betamethasone dipropionate, augmented

0.05%: Diprolene AF (emollient crm); Diprolene (lotion) • Desoximetasone 0.05%: Topicort (gel) • Desoximetasone 0.25%: Topicort (emollient crm, oint) • Diflorasone diacetate 0.05% • Fluocinonide 0.05% • Halcinonide 0.1%3: Halog (crm, oint, soln) • Triamcinolone acetonide 0.5%2

SUPER HIGH POTENCY • Betamethasone dipropionate, augmented

0.05%: Diprolene (oint, gel)

• Clobetasol propionate 0.05%:

Clobex (lotion, shampoo, spray); Olux (foam); Olux-E (foam); Temovate (crm, gel, oint, scalp application); Temovate-E (emollient crm) • Fluocinonide 0.1%: Vanos (crm) • Flurandrenolide 4mcg/sq cm: Cordran (tape) • Halobetasol propionate 0.05%: Ultravate (crm, oint)

Notes 1 Indicates that the product has more than one active ingredient 2 Also available as a cream generically 3 Also available as an emollient cream generically

4 Also available as a cream or ointment generically 5 Also available as a cream, ointment, or lotion generically

The classification is based on vasoconstrictor assays and clinical studies. Potency varies according to the corticosteroid, its concentration, and the vehicle. In general, corticosteroids in lotions, creams, gels, and ointments are increasingly more potent due to increased absorption from these vehicles. Absorption is increased by prolonged therapy, large areas of skin damage, and the use of occlusive dressings which may cause an increase in the incidence of side effects. (Rev. 4/2014)

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