Cancer Therapy Advisor May/June 2016 Issue

JULY/AUGUST 2017 | VOL 3, ISSUE 6

CancerTherapyAdvisor.com

CancerTherapyAdvisor

A22 FEATURE

Gauging Cancer Treatment Cost-effectiveness

FEATURING Cancer Therapy Regimens and Oncology Drug Monographs from

If value is hard to define because it is perceived differently by different people, how can oncologists and policy-makers accurately gauge cost-effectiveness?

1 Bone Cancer 3 Brain Cancer 5 Breast Cancer 12 Endocrine Cancer

A15 LATEST NEWS

16 Gastrointestinal Cancer

Headlines in oncology research, including gynecologic cancers and precision medicine

22 Genitourinary Cancer 32 Gynecologic Cancer

A21 IN THE CLINIC

Diagnosing Gastric Linitis Plastica: Endoscopic and Radiologic Approaches JULY/AUGUST 2017 | VOL 3, ISSUE 6

A27 EXPERT PERSPECTIVE

Engagement Is Survival: Don S. Dizon, MD, FACP, Reflects on ASCO 2017

A24 FACT SHEET Green Tea and Cancer

35 Head and Neck Cancer

37 Hematologic Cancer 76 Lung Cancer 83 Sarcoma

84 Skin Cancer

Regimen included

Visit CancerTherapyAdvisor.com • Browse oncology news and resources • • Read in-depth articles and clinical commentary authored by experts • • Review full listings of cancer treatment regimens • • Gain easy access to an extensive range of current and concise drug information • • Stay up-to-date by registering to receive our e-newsletters •

A12

FEATURED PRODUCTS

A28 REGIMEN & MONOGRAPH INDEX

Drug Descriptions of Alunbrig and Imfinzi

–92 CANCER THERAPY REGIMENS & 1 DRUG MONOGRAPHS

A14 IN THE PIPELINE The Latest on Oncology Drugs

A15

Highlighted topics () contain both treatment regimens and drug monographs.

LATEST NEWS Headlines in Oncology Research and Practice

1 Bone Cancer

A21 IN THE CLINIC Diagnosing Gastric Linitis Plastica: Endoscopic and Radiologic Approaches C. ANDREW KISTLER, MD, PharmD, RPh

3 Brain Cancer

5 Breast Cancer 12 Endocrine Cancer 16 Gastrointestinal Cancer

A22

FEATURE Is It Possible To Gauge Cancer Treatment Cost-effectiveness?

JONATHAN GOODMAN, MPhil

A24

32 Gynecologic Cancer 35 Head and Neck Cancer

FACT SHEET

Green Tea and Cancer

 37 Hematologic Cancer

76 Lung Cancer

BRYANT FURLOW

A27

22 Genitourinary Cancer

83 Sarcoma

EXPERT PERSPECTIVE

 84 Skin Cancer

Engagement Is Survival: My Take on ASCO 2017

DON S. DIZON, MD, FACP

93 ALPHABETICAL INDEX

Cancer Therapy Advisor (ISSN 2375-558X), July/August 2017, Volume 3, Number 6. Published 6 times annually by Haymarket Media, Inc., 275 7th Avenue, 10th 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.

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CancerTherapyAdvisor.com | JULY/AUGUST 2017 | CANCER THERAPY ADVISOR A1

EDITORIAL & BUSINESS STAFF

EDITORIAL ADVISORY BOARD

Managing Editor, Haymarket Oncology

Barbara Ann Burtness, MD

Lauren Burke

Yale Cancer Center  New Haven, CT

Oncology Editor

Steven J. Cohen, MD

Jonathan Goodman, MPhil

Senior Manager, Drug Information Anissa Lee, RPh

Group Art Director, Medical Communications

Thomas Jefferson University Hospital  Philadelphia, PA

E. David Crawford, MD University of Colorado, Denver  Aurora, CO

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Isabel Cunningham, MD

Assistant Art Director

Columbia University College of Physicians & Surgery  New York, NY

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Production Manager

Don S. Dizon, MD, FACP Massachusetts General Hospital Cancer Center  Boston, MA

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Circulation Manager

Fox Chase Cancer Center  Philadelphia, PA

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A2 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

FEATURED PRODUCT

Alunbrig

Rx

Company: Takeda Pharmaceuticals Pharmacologic class: Kinase inhibitor Active ingredients: Brigatinib 30 mg, 90 mg; tabs.

Indication: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non–small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

Pharmacology: Brigatinib is a tyrosine kinase inhibitor with in vitro activity against multiple kinases including ALK, ROS1, IGF-1R, and FLT-3, as well as EGFR deletion and point mutations.

Clinical trials: The efficacy of brigatinib was seen in ALTA, a 2-arm, open-label, multicenter trial that randomly assigned 222 patients to brigatinib 90 mg once daily or 180 mg once daily (after a 7-day lead-in at 90 mg once daily), or crizotinib. The major efficacy outcome measure was confirmed objective response rate (ORR). Complete trial data: see full labeling.

Adults: Swallow whole. Initially 90 mg once daily for first 7 days; if tolerated, increase to 180 mg once daily until disease progression or unacceptable toxicity. Dose modifications or dose reduction levels: see full labeling.

Children: Not established.

Warnings/Precautions: Monitor for new or worsening respiratory symptoms esp. during first week of initiation; if occurs, withhold and evaluate for ILD/pneumonitis; resume at same dose for grade 1 severity or reduced dose for grade 2 severity; permanently discontinue for grade 3/4 or recurrent

grade 1/2 ILD/pneumonitis. Monitor blood pressure (BP) after 2 weeks and at least monthly thereafter; withhold for grade 3 hypertension despite optimal antihypertensive therapy; resume at reduced dose upon improvement to grade 1 severity; consider permanent discontinuation for grade 4 or recurrent grade 3 hypertension.

Monitor heart rate and BP regularly; if symptomatic bradycardia occurs, withhold and evaluate any concomitant drugs that are known to cause bradycardia; resume at same or reduced dose after resolution; discontinue for life-threatening bradycardia if no contributing concomitant medication identified. Withhold and evaluate for new or worsening visual symptoms of grade or worse 2 severity; resume at reduced doses upon recovery to grade 1 or baseline; permanently discontinue for grade 4 visual disturbances.

Monitor CPK, lipase, and amylase levels during treatment; withhold for grade 3/4 elevation; resume at same or reduced dose upon recovery to grade 1 or baseline.

Assess fasting serum glucose prior to initiation and periodically thereafter; if not adequately controlled with optimal antihyperglycemics, withhold then consider dose reduction, or permanently discontinue based on severity.

Embryo-fetal toxicity. Pregnancy: avoid. Females of reproductive potential

A12 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

should use effective non-hormonal contraception during therapy and for at least 4 months after final dose; males should use effective contraception during therapy and for at least 3 months after final dose. Nursing mothers: not recommended (during and for 1 week after final dose).

Interactions: Avoid concomitant strong CYP3A inhibitors (eg, boceprevir, cobicistat, indinavir, lopinavir, nelfi navir, ritonavir, saquinavir, clarithromycin, itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan); if unavoidable, reduce Alunbrig dose by about 50%.

Avoid grapefruit or grapefruit juice. Avoid concomitant strong CYP3A inducers (eg, rifampin, carbamazepine, phenytoin, St John’s wort). May reduce efficacy of CYP3A substrates (eg, hormonal contraceptives). Caution with antihypertensives that cause bradycardia.

Adverse reactions: Nausea, diarrhea, fatigue, cough, headache; ILD/pneumonitis, hypertension, bradycardia, visual disturbances, CPK elevation, pancreatic enzyme elevation, hyperglycemia.

How supplied: Tabs 30 mg—21, 180; 90 mg—7, 30 For more information call (844) 217-6468 or visit www.Alunbrig.com.

FEATURED PRODUCT

Imfinzi

Rx

Company: AstraZeneca Pharmacologic class: Programmed death-ligand 1 (PD-L1) blocking antibody Active ingredients: Durvalumab 50 mg/mL; soln for IV infusion after dilution; preservative-free.

Indication: Locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or after platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

Pharmacology: Durvalumab is a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of PD-L1 with PD-1 and CD80 (B7.1). Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody-dependent cell-mediated cytotoxicity.

Clinical trials: The efficacy of durvalumab was evaluated in Study 1, the urothelial cancer cohort of a multicenter, multi-cohort, open-label clinical study. Patients (182) had started durvalumab at least 13 weeks prior to the data cut-off date.

All patients received durvalumab 10 mg/kg IV infusion every 2 weeks for up to 12 months or until unacceptable toxicity or disease progression. The major efficacy outcome measures were objective response rate (ORR) according to RECIST v1.1 and duration of response (DOR). Tumor assessments were performed at weeks 6, 12, 16, then every 8 weeks for the first year and every 12 weeks thereafter. The median follow-up time was 5.6 months.

Results showed an ORR of 17% (95% CI: 11.9–23.3) with complete response seen in 5 patients and partial response seen in 26 patients. Of the total

responders, 45% had ongoing responses of 6 months or longer and 16% had responses of 12 months or longer.

The DOR was not reached at the time (range 0.9+ to 19.9+ months).

Adults: Give as IV infusion over 60 mins. 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity.

Children: Not established.

Warnings/Precautions: Permanently discontinue if grade 3/4 pneumonitis, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >8 × ULN or total bilirubin >5 × ULN, concurrent AST or ALT >3 × ULN and total bilirubin >2 ×ULN (with no other cause), grade 3/4 colitis or diarrhea, creatinine ≥3 × ULN, grade 3/4 infusion-related reactions, or grade 4 rash/dermatitis.

Withhold for grade 2 pneumonitis, AST or ALT >3–5 × ULN or total bilirubin >1.5–3 × ULN, AST or ALT ≤8 × ULN or total bilirubin ≤5 × ULN, grade 2 colitis or diarrhea, grade 2 or worse hypophysitis/hypopituitarism, grade 2 or worse adrenal insufficiency, grade 2 or worse hyperthyroidism, grade 2 or worse type 1 diabetes, creatinine >1.5–3 × ULN, grade 3/4 infection, grade 2 (if past 1 week) or

grade 3 rash. Monitor for immune-related pneumonitis, hepatitis (obtain LFTs each cycle), colitis/diarrhea, endocrinopathies (thyroid disorders, adrenal insufficiency, diabetes, hypophysitis/hypopituitarism), rash, thrombocytopenia purpura, nephritis; see full labeling for adverse reaction management details. Monitor for signs/ symptoms of infection and treat with anti-infectives for suspected or confirmed infections. Interrupt or slow the infusion rate in patients with mild or moderate infusion reactions. Embryo-fetal toxicity. Pregnancy. Females of reproductive potential should use effective contraception during therapy and for at least 3 months after final dose. Nursing mothers: not recommended (during and for at least 3 months after final dose).

Adverse reactions: Fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, urinary tract infection; other immunerelated reactions (eg, aseptic meningitis, hemolytic anemia), infusion-related reactions, lab abnormalities.

How supplied: Single-dose vial (2.4 mL, 10 mL)—1 For more information call (800) 236-9933 or visit www.Imfinzi.com.

CancerTherapyAdvisor.com | JULY/AUGUST 2017 | CANCER THERAPY ADVISOR A13

IN THE PIPELINE Burtomab Granted Breakthrough Therapy Designation for Metastatic Neuroblastoma

29% at over 60 months. The mean survival of patients who did not receive burtomab was 8.6 months.

The US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to burtomab for the treatment of patients with relapsed/refractory metastatic neuroblastoma.

“Currently, there are no approved drugs to treat this type of advanced neuroblastoma,” Nai-Kong Cheung, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, and creator of burtomab, said in a press release.

Burtomab is a radio-iodinated (iodine-131) murine monoclonal antibody that targets the immunomodulatory glycoprotein, B7-H3.

This glycoprotein is expressed on the cell membrane primarily by solid tumors, with limited expression by normal tissues.

A phase 1 study presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated substantially prolonged overall survival (OS) with burtomab compared with historic controls among patients with neuroblastoma with central nervous system metastasis.

The study enrolled 105 patients with neuroblastoma, of whom 80 received treatment with burtomab in addition to standard intraventricular compartmental chemotherapy with irinotecan, temozolomide, and carboplatin.

The remaining 25 patients were not eligible for burtomab.

Radiologic improvement after burtomab treatment occurred among 36% of patients with measurable disease.

The median duration of response was 49 weeks (range, 2.6–586 weeks).

The median OS was 58 months; 45% of patients were alive at 36 months and

FDA Approves Subcutaneous Rituximab and Hyaluronidase Human for Blood Cancers

For more information visit www.roche.com.

The US Food and Drug Administration (FDA) granted approval to rituximab and hyaluronidase human as a subcutaneous injection for the treatment of follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), and diffuse large B cell lymphoma (DLBCL) in adult patients.

The newly approved treatment is a combination product of rituximab, a humanized chimeric anti-CD20 monoclonal antibody, and hyaluronidase human, a dispersion agent that allows for increased absorption of subcutaneously administered medication.

The subcutaneous formulation shortens the time of administration from several hours of intravenous (IV) infusion to 5 to 7 minutes.

Patients who are candidates for this drug combination should begin treatment only after receiving at least 1 complete dose of IV rituximab. Multiple randomized clinical studies established comparable safety and clinical efficacy, as well as non-inferior concentration levels after subcutaneous administration compared with IV rituximab.

The most common adverse events (AE) observed with subcutaneous administration varied based on the drug’s indication.

The most common AEs in FL were infection, neutropenia, nausea, constipation, cough, and fatigue. The most common AEs in DLBCL were

The phase 3 CASCADE trial evaluating vadastuximab talirine (SGNCD33A) plus chemotherapy among patients with acute myeloid leukemia (AML) was discontinued by Seattle Genetics due to a higher rate of deaths compared with chemotherapy alone.

Vadastuximab talirine is targeted to CD33, which is expressed on most AML and myelodysplastic syndrome (MDS) blast cells.

The CASCADE trial (ClinicalTrials. gov Identifier: NCT02785900) is a randomized, double-blind study that treated older patients with AML with azacitidine or decitabine compared with plus vadastuximab talirine plus or placebo.

Seattle Genetics decided to halt the study following review of unblinded data on June 16, 2017.

The data showed a higher rate of death, including fatal infections, in the vadastuximab talirine arm compared with the chemotherapy-only arm.

Hepatotoxicity, however, was not associated with the deaths.

Patient enrollment and treatment in all vadastuximab talirine clinical trials were suspended.

The data will be reviewed in consult with the US Food and Drug Administration to determine next steps.

For more information visit www.ymabs.com.

A14 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

infection, neutropenia, alopecia, nausea, and anemia. The most common AEs in CLL were infection, n ­ eutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema.

Phase 3 Vadastuximab Talirine Trials Halted Due to Deaths

For more information visit www.seattle genetics.com.

LATEST NEWS

Talimogene laherparepvec plus ipilimumab improves the overall response rate (ORR) over ipilimumab alone among patients with unresected, advanced melanoma, according to a study presented at the 2017 American Society of Clinical Oncology (ASCO) meeting in Chicago, Illinois.

Talimogene laherparepvec, an engineered oncolytic virus, is designed to replicate within tumors and to stimulate antitumor activity through granulocyte-macrophage colony-stimulating factor (GM-CSF) production.

For this phase 2, randomized trial (ClinicalTrials.gov Identifier: NCT01740297), researchers evaluated whether combining talimogene laherparepvec with ipilimumab, a CTLA-4 inhibitor, would improve outcomes among patients with melanoma over ipilimumab alone.

Of 198 included patients, 98 were assigned to the experimental arm (talimogene laherparepvec plus ipilimumab) and 100 were assigned to the control arm (ipilimumab only).

Characteristics were similar between the 2 groups.

ORR, the primary endpoint, was 38.8% in the experimental arm and 18% for the control, including 13 complete responses in the former and 7 in the latter.

At the time the study was presented, 89% and 83% of responders in the experimental and control arms, respectively, remained in response.

Twenty-eight percent of patients in the experimental arm had grade 3 or worse treatment-related adverse events (AEs); this was true of 18% of patients in the control arm.

The authors concluded that the study met its primary endpoint and that the combination’s toxicity was tolerable and had no unexpected AEs.

Favorable 4-year Outcomes for Patients With Myeloma Treated With Elotuzumab Four-year follow-up data of the ELOQUENT-2 trial (ClinicalTrials.gov: NCT01239797) demonstrated that elotuzumab plus lenalidomide/dexamethasone (ELd) has ongoing efficacy among patients with relapsed/refractory multiple myeloma, according to a press release.

The data showed that patients receiving the combination maintained a reduction of risk of disease progression or

death of 29% (hazard ratio [HR], 0.71; 95% CI, 0.59-0.86).

ELd therapy continued to show clinical benefit and a sustained relative improvement of 50% in progression-free survival (PFS) of 21% vs 14% for patients who received lenalidomide/dexamethasone (Ld) alone.

Patients treated with ELd had a doubled median PFS compared with Ld alone (15.2 vs 7.4 months, respectively).

Patients who received ELd had an overall response rate of 79% compared with 66% of patients who received Ld. An overall survival benefit was observed in patients receiving ELd of 48 months vs 40 months with Ld. The rates of adverse effects (AE) remained consistent with findings reported at previous follow-ups. The most commonly reported AEs included diarrhea, fatigue, anemia, pyrexia, constipation, neutropenia, cough, back pain, and muscle spasms.

MRI Imaging in Adjunct With Mammograms Improves Secondary Breast Cancer Detection Younger women (50 years and under) who have undergone breast conservation therapy (BCT) may benefit from an MRI in addition to annual mammogram screenings, according to a study published in JAMA Oncology.

Patients who have undergone BCT are at increased risk for recurrence, and early detection of second breast cancers improves the relative survival of patients.

Study authors wanted to confirm that a combination of imaging techniques would lead to better detection than mammography alone.

The multicenter, prospective, nonrandomized study (ClinicalTrials.gov Identifier: NCT01257152) enrolled 754 women age 50 and younger at initial diagnosis who had undergone BCT. Patients had MRI, ultrasonography, and mammography screenings of the conserved and contralateral breasts annually over 3 years.

A total of 2065 mammograms, ultrasonography, and MRI screenings were performed on study patients. Seventeen cancers were detected, and 76% of diagnosed cancers were early stage (0 or 1).

MRI with mammography had an overall higher sensitivity (100% vs 53%; P = .01) and detection rate (8.2 vs 4.4 per 1000; P = .003) than mammography alone.

Cancer detection rates in ultrasonography in addition to mammography (6.8 vs 4.4 per 1000; P = .03) were higher than that by mammography alone.

CancerTherapyAdvisor.com | JULY/AUGUST 2017 | CANCER THERAPY ADVISOR A15

Š ZORANM / GETTY IMAGES

Talimogene Laherparepvec Plus Ipilimumab Promising for Advanced Melanoma

LATEST NEWS

Patients With Hepatocellular Carcinoma May Benefit From TACE Plus Axitinib Patients with inoperable hepatocellular carcinoma (HCC) may benefit from a combination of transarterial chemoembolization (TACE) and axitinib, according to a study published in Cancer.

While TACE is a standard of care for patients with inoperable HCC, a post-treatment consequence leading to poor clinical outcomes is the upregulation of angiogenic mediators, particularly vascular endothelial growth factors (VEGFs).

The purpose of this study was to determine if adding axitinib, a selective inhibitor of VEGF receptors 1, 2, and 3, to TACE would blunt the VEGF surge and lead to better outcomes.

This single arm, open-label phase 2 study (ClinicalTrials.gov Identifier: NCT01352728) enrolled 50 patients with inoperable HCC who were potential TACE candidates. Patients were given axitinib 5 mg twice daily and were evaluated every 8 weeks for the need for TACE. Axitinib was stopped 24 hours before and after TACE, then resumed. The primary endpoint was 2-year overall survival (OS).

Combining axitinib and TACE resulted in a 2-year OS rate of 43.7%, with a median OS of 18.8 months, which failed to meet the primary endpoint of 2-year OS of 50%.

Hypertension was observed in 24% of patients and was determined to have prognostic value.

Other commonly observed adverse effects (AEs) included hyperbilirubinemia, increase in transaminases, and abdominal pain, which were most likely caused by TACE. Axitinib-related AEs included hand-food skin reactions and hypertension.

The study authors concluded that the combination of axitinib and TACE is safe and potentially efficacious for patients with inoperable HCC. Hypertension was associated with a better OS during treatment.

First-line Nivolumab Fails To Prolong Survival in Stage IV NSCLC Nivolumab failed to provide an additional survival benefit compared with chemotherapy among patients with previously untreated or recurrent stage IV non–small cell lung cancer (NSCLC), according to results from the CheckMate 026 trial published in the New England Journal of Medicine.

Nivolumab is already approved for the second-line treatment of metastatic NSCLC and is associated with prolonged overall survival (OS) among this population. The CheckMate 026 trial (ClinicalTrials.gov Identifier: NCT02041533) evaluated nivolumab in the first-line setting.

The open-label, phase 3 trial randomly assigned 530 patients with previously untreated or recurrent stage IV NSCLC with at least 1% PD-L1 tumor expression to receive nivolumab or platinum-based chemotherapy. Crossover to the nivolumab arm was allowed for patients who progressed during chemotherapy.

The median age at baseline was 64 and 11% of patients were age 75 or older. The disease stage was IV among 92% of patients and recurrent among 8%, and 24% and 76% of patients had squamous or nonsquamous cell histology, respectively.

The majority of patients were former smokers (68%), followed by current smokers (20%) and never smokers (11%). PD-L1 tumor expression was at least 5% among 77% and 50% or higher among 40% of patients.

The response rate was 26% with nivolumab and 33% with chemotherapy among patients with at least 5% PD-L1 tumor expression.

There was no significant difference in progression-free survival (PFS) between arms among patients with at least 5% PD-L1 tumor expression, which was the primary endpoint (hazard ratio [HR], 1.15; 95% CI, 0.91-1.45; P = .25).

The median PFS was 4.2 months (95% CI, 3.0-5.6 months) with nivolumab compared with 5.9 months (95% CI, 5.4-6.9 months) with chemotherapy.

The median OS was also similar between groups, at 14.4 months (95% CI, 11.7-17.4 months) with nivolumab compared with 13.2 months (95% CI, 10.7-17.1) with chemotherapy (HR for death, 1.02; 95% CI, 0.80-1.30).

These data were similar among all patients who were randomly assigned, which included those with PD-L1 tumor expression of at least 1%.

Discontinuation of therapy due to AEs occurred among 10% of patients in the nivolumab arm compared with 13% in the chemotherapy arm.

A16 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

Š SCIENCE PHOTO LIBRARY - STEVE GSCHMEISSNER / GETTY IMAGES

The specificity of mammography with MRI or ultrasonography (87% or 88% vs 96%; P < .001) was lower than that of mammography alone.

The results of the study indicate that MRI imaging in addition to mammogram screening improves the detection rate of early-stage breast cancers at acceptable specificity.

The authors concluded by adding that the results can also help to develop personalized screening guidelines for patients who are at increased risk of breast cancer.

GYNECOLOGIC CANCERS

The US Food and Drug Administration (FDA) granted regular approval to pembrolizumab for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Also granted was accelerated approval for first-line use of pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma ineligible for cisplatin-containing chemotherapy.

The approval for the second-line indication was based on results from the phase 3, open-label KEYNOTE 045 trial (ClinicalTrials. gov Identifier: NCT02256436). The study randomly assigned 542 patients to pembrolizumab 200 mg or investigator’s choice of paclitaxel, docetaxel, or vinflunine every 3 weeks.

Median overall survival was 10.3 months in the pembrolizumab arm vs 7.4 months in the chemotherapy arm. Data from a planned survival analysis presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting confirm these findings; at a median follow-up of 18.5 months, the overall survival remained at 10.3 vs 7.4 months, respectively.

The objective response rate, a secondary endpoint, was 21% for pembrolizumab and 11% for chemotherapy (P = .002). No significant difference in progression-free survival between the 2 arms was observed.

Accelerated approval for the first-line indication was based on data from the single-arm, open-label KEYNOTE-052 trial (ClinicalTrials.gov Identifier: NCT02335424) in 370 patients treated with pembrolizumab 200 mg every 3 weeks.

At a median follow-up of 7.8 months, the objective response rate was 28.6% and the median response duration was not reached (range, 1.4+, 17.8+ months).

According to the FDA, “an additional trial is required to confirm clinical benefit of pembrolizumab for the first-line indication.”

Durvalumab Plus Olaparib or Cediranib Active and Tolerable in Female Cancers Durvalumab plus olaparib or intermittent cediranib is clinically active and tolerable in treating female cancers, according to results from a phase 1 study published in the Journal of Clinical Oncology.

Olaparib is a poly ADP ribose polymerase (PARP) inhibitor and cediranib is a VEGFR 1-3 inhibitor.

“We hypothesized that increased DNA damage by PARP inhibitor and/or reduced VEGF signaling by the VEGFR inhibitor may complement the antitumor activity of immune checkpoint inhibition,” wrote the authors.

This dose-escalation, phase 1 study evaluated the pharmacokinetics, antitumor activity, and safety of durvalumab plus olaparib or cediranib.

The study treated 26 women with recurrent or metastatic solid malignancies who had not received prior immune checkpoint inhibitor therapy. Cancer types included ovarian, triple-negative breast, cervical, and uterine.

All patients received durvalumab 10 mg/kg every 2 weeks or 1500 mg every 4 weeks. Olaparib was administered as 200 or 300 mg twice daily, and cediranib was administered as 20 or 30 mg once daily or 20 mg for 5 days then 2 days off.

The recommended phase 2 dosing was 1500 mg every 4 weeks of durvalumab plus 300 mg twice daily of olaparib or 20 mg of intermittent cediranib. There were no dose-limiting toxicities associated with durvalumab plus olaparib.

Treatment-emergent adverse events were hypertension, diarrhea, pulmonary embolism, pulmonary hypertension, and lymphopenia.

Durvalumab plus olaparib resulted in an objective response rate (ORR) of 17% and a disease control rate of 83%. There were 2 partial responses that lasted at least 11 months, and 8 patients achieved stable disease for at least 4 months.

The ORR was 50% and the disease control rate was 75% with durvalumab plus cediranib, with 6 partial responses of at least 5 months and 3 achieved stable disease for at least 4 months.

PD-L1 expression levels did not influence response.

According to the authors, these findings warrant additional studies. Single-arm, phase 2 expansion trials are ongoing.

Endometrial Cancer: Some Durable Responses to Pembrolizumab A subset of patients with advanced endometrial cancer experienced durable response to pembrolizumab, according to a study published in the Journal of Clinical Oncology.

KEYNOTE-028 (ClinicalTrials.gov Identifier: NCT02054806) is a phase 1b basket trial evaluating pembrolizumab in various solid tumor types. This analysis is of the advanced endometrial cancer cohort.

The cohort enrolled 24 patients with PD-L1–positive, relapsed/refractory, locally advanced or metastatic

CancerTherapyAdvisor.com | JULY/AUGUST 2017 | CANCER THERAPY ADVISOR A17

© RAYCAT / GETTY IMAGES

FDA Approves Pembrolizumab for Advanced or Metastatic Urothelial Carcinoma

| LATEST NEWS

LATEST NEWS | GYNECOLOGIC CANCERS

Promising Activity Reported for Nivolumab in Gynecologic Cancers Nivolumab, a PD-1 inhibitor, showed promising clinical activity in recurrent or metastatic cervical cancers and provides a promising new approach to treatment, according to data from the CheckMate 358 trial (Clinicaltrials.gov Identifier: NCT02488759) reported at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

After first-line therapy, options are limited for women with gynecologic tumors (cervical, vaginal, and vulvar). The expression of PD-1 and its ligand PD-L1 in these tumors provided a rationale for testing nivolumab in this setting.

CheckMate 358 is an ongoing study evaluating the efficacy of nivolumab alone or in combination across 5 virusassociated cancers.

Antoine Hollebecque, MD, of the Gustave Roussy Cancer Institute in Villejuif, France, presented data for the cohort of 24 patients — 19 patients had cervical cancer and 5 had vaginal or vulvar cancers. Patients received nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity.

At a median follow-up of 31 weeks, for the primary endpoint, the objective response rate (ORR) was 20.8% of patients (1/24 showed a complete response [CR]; 4/24 showed a partial response [PR]). The disease control rate (DCR) was 70.8%.

The ORR for cervical cancer was 26.3%, and the DCR was 80%. Responses were seen in patients who had not received prior systemic therapy (28.6%) as well as 1 or more prior systemic therapies (17.6%).

Responses were not dependent on PD-L1 expression or on HPV status, which is associated with at least 90% of all cervical cancers. Median overall survival was not reached.

Treatment-related adverse events of any grade were reported for 70.8% of patients, and grade 3 to 4 events were seen in 12.5% of patients.

Cervical Cancer Progression More Likely With HIV Infection Women with HIV are more likely to experience progressive cervical changes, according to a study published in Cancer Epidemiology, Biomarkers & Prevention.

The study evaluated 1320 women from Senegal, West Africa, between 1994 and 2010. Cytology by Pap test and HPV DNA testing were conducted at approximately 4-month intervals.

The median age at baseline was 35 and 47% of patients were HIV-positive. The baseline cervical natural history stage was normal in 36.1%, HPV-positive in 58.5%, and high-grade squamous intraepithelial lesions (HSIL) were present in 5.4%.

Women who were HIV-positive had a higher risk of cervical adverse transition compared with patients who were HIVnegative, including from HPV to HSIL (HR, 2.55; 95% CI, 1.69-3.86; P < .0001).

Adverse transition was associated with HPV-16/18 and a CD4-positive count lower than 200/mm3.

Infection with HIV-1 was associated with a greater incidence rate of HPV detection and cervical progression from HPV to HSIL compared with HIV-2 infection, with and without adjustment for age and CD4-positive count.

According to the authors, these results can “be used to inform the eventual implementation of comprehensive population-based screening paradigms that are not yet widely available in the limited resource setting of sub-Saharan Africa.”

A18 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

© FSTOP123 / GETTY IMAGES

endometrial cancer to receive 10 mg/kg of pembrolizumab every 2 weeks for up to 24 months or until progression or unacceptable toxicity.

The baseline median age was 67, and 70.8% of patients were Caucasian. The majority of patients had endometroid adenocarcinoma (70.8%), followed by adenocarcinoma other (12.5%), high-grade serous carcinoma (8.3%), and carcinosarcoma (4.2%).

The objective response rate was 13% (95% CI, 2.8-33.6), all of which were partial responses experienced by patients with endometroid adenocarcinoma. The median time to partial response was 8.1 weeks, and the duration of response was at least 64 weeks.

Stable disease was achieved by 13% of patients, with a median duration of 24.6 weeks. There were no complete responses.

The median progression-free survival was 1.8 months (95% CI, 1.6-2.7 months), and median overall survival was not reached.

Treatment-related adverse events (TRAEs) occurred in 54.2% of patients during the 76.2 weeks of median follow-up. The most frequent were fatigue, pruritus, pyrexia, and decreased appetite.

Grade 3 TRAEs occurred in 16.7% and included asthenia and back pain; anemia, hyperglycemia, and hyponatremia; chills and pyrexia; diarrhea. There were no grade 4 or 5 events, and no immune-related adverse events were reported.

According to the authors, the 13% response rate is comparable to that of chemotherapy for this disease.

PRECISION MEDICINE

Adding midostaurin — a multi-targeted kinase inhibitor — to chemotherapy prolongs overall survival (OS) among patients with newly diagnosed acute myeloid leukemia (AML) and an FLT3 mutation, according to a study published in the New England Journal of Medicine.

FLT3 mutations are associated with poor outcomes among patients with AML. The purpose of this trial was to determine if midostaurin plus chemotherapy can improve outcomes.

The multicenter, double-blind, phase 3 RATIFY trial (ClinicalTrials.gov Identifier: NCT00651261) randomly assigned 717 patients aged 18 to 59 with newly diagnosed AML with an FTL3 mutation to receive chemotherapy plus midostaurin or placebo.

The chemotherapy regimen included induction with daunorubicin and cytarabine, and consolidation with high-dose cytarabine. Patients who achieved complete remission after consolidation therapy received maintenance therapy with midostaurin or placebo.

The median age at baseline was 47.9, 68.6% of patients had normal risk disease, and 19% had intermediate II risk disease according to the Modified European LeukemiaNet classification. FLT3 mutations were located within the tyrosine kinase domain (TKD) in 22.6% of patients, or was an internal tandem duplication with low or high allelic ratio in 47.6% and 29.8%, respectively.

The addition of midostaurin significantly prolonged median OS at 74.7 months (95% CI, 31.5-not reached) compared with 25.6 months (95% CI, 18.6-42.9) with placebo (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96; one-sided P = .009), resulting in 4-year OS rates of 51.4% and 44.3%, respectively.

Event-free survival was also significantly longer, at 8.2 months (95% CI, 5.4-10.7) with midostaurin compared with 3.0 months (95% CI, 1.9-5.9) with placebo (HR, 0.78; 95% CI, 0.66-0.93; one-sided P = .002). The midostaurin and placebo arms demonstrated 4-year EFS rates of 28.2% and 20.6%, respectively.

There was, however, no significant difference in the proportion of patients who achieved complete remission between the midostaurin and placebo groups (59% vs 54%; P = .15).

During the trial, 57% of patients underwent allogeneic transplantation. Benefit with midostaurin “was observed

among those who underwent transplantation during first remission, but not among those who underwent transplantation at a later time,” the authors wrote.

Adverse events that occurred more frequently with midostaurin compared with placebo were anemia and rash or desquamation.

According to the authors, the results of this study suggest that midostaurin improved outcomes “among younger adults with AML and a FLT3 mutation, a population with a poor prognosis that represents about one-fourth of all patients with AML.”

Response-based Therapy Intensification Improves Survival in Adult ALL Early response–based treatment intensification with allogeneic stem cell transplant (allo-SCT) improved outcomes, including overall survival (OS) among adult patients with early thymic precursor (ETP) T cell acute lymphoblastic leukemia (ALL), according to a study published in the Journal of Clinical Oncology.

Chemotherapy resistance is a negative prognostic indicator among children with ETP-ALL, but can be abrogated by using early response–based treatment intensification strategies.

This study aimed to determine if the same strategy could improve outcomes among adults with this disease.

This retrospective analysis evaluated clinicobiologic, genetic, and survival data from a cohort of 213 adult patients with T-ALL treated in the phase 2 and 3 GRAALL-2003 and -2005 studies (ClinicalTrials.gov Identifiers: NCT00222027, NCT00327678).

In these studies, patients underwent therapy intensification with allo-SCT if early treatment resistance occurred.

Immunophenotypic analysis identified that 22.1% of patients had ETP-ALL, which showed a distinct gene expression signature compared with non-ETP T-ALL. Patients with ETP were more likely to be female and of older age and to have lower white blood cell counts at diagnosis.

ETP was also associated with higher rates of MLLT10 translocation and lower rates of TLX1 rearrangement. The mutational frequency was also higher among patients with ETP (89.2% of patients) compared with non-ETP T-ALL (63.7% of patients).

Early bone marrow chemotherapy resistance occurred in 87% of patients with ETP, but those treated by the GRAALL protocol of early treatment intensification with allo-SCT had a similar OS as patients with non-ETP T-ALL. The GRAALL protocol resulted in 5-year OS rates of 59.6% (95% CI, 44.2-72.0%) in ETP compared with 66.5% (95%

CancerTherapyAdvisor.com | JULY/AUGUST 2017 | CANCER THERAPY ADVISOR A19

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Midostaurin Plus Chemotherapy Prolongs Survival in AML With FTL3 Mutation

| LATEST NEWS

LATEST NEWS | PRECISION MEDICINE

PD-L2 Expression May Be Associated With Response to Pembrolizumab in HNSCC PD-L2 is associated with progression-free survival (PFS) among patients with head and neck squamous cell carcinoma (HNSCC) treated with pembrolizumab and could be another immune checkpoint target, according to a study published in Clinical Cancer Research.

The study evaluated the expression of PD-L2 of archival samples from 7 different tumor types by immunohistochemistry using a novel anti-PD-L2 antibody. A pathologist scored the resulting staining. The cellular distribution of PD-L2 was assessed by in situ hybridization.

PD-L2 was expressed by all 7 tumor types by stromal, tumor, and endothelial cells. PD-L1 staining was associated with PD-L2 staining (P = .0012 to < .0001), but PD-L2 was also expressed by tumors without PD-L1 expression.

The study also evaluated 172 tumor samples from the KEYNOTE-12 trial (ClinicalTrials.gov Identifier: NCT01848834) of patients with HNSCC positive or unselected for PD-L1 expression for PD-L2 expression levels.

Positive expression was defined as at least 1% of cells stained.

Clinical response to pembrolizumab was significantly associated with PD-L1 and PD-L2 expression. Patients negative for PD-L1 expression demonstrated a 5% (95% CI, 0.1-24.9%) response rate compared with 23% (95% CI, 16-31.4%) and 26.6% (95% CI, 18-36.7%) for patients who expressed PD-L1 or PD-L2, respectively.

Expression of both PD-L1 and PD-L2 increased the response to 27.5% (95% CI, 18.6-37.8) compared with either ligand expressed alone, at 11.4% (95% CI, 3.2-26.7) for PD-L1-positive/PD-L2-negative and 0% (95% CI, 0-70.8%) for PD-L1-negative/PD-L2-negative.

PD-L2 expression was also significantly associated with PFS (P = .005), even after adjustment for PD-L1 expression (P = .013).

The median PFS among patients with PD-L2 expression

was 65 days compared with 59 days among those without PD-L2 expression.

Overall survival (OS) was also associated with PD-L2 expression (P = .030), but not after adjustment for PD-L1 expression (P = .112).

The median OS was 303 days among PD-L2-positive patients compared with 199 among those who were PD-L2-negative.

Early Taxane Switching May Improve PSA Response Rates in Prostate Cancer Early switching from docetaxel to cabazitaxel or vice versa may lead to improved prostate-specific antigen (PSA) response rates, according to a study published in the Journal of Clinical Oncology.

The phase 2, randomized, non-comparative TAXYNERGY trial (ClinicalTrials. gov Identifier: NCT01718353) enrolled chemotherapy-naive patients with metastatic, castration-resistant prostate cancer (mCRPC) to evaluate the clinical benefit of early taxane switch and the usefulness of circulating tumor cells (CTCs) as a biomarker.

Forty-one patients received docetaxel 75 mg/m 2 and 22 received cabazitaxel 25 mg/m 2 every 3 weeks plus daily prednisone 10 mg. Patients who did not see at least a 30% PSA decline by cycle 4 (C4; week 12) switched taxanes, and patients who achieved at least a 30% decline in PSA from baseline were maintained on the initial taxane.

The primary clinical endpoint of this study was achieving at least a 50% PSA decline from baseline vs the historical control (TAX327).

The primary biomarker endpoint was to confirm that clinical response rate correlates with drug target engagement (DTE; demonstrated by decreased percent of androgen receptor nuclear localization [%ARNL] and increased microtubule bundling) as shown by CTC analysis.

Thirty-five patients (55.6%) achieved at least a 50% PSA response vs the 45.5% historical rate.

Thirty-three patients (54.1%) achieved at least a 30% PSA decline by C4 and did not switch taxane, 15 patients (24.6%) did not see at least a 30% PSA decline and switched taxanes.

Of the patients who switched, 7 patients (46.7%) achieved a PSA response exceeding 50%.

In the patients who were CTC-evaluable, decreases in %ARNL were associated with a higher rate of at least a 50% PSA decrease (P = .009).

A20 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

© KATERYNA KON/SCIENCE PHOTO LIBRARY / GETTY IMAGES

CI, 58.7-73.2%; P = .33) in non-ETP T-ALL. This was, in part, driven by allo-SCT, which trended toward improved survival among patients with ETP (hazard ratio [HR], 0.36; P = .07) but not non-ETP T-ALL (HR, 0.70; P = .30).

According to the authors, these data suggest “that transplantation conferred survival benefit in high-risk patients with ETP-ALL who had already received augmented induction regimens suggests that allo-SCT is a key component of therapy escalation.”

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

harmD,

RPh

Diagnosing Gastric Linitis Plastica: Endoscopic and Radiologic Approaches The diagnosis of linitis plastica, a subtype of gastric adenocarcinoma with a poor prognosis, can be difficult and uses a multifaceted approach.

O

ne of the most serious forms of gastric cancer is linitis plastica (LP), a subtype of gastric adenocarcinoma. LP represents up 20% of gastric adenocarcinoma cases and is typically defined by its “signet ring” form seen on biopsy.1 In LP, there is diffuse involvement of the stomach and, frequently, evidence of metastases on clinical presentation.

Patients with LP have a poor prognosis, with a 5-year survival of less than 10%.

Early diagnosis of LP is critical to the patient’s outcome, though that can be extremely challenging.

Patients with gastric cancer will present with abdominal pain and weight loss more than 50% of the time.2 Additional symptoms include nausea, dysphagia, gastrointestinal bleeding (hematemesis, melena), and early satiety. Early satiety may be more prominent in patients with LP based on the diffuse involvement of the stomach, which causes limited distensibility.

As LP will frequently metastasize by the time the patient presents, there can be involvement of the liver and peritoneum leading to right upper quadrant pain, elevated liver function tests, and inability to tolerate adequate oral intake.

As many of the presenting symptoms can be non-specific, there may be a delay in diagnosis. LP can, however, be diagnosed in a multitude of ways.

Non-invasive testing includes upper gastrointestinal studies with barium contrast along with computed tomography (CT) of the abdomen and pelvis with oral contrast. Oral contrast allows visualization of the stomach’s ability to distend and will frequently show a “leather flask” shape due to the poor distensibility in patients with LP.3

Patients with LP have a poor prognosis, with a 5-year survival of less than 10%.

mucosa can, however, also appear normal, which requires high clinical suspicion in further workup. The antrum and pylorus are most commonly involved in LP, while the fundus is the least involved.

In addition to EGD, endoscopic ultrasound (EUS) can be used to visualize the different layers of the stomach and assess the depth of involvement of the malignancy.4 Suspicious mucosa should be biopsied multiple times to increase the pathological yield.

All gastric ulcers, regardless of their endoscopic appearance, should be biopsied. As LP involves the deep layers of the stomach, it is important to obtain an adequate amount of tissue. If there is a high clinical suspicion and traditional biopsies obtained from EGD are negative, EUS can be used for deeper biopsies or the patient may be referred to a surgeon for a full thickness biopsy.

The diagnosis of LP can be difficult and uses a multifaceted approach between endoscopic and radiologic studies. As symptoms are non-specific, a clinician must have strong clinical acumen when recommending the appropriate testing. ■ References 1. Schauer M, Peiper M, Theisen J, Knoefel W.

The patient can also appear to have a functional gastric outlet obstruction based on the diffuse infiltration of the gastric walls. In addition to thickened gastric wall and possible gastric outlet obstruction, CT can also show peritoneal carcinomatosis if the LP spreads by the time of presentation.

Esophagoduodenoscopy (EGD) is a more invasive, albeit safe test that can allow for direct visualization of the gastric mucosa. Upon entering the stomach of a patient with LP, the stomach may not properly insufflate with air based on its diffuse involvement of multiple layers of the gastric wall. The mucosa can appear friable, with thickened, nodular folds. The

Prognostic factors in patients with diffuse type gastric cancer (linitis plastica) after operative treatment. Eur J Med Res. 2011;16(1):29-33.

2. Wanebo HJ, Kennedy BJ, Chmiel J, Steele G Jr, Winchester D, Osteen R. Cancer of the stomach.

A patient care study by the American College of Surgeons. Ann Surg. 1993;218(5):583-92.

3. Mastoraki A, Papanikolaou IS, Sakorafas G, Safioleas M. Facing the challenge of managing linitis plastic-review of the literature.

Hepatogastroenterology. 2009;56(96):1773-8.

4. Yoshida S, Tanaka S, Kunihiro K, et al. Diagnostic ability of high-frequency ultrasound probe sonography in staging early gastric cancer, especially for submucosal invasion. Abdom

Imaging. 2005;30(5):518-23.

CancerTherapyAdvisor.com | JULY/AUGUST 2017 | CANCER THERAPY ADVISOR A21

FEATURE

BY JONATHAN GOODMAN, MPhil

V

alue-based care, an increasingly important concept in oncology, is grounded on the relationship between the efficacy and cost of an anticancer drug. Patients with cancer, the reasoning goes, ought to receive the best value of care, accounting for efficacy, toxicity, comorbidities, price, and so forth.

The authors of an article recently published in The New Bioethics note, however, that the notion of value requires that an arbitrary price be put on life.1 This refers to the often-small improvements in overall survival seen with some newly approved cancer treatments. Some of these benefits improve the average patient’s life expectancy by as little as 10 days.

Yet these survival benefits, no matter how marginal, are often the basis for drug approvals and consequent marketing campaigns. Richard Sullivan, MD, PhD, founding director of the Institute of Cancer Policy in London, England, and co-author of this essay, noted that “the bar for marketing authorisation is set low, and is getting lower. This means greater and greater uncertainty as to the efficacy, toxicity, tolerability, and overall value.

“All the evidence from current studies shows that more cancer medicines are being approved which do not deliver clinically meaningful benefit and this is in the context of clinical trials. We know in the real world most cancer medicines’ efficacy drops some 20 to 40% because we start treating real patients with a variety of comorbidities.”

If value is hard to define because it is perceived differently by different people, how can oncologists and policy-makers accurately gauge cost-effectiveness?

A22 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

Patients in the “real world” do not, according to recent research, resemble patients who participate in clinical trials. This sometimes negates whatever improvements justify drug approvals in the United States and Europe.2,3 Doubts about the true efficacy of recently approved drugs combined with effective marketing campaigns make “value” a difficult term to quantify. If the efficacy for the average patient outside of a clinical trial cannot be guaranteed by the results seen in a clinical trial, the notion of reproducibility — or rather the purpose of reproducibility — is undermined, and a drug’s value determined by a clinical trial is not the value seen in the clinic.

Bishal Gyawali, MD, a medical oncologist working in Japan who is affiliated with the Institute of Cancer Policy and the Anticancer Fund, Belgium, and co-author of the recent essay, noted to me that this issue is particular to cancer treatments, because “cancer medicines usually target metastatic disease where pushing away death is the main focus … paradoxically [these drugs] receive special treatment by the oncology community compared with surgery or radiotherapy services that aim at ‘curing’ early stages of cancer.”

Dr Gyawali noted a recent article published in the Annals of Oncology that questioned the value added by England’s National Health Service (NHS) Cancer Drug Fund, which was established to “improve access” to medications not necessarily approved by the National Institute for Health and Care Excellence (NICE).4 Of 47 indications approved by the Cancer Drug Fund, only 18 “reported

© ADAM GAULT / GETTY IMAGES

Is It Possible To Gauge Cancer Treatment Cost-effectiveness?

© ADAM GAULT / GETTY IMAGES

FEATURE a statistically significant OS [overall survival] benefit, with an overall median survival of 3.1 months.” The authors concluded that the Fund did not meaningfully benefit patients or society.

This problem of marginal benefits is not, Dr Gyawali noted, a consequence only of cancer medicines having a special status in society, but “that the industry can easily hijack the tools of evidence-based medicine to prove small marginal gains as statistically significant while they have no clinical meaning to patients.

“A few such strategies are: overpowered trials that can show even a week of OS gain as significant, using noninferiority trial design to show that the new drug is not inferior rather than superior to a previous drug, using inferior controls to show the intervention arm as doing better, and using excellent patients in trials to show gains that get lost when used in real world patients.”

The foundational qualities upon which a cancer drug is priced and marketed — efficacy and value — are therefore not only difficult to qualify, but difficult to accurately define. Small survival benefits may not be benefits at all, and value may be indeterminate even if the benefit is accurately described: much as NICE and the FDA may have policies about the maximum potential value of a new drug that confers a 10-day survival benefit, no one can tell a patient what his or her last 10 days are worth.

This points to a fundamental disconnect between health care policy and demand from the public for new cancer drugs. Demand from patients with cancer and their families increases the value of drugs, though the consequent high drug prices drive down cost-­ effectiveness. This puts creating demand among patients — which can be achieved through effective marketing campaigns and promotion — in the interest of those setting the drug prices to begin with.

Dr Sullivan added that “we have to get the message across to patients, patient organisations, and policy-makers that demanding good value is a fundamental matter of fairness.

“It is not about denying people life-saving treatment. This means fair price for the outcome the medicine gives as judged by a competent health technology assessment program.

“When a company over-prices we need to focus on this and not on the ‘failure’ of governments to fund the drug for access.”

This system of problems may be a consequence of the financial interests industry has in showing one drug is even marginally more efficacious than another.

To the extent that each approval allows a company to show it offers something new that can extend a patient’s life, pressure from patients, industry, and the public

After 5 months of successful treatment — half as long as it takes acquired resistance to develop — NICE will face pressure from industry, patients and families, and the press to negotiate for the drug.

NICE may be left in an indefensible position, as patients clamor for the continuation of their successful therapy.

A full palbociclib treatment course costs about £79,650.7 In February 2017, NICE recommended against paying for the drug, which they determined to be too expensive for the benefits it provides. ■ References 1. Gyawali B, Sullivan R. Economics of cancer medicines: for whose benefit? New Bioeth.

2017;23(1):95-104.

2. Mailankody S, Prasad V. Overall survival in cancer drug trials as a new surrogate end point for overall survival in the real world.

JAMA Oncol. 2016 Nov 17. doi: 10.1001/jama-

Value may be indeterminate even if the benefit is accurately described.

oncol.2016.5296 [Epub ahead of print] 3. Sanoff HK, Chang Y, Lund JL, O'Neil BH, Dusetzina SB. Sorafenib effectiveness in advanced hepatocellular carcinoma.

Oncologist. 2016;21(9):1113-20.

4. Aggarwal A, Fojo T, Chamberlain C, Davis C, Sullivan R. Do patient access schemes for high-cost cancer drugs deliver value to

will be put on health care systems to provide these drugs. And while cost-effectiveness is driven down by high prices, demand will be high, creating the illusion of great value where only little is offered.

The disconnect between the subjective value a patient places on a survival benefit and the “objective” value of a survival benefit debated by policy makers is, however, exploitable. Pfizer recently announced its intention to offer palbociclib, a CDK4/6 inhibitor used to treat breast cancer, for free on the NHS — for a maximum of about 5 months.5 With letrozole, palbociclib extends progression-free survival by about 10 months over letrozole alone.6

society?-lessons from the NHS Cancer Drugs Fund. Ann Oncol. 2017 Apr 27. doi: 10.1093/ annonc/mdx110 [Epub ahead of print] 5. Burki TK. Pfizer to make palbociclib temporarily free on NHS. Lancet Oncol.

2017;18(6):e309 6. Finn RS, Martin M, Rugo HS, et al. PALOMA-2: primary results from a phase III trial of palbociclib plus letrozole compared with placebo plus letrozole in postmenopausal women with ER+/HER2- advanced breast cancer.

J Clin Oncol. 2016;34(suppl; abstr 507).

7. Breast cancer drug costs too high in relation to benefits for routine NHS funding [news release]. National Institute for Health and Care Excellence; February 3, 2017. http://bit. ly/2kZjIik. Accessed May 26, 2017.

CancerTherapyAdvisor.com | JULY/AUGUST 2017 | CANCER THERAPY ADVISOR A23

FACT SHEET | BY BRYANT FURLOW

There is limited epidemiologic and lab-experiment evidence that green tea and green tea compounds are capable at high concentrations of affecting tumor biology.

G

reen tea (Camellia sinensis) leaves contain bioactive and possibly immunostimulatory polyphenols such as flavonoids, catechins (flavan-3 oils), and tannins, the anticancer effects of which have been assessed almost exclusively in preclinical lab experiments and epidemiologic studies.1-5 Green tea and green tea extracts are widely consumed by patients with cancer.

Yet overall there is no clinical evidence that green tea or its chemical components slow tumor progression in humans — and importantly, there is some evidence that green tea compounds might interfere with anticancer treatment.6 Patients whose treatment regimens include bortezomib or radiotherapy should avoid green tea, and all patients with cancer should inform their care team if they are consuming green tea or green tea supplements, as well as any other herbal supplements.

Several recent epidemiologic studies do suggest possible associations between high levels of green tea consumption and a reduced risk for some cancers.7-9 The few phase 1 (safety) clinical trials of green tea and cancer that are published, however, have not yielded evidence of antitumor activity.1,10,11

at risk of cancer. Results from a phase 1 trial suggest that most adverse reactions to epigallocatechin-3-gallate (EGCG)rich green tea extract were mild and transient (at 843 mg daily) among postmenopausal, mostly Caucasian, women.10 The study participants experienced no serious adverse events, although green tea extract was associated with significantly higher levels of nausea and skin rash, as well as elevated alanine aminotransferase (ALT) enzyme levels compared with placebo-group study participants (6.7% vs 0.7%; P < .001).

Green tea extract consumption was also associated with lower levels of diarrhea (P = .002).10 Systematic reviews and meta-analyses that pool data from epidemiologic and available clinical trials found possible associations between high levels of green tea (7 cups per day) or EGCG

Evidence in Favor There is some evidence that topical application of green tea might speed radiotherapy skin burns.1 Phase 1 clinical trials suggest that green tea consumption is likely to be generally safe for patients and people

A24 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

consumption and reduced risks of prostate, liver, and endometrial cancer.8,9,12-14 A recent multicenter retrospective case control study of 442 adult patients with leukemia and 442 outpatient controls in China suggests that patients with leukemia were half as likely to have consumed green tea for more than 20 years than were non-leukemia patients (odds ratio [OR], 0.50; 95% CI, 0.27-0.93).15 Yet additional prospective research would be required to clarify whether this implies that green tea reduces adult leukemia risk.

There is limited preclinical evidence that green tea polyphenols (GTPs) are immunostimulatory and that high levels of GTP intake suppress tumor progress in lab animals (in experiments with animal models of bladder cancer, for example).4 Poor intestinal absorption and metabolic factors reduce green tea catechins’ (GTCs) bioavailability, however, suggesting that green tea consumption alone may not capture the potential clinical benefits of GTP.16 Research and development efforts are already under way to improve GTP bioavailability for prostate cancer chemoprevention, using nanoparticle polymer formulations that “represent

© LARS MENSEL / EYEEM / GETTY IMAGES

Green Tea and Cancer

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FACT SHEET the main way to translate preclinical results in a real clinical scenario,” Italian researchers reported.16 Findings from a systematic review of preclinical experiments of GTC effects on breast cancer cells similarly suggested chemopreventive promise but only at very high concentrations “that are difficult to achieve in the clinical setting.”3 The authors called for development of more bioavailable formulations and testing of GTC as a potential adjuvant therapy to endocrine treatment for patients with breast cancer.

Preclinical experiments suggest a possible synergy between GTCs and tamoxifen or raloxifene against breast

Take-home Conclusions The evidence base is immature and equivocal. There is limited epidemiologic and lab-experiment evidence that green tea and green tea compounds are capable at high concentrations of affecting tumor biology. There is not, however, substantive clinical evidence that this potential translates to clinically meaningful cancer prevention or treatment benefits in humans. ■

Nutr Cancer. 2017;69(3):353-64.

10. Dostal AM, Samavat H, Bedell S, et al. The safety of green tea extract supplementation in postmenopausal women at risk for breast cancer: results of the Minnesota Green Tea Trial. Food Chem Toxicol. 2015;83:26-35.

11. Choan E, Segal R, Jonker D, et al. A prospective clinical trial of green tea for hormone refrac-

References

complementary/alternative therapy approach.

Urologic Oncol. 2005;108-13.

Cooley K, Fergusson D. Green tea and lung

12. Zhou Q, Li H, Zhou JG, Ma Y, Wu T, Ma H.

cancer: a systematic review. Integr Cancer

Green tea, black tea consumption and risk

Ther. 2013;12(1):7-24.

of endometrial cancer: a systematic review

catechins in the chemoprevention of prostate cancer. Nutr Cancer. 2012;64(1):4-22.

3. Yiannakopoulou EC. Effect of green tea catechins on breast carcinogenesis: a systematic review of in-vitro and in-vivo experimental studies. Eur J Cancer Prev. 2014;23(2):84-9.

4. Matsuo T, Miyata Y, Asai A, et al. Green tea polyphenol induces changes in cancer-related factors in an animal model of bladder cancer.

PLoS One. 2017;12(1):e0171091.

5. Kim YH, Won YS, Yang X, et al. Green tea catechin metabolites exert immunoregulatory effects on CD4(+) T cell and natural killer cell activities. J Agric Food Chem.

2016;64(18):3591-7.

Evidence Against Phase 1 clinical trials among patients with lung cancer failed to identify any objective tumor responses to green tea consumption.1 A meta-analysis conducted by Chinese researchers of published epidemiologic studies found insufficient evidence to conclude that there is an association between green tea consumption and esophageal cancer, despite a subgroup analysis suggesting a possible risk reduction for women.18 Green tea consumption does not appear to affect the risk of pancreatic cancer.19

risk and progression: a systematic review.

1. Fritz H, Seely D, Kennedy DA, Fernandes R,

insights into the mechanisms of green tea

cancer cells, possibly via both estrogen receptor–mediated and estrogen receptor–independent mechanisms.17 No such evidence has been reported for fulvestrant and GTC co-administration.

green tea consumption on prostate cancer

tory prostate cancer: an evaluation of the

2. Connors SK, Chornokur G, Kumar NB. New

There is some evidence that green tea compounds might interfere with anticancer treatment.

9. Jacob SA, Khan TM, Lee LH. The effect of

6. Thomas F, Holly JM, Persad R, Bahl A, Perks

and meta-analysis. Arch Gynecol Obstet.

2016;293(1):143-55.

13. Huang YQ, Lu X, Min H, et al. Green tea and liver cancer risk: a meta-analysis of prospective cohort studies in Asian populations.

Nutrition. 2016;32(1):3-8.

14. Ni CX, Gong H, Liu Y, Qi Y, Jiang CL, Zhang JP. Green tea consumption and the risk of liver cancer: a meta-analysis. Nutr Cancer.

2017;69(2):211-20.

15. Liu P, Zhang M, Xie X, Jin J, Holman CD. Green tea consumption and the glutathione S-transferases genetic polymorphisms on the risk of adult leukemia. Eur J Nutr.

2017;56(2):603-12.

16. Naponelli V, Ramazzina I, Lenzi C, Bettuzzi S, Rizzi F. Green tea catechins for prostate cancer prevention: present achievements and

CM. Green tea extract (epigallocatechin-3-gal-

future challenges. Antioxidants. 2017;6(2).

late) reduces efficacy of radiotherapy on pros-

doi: 10.3390/antiox6020026

tate cancer cells. Urology. 2011;78:475.e21.

7. Lee PM, Ng CF, Liu ZM, et al. Reduced prostate cancer risk with green tea and epigallocatechin 3-gallate intake among Hong Kong Chinese men. Prost Cancer Prost Dis. 2017 Apr 18. doi: 10.1038/pcan.2017.18 [Epub ahead of print] 8. Guo YM, Zhi F, Chen P, et al. Green tea and the risk of prostate cancer: a systematic review and meta-analysis.

17. Yiannakopoulou EC. Interaction of green tea catechins with breast cancer endocrine treatment: a systematic review. Pharmacology.

2014;94:245-8.

18. Sang LX, Chang B, Li XH, Jiang M. Green tea consumption and risk of esophageal cancer: a meta-analysis of published epidemiological studies. Nutr Cancer. 2013;65(6):802-12.

19. Zeng JL, Li ZH, Wang ZC, Zhang HL. Green tea

Medicine. 2017;97(13):e6426. doi: 10.1097/

consumption and risk of pancreatic cancer: a

MD.0000000000006426

meta-analysis. Nutrients. 2014;6(11):4640-50.

A26 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

EXPERT PERSPECTIVE | DON S. DIZON, MD, FACP

Engagement Is Survival: My Take on ASCO 2017 Psychosocial health and well-being are increasingly critical parts of cancer care and should be closely evaluated in every patient undergoing treatment.

T

he American Society of Clinical Oncolog y (ASCO) A nnual Meeting wrapped up early in June, and what a meeting it was.

In addition to important clinical trial outcomes that evaluated novel strategies across tumor types, there were impressive studies aiming to help our patients live with cancer as well — regardless of where they are in their own disease trajectory.

I found the spotlight on the psychosocial and quality of life issues illuminating and refreshing. They also represented an important challenge to those of us who practice oncology: do not accept distress as a normal part of the cancer journey.

This was aptly demonstrated by 3 studies, all of which were part of the Press Program for the Annual Meeting, and all of which I provided comment for as an ASCO expert.

For patients with a new diagnosis, Viviane Hess and colleagues studied the impact of a web-based intervention to improve access to psychological support.1 In their trial, almost 130 patients who initiated treatment within 12 weeks were randomly assigned to the online intervention (called STREAM) or to a control group (all of whom were offered the web-based program subsequently).

Enrollment in STREAM at baseline was associated with significant improvement in quality of life compared with the control group; this was coupled

with a significant reduction in distress.

For those who completed treatment, we learned that over 50% had at least a moderate fear of cancer recurrence.

Even more importantly, Jane McNeil Beith and colleagues showed that we can do something about it. 2 In the “Conquer Fear” randomized trial, over 200 patients in follow-up after curative intent treatment were randomly assigned to a psychological intervention

For those who completed treatment, we learned that over 50% had at least a moderate fear of cancer recurrence.

sessions attended face-to-face by trained professionals of varying specialization, including social workers, oncologists, and palliative care clinicians.

Compared with usual care, those who participated in the CALM intervention experienced significantly less depressive symptoms at both 3- and 6- month time points. Other significant findings associated with the CALM intervention included greater preparation about end of life, less fear of the future, and a greater ability to manage and express feelings.

Studies like this emphasize what is possible and what, even in the era of precision therapy, remains an important aspect of care.

Cancer is much more than just biology.

It is a social disease, with an impact on the psychosocial health and well- being of our patients and those that love them. As oncologists, we cannot accept distress as a normal reaction to cancer. I am hopeful that with this trio of studies we can understand that it affects patients from the point of diagnosis.

Addressing it early can mean tangible improvements in coping and, indeed, in living with cancer. ■ References 1. Hess V, et al. Web-based stress management for newly diagnosed cancer patients (STREAM): A randomized, wait-list con-

or to relaxation exercises. Conquer Fear was set up as therapist-directed, individualized, face-to-face sessions over 10 weeks, and while patients derived a reduction in their fear of recurrence with both arms, Conquer Fear was significantly more effective.

For those living with advanced or metastatic cancer, Gary Rodin and colleagues reported the results of the CALM intervention (Managing Cancer and Living Meaningfully) vs usual care, which enrolled over 300 patients.3 The CALM intervention consisted of 3

trolled intervention study. J Clin Oncol.

2017;35(suppl; abstr LBA10002).

2. Beith JM, et al. Long-term results of a phase II randomized controlled trial (RCT) of a psychological intervention (Conquer Fear) to reduce clinical levels of fear of cancer recurrence in breast, colorectal, and melanoma cancer survivors. J Clin Oncol.

2017;35(suppl; abstr LBA10000).

3. Rodin G, et al. Managing cancer and living meaningfully (CALM): A randomized controlled trial of a psychological intervention for patients with advanced cancer. J Clin

Oncol. 2017;35(suppl; abstr LBA10001).

CancerTherapyAdvisor.com | JULY/AUGUST 2017 | CANCER THERAPY ADVISOR A27

REGIMEN & MONOGRAPH INDEX CANCER THERAPY REGIMENS & DRUG MONOGRAPHS 1

Bone Cancer

3 Brain Cancer 5 Breast Cancer

12 Endocrine Cancer 16 Gastrointestinal Cancer 22 Genitourinary Cancer 32 Gynecologic Cancer 35 Head and Neck Cancer 37 Hematologic Cancer

 Acute Lymphoblastic Leukemia

 Hodgkin Lymphoma

76 Lung Cancer 83 Sarcoma 84 Skin Cancer  Melanoma

To view the complete collection of cancer treatment regimens for all cancer types visit CancerTherapyAdvisor.com/TreatmentRegimens.

To view the complete collection of drug monographs visit CancerTherapyAdvisor.com/DrugMonographs.

A28 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | 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. © 2017 Haymarket Media, Inc.

DRUG MONOGRAPHS

BONE CANCER HALAVEN Eisai

℞

Non-taxane microtubule dynamics inhibitor.

Eribulin mesylate 0.5mg/mL, soln for IV inj.

Indications: Treatment of unresectable or metastatic liposarcoma in patients who have received prior anthracycline-containing regimen.

Adults: Give by IV inj over 2–5mins. 1.4mg/m² on Days 1 and 8 of a 21-day cycle. Mild hepatic impairment (Child-Pugh A) or moderate-to-severe renal impairment (CrCl 15–49mL/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 prior to each dose; 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 (ChildPugh C): insufficient data. Embryo-fetal toxicity.

Pregnancy (avoid). Use effective contraception during treatment and for ≥2 weeks (females) or 3.5 months (male partners) after final dose.

Nursing mothers: not recommended (during and for 2 weeks after final dose).

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, abdominal pain, pyrexia, hypokalemia, hypocalcemia; 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

LARTRUVO Lilly

℞

PDGFR-alpha inhibitor. Olaratumab 500mg/50mL; soln for IV infusion; preservative-free.

Indications: In combination with doxorubicin, for the treatment of adults with soft tissue sarcoma with a histologic subtype for which an anthracycline-containing regimen is appropriate

and which is not amenable to curative treatment with radiotherapy or surgery.

Adults: Premedicate with IV diphenhydramine and IV dexamethasone prior to infusion on Day 1 of cycle 1. Give with doxorubicin for the first 8 cycles: refer to doxorubicin PI for dosing and modifications. Give by IV infusion over 60mins.

15mg/kg on Days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.

Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Have resuscitative equipment available. Monitor for signs/symptoms of infusion-related reactions during and postinfusion. Permanently discontinue for Grade 3/4 infusion-related reactions; interrupt for Grade 1/2 infusion-related reactions; resume at 50% of initial rate after resolution. If neutropenic fever/infection or Grade 4 neutropenia lasts >1 week, discontinue until ANC ≥1,000μL then permanently reduce dose to 12mg/kg. Embryofetal toxicity. Females of reproductive potential should use effective contraception during and for 3 months after last dose. Pregnancy. Nursing mothers: not recommended (during and for 3 months after last dose).

Adverse reactions: With doxorubicin: nausea, fatigue, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, headache, anxiety, dry eyes, lymphopenia, neutropenia, thrombocytopenia, hyperglycemia, elevated aPTT, hypokalemia, hypophosphatemia, increased alkaline phosphatase.

How supplied: Single-dose vial—1

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)

VOTRIENT GlaxoSmithKline

℞

Tyrosine kinase inhibitor. Pazopanib 200mg; tabs.

Indications: Advanced soft tissue sarcoma in patients who have received prior chemotherapy.

Limitation of use: not for treating adipocytic soft tissue sarcoma or gastrointestinal stromal tumors.

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,

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DRUG MONOGRAPHS

BONE CANCER ketoconazole, ritonavir, clarithromycin): avoid and consider alternate drug; if warranted, reduce dose of pazopanib to 400mg; may reduce further if toxicity occurs. Concomitant strong CYP3A4 inducers (eg, rifampin): avoid and consider alternate drug.

Children: Not established.

Warnings/Precautions: Not indicated for use in combination with other cancer agents. Risk of severe and fatal hepatotoxicity (esp. ≥65yrs old). Monitor liver tests before starting and at Weeks 3, 5, 7, and 9, thereafter at Months 3 and 4, then periodically. If ALT between 3xULN and 8xULN continue therapy with weekly monitoring until ALT returns to Grade 1 or baseline. If ALT >8xULN 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>3xULN recurs, permanently discontinue. Permanently discontinue if ALT>3xULN and bilirubin >2xULN. Gilbert’s syndrome (see full labeling). History of QT prolongation. Cardiac dysfunction risk (including previous anthracycline exposure): evaluate LVEF at baseline and periodically; monitor for CHF. Monitor ECG, electrolytes (eg, calcium, magnesium, potassium), thyroid function. 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), thrombotic microangiopathy, interstitial lung disease (ILD)/pneumonitis, GI perforation or fistula.

Monitor BP and manage hypertension promptly.

Discontinue if severe and persistent hypertension (despite antihypertensives and dose reduction), if repeat episodes of proteinuria (despite dose reductions), thrombotic microangiopathy, serious infection, ILD or pneumonitis occurs.

Stop therapy at least 7 days before surgery; discontinue in patients with wound dehiscence.

Embryo-fetal toxicity. Pregnancy: exclude status prior to starting. Females of reproductive potential must use effective contraception and males (use condoms) during therapy and for ≥2 weeks after final dose. Nursing mothers: not recommended (during and for 2 weeks after final dose).

Interactions: See Adult dosing: Potentiated by strong CYP3A4 inhibitors, grapefruit juice. Avoid concomitant strong Pgp or BCRP inhibitors.

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. Avoid concomitant drugs that raise gastric pH (eg, PPIs, H2-blockers). Separate antacids by several hours. 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; hepatotoxicity, QT prolongation, hemorrhagic events, arterial thrombotic events (eg, MI, angina, ischemic stroke, TIA), venous thrombotic events (eg, VTE, PE), GI perforation or fistula, ILD/pneumonitis, 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 (esp. 1st weeks of initiating), phosphorus, magnesium levels and Vit.D intake in susceptible patients (eg, severe renal impairment, receiving dialysis). Risk of osteonecrosis of the jaw (ONJ) in diabetes, gingival infections. Perform oral exam and preventive dentistry before and regularly during therapy. Maintain good oral hygiene. Avoid invasive dental procedures during treatment; consider temporary discontinuation if procedure is necessary. Evaluate for atypical fractures if thigh/groin pain develops; consider withholding therapy until risk/benefit assessment. Monitor for hypercalcemia after treatment discontinuation in patients with growing skeletons. Embryo-fetal toxicity. Pregnancy; exclude status prior to initiation. Use highly effective contraception during therapy and for at least 5 months after last dose. Nursing mothers: not recommended (may impair mammary gland development/lactation).

Interactions: Concomitant other denosumabcontaining products (eg, Prolia): not recommended.

Concomitant drugs that can lower calcium levels; monitor. Increased risk of ONJ with concomitant corticosteroids, chemotherapy, angiogenesis inhibitors or duration of denosumab exposure.

Adverse reactions: Fatigue, asthenia, hypophosphatemia, nausea, arthralgia, headache, back pain, pain in extremity, dyspnea, decreased appetite, peripheral edema, vomiting, anemia, constipation, diarrhea; ONJ, hypocalcemia (may be fatal), hypersensitivity reactions (discontinue if occur).

How supplied: Single-use vial (1.7mL)—1

YONDELIS Janssen

℞

Alkylating agent. Trabectedin 1mg; per vial; lyophilized pwd for IV infusion after reconstitution and dilution; contains sucrose.

Indications: Treatment of unresectable or metastatic liposarcoma or leiomyosarcoma in patients who have received prior anthracyclinecontaining regimen.

Adults: Give by IV infusion over 24hrs.

1.5mg/m2 every 21 days until disease progression or unacceptable toxicity. Moderate hepatic impairment: 0.9mg/m2 every 21 days. Premedicate 30 mins prior to each dose with IV dexamethasone 20mg. Delay, reduce, or permanently discontinue dose according to severity of adverse reactions: see full labeling. Do not increase dose in subsequent cycles once reduced.

Children: <18yrs: not established.

Warnings/Precautions: Assess neutrophil count prior to each dose and periodically during the cycle; withhold if <1,500 cells/μL on day of dosing; permanently reduce dose if lifethreatening or prolonged, severe neutropenia occurs in prior cycle. Assess CPK levels prior to each dose; withhold if serum CPK >2.5XULN; permanently discontinue if rhabdomyolysis occurs. Assess LFTs prior to each dose and as indicated based on pre-existing hepatic impairment; interrupt, reduce, or permanently discontinue dose based on severity/duration.

Assess LVEF by echocardiogram or MUGA scan prior to initiation and every 2–3 months thereafter until discontinued; withhold if LVEF below LLN; permanently discontinue if symptomatic cardiomyopathy occurs or persistent LV dysfunction not recover to LLN within 3 weeks. Monitor for capillary leak syndrome; discontinue and treat promptly if occurs. Severe hepatic impairment: not recommended. Embryo-fetal toxicity. Pregnancy.

Females of reproductive potential should use effective contraception during and for 2 months and males (for 5 months) after final dose.

Nursing mothers: not recommended.

Interactions: Avoid concomitant strong CYP3A inhibitors (eg, oral ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, indinavir, lopinavir, ritonavir, boceprevir, nelfinavir, saquinavir, telaprevir, nefazodone, conivaptan), grapefruit or grapefruit juice; if short-term use (<14 days) necessary, give inhibitor 1 week after infusion and discontinue the day prior to next infusion. Avoid concomitant strong CYP3A inducers (eg, rifampin, phenobarbital, St. John’s wort).

Adverse reactions: Nausea, fatigue, vomiting, constipation, decreased appetite, diarrhea, peripheral edema, dyspnea, headache, neutropenia, increased ALT, thrombocytopenia, anemia, increased AST and CPK; anaphylaxis, neutropenic sepsis, rhabdomyolysis, hepatotoxicity, cardiomyopathy, capillary leak syndrome, extravasation resulting in tissue necrosis, infertility.

How supplied: Single-dose vial—1

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DRUG MONOGRAPHS

BRAIN CANCER AFINITOR Novartis

℞

mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs. ℞ Also: AFINITOR DISPERZ Everolimus 2mg, 3mg, 5mg; tabs for oral susp.

Indications: In adults and children with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected.

Adults and Children: <1yr: not recommended.

Swallow tabs whole with water or use Disperz tabs administered as a suspension only. Take at the same time each day either consistently with or without food. Prepare suspension using 5mL of water in an oral syringe or 25mL of water in a drinking glass; max 10mg dose per syringe or glass. ≥1yrs: initially 4.5mg/m2 once daily. Do not combine the 2 dosage forms to achieve the desired total dose. Use therapeutic drug monitoring to guide subsequent dosing.

Adjust dose at 2 week intervals as needed to achieve and maintain trough concentrations of 5–15ng/mL (see full labeling). Severe hepatic impairment: initiate at 2.5mg/m2 once daily.

Concomitant strong CYP3A4/PgP inhibitors: avoid; moderate CYP3A4/PgP inhibitors: initiate at 2.5mg/m2 once daily, if CYP3A4/PgP inhibitor discontinued, after 2–3 days, return to dose used prior to initiating moderate inhibitor.

Concomitant strong CYP3A4 inducers: avoid, if required, then initiate at 9mg/m2 once daily; if discontinued, then return to dose used prior to initiating strong inducer. Continue therapy until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions, or others: see full labeling.

Contraindications: Allergy to other rapamycin derivatives.

Warnings/Precautions: Monitor for new or worsening respiratory symptoms. Increased risk of infections; some may be severe or fatal; monitor and treat promptly if occur.

Pre-existing invasive fungal infections: treat before starting. Monitor for signs of woundrelated complications. Peri-surgical period.

Hepatic impairment (see Adult dose). Monitor CBCs, renal function, lipids, and blood glucose prior to starting and periodically thereafter.

Avoid close contact with those who have received live vaccines. Pediatrics: complete childhood vaccination series according to ACIP guidelines prior to initiation. Elderly. Females of reproductive potential must use effective contraception during therapy and for 8 weeks

after treatment. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Avoid live vaccines. Potentiated by strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), grapefruit or grapefruit juice; avoid. Caution with moderate CYP3A4/PgP inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem); reduce everolimus dose if used. Antagonized by strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s Wort; avoid.

Adverse reactions: Pneumonitis (interrupt, reduce dose and/or manage with corticosteroids; if severe, discontinue; may reintroduce 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), diarrhea, nausea, abdominal pain, rash, fatigue, edema, fever, asthenia, cough, headache, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see full labeling).

How supplied: Tabs, Disperz—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. 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: Risk of GI perforations, surgery and wound healing complications, and hemorrhage. Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). Do not administer if recent history of hemoptysis of ≥ ½-teaspoon of red blood. Permanently discontinue if GI perforation, tracheoesophageal fistula, any grade 4 fistula, or grade 4 venous thromboembolic event. Discontinue if fistula involving internal organ, wound healing

complications, hemorrhage, severe arterial thromboembolic event (ATE), hypertensive crisis or encephalopathy, posterior reversible encephalopathy syndrome (PRES), or nephrotic syndrome occurs; suspend therapy if severe hypertension, moderate-to-severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Avoid in ovarian cancer if evidence of recto-sigmoid involvement by pelvic exam, bowel involvement on CT scan, or symptoms of bowel obstruction. History of arterial thromboembolism. Diabetes. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis; if ≥2+, do further assessment with a 24-hour urine collection.

Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy: may cause fetal harm; use effective contraception during and for 6 months after last dose. Nursing mothers: not recommended.

Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation and fistulae, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, PRES, infusion reactions, ovarian failure, neutropenia, infection.

How supplied: Single-use vial—1

TEMODAR Merck

℞

Alkylating agent. Temozolomide 5mg, 20mg, 100mg, 140mg, 180mg, 250mg; caps. ℞ Also: TEMODAR INJECTION Temozolomide 100mg; per vial; lyophilized pwd for IV infusion after reconstitution; contains mannitol.

Indications: Newly diagnosed glioblastoma multiforme. Refractory anaplastic astrocytoma.

Adults: See full labeling for monitoring and dose adjustment guidelines. IV: Infuse over 90 mins.

Oral caps: 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

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DRUG MONOGRAPHS

BRAIN CANCER for 5 consecutive days if tolerated; continue until disease progression, discontinue if minimum dose not tolerated.

Children: Not established.

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 prior to treatment initiation and 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. Perform LFTs at baseline, midway through Cycle 1, prior to each subsequent cycle, and 2–4wks after last dose. Screen for HBV infection prior to initiation. Monitor for signs of hepatitis or HBV reactivation during and several months after treatment; discontinue if occurs. 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.

Interactions: Concomitant carbamazepine, phenytoin, sulfamethoxazole/trimethoprim may complicate myelosuppression assessment. May be potentiated by valproic acid.

Adverse reactions: Alopecia, fatigue, nausea, vomiting, anorexia, constipation, headache, convulsions, rash, hemiparesis, diarrhea, asthenia, fever, dizziness, abnormal coordination, viral infection, amnesia, insomnia, edema;

myelosuppression (may be dose-limiting; see full labeling), hepatotoxicity (may be fatal).

How supplied: Caps 5mg, 20mg, 100mg, 140mg 180mg—5, 14; 250mg—5; Single-use vials—1

UNITUXIN United Therapeutics

℞

GD2-binding monoclonal antibody. Dinutuximab 3.5mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: In combination with granulocytemacrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2) and 13-cis-retinoic acid (RA), for the treatment of children with highrisk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy.

Adults: Not applicable.

Children: Confirm adequate hematologic, respiratory, hepatic, and renal function prior to each course. Hydrate and premedicate with antihistamines, analgesics (eg, IV opioids), and antipyretics prior to each dose: see full labeling. Give via IV infusion over 10–20 hours for 4 consecutive days; max 5 cycles. Initial rate: 0.875mg/m2/hr for 30mins; may gradually increase as tolerated up to max 1.75mg/m2/hr.

Cycles 1, 3, and 5 (24-day cycle): 17.5mg/m2/day on Days 4–7. Cycles 2 and 4 (32-day cycle): 17.5mg/m2/day on Days 8–11. Dose modifications: see full labeling.

Warnings/Precautions: Risk of serious infusion reactions; monitor during and at least 4 hours after completion of each infusion; interrupt or discontinue if severe or prolonged infusion reactions occur. Have resuscitative

medications and equipment available. Risk of serious neurotoxicity including severe neuropathic pain and peripheral neuropathy.

Permanently discontinue if life-threatening infusion reactions, Grade 3 pain unresponsive to max supportive measures, Grade 4 sensory neuropathy or Grade 3 sensory neuropathy that interferes with daily activities for more than 2 weeks, Grade ≥2 peripheral motor neuropathy, recurrent signs of eye disorders or vision loss, urinary retention that persists following opioid discontinuation, transverse myelitis, signs/symptoms of RPLS, signs of atypical hemolytic uremic syndrome occurs. Interrupt or discontinue if symptomatic or severe capillary leak syndrome, symptomatic hypotension, systolic BP less than lower limit of normal for age or decreased by >15% compared to baseline develops. Monitor for systemic infection; temporarily discontinue until resolves. Monitor BP, peripheral blood counts during therapy, and serum electrolytes daily. Renal or hepatic impairment. Pregnancy; avoid. Use effective contraception during therapy and for at least 2 months after last dose. Nursing mothers: not recommended.

Adverse reactions: Pain, pyrexia, infusion reactions, hypotension, hyponatremia, hypokalemia, hypocalcemia, hypoalbuminemia, increased ALT/AST, vomiting, diarrhea, capillary leak syndrome, urticaria, infections, bone marrow suppression (eg, thrombocytopenia, anemia, neutropenia, lymphopenia).

How supplied: Single-use vial (5mL)—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.

4 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

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DRUG MONOGRAPHS

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 mins 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. Hepatic impairment (total bilirubin >5XULN or AST >10XULN): not recommended. Monitor for sensory neuropathy, sepsis, or pneumonitis. 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

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 tabs whole with water. 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): 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/PgP 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/PgP inducers: consider doubling the daily dose by increments of 5mg or less. If strong inducer is discontinued, consider washout period of 3–5 days before returning to the dose used prior to initiating the strong inducer. Continue therapy until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions, or others: see full labeling.

Children: Not recommended.

Contraindications: Allergy to other rapamycin derivatives.

Warnings/Precautions: Monitor for new or worsening respiratory symptoms. Increased risk of infections; some may be severe or fatal; monitor and treat promptly if occur. Pre-existing invasive fungal infections: treat before starting. Monitor for signs of wound-related complications. Peri-surgical period. Hepatic impairment (see Adult dose).

Monitor CBCs, renal function, lipids, and blood glucose prior to starting and periodically thereafter.

Avoid close contact with those who have received live vaccines. Pediatrics: complete childhood vaccination series according to ACIP guidelines prior to initiation. Elderly. Females of reproductive potential must use effective contraception during therapy and for 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Avoid live vaccines. Potentiated by strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), grapefruit or grapefruit juice; avoid. Caution

with moderate CYP3A4/PgP inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem); reduce everolimus dose if used. Antagonized by strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s Wort; avoid.

Adverse reactions: Pneumonitis (interrupt, reduce dose and/or manage with corticosteroids; if severe, discontinue; may reintroduce daily dose at approx. 50% lower than previously administered), infections (discontinue if invasive systemic fungal infection develops), stomatitis (treat with nonalcoholic, non-peroxide mouthwash), diarrhea, nausea, abdominal pain, rash, fatigue, edema, fever, asthenia, cough, headache, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see full labeling).

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, 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 inhibitor. Exemestane 25mg; tabs.

Indications: In postmenopausal women: adjuvant treatment of estrogen-receptor positive early breast cancer after 2–3yrs of tamoxifen

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CancerTherapyAdvisor.com | JULY/AUGUST 2017 | CANCER THERAPY ADVISOR 5

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DRUG MONOGRAPHS

BREAST CANCER therapy to complete a total of 5yrs of hormonal therapy; advanced breast cancer with disease progression after tamoxifen therapy.

Adults: Give after a meal. 25mg once daily.

Concomitant strong CYP3A4 inducers (see Interactions): 50mg once daily.

Children: Not established.

Warnings/Precautions: Not for treatment in premenopausal women. Osteoporosis; assess bone mineral density (BMD) at start of treatment.

Monitor all patients for BMD loss and treat as appropriate. Perform routine assessment of Vit. D levels prior to initiation; supplement if deficient. Hepatic or renal impairment. Embryofetal toxicity. Pregnancy. Females of reproductive potential: should undergo pregnancy testing within 7 days prior to initiation; use effective contraception during and for 1 month after final dose. Nursing mothers: not recommended (during and for 1 month after final dose).

Interactions: Antagonized by strong CYP3A4 inducers (eg, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort).

Adverse reactions: Hot flashes, fatigue, arthralgia, headache, insomnia, increased sweating, nausea, increased appetite; reductions in BMD. How supplied: Tabs—30

DELATESTRYL Endo

CIII

Androgen. Testosterone enanthate 200mg/mL; IM inj; in sesame oil; contains chlorobutanol.

Indications: Advancing inoperable metastatic mammary cancer in females who are 1–5 years postmenopausal.

Adults: Give by deep IM inj into gluteal muscle.

200–400mg once every 2–4 weeks. Max 400mg/month. Monitor closely.

Children: Not established.

Contraindications: Male breast or prostate cancer. Pregnancy (Cat.X).

Warnings/Precautions: Discontinue if jaundice, abnormal liver function, hypercalcemia, or edema occurs. Monitor liver function, hemoglobin, hematocrit, cholesterol, urine and serum calcium.

Preexisting cardiac, renal or hepatic disease (discontinue if edema occurs). History of MI or coronary artery disease. Monitor for venous thromboembolism; discontinue if suspected.

Elderly. Nursing mothers: not recommended.

Interactions: May potentiate oral anticoagulants, oxyphenbutazone. May alter insulin requirements. Increased risk of edema with ACTH, corticosteroids. May affect thyroid levels.

Adverse reactions: Amenorrhea, menstrual irregularities, inhibition of gonadotropin secretion, virilization; others: inj site reactions, peliosis hepatis, edema, hepatic carcinoma, nausea, jaundice, hirsutism, acne, polycythemia, headache, anxiety, depression, paresthesia, altered libido, fluid and electrolyte disturbances, suppression of clotting factors, increased serum cholesterol.

How supplied: Multidose vial (5mL)—1

ESTRACE Allergan

℞

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 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 proteinbound 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

FASLODEX AstraZeneca Estrogen receptor antagonist. Fulvestrant 50mg/mL; soln for IM inj.

Indications: Hormone receptor (HR)-positive metastatic breast cancer in postmenopausal

℞

women with disease progression following antiestrogen therapy. In combination with palbociclib: HR-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in women with disease progression after endocrine 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. For combination therapy: give with palbociclib 125mg daily with food for 21 days, followed by 7 days off; in pre/perimenopausal women: also treat with LHRH agonists. Moderate hepatic impairment: 250mg (as one 5mL injection) on Days 1, 15, 29, then once per month thereafter.

Other dose modification: see full labeling.

Children: Not established.

Warnings/Precautions: Bleeding diatheses, thrombocytopenia, or anticoagulant use. Moderateto-severe hepatic impairment. When administering at the dorsogluteal inj site due to proximity of the sciatic nerve. Embryo-fetal toxicity. Pregnancy: do testing within 7 days prior to initiating; use effective contraception during therapy and for 1 year after last dose. Nursing mothers: not recommended (during therapy and for 1 year after last dose).

Interactions: May interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels.

Adverse reactions: Inj site pain (including sciatica, neuralgia, neuropathic pain, peripheral neuropathy), nausea, vomiting, 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,

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DRUG MONOGRAPHS

BREAST CANCER hypercholesterolemia, sweating increased, GI upset, fatigue, dyspnea, cough, insomnia, hypertension, alopecia, anorexia, weight changes, hypercalcemia, pleural effusion, vertigo; thromboembolic or cardioor 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 high-dose 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.

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 inj over 2–5mins. 1.4mg/m² on Days 1 and 8 of a 21-day cycle. Mild hepatic impairment (Child-Pugh A) or moderate-to-severe renal impairment (CrCl 15–49mL/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 prior to each dose; 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): insufficient data. Embryo-fetal toxicity. Pregnancy (avoid). Use effective contraception during treatment and for ≥2 weeks (females) or 3.5 months (male partners) after final dose. Nursing mothers: not recommended (during and for 2 weeks after final dose).

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, abdominal pain, pyrexia, hypokalemia, hypocalcemia; 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: Do not substitute for or with adotrastuzumab emtansine. Give as IV infusion.

Initially 4mg/kg over 90 mins, followed by 2mg/kg over 30 mins weekly; administer until tumor progression. Adjuvant treatment (administer trastuzumab weekly for 52 weeks; therapy >52 weeks: not recommended); In combination therapy: with doxorubicin and cyclophosphamide, followed by either paclitaxel or docetaxel; or with docetaxel/carboplatin: initially 4mg/kg over 90 mins, followed by 2mg/kg over 30 mins 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 mins every 3 weeks. Following multi-modality anthracycline based therapy: initially 8mg/kg over 90 mins, then 6mg/kg over 30–90 mins every 3 weeks.

Infusion reactions or cardiomyopathy: see full labeling.

Children: Not established.

Warnings/Precautions: Increased risk of cardiomyopathy. Conduct cardiac assessment (eg, history, physical exam, LVEF) at baseline, every 3 months during and after therapy or every 6 months for ≥2yrs after therapy (if adjuvant); 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). Embryo-fetal toxicity (eg, oligohydramnios): exclude pregnancy status before initiation. Pregnancy: avoid; use effective contraception during and for 7 months after therapy. Nursing mothers.

Interactions: Increased cardiomyopathy with anthracycline-containing chemotherapy.

Increased toxicity with other myelosuppressives.

Adverse reactions: Fever, diarrhea, nausea, chills, infections, increased cough, headache, CHF, insomnia, fatigue, dyspnea, rash, neutropenia, anemia, thrombocytopenia, stomatitis, mucosal inflammation, weight loss, nasopharyngitis,

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DRUG MONOGRAPHS

BREAST CANCER dysgeusia, myalgia, thrombosis/embolism; severe infusion reactions, febrile neutropenia/exacerbation of chemotherapy-induced neutropenia, pulmonary toxicity (eg, interstitial pneumonitis), cardiomyopathy (eg, left ventricular myocardial dysfunction).

Note: Enroll pregnant women with breast cancer who are using trastuzumab in the MotHER-the Herceptin Pregnancy Registry (800) 690-6720.

Testing considerations: HER2 protein overexpression How supplied: Vial—1 (w. diluent)

IBRANCE Pfizer

℞

Kinase inhibitor. Palbociclib 75mg, 100mg, 125mg; caps.

Indications: Treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women; or fulvestrant in women with disease progression following endocrine therapy.

Adults: Swallow whole. Take with food. 125mg once daily for 21 consecutive days followed by 7 days off to complete a 28-day cycle, in combination with an aromatase inhibitor or with fulvestrant 500mg on Days 1, 15, 29, and once monthly thereafter (see each drug’s full labeling for dosing/duration). In the combination with fulvestrant therapy: pre/perimenopausal women should be treated with LHRH agonists according to clinical practice standards. Dose modification for adverse reactions: First reduction: 100mg/day; Second dose reduction: 75mg/day; discontinue if <75mg/day required. Dose modification for hematologic or non-hematologic toxicities: see full labeling. Concomitant strong CYP3A inhibitors: avoid and consider alternative drug; if use necessary, reduce palbociclib dose to 75mg/day.

Children: Not established.

Warnings/Precautions: Monitor CBCs prior to initiation and at start of each cycle, as well as on Day 15 of first 2 cycles, and as clinically indicated. Interrupt, reduce dose, or delay starting treatment cycles if Grade 3 or 4 neutropenia develops. If maximum of Grade 1–2 neutropenia develops in first 6 cycles, monitor CBCs for subsequent cycles every 3 months, at start of each cycle, and as clinically indicated. Monitor for fever. Moderate or severe hepatic impairment.

Severe renal impairment. Embryo-fetal toxicity.

Pregnancy; exclude status prior to initiation. Use effective contraception during therapy and for at least 3 weeks (females) or 3 months (males) after last dose. Nursing mothers: not recommended (during and for 3 weeks after last dose).

Interactions: Avoid concomitant strong CYP3A inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole), grapefruit or grapefruit juice; if unavoidable, reduce dose (see Adults). Avoid concomitant strong CYP3A

inducers (eg, phenytoin, rifampin, carbamazepine, enzalutamide, St. John’s wort). May potentiate midazolam or other CYP3A substrates with narrow therapeutic index (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus, tacrolimus); reduce dose of these drugs.

Adverse reactions: Neutropenia, leukopenia, infections, fatigue, anemia, nausea, stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting, rash, asthenia, pyrexia; febrile neutropenia.

How supplied: Caps—21

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 >2.5XULN or bilirubin >1XULN (in combination with capecitabine).

Warnings/Precautions: Monitor CBC and liver function at baseline, then periodically. Hepatic impairment (ALT or AST >10XULN or bilirubin >3XULN: not recommended; ALT or AST >5XULN: 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, palmar-plantar 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.

Permanently discontinue if serum transaminases >3XULN and with total bilirubin >2XULN. Risk of left ventricular dysfunction. Assess LVEF prior to initiation and every 3 months during treatment; interrupt and discontinue as appropriate.

Embryo-fetal toxicity: verify pregnancy status prior to initiation. 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: avoid.

Use effective contraception during therapy and for 7 months (females) or 4 months (males) after last dose. Nursing mothers: not recommended (during and for 7 months after last dose).

Interactions: Avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, clarithromycin, atazanavir, indinavir, ritonavir, nefazodone, nelfinavir, saquinavir, telithromycin); if unavoidable, consider delaying therapy. Caution with concomitant anticoagulation or antiplatelet therapy; monitor closely.

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DRUG MONOGRAPHS

BREAST CANCER Adverse reactions: Fatigue, nausea, musculoskeletal pain, hemorrhage, thrombocytopenia, headache; increased transaminases, constipation, epistaxis, oligohydramnios (do fetal testing if occurs), infertility.

Note: Enroll pregnant women who were exposed to Kadcyla in the MotHER Pregnancy Registry (800) 690-6720.

How supplied: Single-use vial—1

KISQALI Novartis

℞

Kinase inhibitor. Ribociclib 200mg; tabs.

Indications: In combination with an aromatase inhibitor, as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)negative advanced or metastatic breast cancer.

Adults: Swallow whole. 600mg once daily for 21 consecutive days followed by 7 days off treatment for a complete 28-day cycle. Take preferably in the AM with letrozole 2.5mg once daily throughout the 28-day cycle (see full labeling of letrozole or for dosing/administration with other aromatase inhibitors). Dose modifications: see full labeling. Moderate and severe hepatic impairment: initially 400mg once daily.

Children: Not established.

Warnings/Precautions: Avoid in patients with long QT syndrome, uncontrolled or significant cardiac disease including recent MI, CHF, unstable angina and bradyarrhythmias, electrolyte abnormalities. Assess ECG prior to initiation; start therapy only if QTcF values <450 msec. Repeat ECG at Day 14 of Cycle 1, beginning of Cycle 2, and as clinically indicated; monitor more frequently if any QTcF prolongation occurs. Monitor serum electrolytes prior to initiation, at the beginning of the first 6 cycles, and as clinically indicated; correct any abnormality before starting. Permanently discontinue if QTcF >500msec or >60msec change from baseline and associated with any of the following: Torsades de Pointes, polymorphic ventricular tachycardia, unexplained syncope, or serious arrhythmia. Perform LFTs prior to initiation; monitor every 2 weeks for first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated; monitor more frequently if Grade ≥2 abnormalities noted. Discontinue if AST/ALT >20XULN, Grade 3 (AST/ALT >5 to 20XULN) recurs, or AST/ALT >3XULN with total bilirubin >2XULN. Perform CBCs prior to initiation; monitor every 2 weeks for first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. Discontinue if any other Grade

4 toxicities occur. Embryo-fetal toxicity. Pregnancy: avoid; exclude status prior to initiation. Females of reproductive potential should use effective contraception during and for ≥3 weeks after last dose. Nursing mothers: not recommended (during and for ≥3 weeks after last dose).

Interactions: Avoid concomitant with strong CYP3A inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, voriconazole); consider alternatives; if unavoidable, reduce to Kisqali 400mg once daily.

Avoid grapefruit, pomegranates, pomegranate juice. Avoid concomitant with strong CYP3A inducers (eg, phenytoin, rifampin, carbamazepine, St. John’s wort); consider alternatives. Caution with concomitant CYP3A substrates with a narrow therapeutic index (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, midazolam, pimozide, quinidine, sirolimus, tacrolimus); may need to reduce these doses. Avoid concomitant with drugs known to prolong QT interval (eg, amiodarone, bepridil, chloroquine, clarithromycin, disopyramide, halofantrine, haloperidol, methadone, moxifloxacin, IV ondansetron, pimozide, procainamide, quinidine, sotalol).

Adverse reactions: Neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, back pain; QT prolongation, hepatobiliary toxicity, possible infertility.

How supplied: Blister pack—14, 21

PERJETA Genentech

℞

Human epidermal growth factor receptor (HER2) dimerization inhibitor. Pertuzumab 420mg/14mL (30mg/mL); soln for IV infusion; preservative-free.

Indications: In combination with trastuzumab and docetaxel: to treat patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease; for 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; verify pregnancy status prior to initiation.

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 7 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).

Note: 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

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DRUG MONOGRAPHS

BREAST CANCER 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, 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.

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: Breast cancer.

Adults: See literature.

Children: Not established.

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,

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DRUG MONOGRAPHS

BREAST CANCER 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

XELODA Genentech

℞

Fluoropyrimidine. Capecitabine (prodrug of 5-fluorouracil) 150mg, 500mg; tabs.

Indications: Metastatic breast cancer resistant to both paclitaxel and an anthracycline-

containing 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 full labeling. Give cyclically (2 weeks on, 1 week off). Swallow whole. 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 full labeling); 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 (eg, 950mg/m2 twice daily).

Children: <18yrs: not established.

Contraindications: Severe renal impairment (CrCl <30mL/min).

Warnings/Precautions: Hepatic or renal impairment. Monitor and correct dehydration at initiation. Coronary artery disease.

Interrupt therapy if Grade 2/3 hand-and-foot syndrome, Grade 2/3 or 4 diarrhea occurs (give antidiarrheals) until resolves or reduces to Grade 1.

Permanently discontinue if severe mucocutaneous reactions (eg, SJS, TEN) occur. Dihydropyrimidine dehydrogenase deficiency. Elderly. Embryo-fetal toxicity. Pregnancy: avoid; exclude status prior to initiation. Females of reproductive potential should use effective contraception (during therapy and for 6 months) and males with female partners (during and for 3 months) after final dose. Nursing mothers: not recommended (during and for 2 weeks after final dose.

Interactions: Increased anticoagulant effect with warfarin; monitor PT/INR frequently.

Potentiated by leucovorin. Monitor phenytoin and other CYP2C9 substrates.

Adverse reactions: Diarrhea, hand-andfoot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, hyperbilirubinemia; lymphopenia, necrotizing enterocolitis, stomatitis, dermatitis, anorexia, cardiotoxicity, blood dyscrasias, paresthesias, eye irritation, edema, myalgia, dehydration, alopecia.

Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase) How supplied: Tabs 150mg—60; 500mg—120

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DRUG MONOGRAPHS

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 mins on Days 1, 8, and 15 of each 28-day cycle. Moderate to severe hepatic impairment (total bilirubin >1.5): not recommended. Dose reductions for hematologic and neurologic adverse reactions: 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. Hepatic impairment (total bilirubin >5XULN or AST >10XULN): not recommended. Monitor for sensory neuropathy, sepsis, or pneumonitis. 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

AFINITOR Novartis

℞

mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs.

Indications: In adults with progressive neuroendocrine tumors of pancreatic origin (PNET) or progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of gastrointestinal or lung origin with unresectable, locally advanced or metastatic disease. Not for treating functional carcinoid tumors.

Adults: Swallow tabs whole with water. 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): 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/PgP 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/PgP inducers: consider doubling the daily dose by increments of 5mg or less. If strong inducer is discontinued, consider washout period of 3–5 days before returning to the dose used prior to initiating the strong inducer. Continue therapy until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions, or others: see full labeling.

Children: Not recommended.

Contraindications: Allergy to other rapamycin derivatives.

Warnings/Precautions: Monitor for new or worsening respiratory symptoms. Increased risk of infections; some may be severe or fatal; monitor and treat promptly if occur. Pre-existing invasive fungal infections: treat before starting.

Monitor for signs of wound-related complications.

Peri-surgical period. Hepatic impairment (see Adult dose). Monitor CBCs, renal function, lipids, and blood glucose prior to starting and periodically thereafter. Avoid close contact with those who have received live vaccines. Pediatrics: complete childhood vaccination series according to ACIP guidelines prior to initiation. Elderly.

Females of reproductive potential must use effective contraception during therapy and for 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Avoid live vaccines. Potentiated by strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), grapefruit or grapefruit juice; avoid. Caution with moderate CYP3A4/PgP inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem); reduce everolimus dose if used. Antagonized by strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s Wort; avoid.

Adverse reactions: Pneumonitis (interrupt, reduce dose and/or manage with corticosteroids; if severe, discontinue; may reintroduce 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), diarrhea, nausea, abdominal pain, rash, fatigue, edema, fever, asthenia, cough, headache, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum

phosphate; proteinuria, renal failure, others (see full labeling).

How supplied: Tabs—28 (4 blister cards × 7 tabs)

CAPRELSA Genzyme

℞

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. Dose adjustments for adverse reactions: see full labeling. Do not take a missed dose within 12hrs of the next dose.

Children: Not established.

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 (Child-Pugh B or C): not recommended. Interrupt therapy and follow-up if acute or worsening pulmonary symptoms, QTcF >500msec, or CTCAE Grade ≥3 toxicity occurs. Monitor for heart failure; consider discontinuing if occurs. Discontinue if confirmed interstitial lung disease, severe ischemic cerebrovascular event, hemorrhage, 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, rifampicin, 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). Potentiates OCT2 transporters (eg, metformin), digoxin; monitor.

Adverse reactions: Diarrhea/colitis (suspend if severe), rash, acneiform dermatitis, nausea, hypertension, headache, upper respiratory tract infections, decreased appetite, abdominal pain, hypocalcemia, hypoglycemia, increased ALT; QT prolongation, torsades de pointes, sudden death, severe skin reactions (eg,

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DRUG MONOGRAPHS

ENDOCRINE CANCER toxic epidermal necrolysis, Stevens-Johnson syndrome; permanently discontinue if occurs), photosensitivity.

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: Not interchangeable with cabozantinib tabs. 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.

Mild-to-moderate hepatic impairment: initially 80mg daily. Concomitant strong CYP3A4 inhibitors: 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. 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.

Severe hepatic impairment: not recommended.

Severe renal impairment. Monitor for bleeding, hypertension, proteinuria (measure urine protein regularly). Pregnancy. Females of reproductive potential should use effective contraception during and for 4 months after final dose. 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, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s Wort): see Adult dose. May be potentiated by MRP2 inhibitors (eg, abacavir, adefovir, cidofovir, furosemide, lamivudine, nevirapine, ritonavir, probenecid, saquinavir, tenofovir); monitor for increased toxicity.

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: 7x80mg and 21x20mg caps); 100mg daily-dose carton—4 blister cards (each: 7x80mg and 7x20mg caps); 60mg daily-dose carton—4 blister cards (each: 21x20mg caps)

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.

Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase).

How supplied: Contact supplier.

LENVIMA Eisai

℞

Kinase inhibitor. Lenvatinib 4mg, 10mg; capsules.

Indications: Treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.

Adults: Swallow whole or may dissolve capsule contents into liquid. 24mg once daily until disease progression or unacceptable toxicity occurs. Severe renal impairment (CrCl <30mL/min) or severe hepatic impairment (Child-Pugh C): 14mg once daily. Dose modifications for adverse reactions or lab abnormalities: see full labeling.

Children: Not established.

Warnings/Precautions: Control blood pressure prior to treatment; monitor after 1 week, every 2 weeks for the first 2 months, and then at least monthly thereafter during therapy.

Discontinue if life-threatening hypertension, Grade 4 cardiac dysfunction or hemorrhage, arterial thrombotic event, hepatic failure, nephrotic syndrome, GI perforation or lifethreatening fistula, or severe and persistent neurologic symptoms occur. Withhold if Grade 3 hypertension persists despite therapy, Grade 3 cardiac dysfunction or hemorrhage, ≥Grade 3 liver impairment or QT prolongation >500ms, Grade 3 or 4 renal failure/impairment, ≥2g of proteinuria/24hrs, or reversible posterior leukoencephalopathy syndrome (RPLS) occurs. Monitor for signs/symptoms of cardiac decompensation. Monitor liver function prior to treatment, every 2 weeks for the first 2 months, then at least monthly during treatment. Monitor for proteinuria prior to, and periodically during treatment. Monitor for dehydration and treat if diarrhea develops; interrupt if Grade 3 or 4 and permanently discontinue if Grade 4 diarrhea persists despite therapy. Hypovolemia. Congenital long QT syndrome, CHF, bradyarrhythmias, or

Access Cancer Therapy Advisor treatment regimens in a user-friendly format.

CancerTherapyAdvisor.com/TreatmentRegimens.

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DRUG MONOGRAPHS

ENDOCRINE CANCER those taking Class Ia or III antiarrhythmic drugs; monitor ECGs. Monitor and correct electrolyte abnormalities. Monitor blood calcium levels at least monthly; replace as needed during treatment. Monitor thyroid function prior to initiation and at least monthly thereafter; treat hypothyroidism as needed. ESRD. Embryofetal toxicity. Pregnancy: avoid. Use effective contraception during and for at least 2 weeks after treatment completion. Nursing mothers: not recommended.

Adverse reactions: Hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight decreased, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, dysphonia.

How supplied: Blister cards—6

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 (Child-Pugh 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

discontinue CYP3A inhibitors at least 1 week before initiating irinotecan.

Adverse reactions: Diarrhea, fatigue/asthenia, vomiting, nausea, decreased appetite, stomatitis, pyrexia; neutropenic fever or sepsis, dehydration, septic shock, pneumonia, acute renal failure, thrombocytopenia.

How supplied: Single-dose vial—1

ONIVYDE Ipsen

SOMATULINE DEPOT Ipsen

℞

Topoisomerase inhibitor. Irinotecan 43mg/10mL; liposomal dispersion for IV infusion after dilution.

Indications: In combination with fluorouracil and leucovorin, for treatment of metastatic adenocarcincoma of the pancreas after disease progression following gemcitabine-based therapy.

Limitations of use: as a single agent, not for the treatment of metastatic adenocarcinoma of the pancreas.

Adults: Do not substitute for other irinotecan HCl-containing drugs. Give by IV infusion over 90 mins prior to fluorouracil and leucovorin.

70mg/m2 every 2 weeks. If homozygous UGT1A1*28 allele: initially 50mg/m2; may increase to 70mg/m2 as tolerated in subsequent cycles.

If serum bilirubin >ULN: no dose recommended.

Premedicate with corticosteroid and antiemetic 30 mins prior to infusion. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Severe and lifethreatening neutropenia, neutropenic sepsis, diarrhea can occur. Monitor CBCs on Days 1 and 8 of every cycle and more frequently if indicated; withhold if ANC <1500/mm3 or neutropenic fever occurs; reduce dose in subsequent cycles for Grade 3–4 neutropenia or neutropenic fever after recovery. Bowel obstruction: do not administer. Withhold for Grade 2–4 diarrhea; initiate loperamide if late onset or atropine IV/SC (unless contraindicated) if early onset; resume at reduced dose after recovery to Grade 1. Withhold if new or progressive dyspnea, cough, and fever occurs, pending evaluation; discontinue if interstitial lung disease confirmed. Permanently discontinue if severe hypersensitivity reaction occurs. Females of reproductive potential should use effective contraception during therapy and for 1 month after final dose; males should use condoms during and for 4 months after final dose. Pregnancy. Nursing mothers: not recommended (during therapy and for 1 month after final dose).

Interactions: Avoid concomitant strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, St. John’s wort) if possible; substitute non-enzyme inducing therapies at least 2 weeks before initiating irinotecan. Avoid concomitant strong CYP3A4 (eg, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) or UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir) if possible;

℞

Somatostatin analogue. Lanreotide 60mg, 90mg, 120mg; prolonged-release soln for SC inj.

Indications: Treatment of unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival.

Adults: Give by deep SC inj into the superior external quadrant of the buttock. Rotate inj site.

120mg every 4 weeks.

Children: Not established.

Warnings/Precautions: Diabetes.

Hypothyroidism. Cardiovascular disease.

Hepatic or severe renal impairment. Monitor thyroid function, gallbladder, glucose. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Potentiates bromocriptine, CYP450 substrates (eg, quinidine, terfenadine), bradycardia-inducing drugs (eg, β-blockers); adjust doses. Antagonizes cyclosporine; adjust dose. May need to adjust antidiabetic agents.

Adverse reactions: Diarrhea, cholelithiasis, abdominal pain, nausea, inj site reactions; gallbladder sludge, gallstones, hyperglycemia, hypoglycemia, sinus bradycardia, hypertension, anemia; rare: hypothyroidism.

How supplied: Single-use pre-filled syringe—1

SUTENT Pfizer

℞

Multikinase inhibitor. Sunitinib (as malate) 12.5mg, 25mg, 37.5mg, 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 events: monitor for CHF during therapy, and LVEF at baseline and periodically;

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DRUG MONOGRAPHS

ENDOCRINE CANCER 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. Monitor blood glucose levels during and after treatment discontinuation.

Monitor for proteinuria; perform baseline and periodic urinalyses; interrupt and reduce dose if 24-hr urine protein ≥3g; discontinue if nephrotic syndrome or repeat urine protein ≥3g persists.

Undergoing major surgery. Stress (monitor for adrenal insufficiency). Discontinue if severe cutaneous reactions (eg, erythema multiforme, SJS, TEN) develop; do not restart if diagnosis suspected. ESRD on dialysis. Severe 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; consider reducing dose or use alternate drug. May be antagonized by CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital); consider increasing dose or use alternate drug. Concomitant St. John’s wort: not recommended. Caution with concomitant antiarrhythmics.

Adverse reactions: Fatigue, asthenia, fever, diarrhea, nausea, vomiting, mucositis/stomatitis, dyspepsia, abdominal pain, constipation, hypertension, peripheral edema, rash, hand-foot 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, osteonecrosis of the jaw, tumor lysis syndrome, thyroid dysfunction, impaired wound healing, hypoglycemia, thrombotic microangiopathy (discontinue if develops), proteinuria, necrotizing fasciitis (discontinue if occurs), others (see full labeling).

How supplied: Caps—28

TARCEVA Astellas and Genentech

℞

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 full labeling). Use until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions: see full labeling. Concomitant strong CYP3A4 inhibitors (see Interactions): reduce by 50mg decrements; avoid use if possible. Concomitant CYP3A4 inducers (see Interactions): increase by 50mg increments at 2-week intervals (max 450mg); avoid use if possible. Concurrent cigarette smoking: increase by 50mg increments at 2-week intervals (max 300mg); upon cessation, reduce to 150mg or 100mg daily.

Children: Not established.

Warnings/Precautions: Discontinue if interstitial lung disease, severe hepatic toxicity, GI perforation, severe bullous, blistering or exfoliating skin conditions, or corneal perforation or severe ulceration occurs. Withhold or consider discontinuing therapy if severe renal failure due to dehydration, or acute/worsening ocular disorders occur. Monitor LFTs periodically; withhold in patients without history of hepatic impairment for total bilirubin >3XULN or transaminases >5XULN, or in patients with history of hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases over baseline. Discontinue if abnormal LFTs do not improve or resolve within 3 weeks. Withhold for acute onset of unexplained pulmonary symptoms pending evaluation, persistent severe diarrhea unresponsive to loperamide, severe rash, grade 3–4 keratitis or grade 2 lasting ≥2 weeks.

Monitor renal function, serum electrolytes, pulmonary function, INR, prothrombin time.

History of peptic ulcers or diverticular disease.

Embryo-fetal toxicity. Pregnancy: avoid. Females of reproductive potential should use effective contraception during therapy and at least 1 month after the last dose. Nursing mothers: not recommended (during and for 2 weeks after the last dose).

Interactions: Potentiated by CYP3A4 inhibitors (eg, atazanavir, boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit) or a combined CYP3A4 and CYP1A2 inhibitor (eg, ciprofloxacin); reduce dose if unavoidable. Plasma

levels decreased by CYP3A4 inducers (eg, rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, St. John’s wort); increase dose if unavoidable. Avoid concomitant moderate CYP1A2 inducers (eg, teriflunomide, rifampin, phenytoin) or smoking tobacco; increase dose if unavoidable. Avoid concomitant proton pump inhibitors if possible. Separate dosing of antacids by several hours or for H2 blockers (take erlotinib 10hrs after and at least 2hrs before next dose).

Increased risk of GI perforation with concomitant anti-angiogenic agents, steroids, NSAIDs, taxanebased chemotherapy. Monitor for bleeding with oral anticoagulants, NSAIDs. Adverse reactions: Rash, diarrhea, nausea, vomiting, 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 with thrombocytopenia, cerebrovascular accident (in pancreatic cancer), 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

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

Take advantage of our free online medical calculators at CancerTherapyAdvisor.com/MedicalCalculators.

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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. 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: Risk of GI perforations, surgery and wound healing complications, and hemorrhage. Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). Do not administer if recent history of hemoptysis of ≥ ½-teaspoon of red blood. Permanently discontinue if GI perforation, tracheoesophageal fistula, any grade 4 fistula, or grade 4 venous thromboembolic event. Discontinue if fistula involving internal organ, wound healing complications, hemorrhage, severe arterial thromboembolic event (ATE), hypertensive crisis or encephalopathy, posterior reversible encephalopathy syndrome (PRES), or nephrotic syndrome occurs; suspend therapy if severe hypertension, moderate-to-severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Avoid in ovarian cancer if evidence of recto-sigmoid involvement by pelvic exam, bowel involvement on CT scan, or symptoms of bowel obstruction. History of arterial thromboembolism.

Diabetes. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis; if ≥2+, do further assessment with a 24-hour urine collection. Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy: may cause fetal harm; use effective contraception during and for 6 months after last dose. Nursing mothers: not recommended.

Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation and fistulae, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, PRES, infusion reactions, ovarian failure, neutropenia, infection.

How supplied: Single-use vial—1

CYRAMZA Lilly

℞

Human IgG1 monoclonal antibody. Ramucirumab 10mg/mL; per vial; soln for IV infusion after dilution; preservative-free.

Indications: As a single agent, or in combination with paclitaxel, for treatment of advanced or metastatic, gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinumcontaining chemotherapy. In combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), for the treatment of metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

Adults: Give by IV infusion over 60 mins.

Premedicate with IV histamine H1-antagonist (eg, diphenhydramine) prior to each infusion; or with dexamethasone and acetaminophen in those who have experienced Grade 1 or 2 infusion reaction. Gastric cancer: 8mg/kg every 2 weeks.

When given in combination: administer prior to paclitaxel. mCRC: 8mg/kg every 2 weeks prior to FOLFIRI. Continue until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Increased risk of hemorrhage; permanently discontinue if severe bleeding occurs. Control hypertension prior to initiating. Monitor blood pressure every 2 weeks or more frequently as indicated; if severe hypertension develops, temporarily suspend until medically controlled. Monitor for infusion-related reactions during therapy. Have emergency resuscitative equipment available.

Permanently discontinue if severe arterial thromboembolic events, severe uncontrolled hypertension (despite antihypertensives), hypertensive crisis or encephalopathy, Grade 3 or 4 infusion-related reactions, urine protein >3g/24hrs, nephrotic syndrome, or GI perforation occurs. Impaired wound healing: withhold Cyramza prior to surgery. Clinical deterioration in patients with Child-Pugh B or C cirrhosis (eg, new or worsening encephalopathy, ascites, hepatorenal syndrome). Discontinue if reversible posterior leukoencephalopathy syndrome develops. Monitor proteinuria by urine dipstick and/or urinary protein creatinine ratio. Monitor thyroid function. Pregnancy: avoid. Use effective contraception during therapy and for ≥3 months after last ramucirumab dose. Nursing mothers: not recommended.

Adverse reactions: Hypertension, diarrhea, headache, fatigue, asthenia, hyponatremia, anemia, intestinal obstruction, neutropenia, epistaxis, stomatitis/mucosal inflammation, rash, decreased appetite; arterial thromboembolic events, proteinuria, GI perforation, infusionrelated reactions.

How supplied: Single-dose vial (10mL, 50mL)—1

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 full labeling. Premedicate with antiemetics. Give by IV infusion every two weeks for a total of 6 months (12 cycles) for adjuvant use or until disease progression or unacceptable toxicity for advanced disease. 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 full labeling for dose adjustments.

Children: Not established.

Contraindications: Known allergy to other platinum compounds.

Warnings/Precautions: Monitor for allergic reactions; discontinue if occurs; do not rechallenge.

Have epinephrine, corticosteroids, antihistamines available during infusion. Monitor for neuropathy; reduce dose or discontinue if needed. Severe neutropenia: delay therapy until neutrophils ≥1.5 × 109/L; withhold for sepsis or septic shock; reduce dose after recovery. Monitor WBCs with differential, hemogloblin, platelets, blood chemistries (including ALT, AST, bilirubin, creatinine) before each cycle. Discontinue if interstitial lung disease or pulmonary fibrosis is suspected. Patients with CHF, bradyarrhythmias, concomitant drugs known to prolong the QT interval, and electrolyte abnormalities: monitor ECG. Correct hypokalemia or hypomagnesemia prior to initiation; monitor periodically during therapy. Congenital long QT syndrome; avoid. Renal impairment. 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, fatigue, stomatitis; allergic reactions, pulmonary fibrosis (may be fatal), hepatotoxicity, QT prolongation, ventricular arrhythmias, rhabdomyolysis (may be fatal; discontinue if occurs).

Testing considerations: ERCC1 overexpression How supplied: Single-use vials (50mg, 100mg)—1

ERBITUX Lilly

℞

Epidermal growth factor receptor blocker.

Cetuximab 100mg/vial, 200mg/vial; soln for IV infusion; preservative-free.

Indications: K-Ras (wild-type), EGFRexpressing metastatic colorectal cancer: for

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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 irinotecan- and oxaliplatin-based regimens or if irinotecanintolerant). Limitation of use: not indicated for Ras mutant colorectal cancer that harbor somatic mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) or when Ras mutation test results are unknown.

Adults: Confirm EGFR expression status (using FDA-approved tests) and absence of Ras mutation prior to initiation. Pretreat with H1 blocker. Give by IV infusion (use filter); max rate: 10mg/min. Initial dose: 400mg/m2 once over 2hrs; then 250mg/m2 once weekly over 1 hour until disease progression or unacceptable toxicity. Complete administration 1hr 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 1hr postinfusion. Skin toxicity: see full labeling.

Children: Not established.

Warnings/Precautions: Monitor for serious infusion reactions; immediately interrupt and permanently discontinue if occur. Risk of cardiopulmonary arrest and/or sudden death; carefully consider use (w. irradiation or platinumbased therapy with 5-FU) in coronary artery disease, CHF, or arrhythmias. Monitor electrolytes (eg, magnesium, potassium, calcium) during and for ≥8wks after cetuximab therapy. Interrupt for acute onset or worsening pulmonary symptoms; permanently discontinue if interstitial lung disease confirmed. Monitor for dermatologic toxicities (eg, acneiform rash) and infection; avoid sun exposure. Additive cutaneous reactions with irradiation. 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 (eg, rash, pruritus, nail changes), headache, diarrhea, infection; infusion reactions (may be severe), cardiopulmonary arrest, interstitial lung disease, dermatologic toxicities, electrolyte abnormalities (eg, hypomagnesemia), sepsis, renal failure, pulmonary embolus.

Testing considerations: EGFR amplification analysis, K-RAS mutation analysis, B-RAF mutation analysis.

How supplied: Single-use vials—1

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.

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; scored 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. Avoid concomitant strong CYP3A4 inducers (eg, rifampin): if needed, 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 and potential toxicities (liver, kidney, cardiac) from long-term

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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. Embryo-fetal toxicity. Pregnancy (avoid); exclude status prior to initiation. Females of reproductive potential should use highly effective contraception during treatment and for 14 days after cessation. Nursing mothers: not recommended (during and for 1 month after final dose).

Interactions: Avoid grapefruit juice.

Potentiated by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by strong CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin, rifabutin, rifampicin); consider alternatives. May potentiate drugs metabolized by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain statins, sirolimus, tacrolimus) or CYP2C9 (use heparin instead of warfarin). Caution with concomitant CYP2D6 substrates that have a narrow therapeutic window.

Adverse reactions: Edema (may be severe), nausea, vomiting, musculoskeletal pain, diarrhea, muscle cramps, rash (may be severe; eg, erythema multiforme, StevensJohnson 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: Do not substitute for or with adotrastuzumab emtasine. Give as IV infusion.

Initially 8mg/kg over 90 mins, followed by 6mg/kg over 30–90 mins every 3 weeks until

disease progression. Infusion reactions or cardiomyopathy: see full labeling.

Children: Not established.

Warnings/Precautions: Increased risk of cardiomyopathy. Conduct cardiac assessment (eg, history, physical exam, LVEF) at baseline, every 3 months during and after therapy or every 6 months for ≥2yrs after therapy (if adjuvant); 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 FDAapproved tests for specific tumor type (breast or gastric/gastroesophageal adenocarcinoma).

Embryo-fetal toxicity (eg, oligohydramnios): exclude pregnancy status before initiation.

Pregnancy: avoid; use effective contraception during and for 7 months after therapy. Nursing mothers.

Interactions: Increased cardiomyopathy with anthracycline-containing chemotherapy.

Increased toxicity with other myelosuppressives.

Adverse reactions: Diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, dysgeusia, infections; severe infusion reactions, febrile neutropenia/exacerbation of chemotherapy-induced neutropenia, pulmonary toxicity (eg, interstitial pneumonitis), cardiomyopathy (eg, left ventricular myocardial dysfunction); pregnant women: possible oligohydramnios (monitor).

Testing considerations: HER2 protein overexpression How supplied: Vial—1 (w. diluent)

KEYTRUDA Merck

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Pembrolizumab 50mg/vial; lyophilized pwd for IV infusion after reconstitution; 25mg/mL; per vial; soln for IV infusion after dilution; both: preservative-free.

Indications: Unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient: colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan; solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. Limitations of use: the safety and efficacy of Keytruda in pediatrics with MSI-H CNS cancers have not been established.

Adults: Give as IV infusion over 30mins.

200mg every 3 weeks until disease progression,

unacceptable toxicity, or up to 24 months in patients without disease progression. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.

Children: Give as IV infusion over 30mins. 2mg/kg (max 200mg) every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.

Warnings/Precautions: Monitor for pneumonitis; withhold dose if Grade 2 pneumonitis; permanently discontinue if Grade 3 or 4, or recurrent Grade 2 develops.

Monitor for colitis; withhold dose if Grade 2 or 3 colitis; permanently discontinue if Grade 4 develops. Monitor for changes in liver function; withhold dose or discontinue based on severity of elevated liver enzymes. Monitor for changes in renal function; withhold dose if Grade 2 nephritis; permanently discontinue if Grade 3 or 4 develops. Monitor for hypophysitis; withhold dose if Grade 2 hypophysitis; withhold or discontinue if Grade 3 or 4 develops. Monitor for changes in thyroid function (at treatment initiation, during, and as clinically indicated) and signs/symptoms of thyroid disorders; withhold or discontinue if Grade 3 or 4 hyperthyroidism develops. Monitor for hyperglycemia and other diabetes symptoms; withhold if severe hyperglycemia until controlled. Withhold dose if Grade 4 hematological toxicity in cHL patients develops. Permanently discontinue if any severe or Grade 3 immune-mediated adverse reaction recurs, for any life-threatening immune-mediated adverse reaction (except endocrinopathies controlled with hormone replacement or hematological toxicity in cHL patients), persistent Grade 2 or 3 reactions that do not recover to Grade 0–1 within 12wks after last dose, or inability to reduce corticosteroid dose to ≤10mg/day of prednisone or equivalent within 12wks. Monitor for infusion-related reactions; permanently discontinue if Grade 3 or 4 develops. Complications of allogeneic HSCT after Keytruda: monitor for hepatic VOD, Grade 3 or 4 acute GVHD, steroid-requiring febrile syndrome, and others. Embryo-fetal toxicity.

Females of reproductive potential should use highly effective contraception during therapy and for 4 months after the final dose. Pregnancy: avoid. Nursing mothers: not recommended (during therapy and for 4 months after the final dose).

Adverse reactions: Fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, nausea; immune-mediated disorders, infusionrelated reactions.

How supplied: Single-use vial 50mg—1; Singleuse vial 25mg/mL—1

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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 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

LONSURF Taiho Oncology

℞

Antineoplastic thymidine-based nucleoside analog + thymidine phosphorylase inhibitor.

Trifluridine, tipiracil; 15mg/6.14mg, 20mg/8.19mg; tabs.

Indications: Treatment of metastatic colorectal cancer in patients previously treated with fluoropyrimidine-, oxaliplatin- and irinotecanbased chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

Adults: Take within 1 hour after completion of AM & PM meals. Initially 35mg/m2 twice daily on Days 1–5 and 8–12 of each 28-day cycle until disease progression or unacceptable toxicity; max 80mg per dose (based on trifluridine component). Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Obtain CBC prior to and on Day 15 of each cycle, and as clinically indicated. Do not initiate cycle until ANC ≥1,500/mm3 or febrile neutropenia is resolved, platelets ≥75,000/mm3 or Grade 3/4 nonhematological adverse reactions resolved to Grade 0/1. Withhold dose if ANC <500/mm3 or febrile neutropenia, platelets <50,000/mm3, or Grade 3/4 non-hematological adverse reactions occur; upon recovery, resume at a reduced dose (see full labeling). Moderate or severe hepatic impairment: do not initiate. Moderate renal impairment: may require dose modification; severe (CrCl <30mL/min) or ESRD: not studied.

Elderly. Pregnancy. Females of reproductive potential must use effective contraception during treatment; males must use condoms during and for ≥3 months after final dose. Nursing mothers: not recommended (during treatment and for 1 day after final dose).

Adverse reactions: Anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, pyrexia.

How supplied: Tabs—20, 40, 60

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

STIVARGA Bayer

℞

Kinase inhibitor. Regorafenib 40mg; tabs.

Indications: Metastatic colorectal cancer in patients who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecanbased chemotherapy, an anti-VEGF therapy, and, if RAS wild type, an anti-EGFR therapy.

Locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) in patients who have been previously treated with imatinib mesylate or sunitinib malate. Hepatocellular carcinoma (HCC) in patients previously treated with sorafenib.

Adults: Swallow whole with water after a lowfat meal (contains <600 calories and <30% fat). 160mg once daily for the first 21 days of each 28-day cycle; until disease progression or unacceptable toxicity. Dose modifications: reduce by 40mg increments (see full labeling).

Children: <18yrs: not established.

Warnings/Precautions: Risk of severe liver injury (may be fatal). Obtain LFTs before starting and at least every 2 weeks during first 2 months of treatment; interrupt and reduce or discontinue if persistent hepatotoxicity or hepatocellular necrosis occurs. Severe hepatic impairment: not recommended. Increased risk of infections; withhold if Grade 3/4 occurs or infection of any grade worsens; resume when resolved. Permanently discontinue if severe or life-threatening hemorrhage occurs. Interrupt and reduce or permanently discontinue if dermatological toxicity occurs (eg, hand-foot skin reaction [a.k.a. palmarplantar erythrodysesthesia], rash). Ensure BP is controlled before starting; monitor weekly for the first 6 weeks then every cycle or as clinically

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER indicated; withhold if severe or uncontrolled.

Increased risk of myocardial ischemia/infarction: withhold if new or acute onset develops; resume when resolved. Discontinue if reversible posterior leukoencephalopathy syndrome (RPLS) or GI perforation/fistula develops. Wound healing complications: stop treatment at least 2 weeks before surgery; discontinue if wound dehiscence occurs. Asian patients (monitor). Dialysis.

Embryo-fetal toxicity. Females and males of reproductive potential should use effective contraception during treatment and up to 2 months after completion. Pregnancy. Nursing mothers: not recommended (during and for 2 weeks after final dose).

Interactions: Potentiated by strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, voriconazole); avoid. Antagonized by strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, St. John’s Wort); avoid. Potentiates BCRP substrates (eg, methotrexate, fluvastatin, atorvastatin); monitor closely. 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, hyperbilirubinemia, 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, 37.5mg, 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 events: monitor for CHF during therapy, and LVEF at baseline and periodically; 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. Monitor blood glucose levels during and after treatment discontinuation.

Monitor for proteinuria; perform baseline and periodic urinalyses; interrupt and reduce dose if 24-hr urine protein ≥3g; discontinue if nephrotic syndrome or repeat urine protein ≥3g persists.

Undergoing major surgery. Stress (monitor for adrenal insufficiency). Discontinue if severe cutaneous reactions (eg, erythema multiforme, SJS, TEN) develop; do not restart if diagnosis suspected. ESRD on dialysis. Severe 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; consider reducing dose or use alternate drug. May be antagonized by CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital); consider increasing dose or use alternate drug. Concomitant St. John’s wort: not recommended. Caution with concomitant antiarrhythmics.

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, osteonecrosis of the jaw, tumor lysis syndrome, thyroid dysfunction, impaired wound healing, hypoglycemia, thrombotic microangiopathy (discontinue if develops), proteinuria, necrotizing fasciitis (discontinue if occurs), others (see full labeling).

How supplied: Caps—28

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 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 Genentech

℞

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 full labeling. Give cyclically (2 weeks on, 1 week off). Swallow whole. 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 full labeling); 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 (eg, 950mg/m2 twice daily).

Children: <18yrs: not established.

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER Contraindications: Severe renal impairment (CrCl <30mL/min).

Warnings/Precautions: Hepatic or renal impairment. Monitor and correct dehydration at initiation. Coronary artery disease.

Interrupt therapy if Grade 2/3 hand-and-foot syndrome, Grade 2/3 or 4 diarrhea occurs (give antidiarrheals) until resolves or reduces to Grade 1. Permanently discontinue if severe mucocutaneous reactions (eg, SJS, TEN) occur.

Dihydropyrimidine dehydrogenase deficiency.

Elderly. Embryo-fetal toxicity. Pregnancy: avoid; exclude status prior to initiation. Females of reproductive potential should use effective contraception (during therapy and for 6 months) and males with female partners (during and for 3 months) after final dose. Nursing mothers: not recommended (during and for 2 weeks after final dose.

Interactions: Increased anticoagulant effect with warfarin; monitor PT/INR frequently.

Potentiated by leucovorin. Monitor phenytoin and other CYP2C9 substrates.

Adverse reactions: Diarrhea, hand-andfoot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, hyperbilirubinemia; lymphopenia, necrotizing enterocolitis, stomatitis, dermatitis, anorexia, cardiotoxicity, blood dyscrasias, paresthesias, eye irritation, edema, myalgia, dehydration, alopecia.

Testing considerations: TS (thymidylate synthase), MSI (microsatellite instability), DPD (dihydropyrimidine dehydrogenase) How supplied: Tabs 150mg—60; 500mg—120

ZALTRAP Sanofi US and Regeneron

℞

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 ≥1.5x109/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

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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DRUG MONOGRAPHS

GENITOURINARY CANCER AFINITOR Novartis

℞

mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs.

Indications: In adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. In adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.

Adults: Swallow tabs whole with water. 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): 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/PgP 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/PgP inducers: consider doubling the daily dose by increments of 5mg or less. If strong inducer is discontinued, consider washout period of 3–5 days before returning to the dose used prior to initiating the strong inducer.

Continue therapy until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions, or others: see full labeling.

Children: Not recommended.

Contraindications: Allergy to other rapamycin derivatives.

Warnings/Precautions: Monitor for new or worsening respiratory symptoms. Increased risk of infections; some may be severe or fatal; monitor and treat promptly if occur.

Pre-existing invasive fungal infections: treat before starting. Monitor for signs of woundrelated complications. Peri-surgical period.

Hepatic impairment (see Adult dose). Monitor CBCs, renal function, lipids, and blood glucose prior to starting and periodically thereafter.

Avoid close contact with those who have received live vaccines. Pediatrics: complete childhood vaccination series according to ACIP guidelines prior to initiation. Elderly. Females of reproductive potential must use effective contraception during therapy and for 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended.

Interactions: Avoid live vaccines. Potentiated by strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), grapefruit or grapefruit juice; avoid. Caution with moderate CYP3A4/PgP inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem); reduce

everolimus dose if used. Antagonized by strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s Wort; avoid.

Adverse reactions: Pneumonitis (interrupt, reduce dose and/or manage with corticosteroids; if severe, discontinue; may reintroduce 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), diarrhea, nausea, abdominal pain, rash, fatigue, edema, fever, asthenia, cough, headache, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see full labeling).

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. 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, non-GI fistula formation, wound healing complications, serious hemorrhage, severe arterial or Grade 4 venous thromboembolic events, hypertensive crisis, nephrotic syndrome, or posterior reversible encephalopathy syndrome occurs; suspend therapy if severe hypertension, moderate to severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Cardiovascular disease. Diabetes. Monitor BP every 2–3 weeks.

Monitor proteinuria by dipstick urine analysis.

Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy (Cat.C). Nursing mothers: not recommended.

Adverse reactions: Epistaxis, headache, hypertension, 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 or venous thromboembolic events, posterior reversible encephalopathy syndrome, infusion reactions, ovarian failure.

How supplied: Single-use vial—1

BAVENCIO EMD Serono

℞

Programmed death-ligand 1 (PD-L1) blocking antibody. Avelumab 20mg/mL; soln for IV infusion after dilution; preservative-free; contains mannitol.

Indications: Treatment of locally advanced or metastatic urothelial carcinoma (UC) in patients who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinumcontaining chemotherapy.

Adults: Premedicate with an antihistamine and acetaminophen prior to the first 4 infusions; then subsequent doses as clinically indicated. Give as IV infusion over 60mins. 10mg/kg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: <12yrs: not established.

Warnings/Precautions: See full labeling.

Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event.

Permanently discontinue for Grade 3/4 pneumonitis or recurrent Grade 2 pneumonitis, Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis, AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, any life-threatening (Grade 4) or recurrent severe (Grade 3) immune-mediated adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2/3 immune-mediated adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2/3 diarrhea or colitis, Grade 3/4 adrenal insufficiency, Grade 3/4 thyroid disorders, Grade 3/4 hyperglycemia, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN; withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if Grade 1/2 infusion reactions occur; permanently discontinue if Grade 3/4. Monitor for abnormal liver tests, adrenal insufficiency, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Embryo-fetal toxicity.

Females of reproductive potential should use effective contraception during and for ≥1 month after final dose. Pregnancy. Nursing mothers: not recommended (during and for ≥1 month after final dose).

Adverse reactions: Fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reactions, rash, decreased appetite, peripheral edema, UTI; other immune-mediated adverse reactions (may be fatal).

How supplied: Single-dose vial (10mL)—1

CABOMETYX Exelixis

℞

Kinase inhibitor. Cabozantinib 20mg, 40mg, 60mg; tabs.

Indications: Treatment of advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy.

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DRUG MONOGRAPHS

GENITOURINARY CANCER Adults: Do not substitute with cabozantinib caps. Swallow whole. 60mg daily. Do not eat at least 2 hours before or 1 hour after dose. Continue until disease progression or unacceptable toxicity. Stop treatment at least 28 days prior to scheduled surgery (including dental). Withhold for Grade 4 adverse reactions, Grade 3 or intolerable Grade 2 adverse reactions that are unmanageable with dose reduction or supportive care. Upon improvement to Grade 1 or to baseline, reduce dose as follows: previously on 60mg daily, resume at 40mg daily; previously on 40mg daily, resume at 20mg daily; previously on 20mg daily, resume at 20mg if tolerated, otherwise discontinue.

Concomitant a strong CYP3A4 inhibitor: reduce daily dose by 20mg; resume dose used prior to starting inhibitor 2–3 days after discontinuation of inhibitor. Concomitant a strong CYP3A4 inducer: increase daily dose by 20mg; resume dose used prior to starting inducer 2–3 days after discontinuation of inducer. Max daily dose: 80mg. Mild or moderate hepatic impairment: initially 40mg once daily.

Children: Not studied.

Warnings/Precautions: Permanently discontinue if the following occurs: unmanageable GI perforation/fistula, severe hemorrhage, serious arterial thromboembolic events (eg, MI, cerebral infarction), hypertensive crisis or severe hypertension despite optimal medical management, nephrotic syndrome, reversible posterior leukoencephalopathy syndrome. Recent history or risk of severe hemorrhage: do not administer. Monitor for GI perforations/fistulas. Monitor BP regularly; withhold for hypertension inadequately controlled with medical management; resume at reduced dose when resolved. Withhold therapy if intolerable Grade 2 diarrhea, unmanageable Grade 3/4 diarrhea, or intolerable Grade 2/3 palmar-plantar erythrodysesthesia syndrome (PPES) develops until improvement to Grade 1; resume at reduced dose. Severe hepatic impairment: not recommended. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for 4 months after final dose. Pregnancy. Nursing mothers: not recommended (during and for 4 months after final dose).

Interactions: Avoid concomitant strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit or grapefruit juice) and strong

CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, rifabutin, rifapentine, St. John’s Wort); if unavoidable, see Adult dose.

Adverse reactions: Diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension, vomiting, weight decreased, constipation, lab abnormalities.

How supplied: Tabs—30

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. Pregnancy.

Warnings/Precautions: Moderate to severe hepatic impairment. Monitor prostate specific antigen and hepatic function (discontinue if ALT >2xULN or if jaundice occurs). Males with female partners of reproductive potential should use effective contraception during therapy and for 130 days after final dose. Nursing mothers.

Interactions: Monitor oral anticoagulants.

Adverse reactions: Hot flashes, gynecomastia, breast pain, diarrhea, pain, asthenia, infection, dyspnea, impotence, loss of libido, others (see full labeling); rare: hepatitis.

How supplied: Tabs—30, 100

DELESTROGEN JHP

℞

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

ELIGARD Tolmar

℞

GnRH analogue. Leuprolide acetate 7.5mg, 22.5mg, 30mg, 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.

Rotate inj sites. 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.

Children: Not established.

Contraindications: 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. Risk of QT prolongation in patients with congenital long QT syndrome, CHF, or frequent electrolyte abnormalities. Correct and monitor electrolyte abnormalities; consider monitoring ECGs. Monitor serum testosterone, PSA periodically. Nursing mothers: not recommended.

Interactions: Caution with concomitant drugs known to prolong the QT interval. May interfere with pituitary-gonadal diagnostic tests.

Adverse reactions: Malaise, fatigue, hot flashes/sweats, testicular atrophy, local reactions (eg, burning/stinging, pain, erythema, bruising, pruritus); transient worsening of signs/symptoms (eg, bone pain, neuropathy, hematuria, bladder outlet obstruction), spinal cord compression, hyperglycemia, decreased bone density; rare: pituitary apoplexy.

How supplied: Single-use kit—1 (with sterile or sterile safety needle)

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DRUG MONOGRAPHS

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 Allergan

℞

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

FIRMAGON Ferring

℞

GnRH 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: Congenital long QT syndrome. CHF. Correct electrolyte abnormalities. Monitor electrolytes and ECG periodically. Monitor serum PSA. Discontinue if serious hypersensitivity reaction occurs; do not rechallenge. Moderate or severe renal impairment (CrCl <50mL/min). Severe hepatic impairment. Nursing mothers: not recommended.

Interactions: Caution with concomitant drugs known to prolong the QT interval.

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)

IMFINZI AstraZeneca ℞

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 ≥2xULN: not recommended.

Warnings/Precautions: Monitor liver function at baseline, monthly for first 4 months, then periodically, and if liver dysfunction occurs; if ALT >2xULN or jaundice occurs, discontinue and monitor closely until resolution. Monitor prostate specific antigen (PSA). Consider monitoring methemoglobin levels in patients susceptible to aniline toxicity (e.g., 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 Baxter Alkylating agent. Ifosfamide 1g, 3g; per vial; pwd for IV infusion after reconstitution.

Indications: Third-line adjunctive treatment of germ cell testicular cancer.

Adults: Give by slow IV infusion over at least 30 mins. 1.2g/m2 per day for 5 consecutive days; repeat every 3 weeks or after hematological recovery (platelets ≥100000/μL, WBC ≥4000/μL).

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 profile before each dose; discontinue if WBCs <2000/μL or platelets <50000/μL. 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: Single-dose vials—1

℞

℞

Programmed death-ligand 1 (PD-L1) blocking antibody. Durvalumab 50mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: Locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or after platinumcontaining chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

Adults: Give as IV infusion over 60mins.

10mg/kg every 2 weeks until disease progression or unacceptable toxicity.

Children: Not established.

Warnings/Precautions: Permanently discontinue if Grade 3/4 pneumonitis, AST or ALT >8×ULN or total bilirubin >5×ULN, concurrent AST or ALT >3×ULN and total bilirubin >2×ULN (with no other cause), Grade 3/4 colitis or diarrhea, creatinine ≥3×ULN, Grade 3/4 infusion-related reactions, or Grade 4 rash/dermatitis.

Withhold for Grade 2 pneumonitis, AST or ALT >3–5×ULN or total bilirubin >1.5–3×ULN, AST or ALT ≤8×ULN or total bilirubin ≤5×ULN, Grade 2 colitis or diarrhea, Grade ≥2 hypophysitis/hypopituitarism, Grade ≥2 adrenal insufficiency, Grade ≥2 hyperthyroidism, Grade ≥2 type 1 diabetes, creatinine >1.5–3×ULN, Grade 3/4 infection, Grade 2 (if >1 week) or Grade 3 rash. Monitor for immune-related pneumonitis, hepatitis (obtain LFTs each cycle), colitis/diarrhea, endocrinopathies

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DRUG MONOGRAPHS

GENITOURINARY CANCER (thyroid disorders, adrenal insufficiency, diabetes, hypophysitis/hypopituitarism), rash, thrombocytopenia purpura, nephritis; see full labeling for adverse reaction management details. Monitor for signs/symptoms of infection and treat with anti-infectives for suspected or confirmed infections. Interrupt or slow the infusion rate in patients with mild or moderate infusion reactions. Embryo-fetal toxicity.

Pregnancy. Females of reproductive potential should use effective contraception during therapy and for ≥3 months after final dose.

Nursing mothers: not recommended (during and for ≥3 months after final dose).

Adverse reactions: Fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, urinary tract infection; other immune-related reactions (eg, aseptic meningitis, hemolytic anemia), infusion-related reactions, lab abnormalities.

How supplied: Single-dose vial (2.4mL, 10mL)—1

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. Monitor for signs/symptoms of cardiac failure during therapy; permanently discontinue if occurs.

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 (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.

How supplied: Tabs 1mg—180; 5mg—60

JEVTANA Sanofi Aventis

℞

Antimicrotubule agent. 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 mins before each dose (see full labeling) and with antiemetic (IV or oral as needed). 25mg/m2

by IV infusion over 1hr 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, grade 2 peripheral neuropathy: delay treatment and/or reduce dose to 20mg/m2 (see full labeling).

Discontinue if grade ≥3 peripheral neuropathy or if any reactions persist after dosing at 20mg/m2.

Hepatic impairment: (mild): reduce starting dose to 20mg/m2; (moderate): reduce to 15mg/m2. If concomitant a strong CYP3A inhibitor necessary, consider a 25% cabazitaxel dose reduction.

Children: Not established.

Contraindications: Baseline neutrophil count ≤1,500cells/mm3. Allergy to polysorbate 80.

Severe hepatic impairment (total bilirubin >3XULN).

Warnings/Precautions: Increased risk of neutropenia complications; consider G-CSF prophylaxis. Do CBC weekly in 1st cycle and before each subsequent cycle. Patients with hemoglobin <10g/dL. Discontinue if hypersensitivity reactions occur. Increased risk of GI disorders in patients with neutropenia, age, or history of pelvic radiotherapy, adhesions, ulceration, and GI bleeding. Evaluate and treat if serious GI toxicity occurs; treatment delay or discontinuation may be needed. Underlying lung disease. Monitor closely for respiratory disorders; interrupt if new or worsening pulmonary symptoms develop. Hepatic impairment (monitor). ESRD (CrCl <15mL/min).

Elderly (increased susceptibility to adverse reactions); monitor closely. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended.

Interactions: Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole); avoid. Antagonized by strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital). Increased GI toxicity with concomitant steroids, NSAIDs, antiplatelets, anticoagulants.

Adverse reactions: Bone marrow suppression (esp. neutropenia, anemia, leukopenia, thrombocytopenia), diarrhea (may be fatal), fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, arthralgia, alopecia; febrile neutropenia, renal failure, hypersensitivity reactions (eg, rash, hypotension, bronchospasm).

How supplied: Kit (single-use vial + diluent)—1

KEYTRUDA Merck

℞

Human programmed death receptor-1 (PD-1)-blocking antibody. Pembrolizumab 50mg/vial; lyophilized pwd for IV infusion after reconstitution; 25mg/mL; per vial; soln for IV infusion after dilution; both: preservative-free.

Indications: Locally advanced or metastatic urothelial carcinoma in patients who are ineligible for cisplatin-containing chemotherapy, or in patients who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or

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DRUG MONOGRAPHS

GENITOURINARY CANCER adjuvant treatment with platinum-containing chemotherapy.

Adults: Give as IV infusion over 30mins.

200mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.

Children: Not established.

Warnings/Precautions: Monitor for pneumonitis; withhold dose if Grade 2 pneumonitis; permanently discontinue if Grade 3 or 4, or recurrent Grade 2 develops.

Monitor for colitis; withhold dose if Grade 2 or 3 colitis; permanently discontinue if Grade 4 develops. Monitor for changes in liver function; withhold dose or discontinue based on severity of elevated liver enzymes. Monitor for changes in renal function; withhold dose if Grade 2 nephritis; permanently discontinue if Grade 3 or 4 develops. Monitor for hypophysitis; withhold dose if Grade 2 hypophysitis; withhold or discontinue if Grade 3 or 4 develops. Monitor for changes in thyroid function (at treatment initiation, during, and as clinically indicated) and signs/symptoms of thyroid disorders; withhold or discontinue if Grade 3 or 4 hyperthyroidism develops. Monitor for hyperglycemia and other diabetes symptoms; withhold if severe hyperglycemia until controlled. Withhold dose if Grade 4 hematological toxicity in cHL patients develops. Permanently discontinue if any severe or Grade 3 immune-mediated adverse reaction recurs, for any life-threatening immune-mediated adverse reaction (except endocrinopathies controlled with hormone replacement or hematological toxicity in cHL patients), persistent Grade 2 or 3 reactions that do not recover to Grade 0–1 within 12wks after last dose, or inability to reduce corticosteroid dose to ≤10mg/day of prednisone or equivalent within 12wks. Monitor for infusion-related reactions; permanently discontinue if Grade 3 or 4 develops. Complications of allogeneic HSCT after Keytruda: monitor for hepatic VOD, Grade 3 or 4 acute GVHD, steroid-requiring febrile syndrome, and others. Embryo-fetal toxicity.

Females of reproductive potential should use highly effective contraception during therapy and for 4 months after the final dose. Pregnancy: avoid. Nursing mothers: not recommended (during therapy and for 4 months after the final dose).

Adverse reactions: Fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, nausea; immune-mediated disorders, infusionrelated reactions.

How supplied: Single-use vial 50mg—1; Singleuse vial 25mg/mL—1

℞

LUPRON DEPOT 7.5mg AbbVie ℞

Kinase inhibitor. Lenvatinib 4mg, 10mg; capsules.

Indications: In combination with everolimus, for treatment of advanced renal cell carcinoma, following one prior anti-angiogenic therapy.

Adults: Swallow whole or may dissolve capsule contents into liquid. 18mg (in combination with everolimus 5mg) once daily until disease progression or unacceptable toxicity occurs.

Severe renal impairment (CrCl <30mL/min) or severe hepatic impairment (Child-Pugh C): 10mg once daily. Dose modifications for adverse reactions or lab abnormalities: see full labeling.

Children: Not established.

Warnings/Precautions: Control blood pressure prior to treatment; monitor after 1 week, every 2 weeks for the first 2 months, and then at least monthly thereafter during therapy.

Discontinue if life-threatening hypertension, Grade 4 cardiac dysfunction or hemorrhage, arterial thrombotic event, hepatic failure, nephrotic syndrome, GI perforation or lifethreatening fistula, or severe and persistent neurologic symptoms occur. Withhold if Grade 3 hypertension persists despite therapy, Grade 3 cardiac dysfunction or hemorrhage, ≥Grade 3 liver impairment or QT prolongation >500ms, Grade 3 or 4 renal failure/impairment, ≥2g of proteinuria/24hrs, or reversible posterior leukoencephalopathy syndrome (RPLS) occurs. Monitor for signs/symptoms of cardiac decompensation. Monitor liver function prior to treatment, every 2 weeks for the first 2 months, then at least monthly during treatment. Monitor for proteinuria prior to, and periodically during treatment. Monitor for dehydration and treat if diarrhea develops; interrupt if Grade 3 or 4 and permanently discontinue if Grade 4 diarrhea persists despite therapy. Hypovolemia. Congenital long QT syndrome, CHF, bradyarrhythmias, or those taking Class Ia or III antiarrhythmic drugs; monitor ECGs. Monitor and correct electrolyte abnormalities. Monitor blood calcium levels at least monthly; replace as needed during treatment. Monitor thyroid function prior to initiation and at least monthly thereafter; treat hypothyroidism as needed. ESRD. Embryofetal toxicity. Pregnancy: avoid. Use effective contraception during and for at least 2 weeks after treatment completion. Nursing mothers: not recommended.

Adverse reactions: Hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight decreased, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, dysphonia.

How supplied: Blister cards—6

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: 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. History of seizures. Risk of QT prolongation: long-term androgen deprivation therapy, congenital long QT syndrome, electrolyte abnormalities, or CHF. Correct and monitor electrolyte abnormalities; consider monitoring ECGs. Instruct patient on correct self administration. Nursing mothers: not recommended.

Interactions: Concomitant 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 disorders, pain, cardiovascular events, CNS and antiandrogenic effects, asthenia, testicular atrophy, urinary disorders, spinal cord compression; hyperglycemia, anaphylactoid, photosensitivity.

How supplied: Depot kit—1 (prefilled dualchamber syringe w. supplies)

LENVIMA Eisai

MENEST Pfizer

℞

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

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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

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

OPDIVO Bristol-Myers Squibb

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol.

Indications: Advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy. Locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinumcontaining chemotherapy.

Adults: Give as IV infusion over 60mins.

240mg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling.

Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderate-to-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or lifethreatening. Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism.

Monitor for transplant-related complications (eg, hyperacute or Grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic venoocclusive disease) and treat promptly. Moderate

or severe hepatic impairment: not studied.

Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥5 months after final dose.

Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended.

Adverse reactions: Asthenia/fatigue, musculoskeletal pain, decreased appetite, nausea, cough, rash, dyspnea, diarrhea, constipation, back pain, arthralgia; immunemediated reactions (may be fatal).

How supplied: Single-use vial (4mL, 10mL)—1

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 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,

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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, 37.5mg, 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 events: monitor for CHF during therapy, and LVEF at baseline and periodically; 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. Monitor blood glucose levels during and after treatment discontinuation.

Monitor for proteinuria; perform baseline and periodic urinalyses; interrupt and reduce dose if 24-hr urine protein ≥3g; discontinue if nephrotic syndrome or repeat urine protein ≥3g persists.

Undergoing major surgery. Stress (monitor for adrenal insufficiency). Discontinue if severe cutaneous reactions (eg, erythema multiforme, SJS, TEN) develop; do not restart if diagnosis suspected. ESRD on dialysis. Severe 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; consider reducing dose or use alternate drug. May be antagonized by CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital); consider increasing dose or use alternate drug. Concomitant St. John’s wort: not recommended. Caution with concomitant antiarrhythmics.

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,

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DRUG MONOGRAPHS

GENITOURINARY CANCER back pain, arthralgia, extremity pain, cough, dyspnea, anorexia, bleeding; hepatotoxicity, left ventricular dysfunction, QT prolongation, osteonecrosis of the jaw, tumor lysis syndrome, thyroid dysfunction, impaired wound healing, hypoglycemia, thrombotic microangiopathy (discontinue if develops), proteinuria, necrotizing fasciitis (discontinue if occurs), others (see full labeling).

How supplied: Caps—28

TECENTRIQ Genentech

℞

Programmed death-ligand 1 (PD-L1) blocking antibody. Atezolizumab 60mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: Locally advanced or metastatic urothelial carcinoma in patients who are ineligible for cisplatin-containing chemotherapy, or who have disease progression during or after any platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy.

Adults: Give as IV infusion over 60mins.

1200mg every 3 weeks until disease progression or unacceptable toxicity. May give subsequent infusions over 30mins if first infusion tolerated.

Children: Not established.

Warnings/Precautions: Permanently discontinue if Grade 3/4 pneumonitis, AST or ALT >5×ULN or total bilirubin >3×ULN, Grade 4 diarrhea or colitis, Grade 4 hypophysitis, myasthenic syndrome/myasthenia gravis, Guillain-Barre or meningoencephalitis, Grade 3/4 ocular inflammatory toxicity, Grade 4 or recurrent pancreatitis, Grade 3/4 infusionrelated reactions, or Grade 4 rash. Withhold for Grade 2 pneumonitis, AST or ALT >3–5×ULN or total bilirubin >1.5–3×ULN, Grade 2/3 diarrhea or colitis, symptomatic hypophysitis, adrenal insufficiency, hypothyroidism, hyperthyroidism, Grade 3/4 hyperglycemia, Grade 2 ocular inflammatory toxicity, Grade 2/3 pancreatitis or Grade 3/4 increases in amylase or lipase levels (>2×ULN), Grade 3/4 infection, Grade 2 infusionrelated reactions, or Grade 3 rash; may be resumed when recover to Grade 0–1. Monitor for immune-related pneumonitis, hepatitis (obtain AST, ALT, bilirubin prior to and during treatment), diarrhea/colitis, endocrinopathies (hypophysitis, thyroid function, adrenal insufficiency, diabetes), meningitis or encephalitis, motor and sensory neuropathy, and acute pancreatitis; see full labeling for adverse reaction management details.

Monitor for signs/symptoms of infection and treat with antibiotics for suspected or confirmed

bacterial infections. Interrupt or slow the infusion rate in patients with mild or moderate infusion reactions. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity.

Pregnancy. Use effective contraception during and for ≥5 months after final dose. Nursing mothers: not recommended (during and for ≥5 months after final dose).

Adverse reactions: Fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, constipation; immune-related reactions, lab abnormalities.

How supplied: Single-dose vial (20mL)—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/week) if adverse reactions resolve to ≤Grade 2. Hepatic impairment: bilirubin >1–1.5xULN or AST > ULN but bilirubin ≤ ULN: reduce to 15mg/week; >1.5xULN: contraindicated.

See Interactions.

Children: Not recommended.

Contraindications: Bilirubin >1.5xULN. Warnings/Precautions: Sirolimus or related allergy. Hemodialysis. Perioperative period (may interfere with wound healing). CNS tumors. Monitor for opportunistic infections; consider prophylaxis for pneumocystis jiroveci pneumonia (PJP) when concomitant corticosteroids, other immunosuppresives required. Monitor for interstitial lung disease (ILD); discontinue if suspected. 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). Angioedema when concomitant with ACEIs (eg, ramipril) or CCBs (eg, amlodipine); monitor.

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, PJP, ILD, bowel perforation, acute renal failure, abnormal wound healing; others (see full labeling).

How supplied: Kit (vial + diluent)—1

TRELSTAR Allergan

℞

GnRH analogue. Triptorelin pamoate 3.75mg, 11.25mg, 22.5mg; lyophilized microgranules 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: Pregnancy (Cat.X).

Warnings/Precautions: Not for use in women.

Must administer under physician supervision.

Discontinue if hypersensitivity occurs. Initial transient increase in serum testosterone may result in worsening of signs/symptoms including bone pain, neuropathy, hematuria, or urethral/bladder obstruction. Spinal cord compression. Renal or hepatic impairment.

Metastatic vertebral lesions. Upper or lower urinary tract obstruction. May prolong QT/QTc interval in patients with congenital long QT syndrome, CHF, frequent electrolyte abnormalities. Correct any electrolyte abnormalities; monitor ECGs and electrolytes periodically. Increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood

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DRUG MONOGRAPHS

GENITOURINARY CANCER glucose and/or HbA1c, and for signs/symptoms of cardiovascular disease. Measure serum testosterone periodically. Nursing mothers: not recommended.

Interactions: Concomitant hyperprolactinemic drugs: not recommended. Avoid concomitant drugs that are known to prolong the QT interval.

May interfere with pituitary gonadotropic function tests.

Adverse reactions: Inj site reactions, hot flushes, skeletal pain, impotence, headache, leg edema/pain, 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: Initial transient increase in serum testosterone may result in worsening signs/symptoms (eg, bone pain, neuropathy, hematuria). 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. May prolong QT/QTc interval in patients with congenital long QT syndrome, CHF, electrolyte abnormalities; monitor ECGs. If electrolyte abnormalities occur, correct and monitor. Measure serum testosterone, PSA levels periodically. Implant not visible on X-ray.

Interactions: May interfere with pituitary gonadotropic and gonadal function tests. Caution with concomitant drugs known to prolong the QT interval.

Adverse reactions: Hot flashes, fatigue, implant site reactions, testicular atrophy, renal impairment; hyperglycemia, diabetes, cardiovascular disease.

How supplied: Kit—1 (w. implant and supplies)

VOTRIENT GlaxoSmithKline

℞

Tyrosine kinase inhibitor. Pazopanib 200mg; tabs.

Indications: Advanced renal cell carcinoma.

Limitation of use: not for treating adipocytic soft tissue sarcoma or gastrointestinal stromal tumors.

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 and consider alternate drug; if warranted, reduce dose of pazopanib to 400mg; may reduce further if toxicity occurs. Concomitant strong CYP3A4 inducers (eg, rifampin): avoid and consider alternate drug.

Children: Not established.

Warnings/Precautions: Not indicated for use in combination with other cancer agents. Risk of severe and fatal hepatotoxicity (esp. ≥65yrs old). Monitor liver tests before starting and at Weeks 3, 5, 7, and 9, thereafter at Months 3 and 4, then periodically. If ALT between 3xULN and 8xULN continue therapy with weekly monitoring until ALT returns to Grade 1 or baseline. If ALT >8xULN 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>3xULN recurs, permanently discontinue. Permanently discontinue if ALT>3xULN and bilirubin >2xULN. Gilbert’s syndrome (see full labeling). History of QT prolongation. Cardiac dysfunction risk (including

previous anthracycline exposure): evaluate LVEF at baseline and periodically; monitor for CHF. Monitor ECG, electrolytes (eg, calcium, magnesium, potassium), thyroid function. 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), thrombotic microangiopathy, interstitial lung disease (ILD)/pneumonitis, GI perforation or fistula.

Monitor BP and manage hypertension promptly.

Discontinue if severe and persistent hypertension (despite antihypertensives and dose reduction), if repeat episodes of proteinuria (despite dose reductions), thrombotic microangiopathy, serious infection, ILD or pneumonitis occurs.

Stop therapy at least 7 days before surgery; discontinue in patients with wound dehiscence.

Embryo-fetal toxicity. Pregnancy: exclude status prior to starting. Females of reproductive potential must use effective contraception and males (use condoms) during therapy and for ≥2 weeks after final dose. Nursing mothers: not recommended (during and for 2 weeks after final dose).

Interactions: See Adult dosing: Potentiated by strong CYP3A4 inhibitors, grapefruit juice. Avoid concomitant strong Pgp or BCRP inhibitors.

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. Avoid concomitant drugs that raise gastric pH (eg, PPIs, H2-blockers). Separate antacids by several hours.

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; hepatotoxicity, QT prolongation, hemorrhagic events, arterial thrombotic events (eg, MI, angina, ischemic stroke, TIA), venous thrombotic events (eg, VTE, PE), GI perforation or fistula, ILD/pneumonitis, 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.

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DRUG MONOGRAPHS

GENITOURINARY CANCER Indications: Treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.

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 X 109/L, platelets ≥100 X 109/L and hemoglobin ≥10g/dL. Before subsequent doses, the ANC should be ≥1 X 109/L and platelets ≥50 X 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; soft gelatin caps.

Indications: Treatment of metastatic castrationresistant prostate cancer.

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 (120mg or 80mg), if warranted. Concomitant strong CYP2C8 inhibitors: avoid if possible. If co-administration necessary, reduce enzalutamide dose to 80mg once daily; if inhibitor is discontinued, return enzalutamide dose to the dose used prior to initiation of inhibitor.

Children: Not established.

Contraindications: Pregnancy.

Warnings/Precautions: Risk of seizure; permanently discontinue if develops during treatment. Severe renal or hepatic impairment.

Nursing mothers: not recommended.

Interactions: Avoid concomitant strong CYP2C8 inhibitors (eg, gemfibrozil) if possible; reduce enzalutamide dose if cannot be avoided.

Avoid concomitant CYP2C8 inducers (eg, rifampin), CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, bosentan, efavirenz, etravirine, modafinil, nafcillin), and St. John’s Wort if possible. Potentiated by CYP3A4 inhibitors (itraconazole). 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. Conduct more INR monitoring if concomitant warfarin cannot be avoided.

Adverse reactions: Asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, dizziness/vertigo.

How supplied: Caps—120

ZYTIGA Janssen Biotech

℞

CYP17 inhibitor. Abiraterone acetate 250mg, 500mg; tabs.

Indications: In combination with prednisone for the treatment of metastatic castration-resistant prostate cancer.

Adults: Take on empty stomach (no food ≥2hrs before or ≥1hr 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; monitor frequently. 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 may become pregnant.

Warnings/Precautions: Risk of mineralocorticoid excess: patients with history of cardiovascular disease, LVEF <50%, Class II-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 hepatotoxicity occurs. Permanently discontinue if concurrent ALT elevation >3xULN and total bilirubin >2xULN develops without biliary obstruction or other causes of elevation. 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 250mg—120; 500mg—60

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.

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DRUG MONOGRAPHS

GYNECOLOGIC CANCER AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free.

Indications: Persistent, recurrent, or metastatic cervical cancer in combination with paclitaxel/cisplatin, or paclitaxel/topotecan.

Recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer (platinum-resistant): in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan in patients who received no more than 2 prior chemotherapy regimens; (platinum-sensitive): in combination with carboplatin/paclitaxel or carboplatin/gemcitabine, followed by Avastin as a single agent.

Adults: Give by IV infusion. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins. Cervical cancer: 15mg/kg every 3 weeks with either paclitaxel/cisplatin, or paclitaxel/topotecan.

Epithelial ovarian, fallopian tube or primary peritoneal cancer (platinum-resistant): 10mg/kg every 2 weeks with either paclitaxel, pegylated liposomal doxorubicin, or topotecan (weekly); or, 15mg/kg every 3 weeks with topotecan (every 3 weeks); (platinum-sensitive): 15mg/kg every 3 weeks with carboplatin/paclitaxel for 6 cycles and up to 8 cycles or carboplatin/gemcitabine for 6 cycles and up to 10 cycles; followed by Avastin 15mg/kg every 3 weeks as a single agent until disease progression.

Children: Not established.

Warnings/Precautions: Risk of GI perforations, surgery and wound healing complications, and hemorrhage. Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). Do not administer if recent history of hemoptysis of ≥ ½-teaspoon of red blood.

Permanently discontinue if GI perforation, tracheoesophageal fistula, any grade 4 fistula, or grade 4 venous thromboembolic event.

Discontinue if fistula involving internal organ, wound healing complications, hemorrhage, severe arterial thromboembolic event (ATE), hypertensive crisis or encephalopathy, posterior reversible encephalopathy syndrome (PRES), or nephrotic syndrome occurs; suspend therapy if severe hypertension, moderate-to-severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Avoid in ovarian cancer if evidence of recto-sigmoid involvement by pelvic exam, bowel involvement on CT scan, or symptoms of bowel obstruction. History of arterial thromboembolism. Diabetes. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis; if ≥2+, do further assessment with a 24-hour urine collection. Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy: may cause fetal harm; use effective contraception during and for 6 months after last dose. Nursing mothers: not recommended.

Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation and fistulae, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, PRES, infusion reactions, ovarian failure, neutropenia, infection.

How supplied: 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 longterm 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

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.

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: Verify dose using BSA. Usual max dose 4mg IV. Confirm baseline neutrophils ≥1,500cells/mm3 and platelets ≥100,000cells/mm3 prior to 1st course of therapy.

Give by IV infusion over 30 mins. 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 (with cisplatin), 2, and 3, repeated every 21 days. Dose adjustments, renal impairment: see full labeling.

Children: Not established.

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. Use effective contraception during and for ≥1 month after last dose (in females), or during and for ≥3 months (in males with female partners). Pregnancy (Cat.D).

Nursing mothers: not recommended.

Interactions: Myelosuppression potentiated with platinum agents. Neutropenia potentiated

by G-CSF; administer ≥24hrs after last topotecan dose.

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DRUG MONOGRAPHS

GYNECOLOGIC CANCER Adverse reactions: See full labeling.

Neutropenia, leukopenia, thrombocytopenia, anemia, nausea, vomiting, diarrhea, 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

LYNPARZA AstraZeneca

℞

Poly (ADP-ribose) polymerase (PARP) inhibitor.

Olaparib 50mg; caps.

Indications: Monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer who have been treated with ≥3 prior lines of chemotherapy.

Adults: Swallow whole. 400mg twice daily; max 800mg daily. Continue until disease progression or unacceptable toxicity. Dose adjustments for adverse reactions: reduce to 200mg twice daily; may further reduce to 100mg twice daily. If concomitant strong CYP3A inhibitor unavoidable: reduce to 150mg twice daily; or if concomitant moderate CYP3A inhibitor unavoidable: reduce to 200mg twice daily. Moderate renal impairment (CrCl 31–50mL/min): reduce to 300mg twice daily; max 600mg daily.

Children: Not established.

Warnings/Precautions: Monitor CBC at baseline and monthly thereafter; do not start therapy until recovery from hematological toxicity due to previous chemotherapy (CTCAE Grade ≤1).

Discontinue if myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) is confirmed.

Interrupt therapy and evaluate if new or worsening respiratory symptoms occur; discontinue if pneumonitis is confirmed. Mild renal impairment: monitor closely. Moderate or severe hepatic impairment, severe renal impairment or ESRD: not studied. Embryo-fetal toxicity. Pregnancy; avoid. Obtain pregnancy testing prior to initiating therapy. Females of reproductive potential should use effective contraception during therapy and for 6 months after last dose. Nursing mothers: not recommended (during and for 1 month after last dose).

Interactions: Increased myelosuppressive toxicity with concomitant other myelosuppressive anticancer agents, including DNA damaging agents. Avoid concomitant strong CYP3A inhibitors (eg, itraconazole, telithromycin, clarithromycin, ketoconazole, voriconazole, nefazodone, posaconazole, ritonavir, lopinavir/ritonavir, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) and moderate CYP3A inhibitors (eg, amprenavir,

aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil); if unavoidable, reduce dose (see Adults). Avoid grapefruit and Seville oranges. Avoid concomitant strong CYP3A inducers (eg, phenytoin, rifampicin, carbamazepine, St. John’s Wort) and moderate CYP3A inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin); if unavoidable, be aware of potential for decreased efficacy.

Adverse reactions: Anemia, nausea, fatigue, asthenia, vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis/pharyngitis/URI, cough, arthralgia/musculoskeletal pain, myalgia, back pain, dermatitis/rash, abdominal pain/discomfort, lab abnormalities (see full labeling); MDS/AML, pneumonitis.

How supplied: Caps—112

RUBRACA Clovis Oncology

℞

Poly (ADP-ribose) polymerase (PARP) inhibitor.

Rucaparib 200mg, 300mg; tabs.

Indications: Monotherapy in patients with deleterious BRCA-mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with ≥2 prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic test.

Adults: Swallow whole. 600mg twice daily until disease progression or unacceptable toxicity.

Dose modifications or adjustments for adverse reactions: 1st reduction: 500mg twice daily; 2nd reduction: 400mg twice daily; 3rd reduction: 300mg twice daily.

Children: Not established.

Warnings/Precautions: Monitor CBC at baseline and monthly thereafter; do not start therapy until recovery from hematological toxicity due to previous chemotherapy (Grade ≤1). Discontinue if myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) is confirmed. Embryo-fetal toxicity.

Pregnancy; avoid. Females of reproductive potential must obtain pregnancy test prior to initiating therapy. Use effective contraception during therapy and for at least 6 months after last dose. Nursing mothers: not recommended (during and for 2 weeks after last dose).

Adverse reactions: Nausea, fatigue, asthenia, vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, dyspnea, lab abnormalities (increased: creatinine, ALT/AST, cholesterol; decreased: hemoglobin, lymphocytes, platelets, ANC).

How supplied: Tabs—60

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: Gestational choriocarcinoma.

Chorioadenoma destruens. Hydatidiform mole.

Adults: See literature. Tablet form is often preferred when low doses are being administered.

Choriocarcinoma and similar trophoblastic diseases: 15–30mg orally or by IM inj daily for 5 days; usually repeated 3–5 times as required with a rest period of ≥1 week between courses.

Children: Not applicable.

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,

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DRUG MONOGRAPHS

GYNECOLOGIC CANCER 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)

ZEJULA Tesaro

℞

Poly (ADP-ribose) polymerase (PARP) inhibitor.

Niraparib 100mg; caps.

Indications: Maintenance treatment in adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Adults: Start treatment within 8 weeks after most recent platinum-containing regimen.

Swallow whole. 300mg once daily until disease progression or unacceptable toxicity. Dose adjustments for adverse reactions: see full labeling.

Children: Not established.

Warnings/Precautions: Discontinue if myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) is confirmed. Monitor CBC weekly for the first month, monthly for the next 11 months then periodically thereafter; do not start therapy until recovery from hematological toxicity due to previous chemotherapy (CTCAE Grade ≤1); discontinue if toxicities unresolved within 28 days after interruption (see full labeling). Monitor BP and heart rate monthly for the first year then periodically thereafter.

Cardiovascular disorders (eg, coronary insufficiency, arrhythmias, hypertension); monitor closely. Embryo-fetal toxicity. Pregnancy; exclude status prior to initiating therapy.

Females of reproductive potential should use effective contraception during therapy and for ≥6 months after last dose. Nursing mothers: not recommended (during and for 1 month after last dose).

Interactions: Concomitant antihypertensives; dose adjustments of Zejula may be needed.

Adverse reactions: Thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue/asthenia, decreased appetite, urinary tract infection, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, hypertension.

How supplied: Caps—90

HEMATOLOGICAL REFERENCE VALUES Analyte

Reference value Conventional units SI units

Antithrombin III • Antigenic • Functional

22–39mg/dL 80–130%

220–390mg/L 0.8–1.30 U/L

Bleeding time

2.0–9.5min

2.0–9.5min

Erythrocyte count • Male • Female

4.50–5.90 × 106/mm3 4.00–5.20 × 106/mm3

4.50–5.90 × 1012/L 4.00–5.20 × 1012/L

Erythrocyte sedimentation rate • Male • Female

0–17mm/hr 1–25mm/hr

0–17mm/hr 1–25mm/hr

Ferritin • Male • Female

30–300ng/mL 10–200ng/mL

30–300μg/L 10–200μg/L

Fibrinogen

150–400mg/dL

1.50–4.00g/L

Folate (folic acid) • Normal • Borderline deficient • Deficient • Excess

3.1–17.5ng/mL 2.2–3.0ng/mL <2.2ng/mL >17.5ng/mL

7.0–39.7nmol/L 5.0–6.8nmol/L <5.0nmol/L >39.7nmol/L

Folic acid

150–450ng/mL/cells

340–1020nmol/L/cells

Hematocrit • Male • Female

41.0–53.0% 36.0–46.0%

0.41–0.53 0.36–0.46

Hemoglobin • Plasma • Whole blood, male • Whole blood, female

1–5mg/dL 13.5–17.5g/dL 12.0–16.0g/dL

0.01–0.05g/L 8.4–10.9mmol/L 7.4–9.9mmol/L

Hemoglobin electrophoresis • Hemoglobin A • Hemoglobin A1c • Hemoglobin A2 • Hemoglobin F • Hemoglobins other than A, A2, or F

95–98% 3.8–6.4% 1.5–3.5% 0–2.0% Absent

0.95–0.98 0.038–0.064Hg fraction 0.015–0.035 0–0.02 Absent

Iron (hematology and coagulation values)

30–160μg/dL

5.4–28.7μmol/L

Iron-binding capacity (hematology and coagulation values)

228–428μg/dL

40.8–76.7μmol/L

Iron (clinical chemistry values)

50–150μg/dL

9–27μmol/L

Iron-binding capacity (clinical chemistry values)

250–370μg/dL

45–66μmol/L

Leukocyte count (WBC)

4.5–11.0 × 103/mm3

4.5–11 × 109/L

Mean corpuscular hemoglobin (MCH)

26.0–34.0pg/cell

26.0–34.0pg/cell

Mean corpuscular hemoglobin concentration (MCHC)

31.0–37.0g/dL

310–370g/L

Mean corpuscular volume (MCV)

80–100μm3

80–100fl

Partial-thromboplastin time (activated)

22.1–35.1sec

22.1–35.1sec

Platelet count

150–350 × 103/mm3

150–350 × 109/L

Prothrombin time

11.1–13.1sec

11.1–13.1sec

Reticulocyte count

0.5–2.5% red cells

0.005–0.025 red cells

Transferrin

230–390mg/dL

2.3–3.9g/L

Vitamin B12 • Normal • Borderline • Deficient

>250pg/mL 125–250pg/mL <125pg/mL

>185pmol/L 92–185pmol/L <92pmol/L

References National Institutes of Health. Third report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). September 2002. Available at: www.nhlbi.

(Rev. 8/2012) nih.gov/guidelines/cholesterol/index.htm. Accessed August 2012.

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DRUG MONOGRAPHS

HEAD AND NECK CANCER ERBITUX Lilly

℞

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 2hrs; 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 1hr post-infusion. Skin toxicity: see full labeling.

Children: Not established.

Warnings/Precautions: Monitor for serious infusion reactions; immediately interrupt and permanently discontinue if occur. Risk of cardiopulmonary arrest and/or sudden death; carefully consider use (w. irradiation or platinum-based therapy with 5-FU) in coronary artery disease, CHF, or arrhythmias. Monitor electrolytes (eg, magnesium, potassium, calcium) during and for ≥8wks after cetuximab therapy. Interrupt for acute onset or worsening pulmonary symptoms; permanently discontinue if interstitial lung disease confirmed. Monitor for dermatologic toxicities (eg, acneiform rash) and infection; avoid sun exposure. Additive cutaneous reactions with irradiation. 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 (eg, rash, pruritus, nail changes), headache, diarrhea, infection; infusion reactions (may be severe), cardiopulmonary arrest, interstitial lung disease,

dermatologic toxicities, electrolyte abnormalities (eg, hypomagnesemia), sepsis, renal failure, pulmonary embolus.

How supplied: Single-use vials—1

HYDREA Bristol-Myers Squibb

℞

Antimetabolite. Hydroxyurea 500mg; caps.

Indications: Adjunct with irradiation therapy in locally advanced squamous cell carcinomas of the head and neck, excluding the lip.

Adults: Base dose on ideal or actual weight, whichever is less. Individualize. Initially 15mg/kg/day. Renal impairment (CrCl <60mL/min or ESRD): initially 7.5mg/kg/day; give dose following dialysis (monitor). Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of severe myelosuppression; reduce dose or discontinue if necessary. Monitor blood counts at baseline and at least once a week during therapy. Correct severe anemia before starting. Markedly depressed bone marrow function: do not initiate. Monitor for malignancies. Avoid sun exposure. Previous irradiation therapy (monitor for skin erythema) or chemotherapy. Macrocytosis may mask folic acid deficiency; prophylactic folic acid is recommended.

Myeloproliferative disorders; discontinue if cutaneous vasculitic ulcerations occur. Renal or hepatic impairment. Elderly. Embryo-fetal toxicity.

Pregnancy; avoid. Exclude pregnancy prior to initiating; use effective contraception during and for ≥6 months (females) or ≥1 year (males) after therapy. Nursing mothers: not recommended.

Interactions: Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [monitor], fatal hepatotoxicity, peripheral neuropathy). Avoid live vaccines.

Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated results in urea, uric acid, and lactic acid assays.

Adverse reactions: Leukopenia, thrombocytopenia, anemia, GI upset, anorexia; secondary malignancies, macrocytosis.

Note: Wear disposable gloves when handling caps or bottle.

How supplied: Caps—100

KEYTRUDA Merck Human programmed death receptor-1 (PD-1)-blocking antibody. Pembrolizumab 50mg/vial; lyophilized pwd for IV infusion after reconstitution; 25mg/mL; per vial; soln for IV infusion after dilution; both: preservative-free.

Indications: Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)

℞

with disease progression on or after platinumcontaining chemotherapy.

Adults: Give as IV infusion over 30mins.

200mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.

Children: Not established.

Warnings/Precautions: Monitor for pneumonitis; withhold dose if Grade 2 pneumonitis; permanently discontinue if Grade 3 or 4, or recurrent Grade 2 develops. Monitor for colitis; withhold dose if Grade 2 or 3 colitis; permanently discontinue if Grade 4 develops. Monitor for changes in liver function; withhold dose or discontinue based on severity of elevated liver enzymes. Monitor for changes in renal function; withhold dose if Grade 2 nephritis; permanently discontinue if Grade 3 or 4 develops. Monitor for hypophysitis; withhold dose if Grade 2 hypophysitis; withhold or discontinue if Grade 3 or 4 develops. Monitor for changes in thyroid function (at treatment initiation, during, and as clinically indicated) and signs/symptoms of thyroid disorders; withhold or discontinue if Grade 3 or 4 hyperthyroidism develops. Monitor for hyperglycemia and other diabetes symptoms; withhold if severe hyperglycemia until controlled.

Withhold dose if Grade 4 hematological toxicity in cHL patients develops. Permanently discontinue if any severe or Grade 3 immune-mediated adverse reaction recurs, for any life-threatening immune-mediated adverse reaction (except endocrinopathies controlled with hormone replacement or hematological toxicity in cHL patients), persistent Grade 2 or 3 reactions that do not recover to Grade 0–1 within 12wks after last dose, or inability to reduce corticosteroid dose to ≤10mg/day of prednisone or equivalent within 12wks. Monitor for infusion-related reactions; permanently discontinue if Grade 3 or 4 develops.

Complications of allogeneic HSCT after Keytruda: monitor for hepatic VOD, Grade 3 or 4 acute GVHD, steroid-requiring febrile syndrome, and others.

Embryo-fetal toxicity. Females of reproductive potential should use highly effective contraception during therapy and for 4 months after the final dose. Pregnancy: avoid. Nursing mothers: not recommended (during therapy and for 4 months after the final dose).

Adverse reactions: Fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, nausea; immune-mediated disorders, infusionrelated reactions.

How supplied: Single-use vial 50mg—1; Singleuse vial 25mg/mL—1

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DRUG MONOGRAPHS

HEAD AND NECK CANCER OPDIVO Bristol-Myers Squibb

reactions occur; discontinue if severe or lifethreatening. Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism.

Monitor for transplant-related complications (eg, hyperacute or Grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic venoocclusive disease) and treat promptly. Moderate or severe hepatic impairment: not studied.

Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥5 months after final dose.

Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended.

Adverse reactions: Fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea; immune-mediated reactions (may be fatal).

How supplied: Single-use vial (4mL, 10mL)—1

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol.

Indications: Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinumbased therapy.

Adults: Give as IV infusion over 60mins.

3mg/kg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling.

Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderate-to-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion

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: Epidermoid cancers of the head and neck.

Adults: See literature.

Children: Not established.

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: Tabs—30; soln (2mL, 4mL, 8mL, 10mL)—10 (single-use vials); pwd (1 gram)—1 (single-use vial)

LIVER FUNCTION ASSESSMENT Child-Pugh Score is used to assess residual liver function and injury severity in cirrhosis patients.

CHILD-PUGH SCORES Criteria

1 point

2 points

3 points

Total serum bilirubin (mg/dL)

<2

2–3

>3

Serum albumin (g/dL)

>3.5

2.8–3.5

<2.8

INR

<1.70

1.71–2.20

>2.20

Ascites

No ascites

Ascites controlled

Ascites not controlled

Encephalopathy

No encephalopathy

Encephalopathy controlled

Encephalopathy not controlled

INTERPRETATION OF CHILD-PUGH SCORES Class A

Class B

Class C

Points

5–6

7–9

10–15

Life expectancy

15–20 years

Candidate for liver transplant

1–3 years

Perioperative mortality

10%

30%

82%

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Leukemia Treatment Regimens: Acute Lymphoblastic Leukemia (ALL) Note: The National Comprehensive Cancer Network (NCCN) Guidelines® for Acute Lymphoblastic Leukemia (ALL) should be consulted for the management of patients with lymphoblastic lymphoma.

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 health care 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.

The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. They 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 NCCN 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.

Ph(+) AYA (Age 15–39 years) 1abc Note: All recommendations are Category 2A unless otherwise indicated.

PROTOCOL

REGIMEN AND DOSING

Children’s Oncology Group (COG) AALL-00312

Induction 4 weeks of standard induction chemotherapy Consolidation Block 1 (3 weeks) Day 1: Methotrexate (MTX) intrathecally (IT), etoposide 100mg/m2/day intravenously (IV), ifosfamide 3.4g/m2/day IV Days 1–21: Imatinib 340mg/m2/day orally Days 6–15: Filgrastim 5g/kg/day subcutaneously (SC) ± imatinib Days 8 and 15: CNS leukemia only: MTX IT, hydrocortisone IT, cytarabine IT. Block 2 (3 weeks) Day 1: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT + MTX 5g/m2 IV over 24 hours Days 1–21: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course) Days 2–3: Leucovorin 75mg/m2 36 hours after MTX, followed by 15mg/m2 IV or orally every 6 hours for 6 doses + cytarabine 3g/m2/dose IV every 12 hours for 4 doses Days 4–13: Filgrastim 5g/kg/day SC ± imatinib.

Reinduction Day 1: Vincristine 1.5mg/m2 IV + age adjusted: MTX IT, hydrocortisone IT, cytarabine IT Days 1–2: Daunorubicin 45mg/m2/day IV bolus Days 1–21: Dexamethasone 6mg/m2/day orally ± imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course) Days 3–4: Cyclophosphamide 250mg/m2/dose IV every 12 hours for 4 doses + mesna 125mg/m2/dose IV every 12 hours for 4 doses Days 4, 6, 8, 10, 12, 15, 17, 19, and 21: L-asparaginase 6,000 IU/m2 intramuscularly (IM) Days 5–14: Filgrastim 5g/kg/day SC Days 8 and 15: Vincristine 1.5mg/m2 IV Day 15: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT. Intensification Day 1: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT + MTX 5g/m2 IV over 24 hours Days 1–63: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course) Days 2–3: Leucovorin 75mg/m2 36 hours after MTX, followed by 15mg/m2 IV or orally every 6 hours for 6 doses Day 8: MTX 5g/m2 IV over 24 hours Days 9–10: Leucovorin 75mg/m2 36 hours after MTX, followed by 15mg/m2 IV or orally every 6 hours for 6 doses Day 15: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT Days 15–19: Etoposide 100mg/m2/day IV + cyclophosphamide 300mg/m2/day IV + mesna 150mg/m2/day IV Days 20–29: Filgrastim 5mcg/kg/day SC Days 36–37: Cytarabine 3g/m2 IV Day 37: L-asparaginase 6,000 IU/m2 IM ± imatinib (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course) Days 43–44: Cytarabine 3g/m2 IV Day 44: L-asparaginase 6,000 IU/m2 IM ± imatinib (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course).

Repeat reinduction block 2 (3 weeks) and intensification block 2 (9 weeks) sequentially. continued

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Leukemia Treatment Regimens: Acute Lymphoblastic Leukemia (ALL) Ph(+) AYA (Age 15–39 years) 1abc (continued) PROTOCOL

REGIMEN AND DOSING

COG AALL-00312 (continued)

Maintenance Cycles 1–4 (8 weeks) Day 1: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT + vincristine 1.5mg/m2 IV + MTX 5g/m2 IV over 24 hours Days 1–5: Dexamethasone 6mg/m2/day orally Days 1–56: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course) Days 2–3: Leucovorin 75mg/m2 36 hours after MTX, followed by 15mg/m2 IV or orally every 6 hours for 6 doses Days 8, 15, and 22: MTX 20mg/m2/week orally Days 8–28: 6-mercaptopurine (MP) 75mg/m2/day Day 29: Age adjusted: MTX IT, hydrocortisone IT, cytarabine IT + vincristine 1.5mg/m2 IV Days 29–33: Dexamethasone 6mg/m2/day orally Days 29–40: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course) Days 36–40: Etoposide 100mg/m2 IV + cyclophosphamide 300mg/m2 IV Days 41–50: Filgrastim 5g/kg/day SC. Cycles 5–12 (8 weeks) Cycle 5 only: Cranial irradiation 12 Gy Day 1: Vincristine 1.5mg/m2 IV Days 1–5: Dexamethasone 6mg/m2/day orally Days 1–14: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course) Days 8, 15, and 22: MTX 20mg/m2/week orally Days 8–28: 6-MP 75mg/m2/day Day 29: Vincristine 1.5mg/m2 IV Days 29–33: Dexamethasone 6mg/m2/day orally Days 29–42: Imatinib 340mg/m2/day orally (hold imatinib if patient does not achieve count recovery within 2 weeks of last dose of previous course) Day 36: MTX 20mg/m2/week orally Days 36–56: 6-MP 75mg/m2/day Days 43 and 50: MTX 20mg/m2/week orally.

EsPhALL regimen (imatinib + backbone of Berlin-FrankfordMunster regimen)3

Induction Standard induction protocols per national guidelines.

Post-Induction Block 1 Days 1–28: 6-MP 60mg/m2 orally + imatinib 300mg/m2 Days 1 and 28: Cyclophosphamide 1000mg/m2 IV Days 3–6, 10–13, 17–20, and 24–27: Cytosine arabinoside (ARA-C) 75mg/m2 SC Days 3 and 7: Age adjusted: MTX IT (dosages: ≥1 year <2 years = 8mg; ≥2 years <3 years = 10mg; ≥3 years = 12mg).

Post-Induction Block 2 Day 1: MTX 5,000mg/m2 IV + Age adjusted: MTX IT + ARA-C IT + prednisone (PRED) IT (dosages: ≥1 year <2 years = MTX 8mg, ARA-C 20mg, PRED 6mg; ≥2 years <3 years = MTX 10mg, ARA-C 26mg, PRED 8mg; ≥3 years = MTX 12mg, ARA-C 30mg, PRED 10mg) Days 1–5: Dexamethasone 20mg/m2 orally or IV Days 1 and 6: Vincristine 1.5mg/m2 IV Days 2–4: Cyclophosphamide 200mg/m2 IV Day 5: ARA-C 2,000mg/m2 IV Day 6: L-Asparaginase 25,000IU/m2 intramuscular (IM) Days 6–20: Imatinib 300mg/m2 orally.

Post-Induction Block 3 Day 1: MTX 5,000mg/m2 IV + Age adjusted: MTX IT + ARA-C IT + PRED IT (dosages: ≥1 year <2 years = MTX 8mg, ARA-C 20mg, PRED 6mg; ≥2 years <3 years = MTX 10mg, ARA-C 26mg, PRED 8mg; ≥3 years = MTX 12mg, ARA-C 30mg, PRED 10mg) Days 1–5: Dexamethasone 20mg/m2 orally or IV Days 1 and 6: Vindesine 3mg/m2 IV Days 2–4: Ifosfamide 800mg/m2 IV Day 5: Daunorubicin 30mg/m2 IV Day 6: L-Asparaginase 25,000IU/m2 IM Days 6–20: Imatinib 300mg/m2 orally.

Post-Induction Block 4 Days 1–2: ARA-C 2,000mg/m2 IV Days 1–5: Dexamethasone 20mg/m2 orally or IV

38 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Ph(+) AYA (Age 15–39 years) 1abc (continued) PROTOCOL

REGIMEN AND DOSING

EsPhALL regimen (imatinib + backbone of Berlin-FrankfordMunster regimen)3 (continued)

Post-Induction Block 4 (continued) Day 1: Age adjusted: MTX IT + ARA-C IT + PRED IT (dosages: ≥1 year <2 years = MTX 8mg, ARA-C 20mg, PRED 6mg; ≥2 years <3 years = MTX 10mg, ARA-C 26mg, PRED 8mg; ≥3 years = MTX 12mg, ARA-C 30mg, PRED 10mg) Days 3–5: Vepeside 100mg/m2 IV Day 6: L-Asparaginase 25,000IU/m2 IM Days 6–20: Imatinib 300mg/m2 orally.

Reinduction Days 1–21 + tapering: Dexamethasone 10mg/m2 orally Days 8, 15, 22, and 29: Vincristine 1.5mg/m2 IV + doxorubicin 25mg/m2 IV Days 8, 11, 15, and 18: L-Asparaginase 10,000IU/m2 IM Day 36: Cyclophosphamide 1000mg/m2 IV Days 36–49: 6-Thioguanine 60mg/m2 orally Days 38–41 and 45–48: ARA-C 75mg/m2 SC Days 38–45: Age adjusted: MTX IT (dosages: ≥1 year <2 years = 8mg; ≥2 years <3 years = 10mg; ≥3 years = 12mg) Days 36–63: Imatinib 300mg/m2 orally. Administer reinduction twice, once before and once after interim maintenance. Omit IT therapy from second administration due to previous cranial irradiation.

Interim Maintenance Days 1–29: 6-MP 50mg/m2 orally Days 8, 15, 22, and 29: MTX 20mg/m2 orally Cranial irradiation 1.4–1.7Gy (total dose per phase: standard = 18Gy; if <2 years = 12Gy; if CNS invasive = 24Gy).

Continuation Therapy (Maintenance) 6-MP 50mg/m2 orally daily until day +728 from diagnosis MTX 20mg/m2 orally weekly till day +728 from diagnosis.

Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) + tyrosine kinase inhibitors (TKIs)4-7

Induction 4 cycles Hyper-CVAD alternating with 4 cycles of high dose cytarabine and MTX. Days 1–14 of each cycle: Dasatinib 50mg orally twice daily (or 100mg daily) OR imatinib 400mg orally daily.

OR Day 1: Cyclophosphamide 1,200mg/m2 IV over 3 hours Days 1–3: Daunorubicin 60mg/m2 IV over 1 hour Days 1–21: Prednisolone 60mg/m2 orally Days 1, 8, 15, and 22: Vincristine 1.3mg/m2 IV bolus Days 8–63: Imatinib 600mg orally Day 29: MTX 15mg IT, cytarabine 40mg IT, dexamethasone 4mg IT. OR Pretreatment for 7 days: Prednisone at increasing doses from 10–40mg/m2/day.

Days 1–45: Imatinib 800mg orally daily + prednisone 40mg/m2 daily (patients >60 years).

OR Pretreatment for 7 days: Prednisone at increasing doses from 10–60mg/m2/day Days 1–48: Dasatinib 70mg orally twice daily Days 1–24: Prednisone 60mg/m2 daily (max 120mg daily) Days 22 and 43: MTX IT Days 25–32: Prednisone taper.

Consolidation Allogeneic hematopoietic cell transplant (HCT), if a donor is available and consider post-HCT TKI. OR Continue multiagent chemotherapy + TKI. Maintenance MTX weekly + 6-MP daily + vincristine pulse monthly + prednisone pulse monthly for 2 to 3 years.

Multiagent chemotherapy + TKIs8,9

Induction Day 1: Cyclophosphamide 1,200mg/m2 IV over 3 hours Days 1–3: Daunorubicin 60mg/m2 IV over 1 hour Days 1, 8, 15, and 22: Vincristine 1.3mg/m2 IV bolus Days 1–21: Prednisolone 60mg/m2 orally daily Days 8–63: Imatinib 600mg orally daily Day 29: MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT. Consolidation 1 Day 1: MTX 1g/m2 IV over 24 hours + MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT Days 1–3: Methylprednisolone 50mg IV over 1 hour × 2 doses Days 2 and 3: Cytarabine 2g/m2 IV over 3 hours. Repeat for 4 cycles. continued

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Leukemia Treatment Regimens: Acute Lymphoblastic Leukemia (ALL) Ph(+) AYA (Age 15–39 years) 1abc (continued) PROTOCOL

REGIMEN AND DOSING

Multiagent chemotherapy + TKIs8,9 (continued)

Consolidation 2 Day 1: MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT. Repeat for 4 cycles.

Day 1–28: Imatinib 600mg orally daily.

Maintenance Day 1: Vincristine 1.3mg/m2 IV bolus Days 1–5: Prednisolone 60mg/m2 orally daily Day 1–28: Imatinib 600mg orally daily Repeat every 4 weeks up to 2 years from the date of complete remission.

Ph(+) Adult (Age ≥40 years) 1abc Hyper-CVAD + TKIs4-7

Induction 4 cycles Hyper-CVAD alternating with 4 cycles of high dose cytarabine and MTX. Days 1–14 of each cycle: Dasatinib 50mg orally twice daily (or 100mg daily)3 OR imatinib 400mg orally daily.

OR Day 1: Cyclophosphamide 1,200mg/m2 IV over 3 hours Days 1–3: Daunorubicin 60mg/m2 IV over 1 hour Days 1–21: Prednisolone 60mg/m2 orally Days 1, 8, 15, and 22: Vincristine 1.3mg/m2 IV bolus Days 8–63: Imatinib 600mg orally Day 29: MTX 15mg IT, cytarabine 40mg IT, dexamethasone 4mg IT. OR Pretreatment for 7 days: Prednisone at increasing doses from 10–40mg/m2/day Days 1–45: Imatinib 800mg orally daily + prednisone 40mg/m2 daily (patients >60 years).

OR Pretreatment for 7 days: Prednisone at increasing doses from 10–60mg/m2/day Days 1–24: Prednisone 60mg/m2 daily (max 120mg daily) Days 1–48: Dasatinib 70mg orally twice daily Days 22 and 43: MTX IT Days 25–32: Prednisone taper.

Consolidation Allogeneic hematopoietic cell transplant (HCT), if a donor is available and consider post-HSCT TKI. OR Continue multiagent chemotherapy + TKI. Maintenance MTX weekly + 6-MP daily + vincristine pulse monthly + prednisone pulse monthly for 2 to 3 years.

Multiagent chemotherapy + TKIs8,9

Induction Day 1: Cyclophosphamide 1,200mg/m2 IV over 3 hours Days 1–3: Daunorubicin 60mg/m2 IV over 1 hour Days 1, 8, 15, and 22: Vincristine 1.3mg/m2 IV bolus Days 1–21: Prednisolone 60mg/m2 orally daily Days 8–63: Imatinib 600mg orally daily Day 29: MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT. Consolidation 1 Day 1: MTX 1g/m2 IV over 24 hours + MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT Days 1–3: Methylprednisolone 50mg IV over 1 hour × 2 Days 2 and 3: Cytarabine 2g/m2 IV over 3 hours.

Repeat for 4 cycles.

Consolidation 2 Day 1: MTX 15mg IT + cytarabine 40mg IT + dexamethasone 4mg IT. Repeat for 4 cycles.

Days 1–28: Imatinib 600mg orally daily Maintenance Day 1: Vincristine 1.3mg/m2 IV bolus Days 1–5: Prednisolone 60mg/m2 orally daily Day 1–28: Imatinib 600mg orally daily.

Repeat every 4 weeks up to 2 years from the date of complete remission.

40 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Ph(+) Adult (Age ≥40 years) 1abc (continued) PROTOCOL Corticosteroids + TKIs

REGIMEN AND DOSING 10-12

Pretreatment Days 1–7: Prednisone at increasing doses from 10–40mg/m2 orally daily.

Induction Days 1–45: Imatinib 800mg orally daily + prednisone 40mg/m2 orally daily.

OR Pretreatment Days 1–7: Prednisone at increasing doses from 10–60mg/m2 orally daily.

Induction Days 1–84: Dasatinib 70mg orally twice daily Days 1–32: Prednisone 60mg/m2 orally daily (maximum 120mg daily) until day 24, then tapered and stopped at day 32 Days 22 and 43: MTX 15mg IT.

Vincristine + dexamethasone + TKIs13,14

Pretreatment Days 1–7: Prednisone at increasing doses from 10–40mg/m2 orally daily.

Induction Cycle 1: Days 1–28: Imatinib 800mg orally daily Days 1, 8, 15, and 22: Vincristine 2mg IV Days 1–2, 8–9, 15–16, and 22–23: Dexamethasone 40mg orally daily.

Cycle 2: Day 1: MTX 1g/m2 IV Days 2 and 3: Cytarabine 3g/m2 IV every 12 hours Days 1–14: Imatinib 800mg orally daily.

OR Pretreatment Days 1–7: Prednisone at increasing doses from 10–40mg/m2 orally daily.

Induction Cycle 1: Days 1–28: Dasatinib 140mg orally once daily (100mg if patient >70 years) Days 1, 8, 15, and 22: Vincristine 1mg IV Days 1–2, 8–9, 15–16, and 22–23: Dexamethasone 40mg orally daily (20mg if patient >70 years).

Consolidation Cycles 1, 3, and 5: Days 1–28: Dasatinib 100mg orally daily Day 1: MTX 1g/m2 IV (500mg/m² if patient >70 years) Day 2: Asparaginase 10,000IU/m2 IM (5,000IU/m² if patient >70 years) Cycles 2, 4, and 6: Days 1–28: Dasatinib 100mg orally daily Day 1, 3, and 5: Cytarabine 1,000mg/m2 every 12 hours IV (500mg/m² if patient >70 years).

Maintenance Dasatinib sequentially with 6-MP and MTX orally one every other month, plus dexamethasone and vincristine every 2 months up to 24 months, followed by dasatinib alone until relapse or death.

Ph(−) AYA (Age 15–39 years) 1abc GRAALL-200315

Corticosteroid Pre-phase 1–7 days before induction therapy: Prednisone 60mg/m2/day 4–7 days before induction therapy: MTX 15mg IT. Induction Day 1: Cyclophosphamide 750mg/m2/day + vincristine 2mg IV Days 1–3: Daunorubicin 50mg/m2/day Days 1–14: Prednisone 60mg/m2/day Day 8: Vincristine 2mg IV + L-asparaginase 6,000IU/m2/day Days 10 and 12: L-asparaginase 6,000IU/m2/day Day 15: Vincristine 2mg IV continued

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Leukemia Treatment Regimens: Acute Lymphoblastic Leukemia (ALL) Ph(−) AYA (Age 15–39 years) 1abc (continued) PROTOCOL

REGIMEN AND DOSING

GRAALL-2003 (continued)

Day 15: For Good Early Responders: Cyclophosphamide 750mg/m2/day.

OR Days 15 and 16: For Poor Early Responders: Cyclophosphamide 500mg/m2/12 hours Days 15 and 16: Daunorubicin 30mg/m2/day Day 17: Lenograstim 150mcg/m2/day to myeloid recovery Days 20 and 22: L-asparaginase 6,000IU/m2/day Day 22: Vincristine 2mg IV Days 24, 26, and 28: L-asparaginase 6,000IU/m2/day.

Salvage Days 1–3: Idarubicin 12mg/m2/day Days 1–4: Cytarabine 2g/m2/12 hours Day 9: Filgrastim to myeloid recovery.

Consolidation Blocks 1, 4, and 7: Days 1 and 2: Cytarabine 2g/m2/12 hours + dexamethasone 10mg/12 hours Day 3: L-asparaginase 10,000IU/m2/day Days 7–13: Filgrastim to myeloid recovery.

Blocks 2, 5, and 8: Day 15: MTX 3g/m2 continuous infusion + vincristine 2mg IV + 6-MP 60mg/m2/day Day 16: L-asparaginase 10,000IU/m2/day Days 16–21: 6-MP 60mg/m2/day Days 22–27: Filgrastim to myeloid recovery.

Blocks 3, 6, and 9: Day 29: MTX 25mg/m2/day Days 29 and 30: Cyclophosphamide 500mg/m2/day + etoposide 75mg/m2/day Day 31: Filgrastim to myeloid recovery.

Late intensification between consolidation blocks 6 and 7 (for patients in complete remission [CR] after the first induction course) Day 1: Vincristine 2mg IV Days 1–3: Daunorubicin 30mg/m2/day Days 1–14: Prednisone 60mg/m2/day Day 8: Vincristine 2mg IV Days 8, 10, and 12: L-asparaginase 6,000IU/m2/day Day 15: Vincristine 2mg IV + cyclophosphamide 500mg/m2/12 hours Days 18, 20, and 22: L-asparaginase 6,000IU/m2/day.

Late intensification between consolidation blocks 6 and 7 (for patients in CR after salvage course) Days 1–3: Idarubicin 9mg/m2/day Days 1–4: Cytarabine 2g/m2/12 hours Day 9: Filgrastim to myeloid recovery.

Maintenance Months 1–12 Day 1: Vincristine 2mg IV Days 1–7: Prednisone 40mg/m2/day.

Months 1–24 Daily: 6-MP 60mg/m²/day Weekly: MTX 25mg/m2/week.

CNS Therapy—Prophylaxis Triple IT Injection 1 IT injection at Days 1 and 8 of induction; 1 IT injection at Day 29 of each series of consolidation blocks; 1 IT injection at Day 1 of late intensification.

Cranial Irradiation 18Gy before maintenance therapy initiation. 6-MP 60mg/m2/day during irradiation.

CNS Therapy—Treatment of patients with initial CNS involvement: Triple IT Injection 8 IT injections starting from 7 days before induction to Day 21 of induction; 4 IT injections during the first 2 consolidation blocks; 1 IT injection at Day 29 of consolidation blocks 3 and 6.

Cranial Irradiation 15Gy before HCT or 24Gy before maintenance therapy initiation 6-MP 60mg/m2/day during irradiation.

15

42 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Ph(−) AYA (Age 15–39 years) 1abc (continued) PROTOCOL

REGIMEN AND DOSING

COG AALL-0434

16

Induction (4 weeks) Day 1: Cytarabine IT Days 1, 8, 15, and 22: Vincristine IV + daunorubicin IV Days 1–28: Prednisone IV or orally twice daily Day 4, 5, or 6: Pegaspargase IM or IV over 1–2 hours Days 8 and 29: MTX IT. Consolidation Days 1–5 and 43–47: Nelarabine IV over 60 minutes Days 15, 22, 57, and 64: MTX IT Days 8 and 50: Cyclophosphamide IV over 30 minutes Days 8–11, 15–18, 50–53, and 57–60: Cytarabine IV over 15–30 minutes or SC Days 8–21 and 50–63: Mercaptopurine orally Days 22, 29, 64, and 71: Vincristine sulfate IV Days 22 and 64: Pegaspargase IM or IV over 1–2 hours.

COG AALL023217,18

Induction Days 1–28: Prednisone oral or IV twice daily Day 1: Cytarabine IT Days 1, 8, 15, and 22: Vincristine IV + daunorubicin IV Days 4, 5, or 6: Pegaspargase IM Days 8 and 29: MTX IT Days 15 and 22: Only patients with CNS3 disease: MTX IT. Extended Induction Only for patients with M2 disease of M1 disease with >1% MRD Days 1–14: Prednisone oral of IV twice daily Days 1 and 8: Vincristine IV Day 1: Daunorubicin IV Days 4, 5, or 6: Pegaspargase IM. Consolidation (7–8 weeks) Days 1 and 29: Cyclophosphamide IV over 30 min Days 2–5, 9–12, 30–33, and 37–40: Cytarabine IV or SC Days 1–14 and 29–42: Mercaptopurine orally Days 15, 22, 43, and 50: Vincristine IV Days 15 and 43: Pegaspargase IM Days 1, 8, 15, and 22: MTX IT (patients with CNS3 disease receive MTX on Days 1 and 8 only).

Interim Maintenance I Days 1, 11, 21, 31, and 41: Vincristine IV + escalating dose MTX IV Days 1 and 21: MTX IT Days 2 and 22: Pegaspargase IM. OR Days 1, 15, 29, and 43: Vincristine IV and high-dose MTX IV over 24 hours Days 1–56: Mercaptopurine orally Days 1 and 29: MTX IT. Delayed Intensification I Days 1, 8, 15, 43, and 50: Vincristine IV Days 1–21: Only patients aged 1–12: Dexamethasone orally or IV twice daily Days 1–7 and 15–21: Only patients aged ≥13 years: Dexamethasone orally or IV twice daily Days 1, 8, and 15: Doxorubicin IV Days 4, 5, or 6 and day 43: Pegaspargase IM Day 29: Cyclophosphamide IV Days 30–33 and 37–40: Cytarabine IV or SC Days 29–42: Oral thioguanine Days 1, 29, and 36: MTX IT. Interim Maintenance II Days 1, 11, 21, 31, and 41: Vincristine IV + MTX IV Days 2 and 22: Pegaspargase IM Days 1 and 21: MTX IT.

continued

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Leukemia Treatment Regimens: Acute Lymphoblastic Leukemia (ALL) Ph(−) AYA (Age 15–39 years) 1abc (continued) PROTOCOL

REGIMEN AND DOSING

COG AALL023217,18 (continued)

Delayed Intensification II Same regimen as delayed intensification I Day 29: CNS3 patients only: Start radiotherapy for 3–10 days; All other slow early response patients: Start prophylactic cranial radiotherapy for 8 days.

Maintenance Therapy Day 1: MTX IT Days 1, 29, and 57: Vincristine IV Days 1–5, 29–33, and 57–61: Dexamethasone orally twice daily Days 1–84: Mercaptopurine orally Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78: MTX orally.

DFCI ALL regimen per DFCI Protocol 00-0119,20

Induction Days 0, 7, 14, and 21: Vincristine 1.5mg/m2 weekly (maximum, 2mg) Days 0–28: Prednisone 40mg/m2/day Days 0 and 1: Doxorubicin 30mg/m2/dose (high-risk patients: with dexrazoxane 300mg/m2/dose) + MTX 4g/m2 (8–24 hours after doxorubicin) with leucovorin rescue 1 dose: L-asparaginase 25,000IU/m2 IM Day 0: Cytarabine IT Day 14 (1 dose): MTX IT + cytarabine IT + hydrocortisone IT CNS Therapy (3 weeks) Day 1: Vincristine 2mg/m2 14 days: 6-Mercaptopurine (6-MP) 50mg/m2/day orally at bedtime Standard-risk patients: MTX IT + cytarabine IT + hydrocortisone IT twice weekly × 4 doses High-risk patients: MTX IT + cytarabine IT twice weekly × 4 doses + doxorubicin 30mg/m2 + dexrazoxane 300mg/m2 + cranial radiation Intensification (30 weeks) Cycle every 3 weeks Day 1: Vincristine 2mg/m2 14 doses: 6-MP 50mg/m²/day orally at bedtime Once Weekly: MTX 30mg/m2 (1mg/kg if <0.6 m2) IV or IM Days 1–5: Prednisone 40mg/m2/day orally ÷ twice daily (20mg/m2 per dose) Weekly: L-asparaginase 25,000IU/m2 IM, weekly × 30 weeks OR 12,500IU/m2 IM (starting dose) weekly, with dose adjusted every 3 weeks to maintain nadir serum asparaginase activity between 0.1–0.14IU/mL Start of a cycle every 9 weeks: MTX IT + cytarabine IT + hydrocortisone IT × 6 doses, then every 18 weeks through completion of therapy (at start of a cycle).

High-risk patients: Same as above, except higher corticosteroid dose Days 1–5: Prednisone 120mg/m2/day) Day 1 of each cycle: Doxorubicin 30mg/m2 (cumulative dose 300mg/m2) + dexrazoxane 300mg/m2/dose [NOTE: No weekly MTX IV/IM until doxorubicin completed, and IT therapy of MTX/cytarabine every 18 weeks] Continuation (74 weeks) Cycle every 3 weeks Standard-risk patients: Same as intensification, except no L-asparaginase High-risk patients: Same as SR patients, including lower corticosteroid dose of dexamethasone 6mg/m2 per day and prednisone 40mg/m2 per day on days 1 to 5.

USC ALL regimen per CCG-188221

Induction Phase I Days 1–3: Daunorubicin 60mg/m2 IV Days 1, 8, 15, and 22: Vincristine 1.4mg/m2 IV (maximum, 2mg) Day 15: Pegaspargase 2,000IU/m2 IV Days 1–28: Prednisone 60mg/m2 orally Days 8 and 15: MTX 12mg IT. Induction Phase II Days 1 and 29: Cyclophosphamide 1g/m2 IV Days 1–4, 8–11, 29–32, and 36–39: Cytarabine 75mg/m2 IV Days 15, 22, 43, and 50: Vincristine 1.4mg/m2 IV (maximum, 2mg) Day 15: Pegaspargase 2,000IU/m2 IV Days 15–29: Prednisone 20mg/m2 orally Days 1– 14 and 29–43: Mercaptopurine 60mg/m2 orally Days 1, 8, 15, and 22: MTX 12mg IT.

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Ph(−) AYA (Age 15–39 years) 1abc (continued) PROTOCOL USC ALL regimen per CCG-1882 (continued)

REGIMEN AND DOSING 21

Intensification Days 1 and 15: MTX 1g/m2 IV (T-cell ALL, 2.5g/m2 IV) + leucovorin 15mg every 6 hours IV starting 36 hours from start of MTX Day 16: Pegaspargase 2,000IU/m2 IV Days 16–30: Prednisone 20mg/m2 orally Consolidation Days 1–5: Cytarabine 75mg/m2 IV + teniposide 60mg/m2 IV. Delayed Reinduction Days 1, 8, and 15: Daunorubicin 25mg/m2 IV Days 1, 8, 15, 43, and 50: Vincristine 1.4mg/m2 IV (maximum, 2mg) Days 15–22 and 43–50: Dexamethasone 10mg/m2 orally Day 15: Pegaspargase 2,000IU/m2 IV Day 29: Cyclophosphamide 1g/m2 Days 29–32 and 36–39: Cytarabine 75mg/m2 IV Days 26–42: Thioguanine 60mg/m2 orally Days 1, 29, and 36: MTX 12mg IT. Maintenance Monthly for 24 months from end of all consolidations Days 1–5: Prednisone 60mg/m2 orally (year 1, monthly; year 2, every 2 months) Day 1: Vincristine 1.4mg/m2 (maximum, 2mg) IV (year 1, monthly; year 2, every 2 months) Days 1–28: Mercaptopurine 60mg/m2 orally Days 1, 8, 15, and 22: MTX 20mg/m2 orally + MTX 12mg IT (year 1, once every 3 months).

Imatinib 600mg once daily from induction until end of standard maintenance regimen added for Philadelphia chromosome–positive patients.

PETHEMA ALL-9622

Induction Days 1, 8, 15, and 22: Vincristine 2mg IV + daunorubicin 30mg/m2 IV Days 1–27: Prednisone 60mg/m2 IV or orally Days 1 and 29: MTX 15mg IT + cytarabine 30mg IT + hydrocortisone 20mg IT Days 10–12, 17–19, and 24–26: Asparaginase 10,000U/m2 Days 28–35: Prednisone 30mg/m2 IV or orally Day 36: Cyclophosphamide 1,000mg/m2 IV. Consolidation Days 1–7: Mercaptopurine 50mg/m2 orally Days 1, 28, and 56: MTX 3g/m2 IV over 24 hours Days 14 and 42: Teniposide 150mg/m2 IV every 12 hours Days 14, 15, 42, and 43: Cytarabine 500mg/m2 IV every 12 hours Days 1, 28, and 56: MTX 15mg IT + cytarabine 30mg IT + hydrocortisone 20mg IT. Consolidation-2/Reinduction Days 1–14: Dexamethasone 10mg/m2 orally or IV daily Days 1, 2, 8, and 9: Daunorubicin 30mg/m2 IV Days 1–3 and 15–17: Asparaginase 10,000U/m2 IM or IV Days 1, 8, and 15: Vincristine 1.5mg/m2 IV Days 1 and 15: Cyclophosphamide 600mg/v IV + MTX 15mg IT + cytarabine 30mg IT + hydrocortisone 20mg IT Days 15–21: Dexamethasone 5mg/m2 orally or IV daily.

Maintenance-1 MTX 20mg/m2 IM weekly until week 52 Mercaptopurine 50mg/m2 orally daily until week 52.

CALGB 1040323

Induction Day 1: Cytarabine IT Days 8 and 29: MTX IT Days 1, 8, 15, and 22: Daunorubicin IV + Vincristine IV Day 4: PEG-asparaginase.

Consolidation Days 1, 8, 15, and 22: MTX IT Days 1 and 29: Cyclophosphamide IV Days 1–4, 8–11, 29–32, and 36–39: Cytarabine Days 1–14 and 29–42: 6-Mercaptopurine orally Days 15, 22, 43, and 50: Vincristine IV Day 15 and 43: PEG-asparaginase. continued

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Leukemia Treatment Regimens: Acute Lymphoblastic Leukemia (ALL) Ph(−) AYA (Age 15–39 years) 1abc (continued) PROTOCOL

REGIMEN AND DOSING

CALGB 10403 (continued)

Interim Maintenance Days 1 and 31: MTX IT Days 1, 11, 21, 31, and 41: Vincristine IV + MTX Days 2 and 22: PEG-asparaginase.

23

Delayed Intensification Days 1, 29, and 36: MTX IT Days 1–7 and 15–21: Dexamethasone orally Days 1, 8, and 15: Doxorubicin IV Days 4 and 43: PEG-asparaginase Day 29: Cyclophosphamide IV Days 29–32 and 36–39: Cytarabine IV Days 29–42: 6-Thioguanine orally.

Maintenance Days 15 and 29: MTX IT of first 4 courses of maintenance Days 1, 29, and 57: Vincristine IV For Females: Days 1–5, 29–33, and 57–61: Dexamethasone orally for 2 years from interim maintenance For Males: Days 1–84: 6-Mercaptopurine orally for 3 years from interim maintenance Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78: MTX; held on Day 29 of first 4 courses of maintenance when methotrexate IT is given.

Ph(−) Adult (Age ≥ 40 years) 1abc CALGB 8811 (Larson Regimen)24

Induction Day 1: Cyclophosphamide 1, 200mg/m2 IV Days 1–3: Daunorubicin 45mg/m2 IV Days 1, 8, 15, and 22: Vincristine 2mg IV Days 1–21: Prednisone 60mg/m2/day orally Days 5, 8, 11, 15, 18, and 22: L-asparaginase 6,000IU/m2 SC. Consolidation Day 1: MTX 15mg IT + cyclophosphamide 1,000mg/m2 IV Days 1–14: 6-Mercaptopurine 60mg/m2/day orally Days 1–4 and 8–11: Cytarabine 75mg/m2/day SC Days 15 and 22: Vincristine 2mg IV Days 15, 18, 22, and 25: L-asparaginase 6,000IU/m2 SC. Repeat cycle every 4 weeks for 2 cycles, followed by: Days 1–12: Cranial irradiation 2,400cGy Days 1, 8, 15, 22, and 29: MTX 15mg IT Days 1–70: 6-Mercaptopurine 60mg/m2/day orally Days 36, 43, 50, 57, and 64: MTX 20mg/m2 orally, followed by: Days 1, 8, and 15: Doxorubicin 30mg/m2 IV Days 1, 8, and 15: Vincristine 2mg IV Days 1–14: Dexamethasone 10mg/m2/day orally Day 29: Cyclophosphamide 1,000mg/m2 IV Days 29–42: 6-Thioguanine 60mg/m2/day orally Days 29–32 and 36–39: Cytarabine 75mg/m2/day SC, followed by: Day 1: Vincristine 2mg IV Days 1–5: Prednisone 60mg/m2/day orally Days 1, 8, 15, and 22: MTX 20mg/m2 orally Days 1–28: 6-Mercaptopurine 60mg/m2/day orally. Repeat cycle every 4 weeks until 24 months from diagnosis.

Linker 4-drug regimen25

Induction Days 1–3: Daunorubicin 50mg/m2/day IV Days 1, 8, 15, and 22: Vincristine 2mg IV Days 1–28: Prednisone 60mg/m2/day orally Days 17–28: L-asparaginase 6,000IU/m2/day IM. If bone marrow on Day 14 has residual leukemia: Day 15: Daunorubicin 50mg/m2 IV. If bone marrow on Day 28 has residual leukemia: Day 29 and 30: Daunorubicin 50mg/m2 IV Days 29–35: L-asparaginase 6,000IU/m2/day IM. Days 29–42: Prednisone 60mg/m2/day orally.

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Ph(−) Adult (Age 40 years) 1abc (continued) PROTOCOL

REGIMEN AND DOSING

Linker 4-drug regimen (continued)

Consolidation Cycles 1, 3, 5, and 7: Days 1 and 2: Daunorubicin 50mg/m2/day IV Days 1 and 8: Vincristine 2mg IV Days 1–14: Prednisone 60mg/m2/day orally Days 4, 7, 9, 11, and 14: L-asparaginase 12,000IU/m2/day IM. Cycles 2, 4, 6, and 8: Days 1, 4, 8, and 11: Teniposide 165mg/m2 IV + cytarabine 300mg/m2 IV. Cycle 9: MTX 690mg/m2 IV over 42 hours, followed by leucovorin 15mg/m2 IV every 6 hours x 12 doses, followed by: MTX 20mg/m2 orally weekly + 6-Mercaptopurine 75mg/m2 orally daily for 30 months.

Hyper-CVAD ± Rituximab26,27

Cycles 1, 3, 5, and 7 Days 1–3: Cyclophosphamide 300mg/m2 IV every 12 hours + mesna 600mg/m2/day continuous IV infusion starting 1 hour before cyclophosphamide until 12 hours after completion of cyclophosphamide Days 1–4 and 11–14: Dexamethasone 40mg orally daily, ± Days 1 and 8: Rituximab 375mg/m2 IV Day 4: Doxorubicin 50mg/m2 IV over 24 hours Days 4 and 11: Vincristine 2mg IV. Cycles 2, 4, 6, and 8 Day 1: MTX 200mg/m2 IV over 2 hours followed by 800mg/m2 continuous IV infusion over 22 hours followed by leucovorin 50mg IV every 6 hours starting 12 hours after completion of MTX until MTX level <0.05uM Days 2–3: Cytarabine 3g/m2 (1g/m2 for patients >60 years old) IV over 2 hours every 12 hours, ± Days 1 and 8: Rituximab 375mg/m2 IV. CNS Prophylaxis Day 2: MTX 12mg IT Day 8: Cytarabine 100mg IT.

MRC UKALLXII/ECOG299328

Induction Phase 1 (Weeks 1–4): Days 1, 8, 15, and 22: Daunorubicin 60mg/m2 IV + vincristine 1.4mg/m2 IV Days 1–28: Prednisone 60mg/m2 orally daily Day 15: MTX 12.5mg IT Days 17–28: L-asparaginase 10,000IU IV or IM. Phase 2 (Weeks 5–8): Days 1, 15, and 29: Cyclophosphamide 650mg/m2 IV Days 1–4, 8–11, 15–18, and 22–25: Cytarabine 75mg/m2 IV Days 1–28: 6-Mercaptopurine 6mg/m2 orally daily Days 1, 8, 15, and 22: MTX 12.5mg IT. Intensification Days 1, 8, and 22: MTX 3g/m2 IV Days 2, 9, and 23: L-asparaginase 10,000IU IM or IV + standard leucovorin rescue.

Consolidation Cycle 1: Days 1–5: Etoposide 100mg/m2 IV + cytarabine 75mg/m2 IV Days 1, 8, 15, and 22: Vincristine 1.4mg/m2 IV Days 1–28: Dexamethasone 10mg/m2 orally daily.

Cycle 2 (4 Weeks After Cycle 1): Days 1–5: Cytarabine 75mg/m2 IV + etoposide 100mg/m2 IV. Cycle 3 (4 Weeks After Cycle 2): Days 1, 8, 15, and 22: Daunorubicin 25mg/m2 IV Day 29: Cyclophosphamide 650mg/m2 IV Days 31–34 and 38–41: Cytarabine 75mg/m2 IV Days 29–42: Thioguanine 60mg/m2 orally daily.

Maintenance: Vincristine 1.4mg/m2 IV every 3 months Prednisone 60mg/m2 orally for 5 days every 3 months 6-Mercaptopurine 75mg/m2 orally daily MTX 20mg/m2 orally or IV once weekly.

Continue for 2.5 years from start of intensification therapy.

25

continued

CancerTherapyAdvisor.com JULY/AUGUST 2017 | CANCER THERAPY ADVISOR 47

CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Leukemia Treatment Regimens: Acute Lymphoblastic Leukemia (ALL) Relapsed or Refractory ALL1,a PROTOCOL

REGIMEN AND DOSING

Ph(+) ALL Dasatinib (preferred)29,30,d

Dasatinib 140mg orally daily. Continue until disease progression or unacceptable toxicity.

Nilotinib31,e

Nilotinib 400mg orally twice daily. Continue until disease progression or unacceptable toxicity.

Imatinib (preferred)

Imatinib 600mg orally daily. Continue until disease progression or unacceptable toxicity.

Ponatinib (preferred)33,f

Ponatinib 45mg orally daily. Continue until disease progression or unacceptable toxicity.

32

Ph(−) ALL Clofarabine-containing regimens (for B-ALL)34,35

Induction Days 1–5: Clofarabine 40mg/m2 IV over 2 hours + etoposide 100mg/m2 IV over 2 hours + cyclophosphamide 440mg/m2 IV over 1 hours.

Consolidation Days 1–4: Clofarabine 40mg/m2 IV over 2 hours + etoposide 100mg/m2 IV over 2 hours + cyclophosphamide 440mg/m2 IV over 1 hours.

Cytarabine-containing regimens36

Days 1–5: Cytarabine 3g/m2 IV over 3 hours Day 3: Idarubicin 40mg/m2.

Alkylator-containing regimens37

Days 1–3: Mitoxantrone 8mg/m2 IV daily Days 1–5: Etoposide 100mg/m2 IV daily + ifosfamide 1.5g/m2 IV daily.

Nelarabine (for T-ALL)38

Days 1, 3, and 5: Nelarabine 1.5g/m2/day IV over 2 hours.

Repeat cycle every 21 days.

Augmented Hyper-CVAD39

Cycles 1, 3, 5, and 7 Day 1: Pegaspargase 2,500units/m2 IV Days 1–3: Cyclophosphamide 300mg/m2 IV every 12 hours for 6 doses + MESNA 600mg/m2 continuous IV infusion over 24 hours daily Day 4: Doxorubicin 50mg/m2 IV over 24 hours Days 1, 8, and 15: Vincristine 2mg IV Days 1–4 and 15–18: Dexamethasone 80mg IV or orally.

Cycles 2, 4, 6, and 8 Day 1: MTX 1g/m2 IV over 24 hours with leucovorin 50mg IV given 12 hours after completion of MTX, followed by leucovorin 15mg IV every 6 hours for 8 doses Days 2–3: Cytarabine 3g/m2 IV every 12 hours for 4 doses Day 5: Pegaspargase 2,500units/m2 IV. Maintenance Mercaptopurine 50mg orally 3 times daily + MTX 20mg/m2 orally weekly + vincristine 2mg IV every 28–35 days + prednisone 200mg orally daily on days 1–5.

Vincristine sulfate liposome injection40,41

Liposomal vincristine sulfate 2.25mg/m2 IV over 1 hour once weekly until response, progression, toxicity, or pursuit of HCT.

Blinatumomab (for B-ALL; preferred)42–44,g

Cycle 1 Days 1–7: Blinatumomab 9mcg/day continuous IV infusion Days 8–28: Blinatumomab 28mcg/day continuous IV infusion.

Subsequent Cycles Days 1–28: Blinatumomab 28mcg/day continuous IV infusion. Repeat cycle every 42 days.

All regimens include CNS prophylaxis with systemic therapy (eg, methotrexate, cytarabine, 6-MP) and/or IT therapy (eg, IT methotrexate, IT cytarabine; triple IT therapy with methotrexate, cytarabine, corticosteroid). b For patients receiving 6-MP, consider testing for TPMT gene polymorphisms, particularly in patients who develop severe neutropenia after starting 6-MP. c Dose modifications for antimetabolites in maintenance should be consistent with the chosen treatment regimen. It may be necessary to reduce dose/eliminate antimetabolite in the setting of myelosuppression and/or hepatotoxicity. d For patients with mutations Y253H, E255K/V or F359V/C/I. e For patients with mutations F317L/V/I/C, T315A or V299L. f Ponatinib has activity against T315I mutations and is effective in treating patients with resistant or progressive disease on multiple TKIs, but is associated with a high frequency of serious vascular events.

The FDA indications are for the treatment of adult patients with T3151-positive PH+ ALL and for the treatment of adult patients with PH+ ALL for whom no other TKI therapy is indicated. g Blinatumuomab may cause severe, life-threatening, or fatal adverse events, including cytokine release syndrome and neurologic toxicities. Understanding the REMS programs and/or experience in the use of the drug as well as resources to monitor the patient closely are essential. It is important that the instruction for blinatumomab product preparation (including admixing) and administrationare strictly followed to minimize medication errors, including underdose and overdose. a

48 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

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HEMATOLOGIC CANCER References 1. NCCN Clinical Practice Guidelines in Oncology®. Acute Lymphoblastic Leukemia. v 2.2016. Available at: http://www.nccn.org/ professionals/physician_gls/pdf/all.pdf.

Accessed May 10, 2017.

2. Schultz KR, Bowman WP, Aledo A, et al. Improved early eventfree survival with imatinib in Philadelphia chromosome-positive ALL: A Children’s Oncology Group Study. J Clin Oncol. 2009; 27(31):5175–5181.

3. Biondi A, Schrappe M, De Lorenzo P, et al. Imatinib after induction for treatment of children and adolescents with Philadelphiachromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study.

Lancet Oncol. 2012; 13(9):936-945.

4. Ravandi F, O’Brien S, Thomas D, et al. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosomepositive ALL. Blood. 2010;116(12):2070–2077.

5. Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosomepositive ALL with hyper-CVAD and imatinib mesylate. Blood.

2004;103(12):4396–4407.

6. Thomas DA, Kantarjian HM, Cortes J, et al. Outcome after frontline therapy with the hyper-CVAD and imatinib mesylate regimen for adults with de novo or minimally treated Philadelphia chromosome-positive ALL [abstract]. Blood. 2008;112 (Supple 11):Abstract 2931.

7. Thomas DA, O’Brien SM, Faderl S, et al. Long-term outcome after hyper-CVAD and imatinib for de novo or minimally treated Philadelphia chromosome-positive ALL [abstract]. J Clin Oncol. 2010;28:Abstract 6506.

8. Mizuta S, Matsuo K, Yagasaki F, et al. Pre-transplant imatinib-based therapy improves the outcome of allogenic hematopoietic stem cell transplantation for BCR-ABL-positive ALL. Leukemia. 2011;25(1):41–47.

9. Yanada M, Takeuchi J, Sugiura I, et al. High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCRABL-positive ALL: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol. 2006;24(3):460–466.

10. Vignetti M, Fazi P, Cimino G, et al. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with ALL without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) LAL0201-B protocol. Blood.

2007;109(9):3676–3678.

11. Foa R, Vitale A, Guarini A, et al. Dasatinib monotherapy effective and feasible as firstline treatment of adult Ph+ ALL patients. Final results of the GIMEMA LAL1205 study [abstract]. Blood. 2008;112(Supple 11):Abstract 305.

12. Foa R, Vitale A, Vignetti M, et al. Dasatinib as first-line treatment for adult patients with Ph+ ALL. Blood. 2011;118(25):6521–6528.

13. Chalandon Y, Thomas X, Hayette S, et al. Is less chemotherapy detrimental in adults with Ph+ ALL treated with high-dose imatinib? Results of the prospective randomized Graaph-2005 study [abstract]. Blood. 2012;120:Abstract 138.

14. Rousselot P, Coude MM, Huguet F, et al. Dasatinib and low intensity chemotherapy for first-line treatment in patients with de novo Ph+ ALL aged 55 and over: final results of the EWALL-Ph-01 study [abstract]. Blood. 2012;120:Abstract 666.

15. Huguet F, Leguay T, Raffoux E, et al. Pediatric-inspired therapy in adults with Ph- ALL: the GRAALL-2003 study. J Clin Oncol. 2009;27(6):911–918.

16. Winter SS, Devidas M, Wood B, et al. Nelarabine may be safely incorporated into a phase III study for newly diagnosed T-lineage ALL: a report from the Children’s Oncology Group [abstract]. Blood. 2010;116:Abstract 865.

17. Borowitz MJ, Wood BL, Devidas M, et al. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children's Oncology Group study AALL0232. Blood. 2015; 126(8):964–971.

18. COG-AALL0232. http://www.ped-onc.org/diseases/ALLtrials/COG0232.html.

Accessed May 20, 2017.

19. Waber DP, McCabe M, Sebree M, et al. Neuropsychological outcomes of a randomized trial of prednisone versus dexamethasone in acute lymphoblastic leukemia: findings from Dana-Farber Cancer Institute ALL Consortium Protocol 0001. Pediatr Blood Cancer. 2013;60:1785–1791.

20. Vrooman LM, Stevenson KE, Supko JG, et al. Postinduction dexamethasone and individualized dosing of Escherichia coli L-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: results from a randomized study—Dana-Farber Cancer Institute ALL Consortium Protocol 00-01. J Clin Oncol. 2013;31(9):1202–1210.

21. Douer D, Aldoss I, Lunning MA, et al. Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia. J Clin Oncol. 2014;32(9):905–911.

22. Ribera JM, Oriol A, Sanz MA, et al. Comparison of the results of the treatment of adolescents and young adults with standard-risk ALL with the Programa Espanol de Tratamiento en Hematologia pediatric-based protocol ALL-96. J Clin Oncol.

2008;26(11):1843–1849.

23. Stock W, Luger SM, Advani AS, et al. Favorable outcomes for older adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL): early results of U.S. Intergroup Trial C10403 [abstract]. Blood. 2014;124:Abstract 796.

24. Larson RA, Dodge RK, Burns CP, et al. A five-drug remission induction regimen with intensive consolidation for adults with ALL: a cancer and leukemia group B study 8811. Blood. 1995;85(8):2025–2037.

25. Linker C, Damon L, Ries C, Navarro W. Intensified and shortened cyclical chemotherapy for adult ALL. J Clin Oncol. 2002; 20:2464–2471.

26. Kantarjian H, Thomas D, O’Brien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult ALL. Cancer.

2004;101(12):2788–2801.

27. Thomas DA, O’Brien S, Faderl S, et al. Chemoimmunotherapy with a modified hyperCVAD and rituximab regimen improves outcome in de novo Ph- precursor B-lineage ALL. J Clin Oncol. 2010;28(24):3880–3889.

28. Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with ALL: results of more than 1500 patients from the international ALL trial: MRC XII/ECOG E2993.

Blood. 2005;106(12):3760–3767.

29. Lilly MB, Ottmann OG, Shah NP, et al. Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph+ ALL who failed imatinib: results from a phase 3 study. Am J Hematol. 2010;85(3):164–170.

30. Ottmann O, Dombret H, Martinelli G, et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Ph+ ALL with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood. 2007;110(7):2309–2315.

31. Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Ph+ ALL. N Engl J Med. 2006;354(24):2542–2551.

32. Ottmann OG, Druker BJ, Sawyers CL, et al. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood. 2002;100(6):1965-1971.

33. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A phase 2 trial of ponatinib in Ph+ leukemias.

N Engl J Med. 2013;369(19):1783–1796.

34. Jeha S, Gaynon PS, Razzouk BI, et al. Phase II study of clofaribine in pediatric patients with refractory or relapsed ALL. J Clin Oncol. 2006;24(12):1917–1923.

35. Miano M, Pistorio A, Putti MC, et al. Clofarabine, cyclophosphamide and etoposide for the treatment of relapsed or resistant ALL in pediatric patients. Leuk Lymphoma.

2012;53(9): 1693–1698.

36. Weiss MA, Aliff TB, Tallman MS, et al. A single, high dose of idarubicin combined with cytarabine as induction therapy for adult patients with recurrent or refractory ALL. Cancer. 2002; 95(3):581–587.

37. Schiller G, Lee M, Territo M, Gajewski J, Nimer S. Phase II study of etoposide, ifosfamide, and mitoxantrone for the treatment of resistant adult ALL. Am J Hematol. 1993;43(3):195–199.

38. DeAngelo DJ, Yu D, Johnson JL, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage ALL or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood. 2007;109(12):5136–5142.

39. Faderl S, Thomas DA, O’Brien S, et al. Augmented hyper-CVAD based on doseintensified vincristine, dexamethasone, and asparaginase in adult ALL salvage therapy. Clin Lymphoma Myeloma Leuk. 2011;11(1):54–59.

40. Deitcher OR, O’Brien S, Deitcher SR, et al. Single-agent vincristine sulfate liposomes injection compared to historical single-agent therapy for adults with advanced, relapsed and/or refractory Ph- ALL [abstract]. Blood. 2011;118:Abstract 2592.

41. O’Brien S, Schiller G, Lister J, et al. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Ph-ALL. J Clin Oncol.

2013;31(6):676–683.

42. Topp MS, Gokbuget N, Zugmaier G, et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood. 2012;120(26):5185–5187.

43. Topp MS, Kufer P, Gokbuget N, et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage ALL patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol. 2011;29(18):2493–2498.

44. Topp MS, Goekbuget N, Stein AS, et al. Confirmatory open-label, single-arm, multicenter phase 2 study of the BiTE antibodyblinatumomab in patients with relapsed/refractory B-precursor ALL [abstract]. J Clin Oncol. 2014;32:Abstract 7005.

(Revised 5/2017) © 2017 by Haymarket Media, Inc.

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Hodgkin Lymphoma 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 health care 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 provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become 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.

Classical Hodgkin Lymphoma1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

Primary Treatment Stage IA, IIA Favorable (No Bulky Disease, <3 Sites of Disease, ESR <50, and No E-lesions) Doxorubicin + bleomycin + vinblastine + dacarbazine (ABVD) (Category 1)2-5

Days 1 and 15: Doxorubicin 25mg/m2 IV push + bleomycin 10units/m2 IV push + vinblastine 6mg/m2 IV over 5–10 minutes + dacarbazine 375mg/m2 IV over 60 minutes.

Repeat cycle every 4 weeks for 2 cycles followed by radiation therapy.

ABVD (Intent to treat with chemotherapy alone)2-5

Days 1 and 15: Doxorubicin 25mg/m2 IV push + bleomycin 10units/m2 IV push + vinblastine 6mg/m2 IV over 5–10 minutes + dacarbazine 375mg/m2 IV over 60 minutes.

Repeat cycle every 4 weeks for 3 cycles.

ABVD (Intent to treat with combined modality therapy)2-5

Days 1 and 15: Doxorubicin 25mg/m2 IV push + bleomycin 10units/m2 IV push + vinblastine 6mg/m2 IV over 5–10 minutes + dacarbazine 375mg/m2 IV over 60 minutes.

Repeat cycle every 4 weeks for 2 cycles.

Doxorubicin + vinblastine + mechlorethamine + etoposide + vincristine + bleomycin + prednisone (Stanford V)6-8

Days 1 and 15: Doxorubicin 25mg/m2 IV push + vinblastine 6mg/m2 IV over 5–10 minutes Day 1: Mechlorethamine 6mg/m2 IV push Days 8 and 22: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5–10 minutes + bleomycin 5units/m2 IV push Days 15 and 16: Etoposide 60mg/m2 IV over 60 minutes Days 1–28: Prednisone 40mg/m2 orally every other day. Taper prednisone dose by 10mg every other day beginning Day 15 of Cycle 2.

Repeat cycle every 4 week for 2 cycles followed by radiation therapy, optimally within 3 weeks of chemotherapy completion.

Stage I–II Unfavorable (Bulky or Non-bulky Disease) Doxorubicin + bleomycin + vinblastine + dacarbazine (ABVD)2-5,9

Days 1 and 15: Doxorubicin 25mg/m2 IV push + bleomycin 10units/m2 IV push + vinblastine 6mg/m2 IV over 5–10 minutes + dacarbazine 375mg/m2 IV over 60 minutes.

Bulky or non-bulky disease: Repeat cycle every 4 weeks for 4–6 cycles with or without subsequent radiation therapy (category 1 for bulky disease); or, for select patients younger than 60 years, repeat for 2 cycles, following 2 cycles of escalated BEACOPP, with or without subsequent radiation therapy.

Doxorubicin + vinblastine + mechlorethamine + etoposide + vincristine + bleomycin + prednisone (Stanford V)6-8

Days 1 and 15: Doxorubicin 25mg/m2 IV push + vinblastine 6mg/m2 IV over 5–10 minutes Day 1: Mechlorethamine 6mg/m2 IV push Days 8 and 22: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5–10 minutes + bleomycin 5units/m2 IV push Days 15 and 16: Etoposide 60mg/m2 IV over 60 minutes Days 1–28: Prednisone 40mg/m2 orally every other day. Taper prednisone dose by 10mg every other day beginning Day 15 of Cycle 3.

Repeat cycle every 4 week for 3 cycles with or without subsequent radiation therapy.

Bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone (Escalated BEACOPP) (In selected patients if IPS≥4, age <60)9,10

Day 1: Cyclophosphamide 1,250mg/m2 IV over 60 minutes + doxorubicin 35mg/m2 IV push Days 1–3: Etoposide 200mg/m2 IV over 2 hours Days 1–7: Procarbazine 100mg/m2 orally.

Day 8: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5–10 minutes + bleomycin 10units/m2 IV push.

Days 1–14: Prednisone 40mg/m2 orally daily.

Repeat cycle every 3 weeks for 2 cycles followed by ABVD and then by radiation therapy.

Stage III–IV Doxorubicin + bleomycin + vinblastine + dacarbazine (ABVD)2-5

Days 1 and 15: Doxorubicin 25mg/m2 IV push + bleomycin 10units/m2 IV push + vinblastine 6mg/m2 IV over 5–10 minutes + dacarbazine 375mg/m2 IV over 60 minutes.

Repeat cycle every 4 weeks for 2 cycles followed by 2–4 cycles of ABVD or 4 cycles of escalated BEACOPP, cycles with or without subsequent radiation.

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HEMATOLOGIC CANCER Classical Hodgkin Lymphoma1 (continued) REGIMEN

DOSING

Primary Treatment (continued) Stage III–IV (continued) Doxorubicin + vinblastine + mechlorethamine + etoposide + vincristine + bleomycin + prednisone (Stanford V) (In selected patients if IPS <3)6-8

Days 1 and 15: Doxorubicin 25mg/m2 IV push + vinblastine 6mg/m2 IV over 5–10 minutes Day 1: Mechlorethamine 6mg/m2 IV push Days 8 and 22: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5–10 minutes + bleomycin 5units/m2 IV push Days 15 and 16: Etoposide 60mg/m2 IV over 60 minutes Days 1–28: Prednisone 40mg/m2 orally every other day. Taper prednisone dose by 10mg every other day beginning Day 15 of Cycle 3. Repeat cycle every 4 week for 3 cycles with or without subsequent radiation therapy.

Bleomycin + etoposide + doxorubicin + ­cyclophosphamide + vincristine + procarbazine + prednisone (Escalated BEACOPP) (In selected patients if IPS≥4, age <60)10

Day 1: Cyclophosphamide 1,250mg/m2 IV over 60 minutes + doxorubicin 35mg/m2 IV push Days 1–3: Etoposide 200mg/m2 IV over 2 hours Days 1–7: Procarbazine 100mg/m2 orally daily.

Day 8: Vincristine 1.4mg/m2 (maximum 2mg) IV over 5–10 minutes + bleomycin 10units/m2 IV push.

Days 1–14: Prednisone 40mg/m2 orally daily. Repeat cycle in selected patients (IPS≥4, aged <60 years) every 3 weeks for 6 cycles, with or without subsequent radiation therapy.

Second-line or Subsequent Therapy Note: No data have established the superiority of any of the subsequent chemotherapy options, and NCCN guidelines recommend an individualized approach.

Brentuximab vedotin11,12

Day 1: Brentuximab 1.8mg/kg (maximum 180mg) IV over 30 minutes; for patients with hepatic impairment: 1.2mg/kg (up to 120mg). Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Cyclophosphamide + vincristine + Day 1: Cyclophosphamide 650mg/m2 IV over 30 minutes + vincristine 1.4mg/m2 (maximum 2mg) IV procarbazine + prednisone (C-MOPP) Days 1–7: Procarbazine 100mg/m2 orally daily (Category 2B)13,14 Days 1–14: Prednisone 40mg/m2 orally daily.

Repeat cycle every 4 weeks for 4–8 cycles.

OR Days 1 and 8: Cyclophosphamide 500mg/m2 IV over 30 minutes + vincristine 1.4mg/m2 (maximum 2mg) IV over 5–10 minutes Days 1–14: Procarbazine 100mg/m2 orally daily.

Days 1–3 and 8–10: Prednisone 40mg/m2 orally daily.

Repeat cycle every 4 weeks for 4–8 cycles.

Dexamethasone + cytarabine + cisplatin (DHAP)15,16

Days 1–4: Dexamethasone 40mg orally or IV daily Day 1: Cisplatin 100mg/m2 IV continuous infusion over 24 hours Day 2: Cytarabine 2,000mg/m2 IV over 3 hours every 12 hours.

Repeat cycle every 3 to 4 weeks for 2–4 cycles (transplant candidates) or 4–8 cycles (nontransplant candidates).

Etoposide + methylprednisolone + cytarabine + cisplatin (ESHAP)17,18

Days 1–4: Etoposide 40mg/m2 IV over 60 minutes + methylprednisolone 500mg IV over 15 minutes + cisplatin 25mg/m2 continuous IV infusion over 24 hours Day 5: Cytarabine 2,000mg/m2 IV over 3 hours.

Repeat cycle every 3–4 weeks for 2–4 cycles (transplant candidates) or 4–8 cycles (nontransplant candidates).

Gemcitabine + carboplatin + dexamethasone (GCD)19

Days 1 and 8: Gemcitabine 1000mg/m2 IV over 30 minutes Day 1: Carboplatin AUC 5mg • min/mL (maximum 800mg) IV over 60 minutes Days 1–4: Dexamethasone 40mg orally daily.

Repeat cycle every 3 weeks for 2–4 cycles (transplant candidates) or 4–8 cycles (nontransplant candidates).

Gemcitabine + vinorelbine + pegylated liposomal doxorubicin (GVD)20

For transplant-naive patients: Days 1 and 8: Gemcitabine 1,000mg/m2 IV over 30 minutes + vinorelbine 20mg/m2 IV over 5–10 minutes + pegylated liposomal doxorubicin 15mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks for 2–4 cycles (transplant candidates) or 4–8 cycles (nontransplant candidates).

For post-transplant patients: Days 1 and 8: Gemcitabine 800mg/m2 IV over 30 minutes + vinorelbine 15mg/m2 IV over 5–10 minutes + pegylated liposomal doxorubicin 10mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks for 2–4 cycles (transplant candidates) or 4–8 cycles (nontransplant candidates).

Ifosfamide + carboplatin + etoposide (ICE)16,21

Days 1–3: Etoposide 100mg/m2 IV over 60 minutes Day 2: Carboplatin AUC 5mg • min/mL (max 800mg) IV + ifosfamide 5,000mg/m2 IV + mesna 5,000mg/m2 IV administered concurrently as a continuous infusion over 24 hours.

Repeat cycle every 2–3 weeks for 2–4 cycles (transplant candidates) or 4–8 cycles (nontransplant candidates). continued

CancerTherapyAdvisor.com | JULY/AUGUST 2017 | CANCER THERAPY ADVISOR 51

CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Hodgkin Lymphoma Treatment Regimens Classical Hodgkin Lymphoma1 (continued) REGIMEN

DOSING

Second-line or Subsequent Therapy (continued) Ifosfamide + gemcitabine + vinorelbine (IGEV)22

Days 1–4: Ifosfamide 200mg/m2 IV over 2 hours plus mesna 2,600mg/m2 IV Days 1 and 4: Gemcitabine 800mg/m2 IV over 30 minutes Day 1: Vinorelbine 20mg/m2 IV over 5–10 minutes Days 1–4: Prednisone 100mg PO daily.

Repeat cycle every 3 weeks for 2–4 cycles (transplant candidates) or 4–8 cycles (nontransplant candidates).

Carmustine + cytarabine + etoposide Days 1: Carmustine 60mg/m2 IV over 2 hours + melphalan (Mini-BEAM)23,24 Days 2–5: Etoposide 75mg/m2 IV over 60 minutes daily + cytarabine 100mg/m2 IV over 3 hours every 12 hours Day 6: Melphalan 30mg/m2 IV over 15 minutes.

Repeat cycle every 4–6 weeks for 2–4 cycles.

Mitoxantrone + ifosfamide + mesna + Days 1–3: Mesna 1.33 g/m2 IV daily, and 500 mg PO daily 4 hours after each IV dose plus ifosfamide 1.33 g/m2 IV daily, etoposide (MINE)25 given concurrently with mesna, for 3 days.

Day 1: Mitoxantrone 8mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 2–4 cycles (transplant candidates) or 4–8 cycles (nontransplant candidates).

Additional Therapy Options Bendamustine26

Days 1 and 2: Bendamustine 70–120mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks until maximal response or unacceptable toxicity.

Everolimus27

Everolimus 10mg orally daily until disease progression or unacceptable toxicity.

Lenalidomide28

Days 1–21: Lenalidomide 25mg orally daily.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Nivolumab29,30

Nivolumab 3mg/kg IV every 2 weeks until disease progression or unacceptable toxicity.

Pembrolizumab31

Pembrolizumab 10mg/kg IV every 2 weeks until disease progression or unacceptable toxicity.

Maintenance Therapy Brentuximab vedotin32

Day 1: Brentuximab 1.8mg/kg (maximum 180mg) IV over 30 minutes.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity for a maximum of 1 year after HDT/ SCR (if primary refractory disease or relapse occurred <12 months after primary therapy).

Nodular Lymphocyte-predominant Hodgkin Lymphoma1 Doxorubicin + bleomycin + Days 1 and 15: Doxorubicin 25mg/m2 IV push + bleomycin 10units/m2 IV push + vinblastine 6mg/m2 IV over vinblastine + dacarbazine (ABVD) ± 5–10 minutes + dacarbazine 375mg/m2 IV over 60 minutes, ± rituximab33-38 Day 1: Rituximab 375mg/m2 IV for all cycles.

OR Days 1, 8, 15, and 22: Rituximab 375mg/m2 IV for cycle 1 only.

Repeat cycle every 4 weeks for 3–4 cycles with subsequent radiation or 6–8 cycles without subsequent radiation.

Cyclophosphamide + doxorubicin + vincristine + prednisone (CHOP) ± rituximab35-39

Day 1: Cyclophosphamide 750mg/m2 over 60 minutes + doxorubicin 50mg/m2 IV push + vincristine 1.4mg/m2 (maximum 2mg) IV over 5–10 minutes Days 1–5: Prednisone 100mg orally daily, ± Day 1: Rituximab 375mg/m2 IV. Repeat cycle every 3 weeks for 6 cycles with or without subsequent radiation therapy.

Cyclophosphamide + vincristine + prednisone (CVP) ± rituximab35-38

Day 1: Cyclophosphamide 750mg/m2 OR 1,000mg/m2 over 60 minutes + vincristine 1.4mg/m2 (maximum 2mg) IV over 5–10 minutes Days 1–5: Prednisone 100mg orally daily, ± Day 1: Rituximab 375mg/m2 IV. Repeat cycle every 3 weeks for 3–4 cycles with subsequent radiation or 6 cycles without subsequent radiation.

Rituximab36

Day 1: Rituximab 375mg/m2 IV. Repeat cycle every 7 days for 4 weeks with or without maintenance rituximab (375mg/m2 IV once weekly for 4 weeks every 6 months for up to 2 years).

52 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER References 1. NCCN Clinical Practice Guidelines in Oncology™. Hodgkin Lymphoma.V.1.2017.

Available at: http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf.

Accessed March 10, 2017.

2. Eich HT, Diehl V, Görgen H, et al. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin’s lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010;28:4199–4206.

3. Engert A, Plutschow A, Eich HT, et al. Reduced treatment ­intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med. 2010;363:640–652.

4. Meyer R, Gospodarowicz M, Connors J, et al. ABVD alone versus radiation based therapy in limited stage Hodgkin’s lymphoma. N Engl J Med. 2012;366:399–408.

5. Bonadonna G, Bonfante V, Viviani S, et al. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin’s disease: long-term results.

J Clin Oncol. 2004;22:2835–2841.

21. Moskowitz CH, Nimer SD, Zelenetz AD, et al. A 2-step com­prehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hogdkin disease: analysis by ­intent to treat and development of a prognostic model. Blood.

2001; 97(3):616–623.

22. Santoro A, Magagnoli M, Spina M, et al. Ifosfamide, gemcita­bine, and vinorelbine: a new induction regimen for r­ efractory and relapsed Hodgkin’s lymphoma. ­ aematologica. 2007; 92(1):35–41.

H 23. Colwill R, Crump M, Couture F, et al. Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin’s disease before intensive therapy and autologous bone marrow transplantation. J Clin Oncol. 1995;13:396–402.

24. Martin A, Fernández-Jiménez MC, Caballero MD, et al. Long-term follow-up in patients treated with Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin’s disease. Br J Haematol. 2001;113(1):161–171.

25. Rodriguez MA et al. A phase II trial of mesna/ifosfamide, ­mitoxantrone and etoposide for refractory lymphoma. Ann Oncol 1995;6:609–612.

6. Gordon LI, Hong F, Fisher RI, et al. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advancedstage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013;31:684–691.

26. Moskowitz AJ, Hamlin PA, Perales M-A, et al. Phase II study of bendamustine in relapsed and refractory classical Hodgkin lymphoma. J Clin Oncol. 2013;31(4): 450–460.

7. Advani RH, Hoppe RT, Baer DM, et al. Efficacy of abbreviated Stanford V chemotherapy and involved field radiotherapy in early stage Hodgkin’s disease: mature results of the G4 trial. Ann Oncol. 2013;24:1044–1048.

27. Johnston PB, Inwards DJ, Colgan JP, et al. A phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. Am J Hematol. 2010;85: 320–324.

8 . Edwards-Bennett SM, Jacks LM, Moskowitz CH, et al. Stanford V program for locally extensive and advanced Hodgkin lymphoma: the Memorial Sloan-Kettering Cancer Center experience. Ann Oncol. 2010;21:574–581.

28. Fehniger TA, Larson S, Trinkaus K, et al. A phase 2 multi-center study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma. Blood.

2011;118:5119–5125.

9 . von Tresckow B, Plutschow A, Fuchs M, et al. Dose-intensification in early unfavorable Hodgkin’s lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012; 30:907–913.

29. Ansell SM, Larson S, Trinkaus K, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372:311–319.

10 . Engert A, Haverkamp H, Cobe C, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomized, open-label, phase 3 non-inferiority trial. The Lancet.

2012;379(9828):1791–1799.

11. Younes A, Bartlett NL, Leonard JP et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;4;363:1812–1821.

12. Adcetris [package insert]. Bothell, WA: Seattle Genetics, Inc; 2015.

13. Montoto S, Camós M, López-Guillermo A, et al. Hybrid chemotherapy consisting of C-MOPP/ABV as first-line treatment for patients with advanced Hodgkin disease.

Cancer. 2000;88(9):2142–2148.

14. Takenaka T, Mikuni C, Miura A, et al. Alternating combination chemotherapy C-MOPP and ABVD in clinical stage II–IV ­Hodgkin’s disease: a multicenter phase II study (JCOG 8905). The Lymphoma Study Group of the Japan Clinical Oncology Group. Jpn J Clin Oncol. 2000;30(3):146–152.

15 . Josting A, Rudolph C, Reiser M, et al. Time-intensified dexamethasone/cisplatin/ cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin’s disease. Ann Oncol. 2002;13(10):1628–1635.

16. Abali H, Urün Y, Oksüzog˘lu B, Budakog˘lu B, et al. Comparison of ICE versus DHAP as salvage chemotherapy in patients with relapsed or refractory lymphoma.

Cancer Invest. 2008;26(4):401–406.

30. Timmerman J, Armand P, Lesokhin AM, et al. Nivolumab in patients with relapsed or refractory lymphoid malignancies and classical Hodgkin lymphoma: Updated results of a phase 1 study (CA 209-039). Hematol Oncol. 2015;33: Abstract 010.

31. Armand P, Shipp MA, Ribrag V, et al. Programmed death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol. 2016;34(31):3733–3739.

32. Moskowitz CH, Nademanee A, Masszi T, et al. Brentuximab vedotin as a consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015; 385(9980)1853–1862.

33. Savage KJ, Skinnider B, Al-Mansour M, et al. Treating limited stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may ­improve outcome. Blood. 2011;118:4585–4590.

34. Canellos GP, Mauch P. What is the appropriate systemic ­chemotherapy for lymphocyte-predominant Hodgkin’s ­Lymphoma? J Clin Oncol. 2010;28:e8.

35. Advani RH, Hoppe RT. How I treat nodular predominant Hodgkin lymphoma.

Blood. 2013;122(26):4182–4188.

17 . Aparicio J, Segura A, Garcera S, et al. ESHAP is an active regimen for relapsing Hodgkin’s disease. Ann Oncol. 1999; 10(5):593–595.

36. Advani RH, Horning SJ, Hoppe RT, et al. Mature results of a phase II study of rituximab therapy for nodular lymphocyte-predominant Hodgkin lymphoma.

J Clin Oncol. 2014; 32(9):912–918.

18. Fernández de Larrea C, Martinez C, et al. Salvage chemotherapy with alternating MINE-ESHAP regimen in relapsed or ­refractory Hodgkin’s lymphoma followed by autologous stem cell transplantation. Ann Oncol. 2010;21(6):1211–1216.

37 . Fanale MA, Lai C-M, McLaughlin P, et al. Outcomes of nodular lymphocyte predominant Hodgkin’s Lymphoma (NLPHL) ­patients treated with R-CHOP. ASH Annual Meeting Abstracts. 2010;116:2812.

19. Gopal AK, Press OW, Shustov AR, et al. Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. Leuk Lymphoma. 2010;51:1523–1529.

38. Schulz H, Rehwald U, Morschhauser F, et al. Rituximab in ­relapsed lymphocytepredominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2008;111:109–111.

20. Bartlett NL, Niedzwiecki D, JL Johnson JL et al. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin’s lymphoma: CALGB 59804. Ann Oncol. 2007;18:1071–1079.

39. Eichenauer DA, Fuchs M, Pluetschow A, et al. Phase 2 study of rituximab in newly diagnosed stage 1A nodular lym­phocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2011; 118:4363–4365.

(Revised 3/2017) © 2017 by Haymarket Media, Inc.

CancerTherapyAdvisor.com | JULY/AUGUST 2017 | CANCER THERAPY ADVISOR 53

DRUG MONOGRAPHS

HEMATOLOGIC CANCER ADCETRIS Seattle Genetics

℞

CD30-directed antibody-drug conjugate.

Brentuximab vedotin 50mg/vial; lyophilized pwd for IV infusion after reconstitution; preservative-free.

Indications: Treatment of patients with classical Hodgkin lymphoma (HL) after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of ≥2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates or are at high risk of relapse or progression as post-auto-HSCT consolidation.

Treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of ≥1 prior multi-agent chemotherapy regimen.

Adults: Give by IV infusion over 30mins. 1.8mg/kg up to max 180mg/dose every 3 weeks; continue until disease progression or unacceptable toxicity.

Post-auto-HSCT consolidation: initiate within 4–6 weeks post-auto-HSCT or upon recovery from auto-HSCT; max 16 cycles. Mild hepatic impairment: initially 1.2mg/kg up to 120mg.

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 G-CSF prophylaxis for subsequent cycles; recurrent Grade 4: consider discontinue or dose reduction to 1.2mg/kg. Patients with prior infusion-related reaction: premedicate with APAP, antihistamine, and corticosteroid for subsequent doses.

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; delay, change dose, or discontinue if new or worsening symptoms occur. Monitor for infusion-related reactions; permanently discontinue and treat if anaphylaxis occurs. Monitor CBCs prior to each dose and frequently for fever or Grade 3 or 4 neutropenia; delay, reduce, discontinue dose or consider G-CSF prophylaxis if develops. Increased risk of tumor lysis syndrome in rapidly proliferating tumor/high tumor burden patients; monitor closely. Monitor for emergence of bacterial, fungal, or viral infections. Monitor for pulmonary toxicity; if symptoms occur, withhold dose during evaluation and until improvement. Monitor liver enzymes and bilirubin; delay, change dose, or discontinue if hepatotoxicity occurs. Severe renal impairment or moderate or severe hepatic impairment: avoid.

Discontinue if serious skin reactions (eg, SJS, TEN) occur. GI complications: evaluate and treat if new or worsening GI symptoms develop. Embryofetal toxicity. Females and males of reproductive potential should use effective contraception during and for ≥6 months after final dose.

Pregnancy: verify status before initiation. Nursing mothers: not recommended.

Interactions: See Contraindications.

Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole) or P-gp inhibitors; monitor closely.

Antagonized by potent CYP3A4 inducers (eg, rifampin).

Adverse reactions: Neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough, vomiting.

How supplied: Single-use vial—1

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, 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 Novartis

℞

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. Extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. Treatment of CLL refractory to fludarabine and alemtuzumab.

Adults: Premedicate with acetaminophen (oral), antihistamine (oral or IV), corticosteroid (IV) 30mins to 2hrs prior to each infusion. Give

by IV infusion (rate varies with dose and during infusion); see full labeling. Previously untreated: initially 300mg on Day 1, then 1 week later by 1000mg on Day 8 (Cycle 1), followed by 1000mg on Day 1 of subsequent 28-day cycles for at least 3 cycles until best response or max 12 cycles.

Extended treatment: initially 300mg on Day 1, then by 1000mg 1 week later on Day 8, followed by 1000mg 7 weeks later and every 8 weeks thereafter for up to max 2 years. Refractory: initially 300mg on Day 1, then 1 week later by 2000mg weekly for 7 doses, followed 4 weeks later by 2000mg every 4 weeks for 4 doses.

Dose modification for infusion reactions: see full labeling.

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) 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

BELEODAQ Spectrum

℞

Histone deacetylase inhibitor. Belinostat 500mg; per vial; lyophilized pwd for IV inj after reconstitution and dilution.

Indications: Relapsed or refractory peripheral T-cell lymphoma.

54 CANCER THERAPY ADVISOR | JULY/AUGUST 2017 | CancerTherapyAdvisor.com

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7/1/17 10:45 AM

DRUG MONOGRAPHS

HEMATOLOGIC CANCER Adults: Give 1000mg/m2 once daily by IV infusion over 30 mins on Days 1–5 of a 21-day cycle; can repeat cycles every 21 days until disease progression or unacceptable toxicity. Dose modifications: Hematologic toxicities: if ANC nadir <0.5x109/L or platelet count <25x109/L: decrease dose by 25% (750mg/m2); discontinue if recurrent ANC <0.5x109/L or platelet count <25x109/L nadirs after 2 dose reductions; Nonhematologic toxicities: if any CTCAE Grade 3/4 reaction: decrease dose by 25% (750mg/m2); discontinue if recurrent CTCAE Grade 3/4 reaction after 2 dose reductions. Patients with homozygous UGT1A1*28 allele: initially 750mg/m2.

Children: Not established.

Warnings/Precautions: Risk of hematologic toxicity; monitor blood counts with differential at baseline and weekly during therapy; adjust dose as necessary. Active infection: do not administer.

History of extensive or intensive chemotherapy: may be at higher risk of life-threatening infections. Renal or hepatic impairment. Monitor serum chemistry, renal and hepatic function before treatment and the start of each cycle; interrupt, adjust, or discontinue dose based on severity of hepatotoxicity. Tumor lysis syndrome; monitor patients with advanced stage disease and/or high tumor syndrome. GI toxicity; may require use of antiemetics and antidiarrheals.

Embryo-fetal toxicity. Pregnancy (Cat. D), nursing mothers: not recommended.

Interactions: Avoid concomitant use of strong UGT1A1 inhibitors.

Adverse reactions: Nausea, fatigue, pyrexia, anemia, vomiting; hematologic toxicity, infection, hepatotoxicity, tumor lysis syndrome, GI toxicity.

How supplied: Single-use vial (30mL)—1

BENDEKA Teva Alkylating agent. Bendamustine HCl 25mg/mL; soln for IV infusion after dilution; preservativefree.

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 10mins.

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 10mins. 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. Delay treatment for Grade 4 hematologic toxicity or clinically significant ≥Grade 2 non-hematologic toxicity.

Children: Not established.

Warnings/Precautions: Myelosuppression; monitor CBCs including leukocytes, platelets, hemoglobin, neutrophils frequently; restart treatment based on ANC and platelet count recovery. Monitor for signs of infection or reactivation of infections (eg, hepatitis B, CMV, tuberculosis, herpes zoster); prophylaxis and treat prior to therapy if occur. Monitor for infusion or skin reactions (may be fatal), tumor lysis syndrome. Monitor LFTs prior to and during therapy. Renal impairment (mild or moderate): caution; (CrCl <40mL/min): not recommended.

Hepatic impairment (mild): caution; (moderate or severe): not recommended. Avoid extravasation.

Embryo-fetal toxicity. Pregnancy (Cat.D); avoid during and for 3 months after therapy cessation.

Nursing mothers: not recommended.

Interactions: May be potentiated by CYP1A2 inhibitors (eg, fluvoxamine, ciprofloxacin) or antagonized by CYP1A2 inducers (eg, omeprazole, smoking); if needed, consider alternatives.

Adverse reactions: Lymphopenia, anemia, leukopenia, thrombocytopenia, neutropenia, pyrexia, nausea, vomiting, fatigue, diarrhea, constipation, anorexia, cough, headache, weight loss, dyspnea, stomatitis; infection, infusion reactions (discontinue if severe), tumor lysis syndrome, skin reactions (if severe or progressive, withhold dose or discontinue), hepatotoxicity, other malignancies (eg, myelodysplastic syndrome, acute myeloid leukemia, bronchial carcinoma).

How supplied: Multi-dose vial (4mL)—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

Visit OncologyNurseAdvisor.com for practical clinical information geared toward oncology nurses and other cancer care professionals.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER BLINCYTO Amgen

℞

Bispecific CD19-directed CD3 T-cell engager.

Blinatumomab 35mcg; per vial; lyophilized pwd for IV infusion after reconstitution; preservativefree.

Indications: Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia.

Adults and Children: Strictly follow preparation and administration instructions. Pre-medicate with dexamethasone 20mg (adults) or 5mg/m2 to max 20mg (pediatrics) 1 hour prior to 1st dose of each cycle, prior to a step dose, or when restarting infusion after interruption (≥4 hours).

Hospitalization recommended for first 9 days of Cycle 1 and first 2 days of Cycle 2. One single cycle = 28 days of continuous IV infusion followed by a 14-day treatment-free interval. Treat up to a total of 5 cycles. ≥45kg: can give by continuous IV infusion at a rate of 10mL/hr over 24 hours, 5mL/hr over 48 hours, or 0.6mL/hr over 7 days (not recommended for patients <22kg). Cycle 1: 9mcg/day on Days 1–7 and 28mcg/day on Days 8–28. Subsequent cycles: 28mcg/day on Days 1–28. <45kg: Cycle 1: 5mcg/m2/day (max 9mcg/day) on Days 1–7 and 15mcg/m2/day (max 28mcg/day) on Days 8–28. Subsequent cycles: 15mcg/m2/day (max 28mcg/day) on Days 1–28.

Dose adjustments or using 7-day infusion of Blincyto (with preservative): see full labeling.

Warnings/Precautions: Monitor for signs/symptoms of cytokine release syndrome or neurological toxicities; interrupt or discontinue as recommended (see full labeling). Monitor for infections; give antibiotic prophylaxis as appropriate. Monitor for tumor lysis syndrome; interrupt or discontinue as needed. Obtain lab tests (including WBC, ANC) during infusion; interrupt if prolonged neutropenia occurs.

Monitor ALT, AST, GGT, and total bilirubin prior to and during treatment; interrupt if transaminases rise >5XULN or if bilirubin rises >3XULN. Evaluate if signs/symptoms of pancreatitis develop; interrupt or discontinue as appropriate. Risk of leukoencephalopathy, esp. in those with prior treatment with cranial irradiation and antileukemic chemotherapy (including high-dose methotrexate or intrathecal cytarabine). Elderly.

Neonates/infants: risk of gasping syndrome (due to benzyl alcohol preservative). Pregnancy; verify status prior to initiation. Females of reproductive potential should use effective contraception during and for at least 48hrs after last dose.

Nursing mothers: not recommended (during and for at least 48hrs after last dose).

Interactions: Concomitant live vaccines: not recommended (for at least 2 weeks prior to initiation, during treatment, and until immune recovery after last cycle). Caution with concomitant CYP450 substrates esp. drugs with narrow therapeutic index (eg, warfarin, cyclosporine); monitor and adjust dose as needed.

Adverse reactions: Pyrexia, headache, nausea, vomiting, edema, hypokalemia, anemia, febrile neutropenia, neutropenia, thrombocytopenia, abdominal pain, infections; pneumonia, sepsis, device-related infection, tremor, overdose, encephalopathy, confusion.

How supplied: Pack—1 (single-use vial + IV solution stabilizer)

BOSULIF Pfizer

℞

Tyrosine kinase inhibitor. Bosutinib 100mg, 500mg; tabs.

Indications: Treatment of chronic, accelerated, or blast phase Philadelphia chromosomepositive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy.

Adults: Take with food. Initially 500mg once daily 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. Hepatic impairment: initially 200mg daily. Renal impairment (CrCl 30–50mL/min): initially 400mg daily; (CrCl <30mL/min): initially 300mg daily. Dose modifications for toxicity: see full labeling.

Children: <18yrs: not established.

Warnings/Precautions: Monitor and manage GI toxicity, fluid retention; withhold, reduce 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. Monitor renal function at baseline and during therapy; consider adjusting dose if renal impairment occurs. Dialysis: not studied. Pregnancy (Cat.D); avoid. Use effective contraception during and for ≥30 days after last dose. Nursing mothers: not recommended.

Interactions: Potentiated by concomitant strong or moderate CYP3A inhibitors (eg, boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole, or amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil, grapefruit products); avoid. Antagonized by concomitant strong or moderate CYP3A inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s Wort, or bosentan, efavirenz, etravirine, modafinil, nafcillin); avoid. Antagonized by proton pump inhibitors (eg, lansoprazole); consider short-acting antacids or H2 blockers instead; separate dosing by ≥2hrs.

Adverse reactions: Diarrhea, nausea, thrombocytopenia, rash, vomiting, abdominal

pain, RTI, anemia, pyrexia, abnormal LFTs, fatigue, cough, headache; fluid retention, hepatic or renal 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 full labeling. Premedicate with anticonvulsants 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 for total of 16 doses (on Days -7, -6, -5, and -4). Give cyclophosphamide after the 16th dose of busulfan (Days -3 and -2).

Give hematopoietic progenitor cells on Day 0.

Obese: base dose on adjusted ideal body weight.

Children: See full labeling.

Warnings/Precautions: Risk of severe and prolonged myelosuppression; requires hematopoietic progenitor cell transplantation.

Seizure disorder. Head trauma. Renal or hepatic impairment. Monitor CBCs with differential, platelet counts, liver enzymes, bilirubin during treatment and until recovery. Monitor for infection and bleeding. Embryo-fetal toxicity. Pregnancy.

Use effective contraception during and after treatment. Nursing mothers: not recommended.

Interactions: Potentiated by itraconazole and acetaminophen. May be antagonized by phenytoin.

Caution with potentially epileptogenic drugs.

Adverse reactions: Myelosuppression, nausea, stomatitis, vomiting, anorexia, diarrhea, insomnia, fever, hypomagnesemia, abdominal pain, anxiety, headache, hyperglycemia, hypokalemia; seizures (with higher doses), hepatic veno-occlusive disease (with high AUC), cardiac tamponade (in pediatric patients with thalassemia), cellular dysplasia; 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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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

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 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

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, platelets, and coagulation parameters during the 5 days of therapy. Discontinue if hypotension develops during administration. 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 occurs, discontinue and treat; may restart at lower dose if organ function recovers and patient is stable. Monitor for venous occlusive disease of the liver in patients who previously received hematopoietic stem cell transplant; discontinue if suspected. Monitor hepatic function; discontinue immediately if Grade ≥3 liver enzyme and/or bilirubin elevation occurs. Monitor for renal toxicity; interrupt or discontinue if Grade ≥3 creatinine elevation occurs. Pregnancy (Cat.D; avoid); 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: Vomiting, nausea, diarrhea, febrile neutropenia, pruritus, headache, bacteremia, pyrexia, rash, tachycardia, abdominal pain, chills, fatigue, anorexia, extremity pain, hypotension, epistaxis, petechiae; bone marrow suppression, infections, hyperuricemia, SIRS/capillary leak syndrome, hemorrhage (may be fatal), enterocolitis (monitor), serious skin reactions (discontinue for exfoliative or bullous rash or if Stevens-Johnson syndrome or toxic epidermal necrolysis suspected), hepatotoxicity (may be fatal), acute renal failure, embryo-fetal toxicity.

How supplied: Single-use vial (20mL)—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 X ULN; active or uncontrolled infection): do not restart until toxicity resolved.

Access Cancer Therapy Advisor treatment regimens in a user-friendly format.

CancerTherapyAdvisor.com/TreatmentRegimens.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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

DARZALEX Janssen Biotech

℞

CD38-directed monoclonal antibody.

Daratumumab 100mg/5mL, 400mg/20mL; per vial; soln for IV infusion after dilution; contains mannitol; preservative-free.

Indications: Treatment of multiple myeloma: as combination therapy with lenalidomide and dexamethasone, or bortezomib and dexamethasone, in patients who have received ≥1 prior therapy; or as monotherapy in patients who have received ≥3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are doublerefractory to a PI and an immunomodulatory agent.

Adults: Pre-medicate with corticosteroids (long- or intermediate-acting), oral antipyretics, oral or IV antihistamines 1–3 hours prior to every infusion and administer oral corticosteroids post-infusion. Give only as IV infusion. Initially infuse at 50mL/hr for first two infusions, then 100mL/hr for subsequent infusions; may increase by 50mL/hr every hour; max 200mL/hr. Monotherapy and combination therapy with lenalidomide and dexamethasone: 16mg/kg weekly at Weeks 1–8, every 2 weeks at Weeks 9–24, then every 4 weeks at Week 25 onwards until disease progression.

Combination therapy with bortezomib and dexamethasone: 16mg/kg weekly at Weeks 1–9, every three weeks at Weeks 10–24, then every four weeks at Week 25 onwards until disease progression. Management of infusion reactions, pre- and post-infusion medications, others: see full labeling. Prophylaxis for herpes zoster reactivation: initiate antiviral prophylaxis within 1 week after starting therapy and continue for 3 months after treatment.

Children: Not established.

Warnings/Precautions: Should be administered by a healthcare professional with immediate access to emergency equipment and appropriate medical support. Monitor frequently for infusion reactions; interrupt treatment for infusion reactions of any severity. Permanently discontinue if life-threatening (Grade 4) or upon 3rd recurrence of Grade 3 infusion reactions occur; for Grade 1, 2, or 3 reactions, reduce the infusion rate when restarting. History of COPD: may require additional post-infusion drugs;

consider prescribing short- or long-acting bronchodilators and inhaled corticosteroids.

Interference with cross-matching and RBC antibody screening; type/screen patients prior to initiating treatment. Increased neutropenia (monitor for infections) and thrombocytopenia: obtain CBCs during therapy; dose delay may be required to allow recovery of neutrophils and platelets. Pregnancy: avoid. Females of reproductive potential should use effective contraception during treatment and for 3 months after cessation. Nursing mothers.

Interactions: Interferes with Indirect Antiglobulin (Coombs) Test, serum protein electrophoresis and immunofixation assays leading to false (+) results.

Adverse reactions: Infusion reactions, neutropenia, thrombocytopenia, fatigue, nausea, diarrhea, muscle spasm, back pain, pyrexia, cough, dyspnea, peripheral edema, peripheral sensory neuropathy, upper respiratory tract infection.

How supplied: Single-dose 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 longterm 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

EMPLICITI Bristol-Myers Squibb

℞

SLAMF7-directed immunostimulatory antibody.

Elotuzumab 300mg, 400mg; per vial; lyophilized pwd for IV infusion after reconstitution; preservative-free.

Indications: In combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received 1–3 prior therapies.

Adults: Give by IV infusion at initial rate of 0.5mL/min; may increase stepwise if no reactions develop; max rate 2mL/min (see full labeling).

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER After 4 cycles, infusion rate may be increased up to max 5mL/min. Administer with lenalidomide and dexamethasone (see full labeling for dosing schedule). 10mg/kg every week for the first 2 cycles then every 2 weeks thereafter; continue until disease progression or unacceptable toxicity.

Premedicate with dexamethasone, H1 blocker, H2 blocker, and acetaminophen before each infusion.

Dose modifications: see full labeling.

Children: Not established.

Contraindications: Consult lenalidomide and dexamethasone prescribing information for contraindications before starting therapy.

Warnings/Precautions: Interrupt infusion if Grade ≥2 infusion reactions occur and manage appropriately. Monitor for development of infections and treat promptly. Monitor for second primary malignancies. Monitor liver function periodically; discontinue if Grade ≥3 elevation of liver enzymes occur; consider resuming after return to baseline values. Pregnancy: not studied.

Nursing mothers: not recommended.

Interactions: May interfere with correct response classification in SPEP and serum immunofixation assays.

Adverse reactions: Fatigue, diarrhea, pyrexia, constipation, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, pneumonia.

Note: For lenalidomide and dexamethasone specific dosing and safety information, refer to the respective full prescribing labels.

How supplied: Single-dose vial—1

ERWINAZE Jazz

℞

Asparagine-specific enzyme. Asparaginase Erwinia chrysanthemi 10,000 IU; per vial; lyophilized pwd for IM or IV 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) or IV (infuse over 1hr). 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. When IV use: consider monitoring nadir serum asparaginase activity (NSAA) levels; switch to IM inj if levels are inadequate.

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 ≥2XULN 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: Systemic hypersensitivity, hyperglycemia, abnormal transaminases, fever, pancreatitis, local reactions, vomiting, nausea, thrombosis, hyperbilirubinemia, abdominal pain/discomfort, diarrhea.

How supplied: Vials (3mL)—5

EVOMELA Spectrum

℞

Alkylating agent. Melphalan HCl 50mg/vial; lyophilized pwd; for IV infusion after reconstitution.

Indications: High-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma. Palliative treatment of multiple myeloma when oral therapy is not appropriate.

Adults: Give prophylactic antiemetics.

Conditioning treatment: Give by IV infusion over 30 minutes. 100mg/m2 daily for 2 consecutive days (Days -3 and -2) prior to transplantation (Day 0). If patient weighs >130% of their ideal body weight, use adjusted ideal body weight.

Palliative treatment: Give by IV infusion over 15–20 minutes. 16mg/m2 as a single infusion at 2-week intervals for 4 doses, then at 4-week intervals after recovery from toxicity. Renal impairment (BUN ≥30mg/dL): consider up to 50% dose reduction for palliative treatment.

Children: Not established.

Warnings/Precautions: Prior irradiation or chemotherapy. Severe bone marrow suppression. Monitor CBCs during treatment; provide supportive care for infections, anemia, thrombocytopenia until adequate recovery.

GI toxicity; provide supportive care. Monitor LFTs. Renal impairment. Embryo-fetal toxicity; use effective contraception during and after treatment. Pregnancy, nursing mothers: not recommended.

Interactions: Caution with cyclosporine, BCNU, nalidixic acid.

Adverse reactions: Decreased neutrophil, WBC, lymphocyte, and platelet counts, diarrhea, nausea, fatigue, hypokalemia, anemia, vomiting; hypersensitivity reactions, hepatic disorders, secondary malignancies, infertility.

How supplied: Single-dose vial (20mL)—1

FARYDAK Novartis

℞

Histone deacetylase inhibitor. Panobinostat 10mg, 15mg, 20mg; caps.

Indications: Multiple myeloma, in patients who have received at least two prior therapies (including bortezomib and an immunomodulatory agent), in combination with bortezomib and dexamethasone.

Adults: Swallow whole with water. Take at same time on scheduled days. Initially 20mg once every other day for 3 doses/wk in Weeks 1 and 2 of each 21-day cycle for up to 8 cycles. Consider 8 more cycles for patients with clinical benefit if no severe or significant toxicity; max 16 cycles (48 wks).

Give with bortezomib inj and oral dexamethasone per scheduled day. Hepatic impairment: mild: initially 15mg; moderate: initially 10mg; severe: avoid. Concomitant strong CYP3A inhibitors: initially 10mg. Dose adjustments and modifications for toxicity: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of severe diarrhea and cardiac toxicities. Monitor hydration and electrolytes at baseline, weekly during therapy, or more as indicated. Initiate antidiarrheals at onset of diarrhea; interrupt dose if 4–6 stools/day.

Do not initiate if history of recent MI or unstable angina, QTcF >450msec, significant baseline ST-segment or T-wave abnormalities, active infections. Perform ECG prior to initiation and repeat during treatment as indicated. Correct electrolyte abnormalities prior to initiation and monitor; interrupt if QTcF ≥480msec; discontinue if QT prolongation does not resolve.

Serious hemorrhage. Obtain CBC prior to initiation; monitor weekly during therapy or more as indicated. Monitor for infections; treat and consider interruption or discontinuation if diagnosed. Monitor liver function prior to and during treatment; consider dose adjustments if abnormal tests observed. ESRD or dialysis: not studied. Elderly: monitor for toxicity more frequently (esp. GI, myelosuppression, cardiac).

Embryo-fetal toxicity. Pregnancy: avoid. Obtain pregnancy test prior to and during treatment. Use effective contraception during and for ≥3 months after last dose; males: use condoms during and

Take advantage of our free online medical calculators at CancerTherapyAdvisor.com/MedicalCalculators.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER for ≥6 months after last dose. Nursing mothers: not recommended.

Interactions: Potentiated by strong CYP3A inhibitors (eg, boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, others); see Adults. Avoid star fruit, pomegranate or grapefruit juice. Avoid concomitant strong CYP3A inducers. Avoid concomitant sensitive CYP2D6 substrates (eg, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine) or substrates with narrow therapeutic index (eg, thioridazine, pimozide); if unavoidable, monitor frequently. Concomitant antiarrhythmics or QT prolonging drugs: not recommended. Antiemetics that prolong QT interval (eg, dolasetron, ondansetron, tropisetron): monitor ECG frequently.

Adverse reactions: Diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, vomiting, electrolyte imbalance, increased creatinine, thrombocytopenia, lymphopenia, leukopenia, neutropenia, anemia.

How supplied: Blister packs—6

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

GAZYVA Genentech

℞

CD20-directed cytolytic monoclonal antibody.

Obinutuzumab 25mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: In combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).

In combination with bendamustine followed

by Gazyva monotherapy, for the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to, a rituximabcontaining regimen.

Adults: See full labeling. Premedicate (eg, glucocorticoid, APAP, antihistamine) before each infusion. Provide prophylactic hydration and antihyperuricemics to those at high risk of TLS. Give by IV infusion for 6 treatment cycles (28 days duration). CLL: Cycle 1: 100mg on Day 1 at 25mg/hr over 4 hours; 900mg on Day 2 at 50mg/hr, can increase at 50mg/hr every 30mins to max 400mg/hr; 1000mg on Days 8 and 15 at 100mg/hr if no infusion reaction occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr; Cycles 2–6: 1000mg on Day 1 at 100mg/hr if no infusion reaction occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr. FL: Cycle 1: 1000mg on Day 1 at 50mg/hr, can increase at 50mg/hr every 30mins to max 400mg/hr; 1000mg on Days 8 and 15 at 100mg/hr if no infusion reaction occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr; Cycles 2–6: 1000mg on Day 1 at 100mg/hr if no infusion reaction occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr; followed by Gazyva monotherapy: 1000mg every 2 months for 2 years at 100mg/hr if no infusion reaction occurred previously, and increased by 100mg/hr increments every 30mins to max 400mg/hr. Management of infusion reactions, premedication: 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 progressive multifocal leukoencephalopathy (PML) develops. Monitor closely for infusion reactions; if Grade 4: discontinue permanently; if Grade 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, high circulating lymphocyte count (>25 × 109/L), or renal impairment. Active infection: do not

administer. Risk of neutropenia; monitor for signs of infection. Severe or prolonged neutropenia, give antimicrobial prophylaxis until resolved to Grade 1 or 2; consider antiviral and antifungal prophylaxis. Monitor for thrombocytopenia and hemorrhagic events esp. during the 1st cycle; obtain blood and platelet counts frequently; transfusion of blood products may be necessary.

Hepatic or renal impairment (CrCl <30mL/min).

Pregnancy; risk of fetal B-cell depletion. Nursing mothers.

Interactions: Concomitant live viral vaccines: not recommended during treatment and until B-cell recovery (esp. neonates/infants if exposed to Gazyva in utero). Consider withholding antihypertensives for 12hrs prior to, during, and for 1hr after infusion until BP is stable. Consider withholding drugs that may increase bleeding risk (eg, platelet inhibitors, anticoagulants) esp. during 1st cycle.

Adverse reactions: Infusion reactions, neutropenia, thrombocytopenia, anemia, pyrexia, cough, nausea, diarrhea; HBV reactivation, PML, TLS, infections.

How supplied: Single-use vial (40mL)—1

GLEEVEC Novartis

℞

Kinase inhibitor. Imatinib (as mesylate) 100mg, 400mg; scored 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 re-arrangements as determined with an FDAapproved test. 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 unknown.

Adults: Take with food and water. May disperse tab in water or apple juice and take promptly. ≥18yrs: Chronic phase CML: 400mg once daily; may increase to 600mg if clinically indicated.

Accelerated phase or blast crisis: 600mg once daily; may increase to 800mg (given as 400mg twice daily) if clinically indicated.

Relapsed/refractory Ph+ ALL: 600mg once daily.

MDS/MPD (determine PDGFRb gene status prior to initiation): 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:

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER reduce dose by 25%. Renal or hematologic reactions: see full labeling. Avoid concomitant strong CYP3A4 inducers (eg, rifampin): if needed, 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.

Avoid concomitant strong CYP3A4 inducers (eg, phenytoin): if needed, 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 and potential toxicities (liver, kidney, cardiac) 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. Embryo-fetal toxicity. Pregnancy (avoid); exclude status prior to initiation. Females of reproductive potential should use highly effective contraception during treatment and for 14 days after cessation. Nursing mothers: not recommended (during and for 1 month after final dose).

Interactions: Avoid grapefruit juice. Potentiated

by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by strong CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin, rifabutin, rifampicin); consider alternatives. May potentiate drugs metabolized

by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain statins, sirolimus, tacrolimus) or CYP2C9 (use heparin instead of warfarin). Caution with

Adverse reactions: Leukopenia, thrombocytopenia, anemia, GI upset, anorexia; secondary malignancies, macrocytosis.

Note: Wear disposable gloves when handling caps or bottle.

How supplied: Caps—100

concomitant CYP2D6 substrates that have a narrow therapeutic window.

Adverse reactions: Edema (may be severe), nausea, vomiting, musculoskeletal pain, diarrhea, muscle cramps, rash (may be severe; eg, erythema multiforme, StevensJohnson 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

HYDREA Bristol-Myers Squibb

ICLUSIG ARIAD

℞

Antimetabolite. Hydroxyurea 500mg; caps.

Indications: Resistant chronic myeloid leukemia.

Adults: Base dose on ideal or actual weight, whichever is less. Individualize. Initially 15mg/kg/day. Renal impairment (CrCl <60mL/min or ESRD): initially 7.5mg/kg/day; give dose following dialysis (monitor). Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of severe myelosuppression; reduce dose or discontinue if necessary. Monitor blood counts at baseline and at least once a week during therapy. Correct severe anemia before starting. Markedly depressed bone marrow function: do not initiate.

Monitor for malignancies. Avoid sun exposure.

Previous irradiation therapy (monitor for skin erythema) or chemotherapy. Macrocytosis may mask folic acid deficiency; prophylactic folic acid is recommended. Myeloproliferative disorders; discontinue if cutaneous vasculitic ulcerations occur. Renal or hepatic impairment.

Elderly. Embryo-fetal toxicity. Pregnancy; avoid. Exclude pregnancy prior to initiating; use effective contraception during and for ≥6 months (females) or ≥1 year (males) after therapy.

Nursing mothers: not recommended.

Interactions: Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [monitor], fatal hepatotoxicity, peripheral neuropathy). Avoid live vaccines. Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated results in urea, uric acid, and lactic acid assays.

℞

Kinase inhibitor. Ponatinib 15mg, 30mg, 45mg; tabs; contains lactose.

Indications: Treatment of adults with chronic, accelerated, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated. Treatment of adults with T315I-positive CML (chronic, accelerated, or blast phase) or T315I-positive Ph+ ALL. Limitations of use: not for treating patients with newly diagnosed chronic phase CML. 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 or hepatic impairment: reduce to 30mg once daily. Dose modification for hematologic and non-hematologic toxicity: see full labeling.

Children: <18yrs: not established.

Warnings/Precautions: Risk of venous thromboembolism and arterial occlusion (including 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. Monitor and manage BP elevations; interrupt, reduce dose or discontinue if not controlled; evaluate for renal artery stenosis if significant worsening, labile or treatment-resistant hypertension occurs. 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 <1.5XULN. Increased toxicity in newly diagnosed chronic phase CML: not recommended. Monitor for neuropathy; consider interrupting and evaluate

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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. Interrupt therapy if reversible posterior leukoencephalopathy syndrome occurs; resume only when resolved and if the benefit outweighs the risk. Elderly.

Embryo-fetal toxicity. Pregnancy (avoid). Females of reproductive potential should use effective contraception during and for 3 weeks after last dose. 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). Caution with concomitant drugs that elevate gastric pH (eg, PPIs), P-gp and ABCG2 substrates.

Adverse reactions: Hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, pyrexia, diarrhea, increased lipase, vomiting, myalgia, extremity pain; myelosuppression.

How supplied: Tabs 15mg—30, 60, 180; 30mg— 30; 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 mins). 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 established.

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.

Interactions: Concomitant drugs that suppress cardiac contractility or cardiotoxic drugs (eg, trastuzumab, cyclophosphamide, paclitaxel): not

recommended; avoid use for 5 half-lives after discontinuing cardiotoxic drug.

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: Singledose vials (5mL, 10mL, 20mL)—1

Pharmacyclics and Janssen Biotech

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; monitor.

Adverse reactions: Neutropenia, thrombocytopenia, diarrhea, anemia, musculoskeletal pain, rash, nausea, bruising, fatigue, hemorrhage, pyrexia.

How supplied: Caps—90, 120

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)/small lymphocytic lymphoma (SLL).

CLL/SLL in patients with 17p deletion.

Waldenstrom’s macroglobulinemia (WM).

Marginal zone lymphoma (MZL) in patients who require systemic treatment and have received at least one prior anti-CD20-based therapy.

Adults: Swallow whole with water. MCL and MZL: 560mg once daily. CLL/SLL (with or without bendamustine/rituximab) and WM: 420mg once daily. Treat until disease progression or unacceptable toxicity. Concomitant moderate CYP3A inhibitors: 140mg once daily. Mild hepatic impairment (Child-Pugh Class A): 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. Periodically monitor for atrial fibrillation (esp. in those with cardiac risk factors, acute infections, history of atrial fibrillation); do ECG if arrhythmic symptoms or new onset dyspnea develop. Monitor for new onset or uncontrolled hypertension; adjust and/or initiate anti-hypertensives as appropriate.

Risk of second primary malignancies (eg, skin cancer or other carcinomas). Monitor for tumor lysis syndrome in patients at risk (eg, high tumor burden). Moderate or severe hepatic impairment: not recommended. Maintain adequate hydration.

Pregnancy; avoid during and for 1 month after treatment cessation. Nursing mothers.

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,

Alpha interferon. Interferon alfa-2b, recombinant; 10 million, 18 million, or 50 million IU per vial; pwd; for inj after reconstitution/dilution; preservativefree; contains albumin. ℞ 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 anthracycline-containing 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: Decompensated liver disease. Autoimmune hepatitis.

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; discontinue if neutrophil count <0.5 X109/L or platelets 25X109/L. Permanently discontinue if severe (Grade 3) hepatic injury or decompensation (Child-Pugh score >6 [Class B and C]) develop.

Thyroid abnormalities; discontinue if uncontrolled by medication. 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).

IMBRUVICA

℞

INTRON A Merck

℞

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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, dental and periodontal disorders; others (see full labeling).

How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial—1; Soln (multidose vials): 18million, 25million IU/vial—1

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: Increased risk of serious infections (eg, pneumonia, sepsis, Epstein Barr, HBV). Prior history of hep B infection; consider monitoring for reactivation and give antiviral prophylaxis. 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-gp and CYP3A4; avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, clarithromycin, telithromycin, 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: Neutropenia, lymphopenia, thrombocytopenia, anemia, nausea, vomiting, fatigue, infections, anorexia, ECG T-wave changes; 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. Treatment of polycythemia vera (PV) in patients with inadequate response to, or intolerant of, hydroxyurea.

Adults: Doses may be given by NG tube if unable to swallow tabs. Myelofibrosis: Platelets >200X109/L: initially 20mg twice daily. Platelets 100–200X109/L: initially 15mg twice daily.

Platelets 50–<100X109/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 4 weeks of therapy and not more frequently than every 2 weeks. Discontinue treatment after 6 months if no reduction in spleen size or symptom improvement.

Interrupt treatment if platelets <50X109/L or ANC <0.5X109/L. May restart after recovery of platelets or ANC (see full labeling for max allowable restarting doses). Consider dose reductions if platelets decrease but remain ≥50X109/L (see full labeling). Dose modifications for patients starting treatment with platelets 50–<100X109/L: see full labeling. PV: initially 10mg twice daily. May increase doses by 5mg twice daily to a max of 25mg twice daily; do not increase during the first 4 weeks of therapy and not more frequently than every 2 weeks.

Consider dose reductions for Hgb and/or platelet decreases (see full labeling). Interrupt treatment if Hgb <8g/dL, platelets <50X109/L, or ANC <1.0X109/L. May restart after recovery of hematologic parameters (see full labeling for max allowable restarting doses). Concomitant strong CYP3A4 inhibitors (see Interactions) or fluconazole ≤200mg (Myelofibrosis): initially 10mg twice daily if platelets ≥100X109/L; if platelets 50–<100X109/L: initially 5mg once daily; (PV): initially 5mg twice daily. Other reductions, hepatic or renal impairment, ESRD: see full labeling.

Children: Not established.

Warnings/Precautions: Monitor for thrombocytopenia, anemia, neutropenia; manage by reducing dose, interrupt, or transfusion 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. May exacerbate myelofibrosis following treatment interruption or discontinuation. Risk of non-melanoma skin cancer; perform periodic skin exams. Increases in lipid parameters including total-C, LDL, triglycerides; assess 8–12 weeks after starting and treat if hyperlipidemia develops. Avoid abrupt cessation. Renal or hepatic impairment.

Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions: Avoid concomitant fluconazole doses >200mg daily. 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 strong CYP3A4 inducers (eg, rifampin).

Adverse reactions: Thrombocytopenia, anemia, bruising, dizziness, headache; herpes zoster, tuberculosis (monitor promptly and test for latent infection), progressive multifocal leukoencephalopathy (discontinue if occurs), Hepatitis B. How supplied: Tabs—60

KEYTRUDA Merck

℞

Human programmed death receptor-1 (PD-1)-blocking antibody. Pembrolizumab 50mg/vial; lyophilized pwd for IV infusion after reconstitution; 25mg/mL; per vial; soln for IV infusion after dilution; both: preservative-free.

Indications: Refractory classical Hodgkin lymphoma (cHL) or in patients who have relapsed after ≥3 prior lines of therapy.

Adults: Give as IV infusion over 30mins.

200mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.

Children: Give as IV infusion over 30mins.

2mg/kg (max 200mg) every 3 weeks until disease progression, unacceptable toxicity, or

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER up to 24 months in patients without disease progression. Dose modifications: see full labeling.

Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.

Warnings/Precautions: Monitor for pneumonitis; withhold dose if Grade 2 pneumonitis; permanently discontinue if Grade 3 or 4, or recurrent Grade 2 develops. Monitor for colitis; withhold dose if Grade 2 or 3 colitis; permanently discontinue if Grade 4 develops.

Monitor for changes in liver function; withhold dose or discontinue based on severity of elevated liver enzymes. Monitor for changes in renal function; withhold dose if Grade 2 nephritis; permanently discontinue if Grade 3 or 4 develops.

Monitor for hypophysitis; withhold dose if Grade 2 hypophysitis; withhold or discontinue if Grade 3 or 4 develops. Monitor for changes in thyroid function (at treatment initiation, during, and as clinically indicated) and signs/symptoms of thyroid disorders; withhold or discontinue if Grade 3 or 4 hyperthyroidism develops.

Monitor for hyperglycemia and other diabetes symptoms; withhold if severe hyperglycemia until controlled. Withhold dose if Grade 4 hematological toxicity in cHL patients develops. Permanently discontinue if any severe or Grade 3 immunemediated adverse reaction recurs, for any lifethreatening immune-mediated adverse reaction (except endocrinopathies controlled with hormone replacement or hematological toxicity in cHL patients), persistent Grade 2 or 3 reactions that do not recover to Grade 0–1 within 12wks after last dose, or inability to reduce corticosteroid dose to ≤10mg/day of prednisone or equivalent within 12wks. Monitor for infusion-related reactions; permanently discontinue if Grade 3 or 4 develops.

Complications of allogeneic HSCT after Keytruda: monitor for hepatic VOD, Grade 3 or 4 acute GVHD, steroid-requiring febrile syndrome, and others.

Embryo-fetal toxicity. Females of reproductive potential should use highly effective contraception during therapy and for 4 months after the final dose. Pregnancy: avoid. Nursing mothers: not recommended (during therapy and for 4 months after the final dose).

Adverse reactions: Fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, nausea; immune-mediated disorders, infusionrelated reactions.

How supplied: Single-use vial 50mg—1; Singleuse vial 25mg/mL—1

KYPROLIS Amgen

℞

Proteasome inhibitor. Carfilzomib 30mg/vial, 60mg/vial; lyophilized pwd for IV inj after reconstitution; preservative-free.

Indications: In combination with dexamethasone or lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received 1–3 lines of therapy. As a single agent for the treatment of patients with relapsed

or refractory multiple myeloma who have received ≥1 lines of therapy.

Adults: See full labeling. Hydrate prior to and following administration as needed. Premedicate with dexamethasone prior to all Cycle 1 doses, during subsequent cycles, and if infusion reactions occur. Give by IV 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).

Lenalidomide/dexamethasone combination: Infuse over 10 mins. In Cycle 1: initially 20mg/m2 per dose on Days 1 and 2; if tolerated increase to 27mg/m2 on Day 8 and subsequent cycles.

From Cycle 13, omit the Day 8 and 9 doses.

Discontinue carfilzomib after Cycle 18. See full labeling for lenalidomide and dexamethasone dosing. Dexamethasone combination: Infuse over 30 mins. In Cycle 1: initially 20mg/m2 per dose on Days 1 and 2; if tolerated increase to 56mg/m2 on Day 8 and subsequent cycles. Monotherapy: initially 20mg/m2 per dose in Cycle 1 on Days 1 and 2; if tolerated increase to 27mg/m2 on Day 8 (by 10-min infusion regimen) or 56mg/m2 on Day 8 (by 30-min infusion regimen) and continue same dose for subsequent cycles. From Cycle 13, omit the Day 8 and 9 doses. All: continue until disease progression or unacceptable toxicity occurs. Toxicity dose modification: see full labeling. Mild or moderate hepatic impairment: reduce dose by 25%. ESRD on dialysis: give dose after session.

Children: Not established.

Warnings/Precautions: Monitor for signs/symptoms of cardiac failure or ischemia; evaluate promptly if toxicity is suspected.

Increased risk of cardiac complications in patients with NYHA Class III and IV heart failure, recent MI, conduction abnormalities, angina, uncontrolled arrhythmias; do full medical assessment prior to starting. Pulmonary hypertension; if suspected, withhold therapy until resolved; may consider restarting after reevaluation.

Discontinue if pulmonary toxicity occurs.

Monitor for dyspnea or tumor lysis syndrome (TLS), and manage promptly if occurs; interrupt therapy until resolved. Maintain adequate hydration. Monitor for volume overload. Monitor platelets frequently during therapy. Evaluate signs/symptoms of blood loss; reduce or withhold dose as appropriate. Monitor for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS); discontinue and evaluate if suspected. Discontinue and evaluate if posterior reversible encephalopathy syndrome (PRES) is suspected. Monitor BP, renal function, liver enzymes, electrolytes (eg, potassium) regularly; reduce or withhold dose as needed. Renal or hepatic impairment. Give thromboprophylaxis for combination therapy. Consider antiviral prophylaxis to prevent herpes zoster reactivation.

Elderly (≥75yrs). Embry-fetal toxicity. Use effective contraception during and for ≥30 days (females) or ≥90 days (males) after therapy completion. Pregnancy: avoid. Nursing mothers.

Interactions: Increased risk of thrombosis with oral or hormonal contraceptives; consider alternatives during combination therapy.

Increased fatal/serious toxicities in combination with melphalan + prednisone in newly diagnosed transplant-ineligible patients.

Adverse reactions: Anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper RTI, hypokalemia, nausea, headache, peripheral edema; cardiac events, pulmonary HTN, acute kidney injury, infusion reactions, hemorrhage, TLS, hepatic toxicity/failure, TTP/HUS, PRES. 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.

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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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)

MUSTARGEN Recordati

℞

Alkylating agent. 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 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 venoocclusive disease, infection (eg, pneumonia, sepsis), mucositis, myasthenia gravis, gonadal suppression, rash; rare: cataracts, bronchopulmonary dysplasia (discontinue if occurs).

How supplied: Tabs—25

NINLARO Takeda

℞

Proteasome inhibitor. Ixazomib 2.3mg, 3mg, 4mg; gel caps.

Indications: In combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.

Adults: Swallow whole. Take ≥1hr before or ≥2hrs after food. Initially 4mg once weekly on Days 1, 8, and 15 of a 28-day cycle; continue until disease progression or unacceptable toxicity. Give with lenalidomide 25mg daily on Days 1–21 and dexamethasone 40mg on Days 1, 8, 15, and 22. Moderate or severe hepatic impairment, severe renal impairment, or ESRD on dialysis: initially 3mg. Prior to new cycle, ensure ANC ≥1,000/mm3, platelets ≥75,000/mm3, recovery of non-hematologic toxicities to baseline or Grade ≤1. Consider antiviral prophylaxis to decrease risk of herpes zoster reactivation. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Thrombocytopenia: monitor platelets at least monthly during treatment; consider more frequently for first 3 cycles. Adjust dose for Grade 3/4 GI symptoms or Grade ≥2 rash. Monitor for peripheral neuropathy; adjust dose if worsens.

Adjust dosing of dexamethasone or ixazomib if Grade 3/4 peripheral edema symptoms occur. Hepatic impairment; monitor enzymes regularly and adjust for Grade 3/4 symptoms.

Severe renal impairment or ESRD. Embryo-fetal toxicity. Pregnancy: avoid. Males and females of reproductive potential must use effective contraception during therapy and for 90 days after final dose. Females using hormonal contraceptives should also use barrier method.

Nursing mothers: not recommended (during and for 90 days after final dose).

Interactions: Avoid concomitant strong CYP3A inducers (eg, rifampin, phenytoin, carbamazepine, St. John’s Wort). Risk of reduced hormonal contraceptives efficacy with concomitant dexamethasone.

Adverse reactions: Diarrhea, constipation, thrombocytopenia, peripheral neuropathy,

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER nausea, peripheral edema, vomiting, back pain; rash, hepatotoxicity, herpes zoster, eye disorders.

How supplied: Caps—1, 3

ONCASPAR Baxalta

OPDIVO Bristol-Myers Squibb

℞

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 1–2hrs 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 1hr post-dose. Monitor serum glucose, coagulation parameters. Discontinue if serious allergic reactions, thrombotic events, or pancreatitis occur. Monitor for hepatotoxicity and abnormal liver function. Pregnancy (Cat.C). Nursing mothers: not recommended.

Adverse reactions: Allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, CNS thrombosis, coagulopathy, hyperbilirubinemia, elevated transaminases, hyperlipidemia.

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

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol.

Indications: Classical Hodgkin lymphoma (cHL) that relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin.

Adults: Give as IV infusion over 60mins.

3mg/kg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling.

Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderate-to-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or lifethreatening. Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism.

Monitor for transplant-related complications (eg, hyperacute or Grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic venoocclusive disease) and treat promptly. Moderate or severe hepatic impairment: not studied.

Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥5 months after final dose.

Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended.

Adverse reactions: Fatigue, upper RTI, pyrexia, diarrhea, cough; immune-mediated reactions (may be fatal).

How supplied: Single-use vial (4mL, 10mL)—1

POMALYST Celgene

℞

Immunomodulator. Pomalidomide 1mg, 2mg, 3mg, 4mg; caps.

Indications: In combination with dexamethasone for multiple myeloma, in patients who have received at least two prior therapies (including lenalidomide and a proteasome inhibitor), and have shown disease progression on or within 60 days of completion of the last therapy.

Adults: Swallow whole; may be taken with water (with or without food). 4mg once daily on Days 1–21 of repeated 28-day cycles until disease progression; give with dexamethasone.

Concomitant strong CYP1A2 inhibitors: consider alternatives, if necessary, reduce Pomalyst dose by 50%. Severe renal impairment requiring dialysis: initially 3mg daily; give dose after dialysis session on hemodialysis days. Hepatic impairment (mild or moderate): initially 3mg daily; (severe): 2mg daily. 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 24hrs 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 and arterial 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. Hepatic or severe renal impairment on hemodialysis: adjust doses (see Adults).

Monitor LFTs monthly; discontinue and evaluate if elevated liver enzymes occur; consider using lower dose when restarting. Risk of second primary malignancies. High tumor burden (monitor).

Discontinue if angioedema, skin exfoliation, bullae, or other severe dermatologic reactions occur; do not restart. Nursing mothers: not recommended.

Interactions: Potentiated by strong CYP1A2 (eg, ciprofloxacin, fluvoxamine), CYP3A or P-gp inhibitors (eg, ketoconazole); avoid. May be antagonized by strong CYP1A2 or CYP3A (eg, carbamazepine) inducers. Smoking may reduce efficacy.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER Adverse reactions: Fatigue, asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, pyrexia; thromboembolism, dizziness, confusion, neuropathy, pneumonia, thrombocytopenia, tumor lysis syndrome.

Note: Available only through Pomalyst REMS program.

How supplied: Caps—21, 100

PURINETHOL Teva

PURIXAN Rare Disease

℞

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.

Pre-existing liver disease (monitor more frequently). Obtain CBCs with differential, hemoglobin, hematocrit, platelets; discontinue if severe bone marrow suppression occurs.

Thiopurine-S-methyltransferase (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

℞

Antimetabolite. Mercaptopurine (6-MP) 20mg/mL; oral susp; contains fruit extract, aspartame.

Indications: Maintenance therapy of acute lymphoblastic leukemia as part of a combination regimen.

Adults and Children: Shake bottle vigorously for at least 30 secs. Initially 1.5–2.5mg/kg (50–75mg/m2) per day as a single dose. Monitor subsequent doses to maintain desirable ANC level and adjust for excessive hematological toxicity. Thiopurine-S-methyltransferase (TPMT)deficient: if homozygous, may require up to a 90% dose reduction; if heterozygous, some may require dose reduction based on toxicities. Renal or hepatic impairment: use lower starting doses; monitor for toxicity. See full labeling.

Warnings/Precautions: Myelosuppression; monitor CBCs and adjust dose for severe neutropenia and thrombocytopenia. Consider testing for TPMT gene polymorphism in patients who experience repeated severe bone marrow toxicities. Monitor serum transaminase, alkaline phosphatase, and bilirubin levels at weekly intervals when starting therapy, then monthly thereafter; interrupt treatment if evidence of hepatotoxicity occurs. Concomitant other hepatotoxic drugs or with pre-existing liver disease; monitor LFTs more frequently.

Immunosuppression. Increased risk of secondary malignancies. Renal or hepatic impairment.

Elderly. Pregnancy (Cat.D); esp. 1st trimester, nursing mothers: not recommended.

Interactions: Avoid concomitant allopurinol.

Increased risk of bone marrow suppression with allopurinol, aminosalicylate derivatives (eg, olsalazine, mesalamine, sulfasalazine), trimethoprim-sulfamethoxazole. Possibly decreased effectiveness with concomitant warfarin; monitor PT or INR; may need warfarin dose adjustments. Concomitant live virus vaccines: may get suboptimal response and risk of infection.

Adverse reactions: Myelosuppression, nausea, vomiting, anorexia, diarrhea, malaise, rashes, oral lesions, elevated transaminases and bilirubin, intestinal ulceration; hepatotoxicity.

How supplied: Susp—100mL

REVLIMID Celgene

℞

Immunomodulator. Lenalidomide 2.5mg, 5mg, 10mg, 15mg, 20mg, 25mg; caps; contains lactose.

Indications: In combination with dexamethasone for treatment of patients with

multiple myeloma (MM). Treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.

Limitations of use: not for treating patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

Adults: Swallow whole with water. ≥18yrs: initially 25mg once daily on Days 1–21 of each 28-day cycle until disease progression or unacceptable toxicity. >75yrs: may reduce dexamethasone initial dose. Renal impairment: MCL: Moderate (CrCl 30–60mL/min): 10mg per day; MM: Moderate (CrCl 30–50mL/min): 10mg per day; consider increasing to 15mg after 2 cycles, if tolerant. Severe (CrCl <30mL/min without dialysis): 15mg every 48hrs. ESRD (CrCl <30mL/min with dialysis): 5mg once daily; administer after dialysis (on dialysis days).

Autologous stem cell transplantation (ASCT) eligible: refer for hematopoietic cell mobilization within 4 cycles; if non-eligible, continue therapy until disease progression or unacceptable toxicity.

Dose adjustments if thrombocytopenia or neutropenia develops: see full labeling.

Children: <18yrs: not established.

Contraindications: Pregnancy (Cat. X).

Warnings/Precautions: Must register patient in Revlimid REMS program; patient must understand toxicity with fetal exposure. Counsel patient on need for contraception; females: use 2 forms of contraception 1 month before, during therapy, during dose interruptions, and 1 month after therapy; males: use condom during and 1 month after therapy; obtain 2 negative pregnancy tests (one within 10–14 days, and then another within 24hrs prior to starting therapy), repeat at least weekly for 1st month then every 4 weeks (regular menstrual cycles) or every 2 weeks (irregular cycles); get informed consent. Do not donate blood during and for 1 month after therapy. Monitor for signs/symptoms of thromboembolic events; base thromboprophylaxis on patient’s risks. For MM: obtain CBCs weekly for the first 2 cycles, on Days 1 and 15 of Cycle 3, and every 28 days thereafter; for MCL: obtain CBCs weekly for the first cycle, every 2 weeks during Cycles 2–4, and then monthly thereafter; both: dose interruption and/or reduction may be needed. May require blood product support and/or growth factors.

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.

Lactose intolerance. Maximum 1 month per ℞.

Nursing mothers: not recommended.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER Interactions: Monitor digoxin. Concomitant warfarin; monitor PT, INR. May increase risk of thrombosis with dexamethasone, erythropoietic agents, or estrogen containing therapies.

Adverse reactions: Birth defects, thrombocytopenia, neutropenia, anemia, leukopenia, constipation, diarrhea, nausea, vomiting, pruritus, rash, fatigue, arthralgia, pyrexia, back pain, cough, dizziness, headache, dyspnea, nasopharyngitis, epistaxis, upper respiratory tract infection, tremor, blurred vision, muscle cramp, decreased appetite, peripheral edema; thrombosis/embolism, allergic reactions (discontinue if occurs; do not resume), tumor flare reaction (monitor; esp. in treating MCL), hepatotoxicity.

Note: Available only through Revlimid REMS 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

℞

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 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

RYDAPT Novartis

℞

Kinase inhibitor. Midostaurin 25mg; caps.

Indications: Treatment of adults with newly diagnosed FLT3 mutation-positive acute myeloid leukemia (AML) as detected by an FDA-approved

test, in combination with standard cytarabine and daunorubicin induction + cytarabine consolidation. Treatment of adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL). Limitations of use: not for use as singleagent induction therapy for AML. Adults: Swallow whole. Take with food approx.

12hrs apart. Give prophylactic antiemetics prior to initiation. AML: 50mg twice daily on Days 8–21 of each induction cycle with cytarabine and daunorubicin, and on Days 8–21 of each consolidation cycle with high-dose cytarabine.

ASM, SM-AHN, MCL: 100mg twice daily until disease progression or unacceptable toxicity.

Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: For ASM, SM-AHN, MCL: Monitor for toxicity at least weekly for first 4 weeks, every other week for next 8 weeks, and monthly thereafter. Discontinue if low ANC, platelet count, or hemoglobin persists >21 days.

Interrupt dose if Grade 3/4 nausea and/or vomiting despite antiemetics or other Grade 3/4 non-hematological toxicities; resume at reduced dose and increase if tolerated (see full labeling). Both: monitor for signs/symptoms of interstitial lung disease or pneumonitis; discontinue if pulmonary toxicity develops.

Embryo-fetal toxicity. Pregnancy; exclude status within 7 days prior to initiation. Females of reproductive potential and males should use effective contraception during and for at least 4 months after last dose. Nursing mothers: not recommended (during and for at least 4 months after last dose).

Interactions: Concomitant drugs that prolong QT interval; monitor EKG periodically. Potentiated by strong CYP3A inhibitors (eg, boceprevir, clarithromycin, cobicistat, conivaptan, danoprevir/ritonavir, diltiazem, elvitegravir/ritonavir, grapefruit juice, idelalisib, indinavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, paritaprevir/ritonavir and [ombitasvir and/or dasabuvir], posaconazole, ritonavir, saquinavir/ritonavir, tipranavir/ritonavir, troleandomycin, voriconazole); consider alternatives; if co-administration needed, monitor (esp. first week) for increased adverse reactions.

Avoid concomitant strong CYP3A inducers (eg, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John’s wort).

Adverse reactions: AML: Febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, upper respiratory tract infection. ASM, SM-AHN, MCL: also diarrhea, edema, abdominal pain, fatigue, constipation, pyrexia, dyspnea; pulmonary toxicity, infertility.

How supplied: Caps—56, 112

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 chromosome-positive 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. Treat until disease progression or unable to tolerate. Concomitant CYP3A4 inhibitors (see Interactions): consider reducing dose. Concomitant CYP3A4 inducers (see Interactions): consider increasing dose. See full labeling for dose adjustments with toxicity.

Children: <18yrs: not established.

Warnings/Precautions: Monitor for signs/symptoms of cardiac dysfunction; treat appropriately if occur. Congenital long QT syndrome. Proarrhythmic conditions. Cumulative high-dose anthracycline therapy. Hypokalemia, hypomagnesemia; correct electrolyte imbalances before starting and during 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 every 2 weeks for 12 weeks, then every 3 months thereafter (chronic phase CML) or weekly for the first 2 months, then monthly thereafter (advanced phase CML or Ph+ ALL). Permanently discontinue if severe skin reactions (eg, StevensJohnson syndrome) occur. Increased risk of tumor lysis syndrome in advanced stage disease and/or high tumor burden. Maintain adequate hydration. Correct uric acid levels before therapy and monitor electrolytes. Hepatic impairment.

Elderly. Pregnancy. Use effective contraception during and for 30 days after last dose. 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 strong 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 antiarrhythmics or other drugs that may lead to QT prolongation.

Adverse reactions: Myelosuppression (eg, severe thrombocytopenia, neutropenia, anemia), fluid retention, diarrhea, headache, dyspnea, musculoskeletal pain, rash, fatigue, nausea, severe hemorrhage (eg, CNS, GI); QT prolongation, cardiac events, PAH, severe skin reactions.

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 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 Valeant

℞

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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 >3xULN 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 Valeant

℞

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.

Cardiovascular status should be evaluated; monitor cardiovascular risk factors and actively manage during therapy. Hereditary galactose intolerance, severe lactase deficiency, glucosegalactose malabsorption: not recommended.

Hepatic impairment. History of pancreatitis.

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.

Monitor lipids and glucose periodically during first year, then yearly. 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, 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, cardiac and arterial vascular occlusive events, severe fluid retention (monitor).

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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 full labeling). Consider dose reduction, delay, or discontinuation in those who develop NCI CTC Grade 3/4 adverse reactions.

Children: <12yrs: not established.

Contraindications: Pregnancy. 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 neuropathy monthly for first 3 months; discontinue if symptoms develop.

Monitor for signs/symptoms of thromboembolic events, neutropenia, bradycardia, syncope, orthostatic hypotension, tumor lysis syndrome.

Reevaluate if ANC <750/mm2; consider withholding if neutropenia persists. Monitor blood and platelet counts. Monitor for signs/symptoms of bleeding including petechiae, epistaxis, and GI bleed. Measure HIV viral load after 1st and 3rd months, and every 3 months thereafter.

Discontinue if pregnancy or severe skin rash occurs. History of seizure. Avoid contact with non-intact capsule or powder content.

Maximum 1 month per ℞. Nursing mothers: not recommended.

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.

Increased risk of thromboembolism with concomitant erythropoietic agents, or estrogencontaining therapies in those receiving thalidomide with dexamethasone.

Adverse reactions: Fatigue, birth defects, somnolence, skin rash (eg, Stevens-Johnson Syndrome, toxic epidermal necrolysis), headache, bradycardia, peripheral neuropathy, seizures, drowsiness, dizziness, orthostatic hypotension, leukopenia, anorexia, nausea, anxiety, asthenia, tremor, fever, weight loss, dry skin, neutropenia, increased HIV viral load, constipation, confusion, hypocalcemia, edema, dyspnea, thrombosis/embolism, thrombocytopenia.

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: Blister packs (50mg)—1, 28; (100mg, 150mg, 200mg)—28

TREANDA Teva

℞

Alkylating agent. Bendamustine HCl 25mg, 100mg; per vial; lyophilized pwd for IV infusion after reconstitution; 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 30mins.

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 60mins. 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. Delay treatment for Grade 4 hematologic toxicity or clinically significant ≥Grade 2 non-hematologic toxicity.

Children: Not established.

Warnings/Precautions: Myelosuppression; monitor CBCs including leukocytes, platelets, hemoglobin, neutrophils frequently; restart treatment based on ANC and platelet count recovery. Monitor for signs of infection or reactivation of infections (eg, hepatitis B, CMV, tuberculosis, herpes zoster); prophylaxis and treat prior to therapy if occur. Monitor for infusion or skin reactions, tumor lysis syndrome.

Monitor LFTs prior to and during therapy. Renal impairment (mild or moderate): caution; (CrCl <40mL/min): not recommended. Hepatic impairment (mild): caution; (moderate or severe): not recommended. Avoid extravasation. Embryofetal toxicity. Pregnancy (Cat.D); avoid during and for 3 months after therapy cessation. Nursing mothers: not recommended.

Interactions: May be potentiated CYP1A2 inhibitors (eg, fluvoxamine, ciprofloxacin) or antagonized by CYP1A2 inducers (eg, omeprazole, smoking); if needed, consider alternatives.

Adverse reactions: Lymphopenia, anemia, leukopenia, thrombocytopenia, neutropenia, pyrexia, nausea, vomiting, fatigue, diarrhea, constipation, anorexia, cough, headache, weight loss, dyspnea, stomatitis, increased bilirubin, increased AST/ALT; infection, infusion reactions (discontinue if severe), tumor lysis syndrome, skin reactions (if severe or progressive, withhold dose or discontinue), other malignancies (eg, myelodysplastic syndrome, acute myeloid leukemia, bronchial carcinoma).

How supplied: Single-use vial—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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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)

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, wraparound 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 Alkylating agent. 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 (Cat.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; lyophilized pwd for IV or SC inj after reconstitution; contains mannitol.

Indications: Multiple myeloma. Mantle cell lymphoma.

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).

Previously untreated mantle cell lymphoma: Treat for six 3-week cycles in combination with IV rituximab, cyclophosphamide, doxorubicin, and oral prednisone. 1.3mg/m2 twice weekly for 2 weeks (Days 1, 4, 8, 11) then 10 day rest period (Days 12–21); if response first documented at Cycle 6, two more cycles are recommended.

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). Multiple myeloma patients who have previously responded to bortezomib (alone or in combination) and have relapsed at least 6 months after completing prior bortezomib therapy: may retreat starting at last tolerated dose, given twice weekly every 3 weeks (Days 1, 4,

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 8, 11); max 8 cycles. Allow at least 72hrs between consecutive doses. May be given as a single agent or in combination with dexamethasone.

Dose modifications: see full labeling. SC inj may be considered for patients with pre-existing or at high-risk of peripheral neuropathy. Moderate-tosevere hepatic impairment: reduce to 0.7mg/m2 in 1st cycle; may consider dose increase to 1mg/m2 or further 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 and/or schedule adjustment. Diabetes (closely monitor blood glucose). History of syncope. Avoid dehydration; give fluids and electrolytes. Heart disease (monitor for CHF). Interrupt therapy and evaluate if new or worsening cardiopulmonary symptoms develop.

Monitor CBC frequently during therapy and platelets prior to each dose; adjust dose/schedule for thrombocytopenia (see full labeling). Monitor 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 strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir); consider reducing bortezomib dose. Caution with hypotensives and hypoglycemics.

Adverse reactions: GI toxicity (eg, nausea, diarrhea, constipation, vomiting; interrupt therapy if severe), thrombocytopenia, neutropenia, anemia, leukopenia, lymphopenia, peripheral neuropathy, fatigue, neuralgia, rash, pyrexia, anorexia, asthenia, herpes reactivation, insomnia, dyspnea, paresthesia, headache, decreased appetite, dizziness, blurred vision, edema, arthralgia, pain, dysesthesia, psychiatric disorders, cough, pruritus, orthostatic hypotension, CHF, decreased LVEF, hepatotoxicity; rare: posterior reversible encephalopathy syndrome (discontinue if occurs).

How supplied: Single-dose vial—1

VENCLEXTA AbbVie and Genentech ℞ BCL-2 inhibitor. Venetoclax 10mg, 50mg, 100mg; tabs.

Indications: Treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion,

as detected by an FDA-approved test, who have received at least one prior therapy.

Adults: Assess for level of tumor lysis syndrome risk; provide prophylactic hydration and antihyperuricemics prior to 1st dose. Swallow whole.

Take with food and water. Initially 20mg once daily for Week 1, then 50mg once daily for Week 2, then 100mg once daily for Week 3, then 200mg once daily for Week 4, then 400mg once daily for Week 5 and beyond until disease progression or unacceptable toxicity. Dose modifications for toxicities: see full labeling.

Children: Not established.

Contraindications: Concomitant strong CYP3A inhibitors at initiation or during dose ramp-up phase.

Warnings/Precautions: Risk of tumor lysis syndrome (esp. with high tumor burden, comorbidities, CrCl <80mL/min); perform tumor burden assessment, radiographic evaluation, blood chemistry; correct preexisting abnormalities prior to initiation. Risk of neutropenia; monitor CBCs during therapy; interrupt or reduce dose if severe. Severe renal impairment or on dialysis. Moderate or severe hepatic impairment: monitor closely.

Embryo-fetal toxicity. Females of reproductive potential: should undergo pregnancy testing prior to initiation. Pregnancy; avoid. Use effective contraception during and for ≥1 month after final dose. Nursing mothers: not recommended.

Interactions: See Contraindications.

Concomitant strong CYP3A inhibitors after ramp-up phase (eg, ketoconazole, conivaptan, clarithromycin, indinavir, itraconazole, lopinavir, ritonavir, telaprevir, posaconazole, voriconazole); avoid use or reduce venetoclax steady daily dose by ≥75%. Avoid concomitant moderate CYP3A inhibitors (eg, erythromycin, ciprofloxacin, diltiazem, dronedarone, fluconazole, verapamil) or P-gp inhibitors (eg, amiodarone, azithromycin, captopril, carvedilol, cyclosporine, felodipine, quercetin, quinidine, ranolazine, rifampin, ticagrelor); consider alternatives; if inhibitor necessary, reduce venetoclax dose by ≥50% and monitor closely. Resume at prior venetoclax dose 2–3 days after discontinuing the inhibitor.

Avoid concomitant strong CYP3A inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s Wort) or moderate CYP3A inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin); consider alternatives. Avoid live attenuated vaccines until B-cell recovery. Avoid grapefruit, Seville oranges, and starfruit during treatment. Monitor INR closely with concomitant warfarin. Avoid P-gp substrates with narrow therapeutic index (eg,

digoxin, everolimus, sirolimus); if necessary, take ≥6hrs before venetoclax.

Adverse reactions: Neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, fatigue.

How supplied: Starting Packs—1; Wallets 10mg—14; 50mg—7; Tabs 100mg—120

VESANOID Roche

℞

Retinoid. Tretinoin 10mg; soft gelatin caps; contain parabens.

Indications: Induction of remission in patients with acute promyelocytic leukemia (APL), French-American-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 >5XULN. 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 anti-fibrinolytic 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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER VIDAZA Celgene

℞

Cytidine analogue. Azacitidine 100mg/vial; lyophilized 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.

Rotate SC inj sites. Initially 75mg/m2 SC (doses >4mL divide equally into 2 syringes and inject into 2 separate sites, must administer within 1hr of reconstitution) or IV (infuse over 10–40mins, must complete within 1hr 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 based on nadir counts, hematologic response, and toxicities (eg, neutropenia, thrombocytopenia, decreased serum bicarbonate, BUN or SCr elevation); see full labeling.

Children: Not established.

Contraindications: Advanced malignant hepatic tumors.

Warnings/Precautions: Myelosuppression.

Monitor CBCs frequently for response and/or toxicity, at a minimum, prior to each dosing cycle.

Renal or hepatic impairment. High tumor burden.

Monitor serum bicarbonate, liver chemistries, and serum creatinine prior to initiation and with each cycle. Monitor for tumor lysis syndrome and treat as appropriate. Elderly. Embryo-fetal toxicity.

Females and males of reproductive potential should use effective contraception. Pregnancy: avoid; verify status prior to initiation. Nursing mothers: not recommended.

Adverse reactions: Nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, inj site erythema, constipation, neutropenia, ecchymosis, petechiae, rigors, weakness, hypokalemia; renal failure/tubular acidosis, hepatic coma.

How supplied: Single-use vial—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

XATMEP Silvergate

℞

Folate analogue inhibitor. Methotrexate 2.5mg/mL; oral soln.

Indications: Treatment of pediatrics with acute lymphoblastic leukemia (ALL) as part of a multiphase, combination chemotherapy maintenance regimen.

Adults: Not applicable.

Children: For oral use only; use other methotrexate formulation if dosing via other routes required. Use accurate measuring device.

Initially 20mg/m2 once weekly; adjust subsequent dosing based on ANC and platelet count.

Contraindications: Pregnancy in patients with non-malignant diseases.

Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if secondary malignant lymphomas occur. Obtain baseline and monitor CBCs for bone marrow suppression, and hepatic, renal and pulmonary function; adjust dose, interrupt, or discontinue if needed. During therapy, monitor hematology at least monthly, renal and hepatic function every 1–2 months, more often during dose changes or when predisposed to toxicity (eg, dehydration).

Increased risk of serious infections (eg, bacterial, fungal, viral) including opportunistic infections; monitor and treat promptly. Peptic ulcer disease.

Ulcerative colitis. Avoid in chronic liver disease.

Increased risk of hepatotoxicity with alcoholism, obesity, diabetes, hyperlipidemia, previous significant exposure to liver toxins, history of liver disease, family history of liver disease, persistent abnormal liver tests, treatment duration, advanced age. Discontinue if anaphylaxis, other serious hypersensitivity or severe dermatologic reactions occur. Evacuate significant thirdspace accumulations prior to administration.

Embryo-fetal toxicity. Exclude pregnancy in females of reproductive potential; use effective

contraception during therapy and for 6 months after final dose and for at least 3 months after final dose for men. Nursing mothers: not recommended.

Interactions: Avoid live virus vaccines. Severe and fatal GI toxicity with concomitant NSAIDs. May be potentiated by penicillins (monitor) or probenecid (consider alternative). May potentiate theophylline. Increased bone marrow suppression with trimethoprim/sulfamethoxazole; monitor.

Increased risk of soft tissue necrosis and osteonecrosis with radiation therapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine).

Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, abdominal distress, elevated liver function tests, malaise, fatigue, chills, fever, dizziness, decreased resistance to infection; bone marrow suppression, infections, renal toxicity, GI toxicity, hepatotoxicity, pulmonary toxicity, hypersensitivity, dermatologic reactions, secondary malignancies, infertility.

How supplied: Oral soln—120mL

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 ≥150,000/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 100,000– 149,000cells/mm3, reduce dose to 0.3 mCi/kg.

Do not treat if platelets <100,000cells/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 <100,000cells/mm3, neutrophil count <1,500cells/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.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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.

Adults: Give by IV infusion over at least 15mins.

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 indicated.

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 0.5mg/dL from a normal pre-treatment level, or by 1mg/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 invasive dental surgery (do preventative dental work before therapy). Pregnancy (Cat.D). Nursing mothers: not recommended.

Interactions: Avoid concomitant other bisphosphonates. Additive hypocalcemic effect with aminoglycosides, calcitonin, loop diuretics.

Caution with other nephrotoxic drugs.

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; osteonecrosis of the jaw, atypical subtrochanteric, diaphyseal femoral fractures, severe hypocalcemia.

How supplied: Single-use vial, ready-to-use bottle—1

ZYDELIG Gilead

℞

Phosphatidylinositol 3-kinase inhibitor. Idelalisib 100mg, 150mg; tabs.

Indications: Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab,

in patients for whom rituximab alone would be considered appropriate due to other co-morbidities. Relapsed follicular B-cell nonHodgkin lymphoma (FL) in patients who have received at least 2 prior systemic therapies.

Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least 2 prior systemic therapies. Limitations of use: not recommended for first-line treatment of CLL, FL, or SLL. Adults: Swallow whole. ≥18yrs: initially 150mg twice daily; continue until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: <18yrs: not established.

Contraindications: History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis.

Warnings/Precautions: Risk of fatal/serious hepatotoxicity: monitor ALT/AST every 2 weeks for the first 3 months, every 4 weeks for the next 3 months, then every 1–3 months thereafter; if ALT/AST >3XULN, monitor weekly until resolved; if ALT/AST >5XULN, withhold and continue monitoring weekly until resolved; if ALT/AST >20XULN, discontinue permanently. Monitor for diarrhea or colitis; withhold if severe or hospitalization; discontinue if life-threatening.

Risk of fatal/serious pneumonitis; monitor for pulmonary symptoms or a decline by >5% in oxygen saturation; if suspected, interrupt or discontinue as indicated. Risk of fatal/serious infections; monitor for signs/symptoms and interrupt if Grade ≥3. Risk of fatal/serious intestinal perforation; discontinue permanently if occurs. Monitor for severe cutaneous or serious allergic reactions; discontinue if occur.

Monitor CBCs at least every 2 weeks for the first 6 months, and at least weekly if neutrophils <1.0Gi/L. Pregnancy (Cat.D); avoid. Use effective contraception during treatment and for at least 1 month after last dose. Nursing mothers: not recommended.

Interactions: Avoid concomitant drugs that may cause hepatotoxicity or diarrhea. Avoid concomitant strong CYP3A inducers (eg, rifampin, phenytoin, St. John’s wort, carbamazepine) or CYP3A substrates (eg, oral midazolam).

Concomitant strong CYP3A inhibitors (eg, ketoconazole); monitor for idelalisib toxicity.

Adverse reactions: Diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, rash, neutropenia, ALT/AST elevations.

How supplied: Tabs—60

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DRUG MONOGRAPHS

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 mins 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. Hepatic impairment (total bilirubin >5XULN or AST >10XULN): not recommended. Monitor for sensory neuropathy, sepsis, or pneumonitis. 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

ALECENSA Genentech

℞

Kinase inhibitor. Alectinib 150mg; caps.

Indications: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

Adults: Swallow whole. Take with food.

600mg twice daily until disease progression or unacceptable toxicity. Dose modifications or dose reduction schedule: see full labeling.

Children: Not established.

Warnings/Precautions: Monitor liver function tests (eg, ALT, AST, total bilirubin) every 2 weeks

for the first 2 months, then monthly and as clinically indicated; test more frequently if transaminase and bilirubin elevated; withhold, resume at reduced dose, or permanently discontinue based on severity. Evaluate if presence of worsening respiratory symptoms; withhold if ILD/pneumonitis diagnosed; permanently discontinue if no other cause identified. Monitor HR, BP regularly. If non-lifethreatening symptomatic bradycardia occurs, withhold until asymptomatic or HR ≥60bpm; permanently discontinue in case(s) of recurrence or life-threatening bradycardia if no contributing concomitant medication identified. Assess CPK every 2 weeks for the first month and as clinically indicated; withhold, resume, or reduce dose based on severity. Embryo-fetal toxicity. Pregnancy: avoid. Females of reproductive potential should use effective contraception during treatment and for 1 week after final dose; males should use effective contraception during treatment and for 3 months after final dose. Nursing mothers: not recommended (during and for 1 week after final dose).

Interactions: Increased bradycardia with concomitant antihypertensives or other drugs known to cause bradycardia.

Adverse reactions: Fatigue, constipation, edema, myalgia; hepatotoxicity, ILD/pneumonitis, bradycardia, CPK elevation.

How supplied: Caps—240

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

ALUNBRIG Takeda

℞

Kinase inhibitor. Brigatinib 30mg, 90mg; tabs.

Indications: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

Adults: Swallow whole. Initially 90mg once daily for first 7 days; if tolerated, increase to 180mg once daily until disease progression or unacceptable toxicity. Dose modifications or dose reduction levels: see full labeling.

Children: Not established.

Warnings/Precautions: Monitor for new or worsening respiratory symptoms esp. during 1st week of initiation; if occurs, withhold and evaluate for ILD/pneumonitis; resume at same dose for Grade 1 or reduced dose for Grade 2 severity; permanently discontinue for Grade 3/4 or recurrent Grade 1/2 ILD/pneumonitis.

Monitor BP after 2 weeks and at least monthly thereafter; withhold for Grade 3 hypertension despite optimal antihypertensive therapy; resume at reduced dose upon improvement to Grade 1 severity; consider permanent discontinuation for Grade 4 or recurrent Grade 3 hypertension. Monitor HR and BP regularly; if symptomatic bradycardia occurs, withhold and evaluate any concomitant drugs that are known to cause bradycardia; resume at same or reduced dose after resolution; discontinue for life-threatening bradycardia if no contributing concomitant medication identified. Withhold and evaluate for new or worsening visual symptoms of Grade ≥2 severity; resume at reduced doses upon recovery to Grade 1 or baseline; permanently discontinue for Grade 4 visual disturbances. Monitor CPK, lipase, and amylase levels during treatment; withhold for Grade 3/4 elevation; resume at same or reduced

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DRUG MONOGRAPHS

LUNG CANCER dose upon recovery to Grade 1 or baseline.

Assess fasting serum glucose prior to initiation and periodically thereafter; if not adequately controlled with optimal antihyperglycemics, withhold then consider dose reduction, or permanently discontinue based on severity.

Embryo-fetal toxicity. Pregnancy: avoid. Females of reproductive potential should use effective non-hormonal contraception during treatment and for at least 4 months after final dose; males should use effective contraception during treatment and for at least 3 months after final dose. Nursing mothers: not recommended (during and for 1 week after final dose).

Interactions: Avoid concomitant strong CYP3A inhibitors (eg, boceprevir, cobicistat, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan); if unavoidable, reduce Alunbrig dose by ~50%.

Avoid grapefruit or grapefruit juice. Avoid concomitant strong CYP3A inducers (eg, rifampin, carbamazepine, phenytoin, St. John’s wort). May reduce efficacy of CYP3A substrates (eg, hormonal contraceptives). Caution with antihypertensives that cause bradycardia.

Adverse reactions: Nausea, diarrhea, fatigue, cough, headache; ILD/pneumonitis, hypertension, bradycardia, visual disturbances, CPK elevation, pancreatic enzyme elevation, hyperglycemia, possible infertility in males.

How supplied: Tabs 30mg—21, 180; 90mg—7, 30

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. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins. 15mg/kg every 3 weeks with carboplatin/paclitaxel.

Children: Not established.

Warnings/Precautions: Risk of GI perforations, surgery and wound healing complications, and hemorrhage. Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). Do not administer if recent history of hemoptysis of ≥ ½-teaspoon of red blood. Permanently

discontinue if GI perforation, tracheoesophageal fistula, any grade 4 fistula, or grade 4 venous thromboembolic event. Discontinue if fistula involving internal organ, wound healing complications, hemorrhage, severe arterial thromboembolic event (ATE), hypertensive crisis or encephalopathy, posterior reversible encephalopathy syndrome (PRES), or nephrotic syndrome occurs; suspend therapy if severe hypertension, moderate-to-severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Avoid in ovarian cancer if evidence of recto-sigmoid involvement by pelvic exam, bowel involvement on CT scan, or symptoms of bowel obstruction. History of arterial thromboembolism. Diabetes. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis; if ≥2+, do further assessment with a 24-hour urine collection.

Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy: may cause fetal harm; use effective contraception during and for 6 months after last dose. Nursing mothers: not recommended.

Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation and fistulae, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, PRES, infusion reactions, ovarian failure, neutropenia, infection.

How supplied: Single-use vial—1 ℞

or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Increased risk of hemorrhage; permanently discontinue if severe bleeding occurs. Control hypertension prior to initiating. Monitor blood pressure every 2 weeks or more frequently as indicated; if severe hypertension develops, temporarily suspend until medically controlled. Monitor for infusion-related reactions during therapy. Have emergency resuscitative equipment available.

Permanently discontinue if severe arterial thromboembolic events, severe uncontrolled hypertension (despite antihypertensives), hypertensive crisis or encephalopathy, Grade 3 or 4 infusion-related reactions, urine protein >3g/24hrs, nephrotic syndrome, or GI perforation occurs. Impaired wound healing: withhold Cyramza prior to surgery. Clinical deterioration in patients with Child-Pugh B or C cirrhosis (eg, new or worsening encephalopathy, ascites, hepatorenal syndrome). Discontinue if reversible posterior leukoencephalopathy syndrome develops. Monitor proteinuria by urine dipstick and/or urinary protein creatinine ratio. Monitor thyroid function. Pregnancy: avoid. Use effective contraception during therapy and for ≥3 months after last ramucirumab dose. Nursing mothers: not recommended.

Adverse reactions: Hypertension, diarrhea, headache, fatigue, asthenia, hyponatremia, anemia, intestinal obstruction, neutropenia, epistaxis, stomatitis/mucosal inflammation, rash, decreased appetite; arterial thromboembolic events, proteinuria, GI perforation, infusionrelated reactions.

How supplied: Single-dose vial (10mL, 50mL)—1

Human IgG1 monoclonal antibody. Ramucirumab 10mg/mL; per vial; soln for IV infusion after dilution; preservative-free.

Indications: In combination with docetaxel, for treatment of metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDAapproved therapy for these aberrations prior to initiation.

Adults: Give by IV infusion over 60 mins.

Premedicate with IV histamine H1-antagonist (eg, diphenhydramine) prior to each infusion; or with dexamethasone and acetaminophen in those who have experienced Grade 1 or 2 infusion reaction. 10mg/kg on Day 1 of a 21-day cycle prior to docetaxel; continue until disease progression

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 have not been established in patients whose tumors have other EGFR mutations.

Treatment of patients with metastatic squamous NSCLC progressing after platinum-based chemotherapy.

Adults: Take on an empty stomach at least 1 hr before or 2 hrs after a meal. 40mg once daily until disease progression or not tolerated. Severe renal

CYRAMZA Lilly

GILOTRIF Boehringer Ingelheim

℞

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DRUG MONOGRAPHS

LUNG CANCER impairment (CrCl 15–29mL/min): 30mg once daily. Concomitant P-gp inhibitors: reduce afatinib daily dose by 10mg if not tolerated; resume previous dose after discontinuing the inhibitor.

Concomitant P-gp inducers: increase afatinib daily dose by 10mg as tolerated; resume previous dose 2–3 days after discontinuing the 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 (ILD), severe druginduced hepatic impairment, persistent ulcerative keratitis, symptomatic left ventricular dysfunction, or severe/intolerable adverse reactions (at dose 20mg/day). Withhold for severe or prolonged diarrhea Grade ≥2 lasting for ≥2 consecutive days while taking antidiarrheal, prolonged cutaneous reaction Grade ≥2 (lasting >7 days) or intolerable, during evaluation of suspected ILD, renal dysfunction Grade ≥2, or worsening liver function. History of keratitis, ulcerative keratitis, or severe dry eye. Obtain LFTs periodically during treatment. Monitor closely in moderate-to-severe renal impairment or severe hepatic impairment; adjust dose if not tolerated.

Embryo-fetal toxicity. Pregnancy (avoid). Females of reproductive potential should use effective contraception during therapy and for at least 2 weeks after final dose. Nursing mothers: not recommended (during therapy and for 2 weeks after final dose).

Interactions: Potentiated by P-gp inhibitors (eg, ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, amiodarone).

Antagonized by P-gp inducers (eg, rifampicin, carbamazepine, phenytoin, phenobarbital, St. John’s wort).

Adverse reactions: Diarrhea, rash/dermatitis acneiform, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, pruritus; bullous/exfoliative skin disorders, ILD, hepatotoxicity, keratitis.

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: Verify dose using BSA. Usual max dose 4mg IV. Confirm baseline neutrophils ≥1,500cells/mm3 and platelets ≥100,000cells/mm3 prior to 1st course of therapy.

Give by IV infusion over 30 mins. 1.5mg/m2 daily for 5 consecutive days starting on Day 1 of a 21-day cycle. Dose adjustments, renal impairment: see full labeling.

Children: Not established. ℞ 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 full labeling.

Children: Not established.

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. Use effective contraception during and for ≥1 month after last dose (in females), or during and for ≥3 months (in males with female partners). Pregnancy (Cat.D). Nursing mothers: not recommended.

Interactions: IV: Myelosuppression potentiated with platinum agents. Neutropenia potentiated by G-CSF; administer ≥24hrs after last topotecan dose. Caps: Avoid concomitant P-glycoprotein inhibitors (eg, amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir, ritonavir, quercetin, quinidine, ranolazine, ticagrelor, verapamil) and BCRP inhibitors (eg, cyclosporine, eltrombopag).

Adverse reactions: See full labeling.

Neutropenia, leukopenia, thrombocytopenia, anemia, nausea, vomiting, diarrhea, 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; Caps—10

IRESSA AstraZeneca

℞

Tyrosine kinase inhibitor. Gefitinib 250mg; tabs.

Indications: First-line treatment of metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

Limitations of use: not established in metastatic NSCLC with EGFR mutations other than exon 19 deletions or exon 21 substitution mutations.

Adults: May disperse tabs in water; drink immediately or give via NG tube. Give 250mg once daily until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions: see full labeling.

Concomitant strong CYP3A4 inducers: increase

to 500mg daily; resume at 250mg seven days after discontinuation of the CYP3A4 inducer.

Children: Not established.

Warnings/Precautions: Permanently discontinue if confirmed interstitial lung disease (ILD), severe hepatic impairment, GI perforation, or persistent ulcerative keratitis occurs. Withhold for up to 14 days if acute onset or worsening pulmonary symptoms, NCI CTCAE Grade ≥2 ALT and/or AST elevations, Grade ≥3 diarrhea or skin reactions, or severe or worsening ocular disorders (including keratitis) occurs. Interrupt or discontinue therapy if severe bullous and exfoliative skin disorders develop. Obtain periodic LFTs. Moderate and severe hepatic impairment; monitor. Use effective contraception during treatment and for at least 2 weeks after completion. Pregnancy, nursing mothers: not recommended.

Interactions: Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole); monitor. Antagonized by strong CYP3A4 inducers (eg, rifampicin, phenytoin, tricyclics); see Adults. May be antagonized by drugs that increase gastric pH (eg, H2-blockers, antacids); take gefitinib 6 hours after or 6 hours before an H2-blocker or antacid. Avoid concomitant PPIs; if necessary, take gefitinib 12 hours after last dose or 12 hours before next PPI dose. May potentiate warfarin; monitor INR. Adverse reactions: Skin reactions, diarrhea, vomiting, decreased appetite, stomatitis; ILD, hepatotoxicity, GI perforation, ocular disorders.

Testing considerations: EGFR mutation analysis.

How supplied: Tabs—30

KEYTRUDA Merck

℞

Human programmed death receptor-1 (PD-1)-blocking antibody. Pembrolizumab 50mg/vial; lyophilized pwd for IV infusion after reconstitution; 25mg/mL; per vial; soln for IV infusion after dilution; both: preservative-free.

Indications: First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥50%)] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

Treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinumcontaining chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda.

First-line treatment of patients with metastatic nonsquamous NSCLC, in combination with pemetrexed and carboplatin.

Adults: Give as IV infusion over 30mins.

200mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In

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DRUG MONOGRAPHS

LUNG CANCER combination with pemetrexed/carboplatin: give prior to chemotherapy when given on the same day (see full labeling). Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.

Children: Not established.

Warnings/Precautions: Monitor for pneumonitis; withhold dose if Grade 2 pneumonitis; permanently discontinue if Grade 3 or 4, or recurrent Grade 2 develops. Monitor for colitis; withhold dose if Grade 2 or 3 colitis; permanently discontinue if Grade 4 develops.

Monitor for changes in liver function; withhold dose or discontinue based on severity of elevated liver enzymes. Monitor for changes in renal function; withhold dose if Grade 2 nephritis; permanently discontinue if Grade 3 or 4 develops.

Monitor for hypophysitis; withhold dose if Grade 2 hypophysitis; withhold or discontinue if Grade 3 or 4 develops. Monitor for changes in thyroid function (at treatment initiation, during, and as clinically indicated) and signs/symptoms of thyroid disorders; withhold or discontinue if Grade 3 or 4 hyperthyroidism develops.

Monitor for hyperglycemia and other diabetes symptoms; withhold if severe hyperglycemia until controlled. Withhold dose if Grade 4 hematological toxicity in cHL patients develops.

Permanently discontinue if any severe or Grade 3 immune-mediated adverse reaction recurs, for any life-threatening immune-mediated adverse reaction (except endocrinopathies controlled with hormone replacement or hematological toxicity in cHL patients), persistent Grade 2 or 3 reactions that do not recover to Grade 0–1 within 12wks after last dose, or inability to reduce corticosteroid dose to ≤10mg/day of prednisone or equivalent within 12wks. Monitor for infusionrelated reactions; permanently discontinue if Grade 3 or 4 develops. Complications of allogeneic HSCT after Keytruda: monitor for hepatic VOD, Grade 3 or 4 acute GVHD, steroidrequiring febrile syndrome, and others. Embryofetal toxicity. Females of reproductive potential should use highly effective contraception during therapy and for 4 months after the final dose. Pregnancy: avoid. Nursing mothers: not recommended (during therapy and for 4 months after the final dose).

Adverse reactions: Fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, nausea; immune-mediated disorders, infusionrelated reactions.

How supplied: Single-use vial 50mg—1; Singleuse vial 25mg/mL—1

MUSTARGEN Recordati

℞

Alkylating agent. 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

OPDIVO Bristol-Myers Squibb

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol.

Indications: Metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

Adults: Give as IV infusion over 60mins. 240mg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling.

Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed

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DRUG MONOGRAPHS

LUNG CANCER SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderateto-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or lifethreatening. Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism.

Monitor for transplant-related complications (eg, hyperacute or Grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic venoocclusive disease) and treat promptly. Moderate or severe hepatic impairment: not studied.

Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥5 months after final dose.

Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended.

Adverse reactions: Fatigue, musculoskeletal pain, decreased appetite, cough, constipation; immune-mediated reactions (may be fatal).

How supplied: Single-use vial (4mL, 10mL)—1

PORTRAZZA Lilly

℞

Human epidermal growth factor receptor (EGFR) inhibitor. Necitumumab 800mg/50mL; soln for IV infusion after dilution; preservative-free.

Indications: In combination with gemcitabine and cisplatin, for first-line treatment of metastatic squamous non-small cell lung cancer. Limitations of use: not for treatment of non-squamous nonsmall cell lung cancer.

Adults: Give by IV infusion over 60 mins prior to gemcitabine and cisplatin infusion. 800mg on Days 1 and 8 of each 3-week cycle; continue until disease progression or unacceptable toxicity.

May premedicate with diphenhydramine HCl (or equivalent) if previously experienced a Grade 1/2 infusion-related reaction. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of cardiopulmonary arrest and/or sudden death, hypomagnesemia. History of coronary artery disease, CHF, or arrhythmias. Monitor serum electrolytes (eg, magnesium, potassium, calcium) prior to each infusion during therapy and for 8 weeks after last dose; withhold for Grade 3/4 electrolyte abnormalities and may resume once improved to Grade ≤2. Discontinue if serious or life-threatening venous/arterial thromboembolic

events or infusion-related reactions occur.

Discontinue if Grade 4 skin reactions or Grade 3 skin induration/fibrosis occurs. Limit sun exposure. Embryo-fetal toxicity. Pregnancy; avoid.

Use effective contraception during treatment and for 3 months after last dose. Nursing mothers: not recommended (during therapy and for 3 months after last dose).

Adverse reactions: Rash, dermatitis acneiform, vomiting, diarrhea, thromboembolic events, hypomagnesemia, hypocalcemia, hypokalemia; cardiopulmonary arrest, dermatologic toxicities, infusion reactions.

How supplied: Single-use vial—1 ℞

partners of reproductive potential) should use effective contraception during and for 4 months after final dose. Pregnancy. Nursing mothers: not recommended (during and for 2 weeks after final dose).

Interactions: Antagonized by strong CYP3A inducers (eg, phenytoin, rifampin, carbamazepine, St. John’s Wort); avoid; if use is unavoidable, increase Tagrisso dose (see Adults).

Potentiates BCRP substrates (eg, rosuvastatin, sulfasalazine, topotecan); monitor closely for related toxicity.

Adverse reactions: Diarrhea, rash, dry skin, nail toxicity, fatigue, lab abnormalities; possibly infertility.

How supplied: Tabs—30

Kinase inhibitor. Osimertinib 40mg, 80mg; tabs.

Indications: Treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDAapproved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy.

Adults: 80mg once daily until disease progression or unacceptable toxicity. If swallowing difficulty, may disperse tab in 2oz (60mL) of non-carbonated water only; stir and swallow immediately, then rinse container with 4–8oz water and drink immediately; or if administration via NG tube is required, disperse tab in 15mL of non-carbonated water and use an additional 15mL of water to transfer any residues to the syringe; give resulting 30mL via NG tube as instructed with appropriate water flushes (~30mL). Concomitant strong CYP3A4 inducers (if use is unavoidable): increase dose to 160mg daily; resume at 80mg 3 weeks after discontinuing CYP3A4 inducer. Dose modification: see full labeling.

Children: Not established.

Warnings/Precautions: Confirm presence of T790M mutation prior to treatment initiation.

Permanently discontinue if interstitial lung disease (ILD)/pneumonitis is confirmed; QTc interval prolongation with signs/symptoms of life-threatening arrhythmia; symptomatic CHF or persistent, asymptomatic LV dysfunction that does not resolve within 4 weeks; or if no improvement within 3 weeks. Withhold dose if worsening respiratory symptoms indicative of ILD occur; if QTc interval >500msec on ≥2 separate ECGs; or adverse reactions of Grade ≥3 severity. Monitor ECGs and electrolytes periodically in patients with congenital long QTc syndrome, CHF, electrolyte abnormalities, or those who are taking drugs known to prolong the QTc interval. Conduct cardiac monitoring (including LVEF at baseline and during treatment in patients with cardiac risk factors).

Evaluate if signs/symptoms of keratitis occur.

ESRD. Severe hepatic impairment. Embryofetal toxicity. Females of reproductive potential should use effective contraception during and for 6 weeks after final dose; males (with female

Kinase inhibitor. Erlotinib (as HCl) 25mg, 100mg, 150mg; tabs.

Indications: Treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test receiving first-line, maintenance, or second or greater line treatment after progression following at least one prior chemotherapy regimen. Limitations of use: not established in patients with NSCLC whose tumors have other EGFR mutations.

Not recommended for use in combination with platinum-based chemotherapy.

Adults: Take on empty stomach. 150mg once daily. Use until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions: see full labeling. Concomitant strong CYP3A4 inhibitors (see Interactions): reduce by 50mg decrements; avoid use if possible.

Concomitant CYP3A4 inducers (see Interactions): increase by 50mg increments at 2-week intervals (max 450mg); avoid use if possible. Concurrent cigarette smoking: increase by 50mg increments at 2-week intervals (max 300mg); upon cessation, reduce to 150mg or 100mg daily.

Children: Not established.

Warnings/Precautions: Discontinue if interstitial lung disease, severe hepatic toxicity, GI perforation, severe bullous, blistering or exfoliating skin conditions, or corneal perforation or severe ulceration occurs. Withhold or consider discontinuing therapy if severe renal failure due to dehydration, or acute/worsening ocular disorders occur. Monitor LFTs periodically; withhold in patients without history of hepatic impairment for total bilirubin >3XULN or transaminases >5XULN, or in patients with history of hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases over baseline. Discontinue if abnormal LFTs do not improve or resolve within 3 weeks. Withhold for acute onset of unexplained pulmonary symptoms pending evaluation, persistent severe diarrhea unresponsive to loperamide, severe rash, grade 3–4 keratitis or grade 2 lasting ≥2 weeks.

TAGRISSO AstraZeneca

TARCEVA Astellas and Genentech

℞

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DRUG MONOGRAPHS

LUNG CANCER Monitor renal function, serum electrolytes, pulmonary function, INR, prothrombin time.

History of peptic ulcers or diverticular disease.

Embryo-fetal toxicity. Pregnancy: avoid. Females of reproductive potential should use effective contraception during therapy and at least 1 month after the last dose. Nursing mothers: not recommended (during and for 2 weeks after the last dose).

Interactions: Potentiated by CYP3A4 inhibitors (eg, atazanavir, boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit) or a combined CYP3A4 and CYP1A2 inhibitor (eg, ciprofloxacin); reduce dose if unavoidable.

Plasma levels decreased by CYP3A4 inducers (eg, rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, St. John’s wort); increase dose if unavoidable. Avoid concomitant moderate CYP1A2 inducers (eg, teriflunomide, rifampin, phenytoin) or smoking tobacco; increase dose if unavoidable. Avoid concomitant proton pump inhibitors if possible. Separate dosing of antacids by several hours or for H2 blockers (take erlotinib 10hrs after and at least 2hrs before next dose). 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, nausea, vomiting, 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 with thrombocytopenia, cerebrovascular accident (in pancreatic cancer), 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

TECENTRIQ Genentech Programmed death-ligand 1 (PD-L1) blocking antibody. Atezolizumab 60mg/mL; soln for IV infusion after dilution; preservative-free.

Indications: Metastatic non-small cell lung cancer (NSCLC) in patients with disease

progression during or after platinum-containing chemotherapy.

Adults: Give as IV infusion over 60mins. 1200mg every 3 weeks until disease progression or unacceptable toxicity. May give subsequent infusions over 30mins if first infusion tolerated.

Children: Not established.

Warnings/Precautions: Permanently discontinue if Grade 3/4 pneumonitis, AST or ALT >5×ULN or total bilirubin >3×ULN, Grade 4 diarrhea or colitis, Grade 4 hypophysitis, myasthenic syndrome/myasthenia gravis, Guillain-Barre or meningoencephalitis, Grade 3/4 ocular inflammatory toxicity, Grade 4 or recurrent pancreatitis, Grade 3/4 infusionrelated reactions, or Grade 4 rash. Withhold for Grade 2 pneumonitis, AST or ALT >3–5×ULN or total bilirubin >1.5–3×ULN, Grade 2/3 diarrhea or colitis, symptomatic hypophysitis, adrenal insufficiency, hypothyroidism, hyperthyroidism, Grade 3/4 hyperglycemia, Grade 2 ocular inflammatory toxicity, Grade 2/3 pancreatitis or Grade 3/4 increases in amylase or lipase levels (>2×ULN), Grade 3/4 infection, Grade 2 infusionrelated reactions, or Grade 3 rash; may be resumed when recover to Grade 0–1. Monitor for immune-related pneumonitis, hepatitis (obtain AST, ALT, bilirubin prior to and during treatment), diarrhea/colitis, endocrinopathies (hypophysitis, thyroid function, adrenal insufficiency, diabetes), meningitis or encephalitis, motor and sensory neuropathy, and acute pancreatitis; see full labeling for adverse reaction management details. Monitor for signs/symptoms of infection and treat with antibiotics for suspected or confirmed bacterial infections. Interrupt or slow the infusion rate in patients with mild or moderate infusion reactions. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity.

Pregnancy. Use effective contraception during and for ≥5 months after final dose. Nursing mothers: not recommended (during and for ≥5 months after final dose).

Adverse reactions: Fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, constipation; immune-related reactions, lab abnormalities.

How supplied: Single-dose vial (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: Lung cancer (squamous cell and small cell types).

Adults: See literature.

Children: Not established.

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: Tabs—30; soln (2mL, 4mL, 8mL, 10mL)—10 (single-use vials); pwd (1 gram)—1 (single-use vial)

Visit OncologyNurseAdvisor.com for practical clinical information geared toward oncology nurses and other cancer care professionals.

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DRUG MONOGRAPHS

LUNG CANCER 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. Treatment of metastatic NSCLC that is ROS1-positive.

Adults: Confirm ALK-positive NSCLC with an FDA-approved test before treating. 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: Monitor ALT, AST 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, or those who are taking drugs known to prolong the 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. Discontinue if onset of severe visual loss; perform eye evaluation. Hepatic impairment. Severe renal impairment. Embryo-fetal toxicity. Pregnancy; avoid. Use effective contraception during therapy and for at least 45 days (females) or 90 days (males) after final dose. Nursing mothers: not recommended (during therapy and for 45 days after final dose).

Interactions: Avoid concomitant strong CYP3A inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, 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); if needed, reduce doses. Avoid concomitant agents known to

cause bradycardia (eg, beta-blockers, nondihydropyridine calcium channel blockers, clonidine, digoxin); adjust dose or discontinue.

Caution with moderate CYP3A inhibitors. Dose reduction may be needed with coadministered drugs metabolized by CYP3A. Adverse reactions: Vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper RTI, dizziness, neuropathy, neutropenia; hepatotoxicity (may be fatal), pneumonitis (may be fatal), QT prolongation, bradycardia.

How supplied: Caps—60

ZYKADIA Novartis

℞

Tyrosine kinase inhibitor. Ceritinib 150mg; hard gel caps.

Indications: Treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

Adults: Take on an empty stomach (at least 1hr before or 2hrs after a meal). 750mg once daily until disease progression or unacceptable toxicity. Discontinue if 300mg once daily not tolerated. Dose modifications: see full labeling.

If concomitant use of strong CYP3A4 inhibitors unavoidable: reduce ceritinib dose by 1/3.

Children: Not established.

Warnings/Precautions: Monitor for severe or persistent GI toxicity; if occurs, withhold until improved; resume at reduced dose.

Monitor ALT/AST and total bilirubin once monthly, and more frequently if elevated transaminases develop; withhold then reduce dose, or permanently discontinue as clinically indicated. Congenital long QT syndrome; avoid.

Patients with CHF, bradyarrhythmias, electrolyte abnormalities, or those who are taking drugs known to prolong the QTc interval; monitor ECG, electrolytes periodically. Permanently discontinue if QTc prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or serious arrhythmia develop. Monitor HR and BP regularly; fasting serum glucose, lipase, amylase prior to initiation and periodically thereafter. Monitor for pulmonary symptoms as clinically indicated.

Permanently discontinue if treatment-related interstitial lung disease (ILD)/pneumonitis, uncontrolled hyperglycemia, or life-threatening bradycardia occur. Moderate-to-severe hepatic impairment: not established. Embryo-fetal toxicity. Pregnancy. Use effective contraception during treatment and for 6 months (females) or 3 months (males) after completion. Nursing mothers: not recommended (during and for 2 weeks after completion).

Interactions: See Adults. Potentiated by strong CYP3A4 inhibitors (eg, ritonavir, macrolides, ketoconazole, nefazodone), grapefruit juice; avoid.

Avoid concomitant strong CYP3A4 inducers (eg,

carbamazepine, phenytoin, rifampin, St. John’s Wort). Avoid concomitant CYP3A substrates (eg, alfentanil, cyclosporine, ergots, fentanyl, pimozide, quinidine, sirolimus, tacrolimus) or CYP2C9 substrates with narrow therapeutic indices (eg, phenytoin, warfarin); if unavoidable, reduce doses of these drugs. Avoid concomitant agents known to cause bradycardia (eg, beta-blockers, nondihydropyridine CCBs, clonidine, digoxin).

Adverse reactions: Diarrhea, nausea, fatigue, vomiting, abdominal pain, decreased appetite, weight loss; hepatotoxicity, ILD/pneumonitis, QT prolongation, hyperglycemia, bradycardia, pancreatitis.

How supplied: Caps—70

SEE LITERATURE Consult the manufacturer’s labeling for full prescribing information.

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.

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.

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

HYPERSENSITIVITY to

a drug or its class is assumed to be a contraindication in all product monographs, although not explicitly stated.

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DRUG MONOGRAPHS

SARCOMA 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 longterm 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

Indications: AIDS-related Kaposi’s sarcoma.

Adults: Use appropriate preparation and route: see full labeling. Use SC route if platelets <50,000/mm3. 30 million IU/m2 IM or SC three times weekly; continue until rapid disease progression or maximal response achieved after 16 weeks; reduce dose by ½ or suspend therapy if severe adverse reactions occur; discontinue if persists.

Children: Not recommended.

Contraindications: Decompensated liver disease. Autoimmune hepatitis.

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; discontinue if neutrophil count <0.5 X109/L or platelets 25X109/L. Permanently discontinue if severe (Grade 3) hepatic injury or decompensation (Child-Pugh score >6 [Class B and C]) develop.

Thyroid abnormalities; discontinue if uncontrolled by medication. 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, dental and periodontal disorders; others (see full labeling).

How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial—1; Soln (multidose vials): 18million, 25million IU/vial—1

INTRON A Merck

PANRETIN Eisai

DOXIL Janssen Biotech

℞

℞

Alpha interferon. Interferon alfa-2b, recombinant; 10 million, 18 million, or 50 million IU per vial; pwd; for inj after reconstitution/dilution; preservativefree; contains albumin. ℞ Also: INTRON A SOLN Interferon alfa-2b, recombinant; 10 million IU, 18 million IU, 25 million IU; per vial; for inj; contains m-cresol.

℞

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

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.

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.

Access Cancer Therapy Advisor treatment regimens in a user-friendly format.

CancerTherapyAdvisor.com/TreatmentRegimens.

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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 health care 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 Metastatic or Unresectable Melanoma1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

First-line Immunotherapy Regimens Nivolumab (Category 1)2,3abcd

Nivolumab 3mg/kg IV every 2 weeks.

Nivolumab + ipilimumab4,5abcdef

Day 1: Nivolumab 1mg/kg followed by ipilimumab 3mg/kg IV every 3 weeks for 4 cycles; then, nivolumab 3mg/kg every 2 weeks.

Pembrolizumab6-9acd

Pembrolizumab 2mg/kg IV every 3 weeks.

First-line Targeted Therapy for BRAF-mutant Melanoma Preferred Regimens Dabrafenib + trametinib (Category 1)10-13ghi

Dabrafenib 150mg orally twice daily + trametinib 2mg/day orally.

Vemurafenib + cobimetinib (Category 1)14-16ghij

Vemurafenib 960mg orally twice daily on days 1–28 + cobimetinib 60mg/day orally on days 1–21.

Repeat cycle every 28 days.

Other Active Regimens Vemurafenib (Category 1)17,18ghi

Vemurafenib 960mg orally twice daily.

Dabrafenib (Category 1)19,20ghi

Dabrafenib 150mg orally twice daily.

Second-line or Subsequent Therapy (PS 0-2) k Pembrolizumab6-9acdl

Pembrolizumab 2mg/kg IV every 3 weeks.

Nivolumab2,3abcd

Nivolumab 3mg/kg IV every 2 weeks.

Nivolumab + ipilimumab4,5abcdefl

Day 1: Nivolumab 1mg/kg followed by ipilimumab 3mg/kg IV every 3 weeks for 4 cycles; then, nivolumab 3mg/kg every 2 weeks.

Ipilimumab (Category 1)21-24cdelm

Day 1: Ipilimumab 3mg/kg IV. Repeat cycle every 3 weeks for 4 cycles.

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.

25-28no

Dacarbazine29

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.

Temozolomide30

Days 1–5: Temozolomide 200mg/m2/day orally for 5 days.

Repeat cycle every 4 weeks.

Paclitaxel31

Paclitaxel 250mg/m2 continuous IV infusion for 24 hours.

Repeat cycle every 21 days.

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CANCER TREATMENT REGIMEN

SKIN CANCER Systemic Therapy Options for Metastatic or Unresectable Melanoma1 (continued) REGIMEN

DOSING

Second-line or Subsequent Therapy (PS 0-2) k (continued) Albumin-bound paclitaxel32,33

Nab-paclitaxel 100mg/m2 (in previously treated patients) or 150mg/m2 (in chemotherapy-naive patients) IV. Repeat every week for 3–4 cycles.

Carboplatin + paclitaxel34-37

Days 1, 8, and 15: Paclitaxel 100mg/m2 IV + carboplatin AUC 2mg min/mL IV. Repeat cycle every 4 weeks until disease progression

Biochemotherapy for metastatic disease (Category 2B)38-42o

Dacarbazine or temozolomide, + cisplatin or carboplatin, ± vinblastine or nitrosourea, + IL-2 + IFN-alpha-2b

Biochemotherapy for adjuvant treatment of high-risk disease (Category 2B)43o

Dacarbazine, cisplatin, vinblastine, IL-2, and interferon alfa-2b

Imatinib44,45p

Imatinib 400mg orally twice daily.

Second-line or Subsequent Therapy for BRAF-mutant Melanoma (PS 0-2) Preferred Regimens Dabrafenib + trametinib10-13ghi

Dabrafenib 150mg orally twice daily + trametinib 2mg/day orally.

Vemurafenib + cobimetinib

Vemurafenib 960mg orally twice daily on days 1–28 + cobimetinib 60mg/day orally on days 1–21.

Repeat cycle every 28 days.

14-16ghij

Other Active Regimens Vemurafenib17,18ghi

Vemurafenib 960mg orally twice daily.

Dabrafenib19,20ghi

Dabrafenib 150mg orally twice daily.

a Nivolumab or pembrolizumab may cause immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, hypophysitis, nephritis, and hyperthyroidism.

For moderate to severe immune-mediated toxicities, discontinue therapy and administer systemic steroids. b Clinically significant (grade 3 and 4) immune-related adverse events are seen more commonly with nivolumab/ipilimumab combination therapy compared with iplimumab or nivolumab monotherapy. This emphasizes the need for careful patient education, selection, and monitoring. c Immune-mediated dermatitis sometimes responds to topical corticosteroids. For patients who do not respond, consider referral to a dermatologist or provider experienced in diagnosing and management cutaneous manifestations of immunotherapy. d Infliximab 5 mg/kg is preferred for treatment of severe immune- related colitis that does not resolve with high-dose steroids. A single dose of infliximab is sufficient to resolve immune-related colitis in most patients. e Ipilimumab has the potential for significant immune-mediated complications. Although no longer required by the FDA, the Risk Evaluation and Mitigation Strategy program and/or experience in use of the drug as well as resources to follow the patient closely are essential for safe use of ipilimumab. It should be used with extreme caution, if at all, in patients with underlying immune disorders. f Nivolumab/ipilimumab combination therapy was associated with better relapse-free survival than either agent used alone in a phase 3 trial, but the combination significantly increased toxicity. The combination’s effect on overall survival (OS) is undetermined. g 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. h Regular dermatologic evaluation and referral to a dermatologist or provider experienced in the diagnosis and management of cutaneous manifestations of targeted therapy is recommended. BRAF inhibitors are associated with cutaneous squamous cell carcinoma, extreme photosensitivity, and other dermatologic toxicities, which occur much less often with concurrent MEK inhibitors.

i Pyrexia (defined as a temperature of 38.5°C or greater) is a common (~55%) side effect of combining BRAF and MEK inhibitors and occurs less frequently with BRAF monotherapy (~20%). The pyrexia is episodic, and onset is often 2 to 4 weeks following the start of therapy with a median duration of 9 days. Pyrexia may be associated with chills, night sweats, rash, dehydration, electrolyte abnormalities, and hypotension. Stopping or holding dabrafenib and trametinib at the onset of pyrexia will often interrupt the episode, and treatment can be resumed with full-dose dabrafenib and trametinib upon cessation of pyrexia and pyrexia-related symptoms. Upon re-exposure to dabrafenib and trametinib, repeat pyrexia events can occur, but grade >3 events are uncommon (21%). In occasional instances of prolonged or severe pyrexia not responsive to discontinuation of dabrafenib and trametinib, low-dose steroids (prednisone 10 mg/day) can be used. Patients with pyrexia should be advised to use antipyretics as needed and increase fluid intake. j Vemurafenib/cobimetinib combination therapy was associated with better PFS and a better response rate than vemurafenib monotherapy in previously untreated patients with unresectable stage IIIC or stage IV disease. The combination’s effect on OS compared to single-agent vemurafenib is unknown. k Consider second-line agents that were not used in first-line therapy and that are not of the same class. l For patients with preexistent hypophysitis due to iplimumab, pembrolizumab may be administered if patients are on appropriate physiologic replacement endocrine therapy. m Ipilimumab reintroduction may be considered for select patients who did not experience significant systemic toxicity during prior ipilimumab therapy and who relapse after initial clinical response or have progression after stable disease > 3 months. n High-dose IL should not be used in patients with inadequate organ reserve, poor performance status, or untreated or active brain metastases. IL-2 may be considered for patients with small brain metastases and without significant peritumoral edema. o Administration of multiagent regimens and high-dose IL-2 is complex and associated with significant toxicities. Therapy should only be administered at an institution with medical staff experienced in the administration and management of these regimens. p For tumors with activating mutations of C-KIT.

continued

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CANCER TREATMENT REGIMEN

SKIN CANCER Melanoma Treatment Regimens References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Melanoma. v 1.2017. Available at: http://www.nccn.org/professionals/ physician_gls/pdf/melanoma.pdf. Accessed March 10, 2017.

2. Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16:375–384.

3. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–330.

4. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34.

5. Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372:2006–2017.

6. Ribas A, Puzanov I, Dummer R, et al. Pembrolizumab versus investigatorchoice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16:908–918.

7. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–2532.

8. Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384:1109–1117.

9. Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (Anti-PD-1) in Melanoma. N Eng J Med. 2013;369:134–144.

10. Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015; 386:444–451.

11. Robert C, Karaszewska B, Schachter J, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30–39.

12. Johnson DB, Flaherty KT, Weber JS, et al. Combined BRAF (Dabrafenib) and MEK inhibition (Trametinib) in patients with BRAF V600-mutant melanoma experiencing progression with single-agent BRAF inhibitor. J Clin Oncol. 2014;32:3697–3704.

13. Sanlorenzo M, Choudhry A, Vujic I, et al. Comparative profile of cutaneous adverse events: BRAF/MEK inhibitor combination therapy versus BRAF monotherapy in melanoma. J Am Acad Dermatol. 2014;71:1102–1109;e1101.

14. Larkin J, Ascierto PA, Dreno B, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371:1867–1876.

15. Ribas A, Gonzalez R, Pavlick A, et al. Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a phase 1b study.

Lancet Oncol. 2014;15:954–965.

16. Pavlick AC, Ribas A, Gonzalez R, et al. Extended follow-up results of phase Ib study (BRIM7) of vemurafenib (VEM) with cobimetinib (COBI) in BRAF-mutant melanoma.

J Clin Oncol. 2015;33:(suppl; abstr 9020).

17. 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.

18. McArthur GA, Chapman PB, Robert C, et al. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol. 2014;15:323–332.

19. Long GV, Trefzer U, Davies MA, et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAKMB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:1087–1095.

20. Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial.

Lancet. 2012;380: 358–365.

21. 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.

22. Weber JS, Kahler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30:2691–2697.

23. Hodi FS, O’Day SJ, McDermott DF, Weber RW, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Eng J Med. 2010;363:711–723.

24. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517–2526.

25. Rosenberg SA, Yang JC, Topalian SL, et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2.

J Am Med Assoc. 1994;271:907–913.

26. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17:2105–2116.

27. Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin2 therapy in patients with metastatic melanoma: long-term survival update.

Cancer J Sci Am. 2000;6 Suppl 1:S11–14.

28. 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: 5610–5618.

29. 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.

30. 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.

31. Wiernik PH, Einzig AI. Taxol in malignant melanoma. J Natl Cancer Inst Monogr.

1993;15:185–187.

32. Hersh EM, O’Day SJ, Ribas A, et al. A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma.

Cancer. 2010;116:155–163.

33. Kottschade LA, Suman VJ, Amatruda T, et al. A phase II trial of nabpaclitaxel (ABI-007) and carboplatin in patients with unresectable stage IV melanoma: a North Central cancer treatment group study, N057E(1). Cancer. 2011;117:1704–1710.

34. 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.

35. Agarwala SS, Keilholz U, Hogg D, et al. Randomized phase III 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.

36. 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;27:2823–2830.

37. Flaherty KT, Lee SJ, Schuchter LM, et al. Final results of E2603: A double-blind, randomized phase III trial comparing carboplatin (C)/paclitaxel (P) with or without sorafenib (S) in metastatic melanoma. J Clin Oncol. 2010. 28:(suppl; abstr 8511).

38. Legha SS, Ring S, Eton O, 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.

39. 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.

40. O’Day SJ, Boasberg 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.

41. Ives NJ, Stowe RL, Lorigan P, Wheatley K. Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2,621 patients. J Clin Oncol. 2007;25:5426–5434.

42. Atkins MB, Hsu J, Lee S, et al. 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.

43. Flaherty LE, Othus M, Atkins MB, et al. Southwest Oncology Group S0008: a phase III trial of high-dose interferon alfa-2b versus cisplatin, vinblastine, and dacarbazine, plus interleukin-2 and interferon in patients with high-risk melanoma—an intergroup study of cancer and leukemia Group B, Children’s Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. J Clin Oncol. 2014;32:3771–3778.

44. Hodi FS, Corless CL, Giobbie-Hurder A, et al. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol. 2013;31:3182–3190.

45. Carvajal RD, Antonescu CR, Wolchok, JD, et al. KIT as a therapeutic target in metastatic melanoma. J Am Med Assoc. 2011;395:2327–2334.

(Revised 3/2017) © 2017 by Haymarket Media, Inc.

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DRUG MONOGRAPHS

SKIN CANCER BAVENCIO EMD Serono

℞

Programmed death-ligand 1 (PD-L1) blocking antibody. Avelumab 20mg/mL; soln for IV infusion after dilution; preservative-free; contains mannitol.

Indications: Treatment of metastatic Merkel cell carcinoma (MCC).

Adults: Premedicate with an antihistamine and acetaminophen prior to the first 4 infusions; then subsequent doses as clinically indicated. Give as IV infusion over 60mins. 10mg/kg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: <12yrs: not established.

Warnings/Precautions: See full labeling.

Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for Grade 3/4 pneumonitis or recurrent Grade 2 pneumonitis, Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis, AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, any life-threatening (Grade 4) or recurrent severe (Grade 3) immune-mediated adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2/3 immune-mediated adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2/3 diarrhea or colitis, Grade 3/4 adrenal insufficiency, Grade 3/4 thyroid disorders, Grade 3/4 hyperglycemia, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN; withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if Grade 1/2 infusion reactions occur; permanently discontinue if Grade 3/4. Monitor for abnormal liver tests, adrenal insufficiency, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥1 month after final dose. Pregnancy. Nursing mothers: not recommended (during and for ≥1 month after final dose).

Adverse reactions: Fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reactions, rash, decreased appetite, peripheral edema, UTI; other immune-mediated adverse reactions (may be fatal).

How supplied: Single-dose vial (10mL)—1

COTELLIC Genentech

℞

Kinase inhibitor. Cobimetinib 20mg; tabs.

Indications: In combination with vemurafenib for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations.

Adults: Confirm presence of BRAF V600E or V600K mutation prior to initiation. In combination with vemurafenib: 60mg once daily for first 21 days of each 28-day cycle until disease progression or unacceptable toxicity.

Concomitant CYP3A inhibitors: see Interactions.

Other dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Review full labeling for vemurafenib prior to initiation. Monitor for new malignancies (cutaneous and non-cutaneous); perform skin evaluations prior to initiation, every 2 months during therapy, and for 6 months after discontinuation. Monitor for signs/symptoms of bleeding; withhold if Grade 3 hemorrhagic events occur; resume at lower dose if improved to Grade 0/1 within 4 weeks; discontinue if no improvement. Risk of cardiomyopathy; assess LVEF prior to initiation, after 1 month, and then every 3 months thereafter until discontinuation.

Patients with baseline LVEF below institutional lower limit of normal or <50%: not established.

Interrupt, reduce dose, or discontinue if severe skin reactions occur. Perform eye exams at regular intervals and for any visual disturbances.

Manage serous retinopathy with treatment interruption, dose reduction, or discontinuation.

Permanently discontinue if retinal vein occlusion occurs. Monitor liver tests prior to initiation, monthly during treatment, or more frequently as indicated; dose interruption, reduction, or discontinuation if Grade 3/4 abnormalities occur.

Obtain baseline CPK and creatinine levels prior to initiation, periodically during treatment, and as clinically indicated for signs/symptoms of rhabdomyolysis. Avoid sun exposure. Severe renal impairment. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during therapy and for 2 weeks after final dose. Pregnancy. Nursing mothers: not recommended (during therapy and for 2 weeks after final dose).

Interactions: Avoid concomitant strong or moderate CYP3A inhibitors (eg, itraconazole, erythromycin, ciprofloxacin). If short-term (≤14 days) use of moderate CYP3A inhibitors is unavoidable for patients taking cobimetinib 60mg, reduce to 20mg and resume at previous dose upon discontinuing the CYP3A inhibitor; for patients taking cobimetinib 20mg or 40mg,

use alternative. Avoid concomitant strong or moderate CYP3A inducers (eg, carbamazepine, efavirenz, phenytoin, rifampin, St. John’s wort).

Adverse reactions: Diarrhea, photosensitivity, nausea, pyrexia, vomiting, increased GGT, CPK, ALT/AST and alkaline phosphatase, hypophosphatemia, lymphopenia, hyponatremia.

How supplied: Tabs—63

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 within 7 days prior to initiation of therapy. Females of reproductive potential should use effective contraception during therapy and for 24 months after final dose; male patients should use condoms (even after a vasectomy) during and for 3 months after final

Take advantage of our free online medical calculators at CancerTherapyAdvisor.com/MedicalCalculators.

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DRUG MONOGRAPHS

SKIN CANCER dose. Advise patients not to donate blood or blood products during therapy and for 24 months after final dose. Advise male patients not to donate semen during and for 3 months after final dose.

Premature fusion of the epiphyses may occur in pediatrics if exposed. Pregnancy: avoid. Nursing mothers: not recommended (during and for 24 months after final dose).

Adverse reactions: Muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, vomiting, decreased appetite, constipation, arthralgias, ageusia; amenorrhea.

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; scored tabs.

Indications: Adults with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation as determined with an FDA-approved test 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 (determine D816V c-Kit mutation status prior to initiation): 400mg once daily. ASM associated with eosinophilia: initially 100mg once daily; may increase to 400mg once daily if insufficient response. DFSP: 400mg twice daily.

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. Avoid concomitant strong CYP3A4 inducers (eg, rifampin): if needed, 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 and potential toxicities (liver, kidney, cardiac) 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. Embryo-fetal toxicity. Pregnancy (avoid); exclude status prior to initiation. Females

of reproductive potential should use highly effective contraception during treatment and for 14 days after cessation. Nursing mothers: not recommended (during and for 1 month after final dose).

Interactions: Avoid grapefruit juice. Potentiated

by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by strong CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin, rifabutin, rifampicin); consider alternatives. May potentiate drugs metabolized

by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain statins, sirolimus, tacrolimus) or CYP2C9 (use heparin instead of warfarin). Caution with concomitant CYP2D6 substrates that have a narrow therapeutic window.

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

IMLYGIC Amgen

℞

Genetically modified oncolytic viral therapy.

Talimogene laherparepvec 106 (1 million) PFU/mL, 108 (100 million) PFU/mL; susp for intralesional inj; preservative-free.

Indications: Treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Limitations of use: not shown to improve overall survival or have an effect on visceral metastases.

Adults: See full labeling. Inject intralesionally into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound guidance. Total inj volume per treatment visit: max 4mL for all injected lesions combined. Initial dose: up to 4mL of 106 (1 million) PFU/mL. 2nd dose: up to 4mL of 108 (100 million) PFU/mL given 3 weeks later. All subsequent doses (including reinitiation): up to 4mL of 108 (100 million) PFU/mL given 2 weeks apart.

Continue for ≥6 months unless other treatment required or until no injectable lesions to treat; reinitiate if new lesions appear after a complete response.

Children: Not established.

Contraindications: Immunocompromised or pregnant patients.

Warnings/Precautions: For intralesional inj only. Avoid accidental exposure (esp. skin, eyes,

mucous membranes) and direct contact with patient’s injected lesions, dressings, or body fluids. Advise patients to avoid inadvertent transfer of drug to other areas of the body (eg, touching/scratching inj sites or occlusive dressings). Evaluate lesions if suspected herpetic infection occurs. Inj site complications (eg, necrosis or ulceration of tumor tissue, cellulitis, systemic bacterial infection).

Persistent infection or delayed healing of inj site. Underlying autoimmune disease. Multiple myeloma or plasmacytoma. Pregnancy. Women of childbearing potential should use effective method of contraception. Nursing mothers: not recommended.

Interactions: Acyclovir or other antiherpetic viral agents may interfere with efficacy.

Adverse reactions: Fatigue, chills, pyrexia, nausea, influenza-like illness, inj site pain; immune-mediated events.

Note: Report suspected herpetic lesions to Amgen at (855) 465-9442.

How supplied: Single-use vial (1mL)—1

INTRON A Merck

℞

Alpha interferon. Interferon alfa-2b, recombinant; 10 million, 18 million, or 50 million IU per vial; pwd; for inj after reconstitution/dilution; preservativefree; contains albumin. ℞ 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 full labeling for appropriate preparation and route and for dose adjustments.

Children: Not recommended.

Contraindications: Decompensated liver disease. Autoimmune hepatitis.

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; discontinue if neutrophil count <0.5 X109/L or platelets 25X109/L. Permanently discontinue if severe (Grade 3) hepatic injury or decompensation (Child-Pugh score >6 [Class B and C]) develop.

Thyroid abnormalities; discontinue if uncontrolled by medication. 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.

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DRUG MONOGRAPHS

SKIN CANCER 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, dental and periodontal disorders; others (see full labeling).

How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial—1; Soln (multidose vials): 18million, 25million IU/vial—1

KEYTRUDA Merck

℞

Human programmed death receptor-1 (PD-1)-blocking antibody. Pembrolizumab 50mg/vial; lyophilized pwd for IV infusion after reconstitution; 25mg/mL; per vial; soln for IV infusion after dilution; both: preservative-free.

Indications: Unresectable or metastatic melanoma.

Adults: Give as IV infusion over 30mins. 200mg every 3 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.

Children: Not established.

Warnings/Precautions: Monitor for pneumonitis; withhold dose if Grade 2 pneumonitis; permanently discontinue if Grade 3 or 4, or recurrent Grade 2 develops. Monitor for colitis; withhold dose if Grade 2 or 3 colitis; permanently discontinue if Grade 4 develops.

Monitor for changes in liver function; withhold dose or discontinue based on severity of elevated liver enzymes. Monitor for changes in renal function; withhold dose if Grade 2 nephritis; permanently discontinue if Grade 3 or 4 develops.

Monitor for hypophysitis; withhold dose if Grade 2 hypophysitis; withhold or discontinue if Grade 3 or 4 develops. Monitor for changes in thyroid function (at treatment initiation, during, and as clinically indicated) and signs/symptoms of thyroid disorders; withhold or discontinue if Grade 3 or 4 hyperthyroidism develops. Monitor for hyperglycemia and other diabetes symptoms; withhold if severe hyperglycemia until controlled.

Withhold dose if Grade 4 hematological toxicity in cHL patients develops. Permanently discontinue if any severe or Grade 3 immune-mediated adverse reaction recurs, for any life-threatening immune-mediated adverse reaction (except endocrinopathies controlled with hormone replacement or hematological toxicity in cHL patients), persistent Grade 2 or 3 reactions that

do not recover to Grade 0–1 within 12wks after last dose, or inability to reduce corticosteroid dose to ≤10mg/day of prednisone or equivalent within 12wks. Monitor for infusion-related reactions; permanently discontinue if Grade 3 or 4 develops. Complications of allogeneic HSCT after Keytruda: monitor for hepatic VOD, Grade 3 or 4 acute GVHD, steroid-requiring febrile syndrome, and others. Embryo-fetal toxicity.

Females of reproductive potential should use highly effective contraception during therapy and for 4 months after the final dose. Pregnancy: avoid. Nursing mothers: not recommended (during therapy and for 4 months after the final dose).

Adverse reactions: Fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, nausea; immune-mediated disorders, infusionrelated reactions.

How supplied: Single-use vial 50mg—1; Singleuse vial 25mg/mL—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. Monitor for colitis and GI perforations. Permanently discontinue if life-threatening pulmonary embolism occurs. 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. Embryo-fetal toxicity. Females of reproductive potential should use highly effective contraception during and for 4 months after treatment. Pregnancy. Nursing mothers: not recommended (during and for 4 months after final dose).

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, colitis, GI perforation, infertility.

How supplied: Tabs—30

ODOMZO Novartis

℞

Hedgehog pathway inhibitor. Sonidegib 200mg; caps.

Indications: Treatment of adults with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation, or those who are not candidates for surgery or radiation therapy.

Adults: Take on empty stomach. 200mg once daily until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Risk of embryofetal death or severe birth defects in pregnant women. Verify pregnancy status of females of reproductive potential prior to initiation. Advise females to use effective contraception during therapy and for at least 20 months after the last dose; male patients must use condoms and not to donate semen during therapy and for at least 8 months after last dose. Advise patients not to donate blood or blood products during therapy and for at least 20 months after last dose. Risk of musculoskeletal adverse reactions accompanied by serum creatine kinase (CK) elevations; temporarily interrupt or discontinue based on severity of reactions. Obtain baseline serum CK and creatinine (SCr) levels prior to initiation; periodically during treatment and as clinically indicated. Obtain serum CK and SCr levels at least weekly in those with musculoskeletal adverse reactions with concurrent serum CK elevation

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DRUG MONOGRAPHS

SKIN CANCER >2.5XULN until symptoms resolve. Pregnancy.

Nursing mothers: not recommended during therapy and for 20 months after last dose.

Interactions: Avoid concomitant strong CYP3A inhibitors (eg, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone) or moderate CYP3A inhibitors (eg, atazanavir, diltiazem, fluconazole); if moderate CYP3A inhibitor use necessary, administer for <14 days and monitor closely.

Avoid concomitant strong or moderate CYP3A inducers (eg, carbamazepine, efavirenz, modafinil, phenobarbital, phenytoin, rifabutin, rifampin, St. John’s Wort).

Adverse reactions: Muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, pruritus; anemia, hyperglycemia, increased SCr, CK, and LFTs. Note: To report exposure to Odomzo during pregnancy, call Novartis at (888) 669-6682.

How supplied: Caps—30

OPDIVO Bristol-Myers Squibb

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol.

Indications: As a single agent for patients with BRAF V600 wild-type or BRAF V600 mutation (+) unresectable or metastatic melanoma. In combination with ipilimumab for unresectable or metastatic melanoma.

Adults: Give as IV infusion over 60mins.

240mg every 2 weeks until disease progression or unacceptable toxicity. In combination with ipilimumab: 1mg/kg (followed by ipilimumab on the same day) every 3 weeks for 4 doses, then followed by 240mg every 2 weeks (as single agent) until disease progression or unacceptable toxicity. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: See full labeling.

Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade

2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderate-to-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or life-threatening.

Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Monitor for transplantrelated complications (eg, hyperacute or Grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease) and treat promptly. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥5 months after final dose. Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended.

Adverse reactions: Fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper RTI; also with Ipilimumab: pyrexia, vomiting; immune-mediated reactions (may be fatal).

How supplied: Single-use vial (4mL, 10mL)—1

PROLEUKIN Prometheus

℞

Interleukin-2, recombinant. Aldesleukin 22 million IU/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol; preservative-free.

Indications: Metastatic melanoma.

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

SYLATRON Merck

℞

Alpha interferon. Peginterferon alfa-2b 296mcg, 444mcg, 888mcg; per vial; lyophilized 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: Give by SC inj. Rotate inj sites.

Premedicate with acetaminophen. ≥18yrs: 6mcg/kg/week for 8 doses, followed by 3mcg/kg/week for up to 5yrs. Renal impairment (moderate): initially 4.5mcg/kg/week for 8 doses, followed by 2.25mcg/kg/week for up to 5yrs; (severe or ESRD on dialysis): initially 3mcg/kg/week for 8 doses, followed by 1.5mcg/kg/week for up to 5yrs. Withhold dose if ANC <0.5x109/L, platelets <50x109/L, ECOG PS ≥2, or for non-hematologic toxicity ≥ Grade 3.

Resume at reduced dose (see full labeling) when: ANC ≥0.5x109/L, platelets ≥50x109/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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DRUG MONOGRAPHS

SKIN CANCER Warnings/Precautions: Increased risk of serious depression, suicidal ideation, 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; Grade 4 non-hematologic toxicity; 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: Potentiates CYP1A2 (eg, caffeine) or CYP2D6 (eg, desipramine) substrates.

Concomitant drugs with narrow therapeutic range metabolized by CYP1A2 or CYP2D6; monitor for increased toxicities.

Adverse reactions: Fatigue, increased ALT/AST, pyrexia, headache, anorexia, myalgia, nausea, chills, inj site reactions; neuropsychiatric disorders.

How supplied: Single-use vial—1 (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 FDAapproved 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 nonhormonal 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, palmar-plantar 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. Adjuvant treatment of cutaneous melanoma in patients with pathologic involvement of regional lymph nodes >1mm who have undergone complete resection, including total lymphadenectomy.

Adults: Give by IV infusion over 90 mins.

Unresectable, metastatic: 3mg/kg every 3 weeks for a maximum of 4 doses; may delay doses if toxicity occurs, but all treatment must be given

within 16 weeks of the first dose. Adjuvant: 10mg/kg every 3 weeks for 4 doses, followed by 10mg/kg every 12 weeks for up to 3 years; may omit doses if toxicity occurs. Dose modifications: see full labeling.

Children: Not established.

Warnings/Precautions: Severe and fatal immune-mediated adverse reactions can develop. Permanently discontinue therapy and initiate systemic high-dose corticosteroids for severe, persistent, or recurring immunemediated reactions. Withhold dose for moderate immune-mediated adverse reactions until return to baseline, improvement to mild severity, or complete resolution, and patient is receiving <7.5mg prednisone or equivalent per day. Monitor for enterocolitis, hepatitis, dermatitis, neuropathy, endocrinopathy, and others including ocular manifestations; perform clinical chemistries including LFTs, ACTH levels, and thyroid tests at baseline and before each dose. Moderate or severe hepatic impairment. Pregnancy; avoid. Use effective contraception during therapy and for 3 months after final dose. Nursing mothers: not recommended (during therapy and for 3 months after final dose).

Adverse reactions: Fatigue, diarrhea, pruritus, rash, colitis, headache, weight loss, nausea, pyrexia, decreased appetite, vomiting, insomnia.

How supplied: Single-use vial (50mg, 200mg)—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

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DRUG MONOGRAPHS

SKIN CANCER ZELBORAF Genentech

HEMATOLOGICAL REFERENCE VALUES

℞

Kinase inhibitor. Vemurafenib 240mg; tabs.

Indications: Treatment of unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Limitation of use: not for treatment of wild-type BRAF melanoma.

Adults: Swallow whole. ≥18yrs: 960mg every 12hrs; until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions: see full labeling.

Children: <18yrs: not established.

Warnings/Precautions: Confirm BRAF V600E mutation-positive melanoma with FDA-approved test before initiating. Risk of cutaneous squamous cell carcinoma (cuSCC): ≥65yrs, prior skin cancer, chronic sun exposure; if occurs, do excision and evaluate. Perform dermatologic evaluation before therapy, every 2 months during, and consider monitoring 6 months after discontinuation. 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.

Prior to and following initiation or after dose adjustment for QTc prolongation, evaluate ECG and electrolytes after 15 days, monthly during the 1st 3 months, then every 3 months thereafter, or more as clinically indicated. Severe hepatic or renal impairment. Monitor liver enzymes, bilirubin before initiating and monthly during treatment, or as needed. Measure SCr before initiating and periodically during treatment.

Monitor for ophthalmologic reactions routinely.

Avoid sun exposure. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during therapy and for at least 2 weeks after final dose. Pregnancy. Nursing mothers: not recommended (during and for 2 weeks after final dose).

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. Avoid concomitant CYP1A2 (eg, tizanidine) and P-gp (eg, digoxin) substrates with narrow therapeutic indices; if unavoidable, consider dose reduction of substrates and monitor. Increased transaminase and bilirubin with concomitant ipilimumab. Concomitant or sequential administration with radiation treatment; monitor closely.

Adverse reactions: Arthralgia, rash, alopecia, fatigue, photosensitivity, nausea, pruritus, skin papilloma; severe hypersensitivity or dermatologic reactions (permanently discontinue if occur), QT prolongation, hepatotoxicity, uveitis, blurry vision, photophobia, other malignancies, radiation sensitization and recall, renal failure.

How supplied: Tabs—112, 120

Analyte

Reference value Conventional units SI units

Antithrombin III • Antigenic • Functional

22–39mg/dL 80–130%

220–390mg/L 0.8–1.30 U/L

Bleeding time

2.0–9.5min

2.0–9.5min

Erythrocyte count • Male • Female

4.50–5.90 × 106/mm3 4.00–5.20 × 106/mm3

4.50–5.90 × 1012/L 4.00–5.20 × 1012/L

Erythrocyte sedimentation rate • Male • Female

0–17mm/hr 1–25mm/hr

0–17mm/hr 1–25mm/hr

Ferritin • Male • Female

30–300ng/mL 10–200ng/mL

30–300μg/L 10–200μg/L

Fibrinogen

150–400mg/dL

1.50–4.00g/L

Folate (folic acid) • Normal • Borderline deficient • Deficient • Excess

3.1–17.5ng/mL 2.2–3.0ng/mL <2.2ng/mL >17.5ng/mL

7.0–39.7nmol/L 5.0–6.8nmol/L <5.0nmol/L >39.7nmol/L

Folic acid

150–450ng/mL/cells

340–1020nmol/L/cells

Hematocrit • Male • Female

41.0–53.0% 36.0–46.0%

0.41–0.53 0.36–0.46

Hemoglobin • Plasma • Whole blood, male • Whole blood, female

1–5mg/dL 13.5–17.5g/dL 12.0–16.0g/dL

0.01–0.05g/L 8.4–10.9mmol/L 7.4–9.9mmol/L

Hemoglobin electrophoresis • Hemoglobin A • Hemoglobin A1c • Hemoglobin A2 • Hemoglobin F • Hemoglobins other than A, A2, or F

95–98% 3.8–6.4% 1.5–3.5% 0–2.0% Absent

0.95–0.98 0.038–0.064Hg fraction 0.015–0.035 0–0.02 Absent

Iron (hematology and coagulation values)

30–160μg/dL

5.4–28.7μmol/L

Iron-binding capacity (hematology and coagulation values)

228–428μg/dL

40.8–76.7μmol/L

Iron (clinical chemistry values)

50–150μg/dL

9–27μmol/L

Iron-binding capacity (clinical chemistry values)

250–370μg/dL

45–66μmol/L

Leukocyte count (WBC)

4.5–11.0 × 103/mm3

4.5–11 × 109/L

Mean corpuscular hemoglobin (MCH)

26.0–34.0pg/cell

26.0–34.0pg/cell

Mean corpuscular hemoglobin concentration (MCHC)

31.0–37.0g/dL

310–370g/L

Mean corpuscular volume (MCV)

80–100μm3

80–100fl

Partial-thromboplastin time (activated)

22.1–35.1sec

22.1–35.1sec

Platelet count

150–350 × 103/mm3

150–350 × 109/L

Prothrombin time

11.1–13.1sec

11.1–13.1sec

Reticulocyte count

0.5–2.5% red cells

0.005–0.025 red cells

Transferrin

230–390mg/dL

2.3–3.9g/L

Vitamin B12 • Normal • Borderline • Deficient

>250pg/mL 125–250pg/mL <125pg/mL

>185pmol/L 92–185pmol/L <92pmol/L

References National Institutes of Health. Third report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). September 2002. Available at: www.nhlbi.

(Rev. 8/2012) nih.gov/guidelines/cholesterol/index.htm. Accessed August 2012.

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Brand name–bold type Generic name–light type Medical condition–red type *-product contains other active ingredients ext-external inj-injectable.

A

B

Abiraterone Zytiga 31 Abraxane (inj) cancer, breast 5 cancer, pancreatic 12 non-small cell lung cancer 76 Actinic keratoses 87 Adcetris (inj) 54 Ado-trastuzumab Kadcyla 8 Afatinib Gilotrif 77 Afinitor cancer, breast 5 cancer, renal 22 progressive neuroendocrine tumors of pancreatic origin (pnet) 12 progressive non-functional neuroendocrine tumors (net) of gastrointestinal or lung origin 12 subependymal giant cell astrocytoma (sega) 3 Aldesleukin Proleukin (inj) 28, 90 Alecensa 76 Alectinib Alecensa 76 Alemtuzumab Campath (inj) 56 Alimta (inj) 76 Alitretinoin Panretin (ext) 83 Altretamine Hexalen 32 Alunbrig 76 Anaplastic astrocytoma 3 Anastrozole Arimidex 5 Arimidex 5 Aromasin 5 Arranon 54 Arsenic trioxide Trisenox (inj) 72 Arzerra (inj) 54 Asparaginase Erwinia chrysanthemi Erwinaze (inj) 59 Atezolizumab Tecentriq (inj) 29, 81 Avastin (inj) cancer, cervical 3, 16, 22, 32, 77 cancer, colorectal 3, 16, 22, 32, 77 cancer, ovarian 3, 16, 32, 77 cancer, renal 3, 16, 22, 32, 77 glioblastoma 3, 16, 22, 32, 77 non-small cell lung cancer 3, 16, 22, 32, 77 Avelumab Bavencio (inj) 22, 87 Axitinib Inlyta 25 Azacitidine Vidaza (inj) 74

Basal cell carcinoma Bavencio (inj) cancer, bladder cancer, renal melanoma Beleodaq (inj) Belinostat Beleodaq (inj) Bendamustine Bendeka (inj) Treanda (inj) Bendeka (inj) Bevacizumab Avastin (inj) Bexarotene Targretin Targretin (ext) Bexxar Bicalutamide Casodex Blinatumomab Blincyto (inj) Blincyto (inj) Bone metastases Bortezomib Velcade (inj) Bosulif Bosutinib Bosulif Brentuximab vedotin Adcetris (inj) Brigatinib Alunbrig Busulfan Busulfex (inj) Myleran Busulfex (inj)

ALPHABETICAL INDEX 87, 89 22 22 87 54 54 55 71 55 3, 16, 22, 32, 77 69 70 55 23 56 56 2, 75 72 56 56 54 76 56 65 56

C Cabazitaxel Jevtana (inj) Cabometyx Cabozantinib Cabometyx Cometriq Campath (inj) Cancer, bladder Cancer, breast

Cancer, prostate Cancer, renal

6, 23–31 3, 16, 19, 22, 25–30, 32, 77, 81, 90 1–2 7, 13, 17 24 12–14, 19, 27

Cancer, sarcoma Cancer, stomach Cancer, testicular Cancer, thyroid Capecitabine Xeloda 11, 20 Caprelsa 12 Carfilzomib Kyprolis (inj) 64 Casodex 23 Ceritinib Zykadia 82 Cerubidine (inj) 57 Cetuximab Erbitux (inj) 16, 35 Chlorambucil Leukeran 64 Chorioadenoma destruens 1, 10, 33, 36, 71, 81 Choriocarcinoma, gestational 1, 10, 33, 36, 71, 81 Clofarabine Clolar (inj) 57 Clolar (inj) 57 Cobimetinib Cotellic 87 Colorectal cancer 17–18 Cometriq 13 Cotellic 87 Crizotinib Xalkori 82 Cyramza (inj) cancer, gi 16 cancer, lung 77 Cytarabine DepoCyt (inj) 58

D 25 22

22 13 56 22, 24–25, 29–30, 81 1, 5–11, 13, 17–18, 20, 24, 33, 36, 71, 81 Cancer, cervical 3, 16, 22, 32, 77–78 Cancer, colorectal 3, 7, 11, 13, 16–17, 19–22, 32, 35, 77 Cancer, GI 7, 16, 18 Cancer, head and neck 1, 4, 10, 16, 33, 35–36, 71, 81 Cancer, liver 19, 27 Cancer, lung 1, 10, 32–33, 36, 65, 71, 76–81 Cancer, ovarian 3, 16, 32–34, 58, 77–78, 83 Cancer, pancreatic 7, 12–15, 17, 20, 28, 80

Dabrafenib Tafinlar Dacogen (inj) Daratumumab Darzalex (inj) Darzalex (inj) Dasatinib Sprycel Daunorubicin Cerubidine (inj) Decitabine Dacogen (inj) Degarelix Firmagon (inj) Delatestryl Delestrogen (inj) Denileukin diftitox Ontak (inj) Denosumab Xgeva (inj)

91 57 58 58 69 57 57 24 6 23 66 2

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ALPHABETICAL INDEX DepoCyt (inj) 58 Dermatofibrosarcoma protuberans 17, 60, 88 Dinutuximab Unituxin (inj) 4 Doxil (inj) cancer, ovarian 32, 58, 83 kaposi’s sarcoma 32, 58, 83 multiple myeloma 32, 58, 83 Doxorubicin, liposomal Doxil (inj) 32, 58, 83 Durvalumab Imfinzi (inj) 24

E Efudex (ext) Eligard (inj) Elotuzumab Empliciti (inj) Eloxatin (inj) Emcyt Empliciti (inj) Enzalutamide Xtandi Erbitux (inj) cancer, colorectal cancer, head and neck Eribulin Halaven (inj) Erivedge Erlotinib Tarceva Erwinaze (inj) Erythema nodosum leprosum Estrace cancer, breast cancer, prostate Estradiol Estrace Estradiol valerate Delestrogen (inj) Estramustine Emcyt Estrogens, conjugated Premarin Estrogens, esterified Menest Everolimus Afinitor Evista Evomela (inj) Exemestane Aromasin

Fluorouracil Efudex (ext) Fluorouracil Fluorouracil cancer, breast cancer, colorectal cancer, pancreatic cancer, stomach Flutamide Fulvestrant Faslodex (inj) Fusilev (inj)

87 7, 13, 17 7, 13, 17 7, 13, 17 7, 13, 17 7, 13, 17 24 6 17

G 87 23 58 16 24 58 31 16, 35 16, 35 1, 7 87 15, 80 59 70 6, 24 6, 24 6, 24 23 24 9, 27 26 3, 5, 12, 22 6 59 5

F Farydak Faslodex (inj) Femara Firmagon (inj) Fludara (inj) Fludarabine Fludara (inj)

Brand name–bold type Generic name–light type Medical condition–red type *-product contains other active ingredients ext-external inj-injectable.

59 6 6 24 60 60

Gazyva (inj) 60 Gefitinib Iressa 78 GI stromal tumors 14, 17, 20, 28, 60, 88 Gilotrif 77 Gleevec dermatofibrosarcoma protuberans 17, 60, 88 gi stromal tumors 17, 60, 88 hypereosinophilic syndrome 17, 60, 88 leukemia, acute myeloid 17, 60, 88 leukemia, chronic eosinophilic 17, 60, 88 leukemia, chronic myelogenous 17, 60, 88 mastocytosis 17, 60, 88 myelodysplastic syndromes 17, 60, 88 Glioblastoma 3, 16, 22, 32, 77

H Halaven (inj) cancer, breast 7 cancer, sarcoma 1 Herceptin (inj) cancer, breast 7, 18 cancer, gi 7, 18 Hexalen 32 Histrelin Vantas 30 Hodgkin lymphoma 54, 63, 66 Hodgkin’s disease 65, 79 Hycamtin cancer, cervical 32, 78 cancer, lung 32, 78 cancer, ovarian 32, 78 Hydatidiform mole 1, 10, 33, 36, 71, 81 Hydrea cancer, head and neck 35 leukemia, chronic myeloid 61 Hydroxyurea Hydrea 35, 61 Hypercalcemia 75 Hypereosinophilic syndrome 17, 60, 88

I Ibrance Ibritumomab Zevalin (inj) Ibrutinib Imbruvica

Iclusig Idamycin (inj) Idarubicin Idamycin (inj) Idelalisib Zydelig Ifex (inj) Ifosfamide Ifex (inj) Imatinib Gleevec Imbruvica Imfinzi (inj) Imlygic (inj) Inlyta Interferon alfa-2b Intron A (inj) Intron A (inj) kaposi’s sarcoma leukemia, hairy cell lymphoma, follicular melanoma Iodine I 131 Tositumomab Bexxar* Ipilimumab Yervoy (inj) Iressa Irinotecan Onivyde (inj) Istodax Ixabepilone Ixempra (inj) Ixazomib Ninlaro Ixempra (inj)

61 62 62 75 24 24 17, 60, 88 62 24 88 25 62, 83, 88 62, 83, 88 62, 83, 88 62, 83, 88 62, 83, 88 55 91 78 14 63 8 65 8

J Jakafi Jevtana (inj)

63 25

K Kadcyla 8 Kaposi’s sarcoma 32, 58, 62, 83, 88 Keytruda (inj) cancer, bladder 25 cancer, head and neck 35 cancer, renal 25 colorectal cancer 18 hodgkin lymphoma 63 melanoma 89 non-small cell lung cancer 78 Kisqali 9 Kyprolis (inj) 64

L 8 74 62

Lanreotide Somatuline Depot (inj) Lapatinib Tykerb Lartruvo (inj)

14 11 1

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Brand name–bold type Generic name–light type Medical condition–red type *-product contains other active ingredients ext-external inj-injectable.

Lenalidomide Revlimid 67 Lenvatinib Lenvima 13, 26 Lenvima cancer, renal 26 cancer, thyroid 13 Letrozole Femara 6 Leucovorin 19 Leukemia 64–65, 79 Leukemia, acute lymphoblastic 56–57, 59, 61, 64, 66–67, 69, 74 Leukemia, acute lymphocytic 57, 67 Leukemia, acute myeloid 17, 60, 62, 68, 88 Leukemia, acute nonlymphocytic 57, 69 Leukemia, acute promyelocytic 72–73 Leukemia, B-cell chronic lymphocytic 56, 60 Leukemia, chronic eosinophilic 17, 60, 88 Leukemia, chronic lymphocytic 54–55, 60, 62, 68, 71, 73, 75 Leukemia, chronic myelogenous 17, 56, 60, 65, 69–70, 88 Leukemia, chronic myeloid 61 Leukemia, hairy cell 62, 83, 88 Leukemia, T-cell acute lymphoblastic 54 Leukeran 64 Leuprolide Eligard (inj) 23 Lupron Depot 7.5mg (inj) 26 Levoleucovorin Fusilev (inj) 17 Lonsurf 19 Lupron Depot 7.5mg (inj) 26 Lymphoma, cutaneous T-cell 63, 66, 69–70, 72, 75 Lymphoma, follicular 62, 75, 83, 88 Lymphoma, malignant 64 Lymphoma, mantle cell 62, 72 Lymphoma, marginal zone 62 Lymphoma, peripheral T-cell 54, 63 Lymphoma, small lymphocytic 62, 75 Lymphoma, T-cell lymphoblastic 54 Lymphomatous meningitis 58 Lymphosarcoma 65, 79 Lynparza 33

M Malignant pleural mesothelioma 76 Mantle cell lymphoma 67 Marqibo (inj) 64 Mastocytosis 17, 60, 68, 88 Mechlorethamine Mustargen (inj) 65, 79 Valchlor (ext) 72 Mekinist 89 Melanoma 62, 83, 87–92 Melanoma, metastatic 28, 90

Melphalan Evomela (inj) Menest Mercaptopurine Purinethol Purixan Methotrexate Trexall Xatmep Methoxsalen Uvadex Midostaurin Rydapt Multiple myeloma

ALPHABETICAL INDEX 59 26 67 67 1, 10, 33, 36, 71, 81 74 72 68 32, 58–59, 64–67, 70, 72, 75, 83

Mustargen (inj) cancer, lung hodgkin’s disease leukemia lymphosarcoma mycosis fungoides polycythemia vera Mycosis fungoides

65, 79 65, 79 65, 79 65, 79 65, 79 65, 79 1, 10, 33, 36, 65, 71, 79, 81 Mycosis fungoides-type cutaneous T-cell lymphoma 72 Myelodysplastic syndromes 17, 57, 60, 74, 88 Myleran 65

N Navelbine (inj) 79 Necitumumab Portrazza (inj) 80 Nelarabine Arranon 54 Neoplasms 24, 29 Neuroblastoma 4 Neuroendocrine tumors 14, 20, 28 Nexavar cancer, liver 19, 27 cancer, renal 19, 27 cancer, thyroid 14, 19, 27 Nilotinib Tasigna 70 Ninlaro 65 Niraparib Zejula 34 Nivolumab Opdivo (inj) 27, 36, 66, 79, 90 Non-Hodgkin’s lymphoma 1, 10, 33, 36, 55, 68, 71, 74, 81 Non-small cell lung cancer 3, 15–16, 22, 32, 76–80, 82

O Obinutuzumab Gazyva (inj) Odomzo Ofatumumab Arzerra (inj) Olaparib Lynparza

60 89 54 33

Olaratumab Lartruvo (inj) Omacetaxine mepesuccinate Synribo (inj) Oncaspar (inj) Onivyde (inj) Ontak (inj) Opdivo (inj) cancer, head and neck cancer, lung cancer, renal hodgkin lymphoma melanoma Osimertinib Tagrisso Oxaliplatin Eloxatin (inj)

1 69 66 14 66 36 79 27 66 90 80 16

P Paclitaxel, protein-bound Abraxane (inj) 5, 12, 76 Palbociclib Ibrance 8 Panitumumab Vectibix (inj) 20 Panobinostat Farydak 59 Panretin (ext) 83 Pazopanib Votrient 1, 30 Pegaspargase Oncaspar (inj) 66 Peginterferon alfa-2b Sylatron (inj) 90 Pembrolizumab Keytruda (inj) 18, 25, 35, 63, 78, 89 Pemetrexed Alimta (inj) 76 Perjeta (inj) 9 Pertuzumab Perjeta (inj) 9 Polycythemia vera 63, 65, 79 Pomalidomide Pomalyst 66 Pomalyst 66 Ponatinib Iclusig 61 Portrazza (inj) 80 Premarin cancer, breast 9 cancer, prostate 27 Progressive neuroendocrine tumors of pancreatic origin (pNET) 12 Progressive non-functional neuroendocrine tumors (NET) of gastrointestinal or lung origin 12 Proleukin (inj) cancer, renal 28, 90 melanoma, metastatic 28, 90 Provenge (inj) 28 Purinethol 67 Purixan 67

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ALPHABETICAL INDEX R Radium Ra 223 dichloride Xofigo (inj) Raloxifene Evista Ramucirumab Cyramza (inj) Regorafenib Stivarga Revlimid Ribociclib Kisqali Rituxan (inj) Rituximab Rituxan (inj) Romidepsin Istodax Rubraca Rucaparib Rubraca Ruxolitinib Jakafi Rydapt

30 6 16, 77 19 67 9 68 68 63 33 33 63 68

S Sarcoma, soft tissue Sipuleucel-T Provenge (inj) Skeletal-related events Soltamox Somatuline Depot (inj) Sonidegib Odomzo Sorafenib Nexavar Sprycel Stivarga Subependymal giant cell astrocytoma (SEGA) Sunitinib Sutent Superficial basal cell carcinoma Sutent cancer, pancreatic gi stromal tumors neuroendocrine tumors Sylatron (inj) Synribo (inj) Systemic anaplastic large cell lymphoma (sALCL)

1 28 2 10 14 89 14, 19, 27 69 19 3 14, 20, 28 87 14, 20, 28 14, 20, 28 14, 20, 28 90 69 54

T Tabloid Tafinlar Tagrisso Talimogene laherparepvec Imlygic (inj) Tamoxifen Soltamox Tamoxifen

69 91 80

Brand name–bold type Generic name–light type Medical condition–red type *-product contains other active ingredients ext-external inj-injectable.

Tarceva cancer, pancreatic 15, 80 non-small cell lung cancer 15, 80 Targretin 69 Targretin (ext) 70 Tasigna 70 Tecentriq (inj) cancer, bladder 29, 81 cancer, renal 29, 81 Temodar 3 Temozolomide Temodar 3 Temsirolimus Torisel (inj) 29 Teniposide Vumon (inj) 74 Testosterone enanthate Delatestryl 6 Thalidomide Thalomid 70 Thalomid 70 Thioguanine Tabloid 69 Tipiracil Lonsurf* 19 Topotecan Hycamtin 32, 78 Torisel (inj) 29 Tositumomab Bexxar* 55 Trabectedin Yondelis (inj) 2 Trametinib Mekinist 89 Trastuzumab Herceptin (inj) 7, 18 Treanda (inj) 71 Trelstar (inj) 29 Tretinoin Vesanoid 73 Trexall cancer, breast 1, 10, 33, 36, 71, 81 cancer, head and neck 1, 10, 33, 36, 71, 81 cancer, lung 1, 10, 33, 36, 71, 81 chorioadenoma destruens 1, 10, 33, 36, 71, 81 choriocarcinoma, gestational 1, 10, 33, 36, 71, 81 hydatidiform mole 1, 10, 33, 36, 71, 81 mycosis fungoides 1, 10, 33, 36, 71, 81 non-hodgkin’s lymphoma 1, 10, 33, 36, 71, 81 Trifluridine Lonsurf* 19 Triptorelin Trelstar (inj) 29 Trisenox (inj) 72 Tykerb 11

88

U

10 10

Unituxin (inj) Uvadex

4 72

V Valchlor (ext) Valrubicin Valstar Valstar Vandetanib Caprelsa Vantas Vectibix (inj) Velcade (inj) Vemurafenib Zelboraf Venclexta Venetoclax Venclexta Vesanoid Vidaza (inj) Vincristine sulfate liposome Marqibo (inj) Vinorelbine Navelbine (inj) Vismodegib Erivedge Vorinostat Zolinza Votrient cancer, renal cancer, sarcoma Vumon (inj)

72 30 30 12 30 20 72 92 73 73 73 74 64 79 87 75 30 1 74

X Xalkori Xatmep Xeloda cancer, breast cancer, colorectal Xgeva (inj) Xofigo (inj) Xtandi

82 74 11, 20 11, 20 2 30 31

Y Yervoy (inj) Yondelis (inj)

91 2

Z Zaltrap (inj) Zejula Zelboraf Zevalin (inj) Ziv-aflibercept Zaltrap (inj) Zoledronic acid Zometa Zolinza Zometa Zydelig Zykadia Zytiga

21 34 92 74 21 75 75 75 75 82 31

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