Cancer Therapy Advisor November/December 2017 Issue by Haymarket Media

NOVEMBER/DECEMBER 2017 | VOL 4, ISSUE 2

CancerTherapyAdvisor.com

CancerTherapyAdvisor

A22 FEATURE

Hurricane Aftermath Tests Cancer Centers in Puerto Rico, Florida, and Houston

FEATURING Cancer Therapy Regimens and Oncology Drug Monographs from

The floods resulting from hurricanes Harvey, Irma, and Maria disrupted cancer care in several affected locations.

1 Bone Cancer 3 Brain Cancer



5 Breast Cancer 17 Endocrine Cancer

A15 LATEST NEWS

21 Gastrointestinal Cancer

Headlines in Oncology Research, Including Head and Neck Cancer and Skin Cancer

27 Genitourinary Cancer

A21 IN THE CLINIC

40 Head and Neck Cancer

NOVEMBER/DECEMBER 2017 | VOL 4, ISSUE 2

Celiac Plexus Neurolysis for Pain Management in Patients With Pancreatic Cancer

37 Gynecologic Cancer

 42 Hematologic Cancer  71 Lung Cancer 88 Sarcoma

A24 VIEWPOINT

Should Nicotinamide Be Used for Melanoma Prevention?

A26 EXPERT PERSPECTIVE Long-term Survival From Ipilimumab/Nivolumab in Metastatic Melanoma

89 Skin Cancer



Regimen included

TRANSPORT YOURSELF TO THE

59TH AMERICAN SOCIETY OF HEMATOLOGY (ASH) ANNUAL MEETING 12/9–12/12 | ATLANTA, GA With comprehensive coverage from Cancer Therapy Advisor, you won’t miss a thing. Review video interviews and articles on late-breaking data, presentations, and more. Stay up to date wherever you are. Subscribe to e-newsletters at www.CancerTherapyAdvisor.com.

A12

FEATURED PRODUCTS Drug Descriptions of Idhifa and Nerlynx

A14 IN THE PIPELINE The Latest on Oncology Drugs A15

LATEST NEWS Headlines in Oncology Research and Practice

A21 IN THE CLINIC Celiac Plexus Neurolysis for Pain Management in Patients With Pancreatic Cancer C. ANDREW KISTLER, MD, PharmD, RPh

A22

FEATURE Hurricane Aftermath Tests Cancer Centers in Puerto Rico, Florida, and Houston BRYANT FURLOW

A24

VIEWPOINT Should Nicotinamide Be Used for Melanoma Prevention? LEAH LAWRENCE

A26 EXPERT PERSPECTIVE Long-term Survival From Ipilimumab/ Nivolumab in Metastatic Melanoma MARIO SZNOL, MD

A28 REGIMEN & MONOGRAPH INDEX 1-94 CANCER THERAPY REGIMENS & ONCOLOGY DRUG MONOGRAPHS Highlighted topics () contain both treatment regimens and drug monographs. 1 Bone Cancer 3 Brain Cancer

 5 Breast Cancer 17 Endocrine Cancer 21 Gastrointestinal Cancer 27 Genitourinary Cancer 37 Gynecologic Cancer 40 Head and Neck Cancer  42 Hematologic Cancer  71 Lung Cancer 88 Sarcoma 89 Skin Cancer

95 ALPHABETICAL INDEX 100 MANUFACTURERS INDEX

Cancer Therapy Advisor (ISSN 2375-558X), November/December 2017, Volume 4, Number 2. 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. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher.

CancerTherapyAdvisor.com | NOVEMBER/DECEMBER 2017 | CANCER THERAPY ADVISOR A1

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Lifespan Cancer Institute  Providence, RI

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A2 CANCER THERAPY ADVISOR | NOVEMBER/DECEMBER 2017 | CancerTherapyAdvisor.com

VOTRIENT® (pazopanib) tablets is indicated for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated.

Learn more about your next move at VOTRIENT.com

Important Safety Information for VOTRIENT® (pazopanib) tablets WARNING: HEPATOTOXICITY Severe and fatal hepatotoxicity has been observed in clinical trials. Monitor hepatic function and interrupt, reduce, or discontinue dosing as recommended. See “Warnings and Precautions,” Section 5.1, in complete Prescribing Information. Hepatic Toxicity and Hepatic Impairment: Severe and fatal hepatotoxicity has occurred. Patients older than 65 years are at an increased risk. Increases in serum transaminase levels (ALT, AST) and bilirubin were observed. Transaminase elevations occur early in the course of treatment (92.5% of all transaminase elevations of any grade occurred in the first 18 weeks). In patients with preexisting moderate hepatic impairment, the starting dose of VOTRIENT should be reduced to 200 mg per day or alternatives to VOTRIENT should be considered. Treatment with VOTRIENT is not recommended in patients with severe hepatic impairment. Concomitant use of VOTRIENT and simvastatin increases the risk of ALT elevations and should be undertaken with caution [see Drug Interactions]. Before the initiation of treatment and regularly during treatment, monitor hepatic function and interrupt, reduce, or discontinue dosing as recommended.

Please see additional Important Safety Information and Brief Summary of Prescribing Information, including Boxed WARNING, on subsequent pages.

Important Safety Information for VOTRIENTÂŽ (pazopanib) tablets (cont) QT Prolongation and Torsades de Pointes: Prolonged QT intervals and arrhythmias, including torsades de pointes, have occurred. Use with caution in patients with a history of QT interval prolongation, patients taking antiarrhythmics or other medications that may prolong QT interval, and those with relevant preexisting cardiac disease. Baseline and periodic monitoring of electrocardiograms and maintenance of electrolytes (eg, calcium, magnesium, and potassium) within the normal range should be performed. Cardiac Dysfunction: Cardiac dysfunction, such as congestive heart failure (CHF) and decreased left ventricular ejection fraction (LVEF), has occurred. In the randomized STS trial, in patients who had baseline and follow-up LVEF measurements, myocardial dysfunction occurred in 11% (16/142) of patients on VOTRIENTÂŽ (pazopanib) tablets compared to 5% (2/40) of patients on placebo. One percent (3/240) of patients on VOTRIENT had CHF, which did not resolve in 1 patient. Monitor blood pressure (BP), and manage promptly using a combination of antihypertensive therapy and dose modification of VOTRIENT (interruption and reinitiation at a reduced dose based on clinical judgment). Carefully monitor patients for clinical signs or symptoms of CHF. Baseline and periodic evaluation of LVEF is recommended in patients at risk of cardiac dysfunction, including previous anthracycline exposure. Hemorrhagic Events: Hemorrhagic events have occurred and can be fatal. In the randomized STS trial, 22% (53/240) of patients treated with VOTRIENT compared to 8% (10/123) treated with placebo experienced at least 1 hemorrhagic event. The most common hemorrhagic events were epistaxis (8%), mouth hemorrhage (3%), and anal hemorrhage (2%). VOTRIENT should not be used in patients who have a history of hemoptysis, cerebral, or clinically significant gastrointestinal (GI) hemorrhage in the past 6 months. Arterial Thromboembolic Events: Arterial thromboembolic events have occurred and can be fatal. In the randomized STS trial, 2% (4/240) of patients receiving VOTRIENT experienced myocardial infarction or ischemia, 0.4% (1/240) had a cerebrovascular accident, and there were no incidents of transient ischemic attack. No arterial thromboembolic events were reported in patients who received placebo. Use with caution in patients who are at increased risk for these events or have a history of these events. Do not use VOTRIENT in patients who have had an arterial thromboembolic event in the past 6 months. Venous Thromboembolic Events (VTEs): VTEs have occurred, including venous thrombosis and fatal pulmonary emboli. In the randomized STS trial, VTEs were reported in 5% of patients treated with VOTRIENT compared to 2% with placebo. Fatal pulmonary embolus occurred in 1% (2/240) of STS patients receiving VOTRIENT and in no patients receiving placebo. Monitor for signs and symptoms. Thrombotic Microangiopathy (TMA): TMA, including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), has been reported in clinical trials of VOTRIENT as monotherapy, in combination with bevacizumab, and in combination with topotecan. VOTRIENT is not indicated for use in combination with other agents. Six of the 7 TMA cases occurred within 90 days of the initiation of VOTRIENT. Improvement of TMA was observed after treatment was discontinued. Monitor for signs and symptoms of TMA. Permanently discontinue VOTRIENT in patients developing TMA. Manage as clinically indicated. GI Perforation and Fistula: In STS trials, GI perforation or fistula occurred in 1% (4/382) of patients receiving VOTRIENT. Fatal perforations occurred in 0.3% (1/382) of these patients. Use with caution in patients at risk for these events, and monitor for signs and symptoms. Interstitial Lung Disease (ILD)/Pneumonitis: ILD/pneumonitis, which can be fatal, has been reported in 0.1% of patients in the clinical trials treated with VOTRIENT. Monitor patients for ILD/pneumonitis, and discontinue VOTRIENT if symptoms of ILD or pneumonitis develop. Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS has been reported and may be fatal. Permanently discontinue VOTRIENT in patients developing RPLS.

Please see additional Important Safety Information and Brief Summary of Prescribing Information, including Boxed WARNING, on subsequent pages.

Important Safety Information for VOTRIENT® (pazopanib) tablets (cont) Hypertension (HTN): HTN, including hypertensive crisis, has occurred in clinical trials. HTN occurs early in the course of treatment (approximately 40% of cases occurred by Day 9, and 90% of cases occurred in the first 18 weeks). BP should be well controlled prior to initiating VOTRIENT® (pazopanib) tablets, monitored early after starting treatment (no longer than 1 week), and frequently thereafter. Treat increased BP promptly with standard antihypertensive therapy and dose reduction or interruption of VOTRIENT, as clinically warranted. Discontinue VOTRIENT if there is evidence of hypertensive crisis or if HTN is severe and persistent despite antihypertensive therapy and dose reduction of VOTRIENT. Approximately 1% of patients required permanent discontinuation of VOTRIENT because of HTN. Wound Healing: VOTRIENT may impair wound healing. Interruption of therapy is recommended in patients undergoing surgical procedures. Treatment with VOTRIENT should be stopped at least 7 days prior to scheduled surgery. VOTRIENT should be discontinued in patients with wound dehiscence. Hypothyroidism: Hypothyroidism was reported in 5% (11/240) of patients treated with VOTRIENT in the randomized STS trial and in no patients receiving placebo. Monitoring of thyroid function tests is recommended. Proteinuria: In the randomized STS trial, proteinuria was reported as an adverse reaction in 1% (2/240) of patients, and nephrotic syndrome was reported in 1 patient treated with VOTRIENT compared to none in patients receiving placebo. Treatment was withdrawn in the patient with nephrotic syndrome. Monitor urine protein at baseline and periodically as clinically indicated. Interrupt treatment for 24-hour urine protein ≥3 grams, and discontinue for repeat episodes despite dose reductions. Infection: Serious infections (with or without neutropenia), some with fatal outcomes, have been reported. Monitor for signs and symptoms, and treat active infection promptly. Consider interruption or discontinuation of VOTRIENT. Increased Toxicity With Other Cancer Therapy: VOTRIENT is not indicated for use in combination with other agents. Increased toxicity and mortality have been observed in clinical trials administering VOTRIENT in combination with lapatinib or with pemetrexed. The fatal toxicities observed included pulmonary hemorrhage, GI hemorrhage, and sudden death. A safe and effective combination dose has not been established with these regimens. Increased Toxicity in Developing Organs: The safety and effectiveness of VOTRIENT in pediatric patients have not been established. VOTRIENT is not indicated for use in pediatric patients. Animal studies have demonstrated pazopanib can severely affect organ growth and maturation during early postnatal development, and resulted in toxicity to the lungs, liver, heart, and kidney, and in death. VOTRIENT may potentially cause serious adverse effects on organ development in pediatric patients, particularly in patients younger than 2 years of age. Females and Males of Reproductive Potential: VOTRIENT can cause fetal harm when administered to a pregnant woman based on animal reproduction studies and its mechanism of action. In animal developmental and reproductive toxicology studies, oral administration of pazopanib to pregnant rats and rabbits throughout organogenesis resulted in teratogenicity, and abortion at systemic exposures lower than that observed at the maximum recommended human dose of 800 mg. Verify pregnancy status of females of reproductive potential prior to starting treatment with VOTRIENT. Advise females of reproductive potential to use effective contraception during treatment and for at least 2 weeks after the last dose of VOTRIENT. To avoid potential drug exposure to pregnant partners and female partners of reproductive potential, advise male patients (including those who have had vasectomies) with female partners of reproductive potential to use condoms during treatment with VOTRIENT and for at least 2 weeks after the last dose. VOTRIENT may impair fertility in females and males of reproductive potential while receiving treatment. Because of the potential for serious adverse reactions in breastfed infants from VOTRIENT, advise a lactating woman not to breastfeed during treatment with VOTRIENT and for 2 weeks after the final dose. Diarrhea: Diarrhea occurred frequently and was predominantly mild to moderate in severity. Patients should be advised how to manage mild diarrhea and to notify their health care provider if moderate to severe diarrhea occurs so appropriate management can be implemented to minimize its impact.

Please see additional Important Safety Information and Brief Summary of Prescribing Information, including Boxed WARNING, on subsequent pages.

Important Safety Information for VOTRIENT® (pazopanib) tablets (cont) Pneumothorax: Pneumothorax has occurred (8/240 STS patients [3%] treated with VOTRIENT® (pazopanib) tablets vs 0% in the placebo group). Bradycardia: In the randomized trial of VOTRIENT for the treatment of STS, bradycardia based on vital signs (<60 beats per minute) was observed in 19% (45/238) of patients treated with VOTRIENT and in 4% (5/121) of patients on the placebo arm. Drug Interactions: Coadministration with strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir, clarithromycin) increases concentrations of pazopanib and should be avoided, but, if warranted, reduce the dose of VOTRIENT to 400 mg. Avoid grapefruit and grapefruit juice. Concomitant use of strong CYP3A4 inducers (eg, rifampin) should be avoided due to the potential to decrease concentrations of pazopanib. VOTRIENT should not be used in patients who cannot avoid chronic use of CYP3A4 inducers. Concomitant treatment with strong inhibitors of P-glycoprotein (PgP) or breast cancer resistance protein (BCRP) should be avoided due to risk of increased exposure to pazopanib. CYP Substrates: Concomitant use of VOTRIENT with agents with narrow therapeutic windows that are metabolized by CYP3A4, CYP2D6, or CYP2C8 is not recommended. Coadministration may result in inhibition of the metabolism of these products and create the potential for serious adverse events. Concomitant use of VOTRIENT and simvastatin increases the incidence of ALT elevations. If a patient develops ALT elevations, follow dosing guidelines for VOTRIENT, consider alternatives to VOTRIENT, or consider discontinuing simvastatin. There are insufficient data to assess the risk of concomitant administration of alternative statins and VOTRIENT. Drugs That Raise Gastric pH: Avoid concomitant use of VOTRIENT with drugs that raise gastric pH (eg, esomeprazole) due to the potential to decrease concentrations of pazopanib. Consider short-acting antacids in place of proton pump inhibitors (PPIs) and H2 receptor antagonists. Separate antacid and pazopanib dosing by several hours. Adverse Reactions in the Randomized STS Trial: A dose interruption was required for 58% of patients on VOTRIENT. The VOTRIENT dose was reduced for 38% of patients. Therapy was discontinued due to adverse reactions for 17% of patients who received VOTRIENT. The most common adverse reactions (≥20%) in patients who received VOTRIENT vs placebo were fatigue (65% vs 48%), diarrhea (59% vs 15%), nausea (56% vs 22%), decreased weight (48% vs 15%), HTN (42% vs 6%), decreased appetite (40% vs 19%), hair color changes (39% vs 2%), vomiting (33% vs 11%), tumor pain (29% vs 21%), dysgeusia (28% vs 3%), headache (23% vs 8%), musculoskeletal pain (23% vs 20%), myalgia (23% vs 9%), GI pain (23% vs 9%), and dyspnea (20% vs 17%). Laboratory abnormalities occurring in >10% of STS patients and more commonly (≥5%) in patients receiving VOTRIENT vs placebo included increases in AST (51% vs 22%), ALT (46% vs 18%), glucose (45% vs 35%), alkaline phosphatase (32% vs 23%), total bilirubin (29% vs 7%), and potassium (16% vs 11%); decreases in albumin (34% vs 21%) and sodium (31% vs 20%); and leukopenia (44% vs 15%), lymphocytopenia (43% vs 36%), thrombocytopenia (36% vs 6%), and neutropenia (33% vs 7%). In a pooled analysis of VOTRIENT clinical trials, East Asian patients had a higher frequency of neutropenia, thrombocytopenia, and palmar-plantar erythrodysesthesia syndrome than non-East Asian patients. (See Adverse Reactions, Section 6.1, in complete Prescribing Information.)

Please see Brief Summary of Prescribing Information, including Boxed WARNING, on subsequent pages.

Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936-1080

7/17

VRN-1166379

BRIEF SUMMARY VOTRIENT® (pazopanib) Tablets The following is a brief summary only; see full prescribing information for complete product information. WARNING: HEPATOTOXICITY Severe and fatal hepatotoxicity has been observed in clinical trials. Monitor hepatic function and interrupt, reduce, or discontinue dosing as recommended [see Warnings and Precautions (5.1)]. 1 INDICATIONS AND USAGE VOTRIENT is indicated for the treatment of patients with advanced soft tissue sarcoma (STS) who have received prior chemotherapy. Limitation of Use: The efficacy of VOTRIENT for the treatment of patients with adipocytic STS or gastrointestinal stromal tumors has not been demonstrated. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosing The recommended starting dose of VOTRIENT is 800 mg orally once daily without food (at least 1 hour before or 2 hours after a meal) [see Clinical Pharmacology (12.3) in the full prescribing information]. The dose of VOTRIENT should not exceed 800 mg. Do not crush tablets due to the potential for increased rate of absorption which may affect systemic exposure [see Clinical Pharmacology (12.3) in the full prescribing information]. If a dose is missed, it should not be taken if it is less than 12 hours until the next dose. 2.2 Dose Modification Guidelines In STS, a decrease or increase should be in 200-mg steps based on individual tolerability. Hepatic Impairment: No dose adjustment is required in patients with mild hepatic impairment. In patients with moderate hepatic impairment, alternatives to VOTRIENT should be considered. If VOTRIENT is used in patients with moderate hepatic impairment, the dose should be reduced to 200 mg per day. VOTRIENT is not recommended in patients with severe hepatic impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3) in the full prescribing information]. Concomitant Strong CYP3A4 Inhibitors: The concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin) increases pazopanib concentrations and should be avoided. Consider an alternate concomitant medication with no or minimal potential to inhibit CYP3A4. If coadministration of a strong CYP3A4 inhibitor is warranted, reduce the dose of VOTRIENT to 400 mg. Further dose reductions may be needed if adverse effects occur during therapy [see Drug Interactions (7.1), Clinical Pharmacology (12.3) in the full prescribing information]. Concomitant Strong CYP3A4 Inducer: The concomitant use of strong CYP3A4 inducers (e.g., rifampin) may decrease pazopanib concentrations and should be avoided. Consider an alternate concomitant medication with no or minimal enzyme induction potential. VOTRIENT should not be used in patients who cannot avoid chronic use of strong CYP3A4 inducers [see Drug Interactions (7.1)]. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Hepatic Toxicity and Hepatic Impairment In clinical trials with VOTRIENT, hepatotoxicity, manifested as increases in serum transaminases (ALT, AST) and bilirubin, was observed. This hepatotoxicity can be severe and fatal. Patients older than 65 years are at greater risk for hepatotoxicity [see Use in Specific Populations (8.5)]. Transaminase elevations occur early in the course of treatment (92.5% of all transaminase elevations of any grade occurred in the first 18 weeks) [see Dosage and Administration (2.2)]. In the randomized STS trial, ALT >3 X ULN was reported in 18% and 5% of the groups receiving VOTRIENT and placebo, respectively. ALT >8 X ULN was reported in 5% and 2% of the groups receiving VOTRIENT and placebo, respectively. Concurrent elevation in ALT >3 X ULN and bilirubin >2 X ULN in the absence of significant alkaline phosphatase >3 X ULN occurred in 2% (4/240) of patients on VOTRIENT and <1% (1/123) on placebo. Four-tenths percent of the patients (1/240) in the randomized STS trial died of hepatic failure. • Monitor serum liver tests before initiation of treatment with VOTRIENT and at Weeks 3, 5, 7, and 9. Thereafter, monitor at Month 3 and at Month 4, and as clinically indicated. Periodic monitoring should then continue after Month 4. • Patients with isolated ALT elevations between 3 X ULN and 8 X ULN may be continued on VOTRIENT with weekly monitoring of liver function until ALT returns to Grade 1 or baseline.

• Patients with isolated ALT elevations of >8 X ULN should have VOTRIENT interrupted until they return to Grade 1 or baseline. If the potential benefit for reinitiating treatment with VOTRIENT is considered to outweigh the risk for hepatotoxicity, then reintroduce VOTRIENT at a reduced dose of no more than 400 mg once daily and measure serum liver tests weekly for 8 weeks [see Dosage and Administration (2.2)]. Following reintroduction of VOTRIENT, if ALT elevations >3 X ULN recur, then VOTRIENT should be permanently discontinued. • If ALT elevations >3 X ULN occur concurrently with bilirubin elevations >2 X ULN, VOTRIENT should be permanently discontinued. Patients should be monitored until resolution. VOTRIENT is a uridine diphosphate (UDP)glucuronosyl transferase 1A1 (UGT1A1) inhibitor. Mild, indirect (unconjugated) hyperbilirubinemia may occur in patients with Gilbert’s syndrome [see Clinical Pharmacology (12.5) in the full prescribing information]. Patients with only a mild indirect hyperbilirubinemia, known Gilbert’s syndrome, and elevation in ALT >3 X ULN should be managed as per the recommendations outlined for isolated ALT elevations. Concomitant use of VOTRIENT and simvastatin increases the risk of ALT elevations and should be undertaken with caution and close monitoring [see Drug Interactions (7.4)]. Insufficient data are available to assess the risk of concomitant administration of alternative statins and VOTRIENT. In patients with pre-existing moderate hepatic impairment, the starting dose of VOTRIENT should be reduced or alternatives to VOTRIENT should be considered. Treatment with VOTRIENT is not recommended in patients with pre-existing severe hepatic impairment, defined as total bilirubin >3 X ULN with any level of ALT [see Dosage and Administration (2.2), Use in Specific Populations (8.6), Clinical Pharmacology (12.3) in the full prescribing information]. 5.2 QT Prolongation and Torsades de Pointes In the randomized STS trial, 0.4% (1/240) of patients who received VOTRIENT had post-baseline values between 500 to 549 msec. Post-baseline QT data were only collected in the STS trial if ECG abnormalities were reported as an adverse reaction. None of the 123 patients who received placebo on the trial had post-baseline QTc values ≥500 msec. VOTRIENT should be used with caution in patients with a history of QT interval prolongation, in patients taking antiarrhythmics or other medications that may prolong QT interval, and those with relevant pre-existing cardiac disease. When using VOTRIENT, baseline and periodic monitoring of electrocardiograms and maintenance of electrolytes (e.g., calcium, magnesium, potassium) within the normal range should be performed. 5.3 Cardiac Dysfunction In clinical trials with VOTRIENT, events of cardiac dysfunction such as decreased left ventricular ejection fraction (LVEF) and congestive heart failure have occurred. In the randomized STS trial, myocardial dysfunction occurred in 11% (16/142) of patients on VOTRIENT compared with 5% (2/40) of patients on placebo. One percent (3/240) of patients on VOTRIENT in the STS trial had congestive heart failure which did not resolve in one patient. Fourteen of the 16 patients with myocardial dysfunction treated with VOTRIENT in the STS trial had concurrent hypertension which may have exacerbated cardiac dysfunction in patients at risk (e.g., those with prior anthracycline therapy) possibly by increasing cardiac afterload. Blood pressure should be monitored and managed promptly using a combination of anti-hypertensive therapy and dose modification of VOTRIENT (interruption and re-initiation at a reduced dose based on clinical judgment) [see Warnings and Precautions (5.11)]. Patients should be carefully monitored for clinical signs or symptoms of congestive heart failure. Baseline and periodic evaluation of LVEF is recommended in patients at risk of cardiac dysfunction including previous anthracycline exposure. 5.4 Hemorrhagic Events There were no reports of fatal hemorrhage in the STS trials. In the randomized STS trial, 22% (53/240) of patients treated with VOTRIENT compared with 8% (10/123) treated with placebo experienced at least 1 hemorrhagic event. The most common hemorrhagic events were epistaxis (8%), mouth hemorrhage (3%), and anal hemorrhage (2%). Grade 4 hemorrhagic events in the STS population occurred in 1% (3/240) of patients and included intracranial hemorrhage, subarachnoid hemorrhage, and peritoneal hemorrhage. VOTRIENT has not been studied in patients who have a history of hemoptysis, cerebral hemorrhage, or clinically significant gastrointestinal hemorrhage in the past 6 months and should not be used in those patients. 5.5 Arterial Thromboembolic Events Fatal arterial thromboembolic events were observed in no patients in the STS trials. In the randomized STS trial, 2% (4/240) of patients receiving VOTRIENT experienced a myocardial infarction or ischemia, 0.4% (1/240) had a cerebrovascular accident, and there were no incidents of transient ischemic attack. No arterial thromboembolic events were reported in patients who received placebo. VOTRIENT should be used with caution in patients who are at increased risk for these events or who have had a history of these events. VOTRIENT has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months and should not be used in those patients.

5.6 Venous Thromboembolic Events In trials of VOTRIENT, venous thromboembolic events (VTE) including venous thrombosis and fatal pulmonary embolus (PE) have occurred. In the randomized STS trial, venous thromboembolic events were reported in 5% of patients treated with VOTRIENT compared with 2% with placebo. Fatal pulmonary embolus occurred in 1% (2/240) of STS patients receiving VOTRIENT and in no patients receiving placebo. Monitor for signs and symptoms of VTE and PE. 5.7 Thrombotic Microangiopathy Thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), has been reported in clinical trials of VOTRIENT as monotherapy, in combination with bevacizumab, and in combination with topotecan. VOTRIENT is not indicated for use in combination with other agents. Six of the 7 TMA cases occurred within 90 days of the initiation of VOTRIENT. Improvement of TMA was observed after treatment was discontinued. Monitor for signs and symptoms of TMA. Permanently discontinue VOTRIENT in patients developing TMA. Manage as clinically indicated. 5.8 Gastrointestinal Perforation and Fistula In STS trials, gastrointestinal perforation or fistula occurred in 1% (4/382) of patients receiving VOTRIENT. Fatal perforations occurred in 0.3% (1/382) of these patients in the STS trials. Monitor for signs and symptoms of gastrointestinal perforation or fistula. 5.9 Interstitial Lung Disease (ILD)/Pneumonitis ILD/pneumonitis, which can be fatal, has been reported in association with VOTRIENT. In clinical trials, ILD/pneumonitis occurred in 0.1% of patients treated with VOTRIENT. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis and discontinue VOTRIENT in patients developing ILD or pneumonitis. 5.10 Reversible Posterior Leukoencephalopathy Syndrome Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been reported in patients receiving VOTRIENT and may be fatal. RPLS is a neurological disorder which can present with headache, seizure, lethargy, confusion, blindness, and other visual and neurologic disturbances. Mild to severe hypertension may be present. The diagnosis of RPLS is optimally confirmed by magnetic resonance imaging. Permanently discontinue VOTRIENT in patients developing RPLS. 5.11 Hypertension In clinical trials, hypertension (systolic blood pressure ≥150 or diastolic blood pressure ≥100 mm Hg) and hypertensive crisis were observed in patients treated with VOTRIENT. Blood pressure should be well controlled prior to initiating VOTRIENT. Hypertension occurs early in the course of treatment (40% of cases occurred by Day 9 and 90% of cases occurred in the first 18 weeks). Blood pressure should be monitored early after starting treatment (no longer than one week) and frequently thereafter to ensure blood pressure control. Approximately 40% of patients who received VOTRIENT experienced hypertension. Grade 3 hypertension was reported in 4% to 7% of patients receiving VOTRIENT [see Adverse Reactions (6.1)]. Increased blood pressure should be treated promptly with standard antihypertensive therapy and dose reduction or interruption of VOTRIENT as clinically warranted. VOTRIENT should be discontinued if there is evidence of hypertensive crisis or if hypertension is severe and persistent despite antihypertensive therapy and dose reduction. Approximately 1% of patients required permanent discontinuation of VOTRIENT because of hypertension [see Dosage and Administration (2.2)]. 5.12 Wound Healing No formal trials on the effect of VOTRIENT on wound healing have been conducted. Since vascular endothelial growth factor receptor (VEGFR) inhibitors such as pazopanib may impair wound healing, treatment with VOTRIENT should be stopped at least 7 days prior to scheduled surgery. The decision to resume VOTRIENT after surgery should be based on clinical judgment of adequate wound healing. VOTRIENT should be discontinued in patients with wound dehiscence. 5.13 Hypothyroidism Hypothyroidism, confirmed based on a simultaneous rise of TSH and decline of T4, was reported in 5% (11/240) of patients treated with VOTRIENT in the randomized STS trial. No patients on the placebo arm had hypothyroidism. In STS trials of VOTRIENT, hypothyroidism was reported as an adverse reaction in 5% (20/382) of patients. Proactive monitoring of thyroid function tests is recommended. 5.14 Proteinuria In the randomized STS trial, proteinuria was reported as an adverse reaction in 1% (2/240) of patients, and nephrotic syndrome was reported in 1 patient treated with VOTRIENT compared with none in patients receiving placebo. Treatment was withdrawn in the patient with nephrotic syndrome. Baseline and periodic urinalysis during treatment is recommended with follow up measurement of 24-hour urine protein as clinically indicated. Interrupt VOTRIENT and dose reduce for 24-hour urine protein ≥3 grams;

discontinue VOTRIENT for repeat episodes despite dose reductions [see Dosage and Administration (2.2)]. 5.15 Infection Serious infections (with or without neutropenia), including some with fatal outcome, have been reported. Monitor patients for signs and symptoms of infection. Institute appropriate anti-infective therapy promptly and consider interruption or discontinuation of VOTRIENT for serious infections. 5.16 Increased Toxicity with Other Cancer Therapy VOTRIENT is not indicated for use in combination with other agents. Clinical trials of VOTRIENT in combination with pemetrexed and lapatinib were terminated early due to concerns over increased toxicity and mortality. The fatal toxicities observed included pulmonary hemorrhage, gastrointestinal hemorrhage, and sudden death. A safe and effective combination dose has not been established with these regimens. 5.17 Increased Toxicity in Developing Organs The safety and effectiveness of VOTRIENT in pediatric patients have not been established. VOTRIENT is not indicated for use in pediatric patients. Based on its mechanism of action, pazopanib may have severe effects on organ growth and maturation during early post-natal development. Administration of pazopanib to juvenile rats less than 21 days old resulted in toxicity to the lungs, liver, heart, and kidney and in death at doses significantly lower than the clinically recommended dose or doses tolerated in older animals. VOTRIENT may potentially cause serious adverse effects on organ development in pediatric patients, particularly in patients younger than 2 years of age [see Use in Specific Populations (8.4)]. 5.18 Pregnancy VOTRIENT can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action, VOTRIENT is expected to result in adverse reproductive effects. In pre-clinical studies in rats and rabbits, pazopanib was teratogenic, embryotoxic, fetotoxic, and abortifacient. There are no adequate and well-controlled studies of VOTRIENT in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while taking VOTRIENT [see Use in Specific Populations (8.1)]. 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Potentially serious adverse reactions with VOTRIENT included: • Hepatotoxicity [see Warnings and Precautions (5.1)] • QT prolongation and torsades de pointes [see Warnings and Precautions (5.2)] • Cardiac dysfunction [see Warnings and Precautions (5.3)] • Hemorrhagic events [see Warnings and Precautions (5.4)] • Arterial and venous thromboembolic events [see Warnings and Precautions (5.5 and 5.6)] • Thrombotic microangiopathy [see Warnings and Precautions (5.7)] • Gastrointestinal perforation and fistula [see Warnings and Precautions (5.8)] • Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.9)] • Reversible Posterior Leukoencephalopathy Syndrome (RPLS) [see Warnings and Precautions (5.10)] • Hypertension [see Warnings and Precautions (5.11)] • Infection [see Warnings and Precautions (5.15)] • Increased toxicity with other cancer therapies [see Warnings and Precautions (5.16)] Soft Tissue Sarcoma: The safety of VOTRIENT has been evaluated in 382 patients with advanced soft tissue sarcoma, with a median duration of treatment of 3.6 months (range: 0 to 53). The most commonly observed adverse reactions (≥20%) in the 382 patients were fatigue, diarrhea, nausea, decreased weight, hypertension, decreased appetite, vomiting, tumor pain, hair color changes, musculoskeletal pain, headache, dysgeusia, dyspnea, and skin hypopigmentation. The data described below reflect the safety profile of VOTRIENT in 240 patients who participated in a randomized, double-blind, placebo-controlled trial [see Clinical Studies (14.2) in the full prescribing information]. The median duration of treatment was 4.5 months (range: 0 to 24) for patients who received VOTRIENT and 1.9 months (range: 0 to 24) for the placebo arm. Fifty-eight percent of patients on VOTRIENT required a dose interruption. Thirty-eight percent of patients on VOTRIENT had their dose reduced. Seventeen percent of patients who received VOTRIENT discontinued therapy due to adverse reactions. Table 3 presents the most common adverse reactions occurring in ≥10% of patients who received VOTRIENT.

Table 3. Adverse Reactions Occurring in ≥10% of Patients with STS Who Received VOTRIENT VOTRIENT

Placebo

(N = 240)

(N = 123)

All Grade Gradesa 3 Adverse Reactions

Grade 4

All Grade Gradesa 3

Table 4. Selected Laboratory Abnormalities Occurring in >10% of Patients with STS Who Received VOTRIENT and More Commonly (≥5%) in Patients Who Received VOTRIENT versus Placebo

Grade 4

Fatigue

Diarrhea

Nausea

Weight decreased

Hypertension

Appetite decreased

Hair color changes

Vomiting

Tumor pain

Dysgeusia

Headache

Musculoskeletal pain

Myalgia

Gastrointestinal pain

Dyspnea

Exfoliative rash

Cough

Peripheral edema

Mucositis

Alopecia

Dizziness

Skin

disorderb

Skin hypopigmentation

Stomatitis

Chest pain

National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. b 27 of the 28 cases of skin disorder were palmar-plantar erythrodysesthesia. Other adverse reactions observed more commonly in patients treated with VOTRIENT that occurred in ≥5% of patients and at an incidence of more than 2% difference from placebo included insomnia (9% versus 6%), hypothyroidism (8% versus 0%), dysphonia (8% versus 2%), epistaxis (8% versus 2%), left ventricular dysfunction (8% versus 4%), dyspepsia (7% versus 2%), dry skin (6% versus <1%), chills (5% versus 1%), vision blurred (5% versus 2%), and nail disorder (5% versus 0%). Table 4 presents the most common laboratory abnormalities occurring in >10% of patients who received VOTRIENT and more commonly (≥5%) in patients who received VOTRIENT versus placebo.

Placebo

(N = 240)

(N = 123)

All Grade Gradesa 3 Parameters

Placebo

(N = 240)

(N = 123)

All Grade Gradesa 3 Parameters

Grade All 4 Gradesa

Grade 3

Grade 4

AST increased

ALT increased

Glucose increased

Albumin decreased

Alkaline phosphatase increased

Sodium decreased

Total bilirubin increased

Potassium increased

Chemistry

National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. Diarrhea: Diarrhea occurred frequently and was predominantly mild to moderate in severity in the STS clinical trial. Patients should be advised how to manage mild diarrhea and to notify their healthcare provider if moderate to severe diarrhea occurs so appropriate management can be implemented to minimize its impact. Pneumothorax: In the randomized trial of VOTRIENT for the treatment of STS, pneumothorax occurred in 3% (8/240) of patients treated with VOTRIENT and in no patients on the placebo arm. Bradycardia: In the randomized trial of VOTRIENT for the treatment of STS, bradycardia based on vital signs (<60 beats per minute) was observed in 19% (45/238) of patients treated with VOTRIENT and in 4% (5/121) of patients on the placebo arm. Bradycardia was reported as an adverse reaction in 2% (4/240) of patients treated with VOTRIENT compared with <1% (1/123) of patients treated with placebo. Adverse Reactions in East Asian Patients: In an analysis of pooled clinical trials (N=1938) with VOTRIENT, Grade 3 and Grade 4 adverse reactions were observed more frequently in patients of East Asian descent than in patients of non-East Asian descent for neutropenia (12% vs. 2%), thrombocytopenia (6% vs. <1%) and palmar-plantar erythrodysethesia syndrome (6% vs. 2%). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of VOTRIENT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure. Eye Disorders: Retinal detachment/tear. Gastrointestinal Disorders: Pancreatitis.

Table 4. Selected Laboratory Abnormalities Occurring in >10% of Patients with STS Who Received VOTRIENT and More Commonly (≥5%) in Patients Who Received VOTRIENT versus Placebo VOTRIENT

VOTRIENT

Grade 4

All Gradesa

Grade 3

Grade 4

% 0

Hematologic Leukopenia

Lymphocytopenia

Thrombocytopenia

Neutropenia

0 (continued)

7 DRUG INTERACTIONS 7.1 Drugs that Inhibit or Induce Cytochrome P450 3A4 Enzymes In vitro studies suggested that the oxidative metabolism of pazopanib in human liver microsomes is mediated primarily by CYP3A4, with minor contributions from CYP1A2 and CYP2C8. Therefore, inhibitors and inducers of CYP3A4 may alter the metabolism of pazopanib. CYP3A4 Inhibitors: Coadministration of pazopanib with strong inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir, clarithromycin) increases pazopanib concentrations and should be avoided. Consider an alternate concomitant medication with no or minimal potential to inhibit CYP3A4 [see Clinical Pharmacology (12.3) in the full prescribing information]. If coadministration of a strong CYP3A4 inhibitor is warranted, reduce the dose of VOTRIENT to 400 mg [see Dosage and Administration (2.2)]. Grapefruit or grapefruit juice should be avoided as it inhibits CYP3A4 activity and may also increase plasma concentrations of pazopanib. CYP3A4 Inducers: CYP3A4 inducers such as rifampin may decrease plasma pazopanib concentrations. Consider an alternate concomitant medication with no or minimal enzyme induction potential. VOTRIENT should not be used if chronic use of strong CYP3A4 inducers cannot be avoided [see Dosage and Administration (2.2)].

7.2 Drugs that Inhibit Transporters In vitro studies suggested that pazopanib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Therefore, absorption and subsequent elimination of pazopanib may be influenced by products that affect P-gp and BCRP. Concomitant treatment with strong inhibitors of P-gp or BCRP should be avoided due to risk of increased exposure to pazopanib. Selection of alternative concomitant medicinal products with no or minimal potential to inhibit P-gp or BCRP should be considered. 7.3 Effects of Pazopanib on CYP Substrates Results from drug-drug interaction trials conducted in cancer patients suggest that pazopanib is a weak inhibitor of CYP3A4, CYP2C8, and CYP2D6 in vivo, but had no effect on CYP1A2, CYP2C9, or CYP2C19 [see Clinical Pharmacology (12.3) in the full prescribing information]. Concomitant use of VOTRIENT with agents with narrow therapeutic windows that are metabolized by CYP3A4, CYP2D6, or CYP2C8 is not recommended. Coadministration may result in inhibition of the metabolism of these products and create the potential for serious adverse events [see Clinical Pharmacology (12.3) in the full prescribing information]. 7.4 Effect of Concomitant Use of VOTRIENT and Simvastatin Concomitant use of VOTRIENT and simvastatin increases the incidence of ALT elevations. Across monotherapy trials with VOTRIENT, ALT >3 X ULN was reported in 126/895 (14%) of patients who did not use statins, compared with 11/41 (27%) of patients who had concomitant use of simvastatin. If a patient receiving concomitant simvastatin develops ALT elevations, follow dosing guidelines for VOTRIENT or consider alternatives to VOTRIENT [see Warnings and Precautions (5.1)]. Alternatively, consider discontinuing simvastatin [see Warnings and Precautions (5.1)]. Insufficient data are available to assess the risk of concomitant administration of alternative statins and VOTRIENT. 7.5 Drugs that Raise Gastric pH In a drug interaction trial in patients with solid tumors, concomitant administration of pazopanib with esomeprazole, a proton pump inhibitor (PPI), decreased the exposure of pazopanib by approximately 40% (AUC and Cmax). Therefore, concomitant use of VOTRIENT with drugs that raise gastric pH should be avoided. If such drugs are needed, short-acting antacids should be considered in place of PPIs and H2-receptor antagonists. Separate antacid and pazopanib dosing by several hours to avoid a reduction in pazopanib exposure [see Clinical Pharmacology (12.3) in the full prescribing information]. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category D [see Warnings and Precautions (5.18)]. VOTRIENT can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of VOTRIENT in pregnant women. In developmental toxicity studies in rats and rabbits, pazopanib was teratogenic, embryotoxic, fetotoxic, and abortifacient. Administration of pazopanib to pregnant rats during organogenesis at a dose level of ≥3 mg/kg/day (approximately 0.1 times the human clinical exposure based on AUC) resulted in teratogenic effects including cardiovascular malformations (retroesophageal subclavian artery, missing innominate artery, changes in the aortic arch) and incomplete or absent ossification. In addition, there was reduced fetal body weight, and pre- and post-implantation embryolethality in rats administered pazopanib at doses ≥3 mg/kg/day. In rabbits, maternal toxicity (reduced food consumption, increased post-implantation loss, and abortion) was observed at doses ≥30 mg/kg/day (approximately 0.007 times the human clinical exposure). In addition, severe maternal body weight loss and 100% litter loss were observed at doses ≥100 mg/kg/day (0.02 times the human clinical exposure), while fetal weight was reduced at doses ≥3 mg/kg/day (AUC not calculated). If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 2 weeks after the last dose of VOTRIENT. 8.3 Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from VOTRIENT, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use The safety and effectiveness of VOTRIENT in pediatric patients have not been established.

In rats, weaning occurs at Day 21 postpartum which approximately equates to a human pediatric age of 2 years. In a juvenile animal toxicology study performed in rats, when animals were dosed from Day 9 through Day 14 postpartum (pre-weaning), pazopanib caused abnormal organ growth/maturation in the kidney, lung, liver, and heart at approximately 0.1 times the clinical exposure, based on AUC in adult patients receiving VOTRIENT. At approximately 0.4 times the clinical exposure (based on the AUC in adult patients), pazopanib administration resulted in mortality. In repeat-dose toxicology studies in rats including 4-week, 13-week, and 26-week administration, toxicities in bone, teeth, and nail beds were observed at doses ≥3 mg/kg/day (approximately 0.07 times the human clinical exposure based on AUC). Doses of 300 mg/kg/day (approximately 0.8 times the human clinical exposure based on AUC) were not tolerated in 13- and 26-week studies and animals required dose reductions due to body weight loss and morbidity. Hypertrophy of epiphyseal growth plates, nail abnormalities (including broken, overgrown, or absent nails) and tooth abnormalities in growing incisor teeth (including excessively long, brittle, broken, and missing teeth, and dentine and enamel degeneration and thinning) were observed in rats at doses ≥30 mg/kg/day (approximately 0.35 times the human clinical exposure based on AUC) at 26 weeks, with the onset of tooth and nail bed alterations noted clinically after 4 to 6 weeks. Similar findings were noted in repeat-dose studies in juvenile rats dosed with pazopanib beginning Day 21 postpartum (post-weaning). In the postweaning animals, the occurrence of changes in teeth and bones occurred earlier and with greater severity than in older animals. There was evidence of tooth degeneration and decreased bone growth at doses ≥30 mg/kg (approximately 0.1 to 0.2 times the AUC in human adults at the clinically recommended dose). Pazopanib exposure in juvenile rats was lower than that seen at the same dose levels in adult animals, based on comparative AUC values. At pazopanib doses approximately 0.5 to 0.7 times the exposure in adult patients at the clinically recommended dose, decreased bone growth in juvenile rats persisted even after the end of the dosing period. Finally, despite lower pazopanib exposures than those reported in adult animals or adult humans, juvenile animals administered 300 mg/kg/dose pazopanib required dose reduction within 4 weeks of dosing initiation due to significant toxicity, although adult animals could tolerate this same dose for at least 3 times as long [see Warnings and Precautions (5.17)]. 8.5 Geriatric Use In pooled clinical trials with VOTRIENT, 30% (618/2,080) of patients were aged ≥65 years. Patients aged ≥65 years had an increase in ALT elevations of >3 X ULN compared to patients aged <65 years (23% versus 18%) [see Warnings and Precautions (5.1)]. In the STS trials, 24% (93/382) of patients were aged ≥65 years. Patients aged ≥65 years had increased Grade 3 or 4 fatigue (19% versus 12% for <65), hypertension (10% versus 6%), decreased appetite (11% versus 2%), and ALT (3% versus 2%) or AST elevations (4% versus 1%). Other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. 8.6 Hepatic Impairment In clinical trials for VOTRIENT, patients with total bilirubin ≤1.5 X ULN and AST and ALT ≤2 X ULN were included [see Warnings and Precautions (5.1)]. An analysis of data from a pharmacokinetic trial of pazopanib in patients with varying degrees of hepatic dysfunction suggested that no dose adjustment is required in patients with mild hepatic impairment (either total bilirubin within normal limit [WNL] with ALT >ULN or bilirubin >1 X to 1.5 X ULN regardless of the ALT value). The maximum tolerated dose in patients with moderate hepatic impairment (total bilirubin >1.5 X to 3 X ULN regardless of the ALT value) was 200 mg per day (N=11). The median steady-state Cmax and AUC(0-24) achieved at this dose was approximately 40% and 29%, respectively, of that seen in patients with normal hepatic function at the recommended daily dose of 800 mg. The maximum dose explored in patients with severe hepatic impairment (total bilirubin >3 X ULN regardless of the ALT value) was 200 mg per day (N=14). This dose was not well tolerated. Median exposures achieved at this dose were approximately 18% and 15% of those seen in patients with normal liver function at the recommended daily dose of 800 mg. Therefore, VOTRIENT is not recommended in these patients [see Clinical Pharmacology (12.3) in the full prescribing information]. 8.7 Renal Impairment There are no clinical or pharmacokinetic data in patients with severe renal impairment or in patients undergoing peritoneal dialysis or hemodialysis. However, renal impairment is unlikely to significantly affect the pharmacokinetics of pazopanib since <4% of a radiolabeled oral dose was recovered in the urine. In a population pharmacokinetic analysis using 408 patients with various cancers, creatinine clearance (30- to 150 mL/min) did not influence clearance of pazopanib. Therefore, renal impairment is not expected to influence pazopanib exposure, and dose adjustment is not necessary.

10 OVERDOSAGE Pazopanib doses up to 2,000 mg have been evaluated in clinical trials. Doselimiting toxicity (Grade 3 fatigue) and Grade 3 hypertension were each observed in 1 of 3 patients dosed at 2,000 mg daily and 1,000 mg daily, respectively. Treatment of overdose with VOTRIENT should consist of general supportive measures. There is no specific antidote for overdosage of VOTRIENT. Hemodialysis is not expected to enhance the elimination of VOTRIENT because pazopanib is not significantly renally excreted and is highly bound to plasma proteins. 17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). The Medication Guide is contained in a separate leaflet that accompanies the product. However, inform patients of the following: • Therapy with VOTRIENT may result in hepatobiliary laboratory abnormalities. Monitor serum liver tests (ALT, AST, and bilirubin) prior to initiation of VOTRIENT and at Weeks 3, 5, 7, and 9. Thereafter, monitor at Month 3 and at Month 4, and as clinically indicated. Inform patients that they should report signs and symptoms of liver dysfunction to their healthcare provider right away. • Prolonged QT intervals and torsades de pointes have been observed. Patients should be advised that ECG monitoring may be performed. Patients should be advised to inform their physicians of concomitant medications. • ILD has been reported in association with VOTRIENT. Patients should be advised to report pulmonary signs or symptoms indicative of ILD or pneumonitis. • Cardiac dysfunction (such as CHF and LVEF decrease) has been observed in patients at risk (e.g., prior anthracycline therapy) particularly in association with development or worsening of hypertension. Patients should be advised to report hypertension or signs and symptoms of congestive heart failure. • Serious hemorrhagic events have been reported. Patients should be advised to report unusual bleeding. • Arterial thrombotic events have been reported. Patients should be advised to report signs or symptoms of an arterial thrombosis. • Reports of pneumothorax and venous thromboembolic events, including pulmonary embolus, have been reported. Patients should be advised to report if new onset of dyspnea, chest pain, or localized limb edema occurs.

• Advise patients to inform their doctor if they have worsening of neurological function consistent with RPLS (headache, seizure, lethargy, confusion, blindness, and other visual and neurologic disturbances). • Hypertension and hypertensive crisis have been reported. Patients should be advised to monitor blood pressure early in the course of therapy and frequently thereafter and report increases of blood pressure or symptoms such as blurred vision, confusion, severe headache, or nausea and vomiting. • GI perforation or fistula has occurred. Advise patients to report signs and symptoms of a GI perforation or fistula. • VEGFR-inhibitors such as VOTRIENT may impair wound healing. Advise patients to stop VOTRIENT at least 7 days prior to a scheduled surgery. • Hypothyroidism and proteinuria have been reported. Advise patients that thyroid function testing and urinalysis will be performed during treatment. • Serious infections, including some with fatal outcomes, have been reported. Advise patients to promptly report any signs or symptoms of infection. • Advise females of reproductive potential of the potential hazard to the fetus and to use effective contraception during treatment and for at least 2 weeks after the last dose of VOTRIENT. • Gastrointestinal adverse reactions such as diarrhea, nausea, and vomiting have been reported with VOTRIENT. Patients should be advised how to manage diarrhea and to notify their healthcare provider if moderate to severe diarrhea occurs. • Patients should be advised to inform their healthcare providers of all concomitant medications, vitamins, or dietary and herbal supplements. • Patients should be advised that depigmentation of the hair or skin may occur during treatment with VOTRIENT. • Patients should be advised to take VOTRIENT without food (at least 1 hour before or 2 hours after a meal). Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 © Novartis T2016-64 August 2016

LATEST NEWS | SKIN CANCER

Alcohol Intake May Increase Risk for Non-melanoma Skin Cancer Alcohol intake may increase one’s risk of developing basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) in a dose-dependent manner, according to an article published in the British Journal of Dermatology. Non-melanoma skin malignancies are the most common cancer types in the US. While ultraviolet radiation is directly linked to BCC and cSCC risk, the relationship between alcohol and these cancers is indeterminate. For this meta-analysis, researchers reviewed findings from 13 case-control/cohort studies, which comprised 91,942 BCC cases and 3299 sCC cases, to determine any link between alcohol intake and non-melanoma skin cancer incidence. The summary relative risk of developing BCC increased by 1.07 (95% CI, 1.04-1.09) for each 10-gram increase of alcohol intake per day; for cSCC the summary relative risk was 1.11 (95% CI, 1.06-1.16). The authors noted, however, that while the association between BCC and alcohol intake may not be linear, data are inconclusive among individuals with high alcohol intake. One factor that may contribute to the association between alcohol intake and non-melanoma skin cancer is the prevalence of behaviors leading to sunburn among drinkers.

Adjuvant Therapy With Dabrafenib Plus Trametinib May Provide Benefit in Melanoma Dabrafenib plus trametinib adjuvant therapy significantly lowered the risk of recurrence in patients with BRAFV600E or V600K –mutation positive stage III melanoma compared with placebo, according to a study published in The New England Journal of Medicine. Complete resection is the standard therapy for patients with early-stage melanoma, leading to 5-year survival rates of 98%

for stage I and 90% for stage II. Patients with advanced melanoma, however, have much higher rates of recurrence even after resection, as there is regional involvement at diagnosis. For the phase 3 COMBI-AD study (ClinicalTrials.gov Identifier: NCT01682083), investigators randomly assigned 870 patients with advanced melanoma with BRAF V600E/K mutations who had undergone complete resection to receive oral trametinib 2 mg once daily and dabrafenib 150 mg twice daily vs placebo for 1 year. The median follow-up was 2.8 years. Patients who received adjuvant therapy with dabrafenib and trametinib had an estimated 3-year rate of relapse-free survival of 58% vs 39% in patients who received placebo (hazard ratio [HR], 0.47; 95% CI, 0.39-0.58; P < .001). The 3-year overall survival rate in the combination therapy arm and placebo arm was 86% and 77%, respectively (HR, 0.57; 95% CI, 0.42-0.79; P = .0006), but did not meet the pre-specified interim analysis boundary of P = .000019 to meet statistical significance. The combination group also had higher rates distant metastasis-free survival.

Pembrolizumab Plus Reduced-dose Ipilimumab Safe in Advanced Melanoma Patients with advanced melanoma may have good outcomes when treated with standard-dose pembrolizumab with 4 doses of reduced-dose ipilimumab, according to a study published in The Lancet Oncology. Previous studies demonstrated that combining standard-dose ipilimumab and reduced-dose nivolumab improved objective response (OR) and progression-free survival (PFS) in patients with advanced melanoma, but had increased toxicity. The phase 1b KEYNOTE-029 trial (ClinicalTrials.gov Identifier: NCT02089685) enrolled 153 patients with advanced melanoma who were immune checkpoint inhibitor–naive to receive intravenous (IV) pembrolizumab 2 mg/kg plus IV ipilimumab 1 mg/kg every 3 weeks for 4 doses, followed by IV pembrolizumab 2 mg/kg every 3 weeks for up to 2 years. Of the 153 patients, 72% received all 4 doses of the pembrolizumab plus ipilimumab combination, and 42% remained on pembrolizumab therapy. Forty-five percent of patients had grade 3 to 4 treatment-related adverse effects (AE), which led to discontinuation in 14% of patients. OR was observed in 61% (95% CI, 53%-69%) of patients. One-year OS was 89% (95% CI, 83%-93%); 1-year PFS was 69% (95% CI, 60%-75%). No treatment-related deaths were observed.

A20 CANCER THERAPY ADVISOR | NOVEMBER/DECEMBER 2017 | CancerTherapyAdvisor.com

The trials resulted in 17 patients having objective responses, as well as 1 partial response that was sustained for 16 months. The approved dose is 3 mg/kg IV administered over 90 minutes every 3 weeks for 4 cycles. The most frequently observed adverse events associated with ipilimumab are immune-mediated and include enterocolitis, dermatitis, hepatitis, endocrinopathy, and neuropathy.

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

harmD,

RPh

Celiac Plexus Neurolysis for Pain Management in Patients With Pancreatic Cancer CPN may provide significant pain relief and a chance to reduce the number of required narcotics.

ne of the most challenging aspects of pancreatic cancer treatment is pain management. Nearly 80% of patients will have abdominal pain at time of diagnosis, and while the pain is typically epigastric, it may also occur in the upper abdomen and back.1 These patients also frequently experience additional gastrointestinal (GI) symptoms including nausea, vomiting, and weight loss. Narcotics and non-narcotics are used to treat pancreatic cancer–associated pain, though non-narcotics, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are frequently ineffective or may be contraindicated. Narcotics provide some pain relief but are associated with numerous side effects, such as nausea and constipation, which can compound the already-debilitating GI symptoms. The celiac plexus, which is located in a branch of the abdominal aorta, is a nerve network linked with pancreatic cancer–associated pain. Procedures that target this network to modulate pain include celiac plexus block (CPB), which uses steroids such as triamcinolone, and celiac plexus neurolysis (CPN), which uses alcohol and bupivacaine.2,3 While CPB is a temporary treatment more often used for patients with chronic pancreatitis, CPN is a permanent treatment based on the use of alcohol as a neurolytic agent, and is more frequently used for patients with pancreatic cancer.

Both procedures can be performed endoscopically (endoscopic ultrasound [EUS]) or non-endoscopically (surgery, percutaneous), though the endoscopic route is performed more frequently. For CPB, triamcinolone is injected; CPN uses bupivacaine and alcohol. Studies evaluating CPN for pancreatic cancer-associated pain report pain relief among up to 80% of patients.4

Patients can also experience post-procedural diarrhea, which in about 1% of cases is permanent. There are also reports of an increased infection risk among patients undergoing CPB who are on acid-suppressing medications.6 This AE is not as much of a concern in patients undergoing CPN, however, as the alcohol may also function as a bactericidal agent. CPN may provide significant pain relief and an opportunity to reduce the amount of required narcotics. ■ REFERENCES

1. Porta M, Fabregat X, Malats N, et al. Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage. Clin Transl Oncol. 2005;7(5):189-97. 2. Puli SR, Reddy JB, Bechtold ML, Antillon MR, Brugge WR. EUS-guided celiac plexus neurolysis for pain due to chronic pancreatitis or pancreatic cancer related pain: a

Narcotics provide pain relief but are associated with side effects, such as nausea and constipation.

meta-analysis and literature review. Dig Dis

Sci. 2009;54(11):2330-7. 3. Kaufman M, Singh G, Das S, et al. Efficacy of endoscopic ultrasound-guided celiac plexus block and celiac plexus neurolysis for managing abdominal pain associated with chronic pancreatitis and pancreatic cancer.

J Clin Gastroenterol. 2010;44(2):127. 4. Gunaratnam NT, Sarma AV, Norton ID,

Most adverse events (AEs) associated with these procedures are secondary to manipulation of the celiac plexus and the resulting alteration in the neurologic innervation. One study found a serious complication rate of less than 2%; observed AEs included hypotension, severe abdominal pain, and intra-abdominal abscess. 5 Patients should therefore be closely monitored for hypotension both during and immediately after the procedure for hypotension. Hypotension may be seen beyond the immediate post-procedural monitoring period in these patients, but this is rare.

Wiersema MJ. A prospective study of EUSguided celiac plexus neurolysis for pancreatic cancer pain. Gastrointest Endosc. 2001;54(3):316-24. 5. O’Toole TM, Schmulewitz N. Complication rates of EUS-guided celiac plexus blockade and neurolysis: results of a large case series.

Endoscopy. 2009;41(7):593-7. 6. Gress F, Schmitt C, Sherman S, Ciaccia D, Ikenberry S, Lehman G. Endoscopic ultrasound-guided celiac plexus block for managing abdominal pain associated with chronic pancreatitis: a prospective single center experience. Am J Gastroenterol. 2001;96(2):409-16.

CancerTherapyAdvisor.com | NOVEMBER/DECEMBER 2017 | CANCER THERAPY ADVISOR A21

FEATURE

BRYANT FURLOW

n quick succession, Hurricanes Harvey, Irma, and Maria hit the Texas gulf coast, Florida, Puerto R ico, and other Caribbean islands. The storms and ensuing flooding briefly shut down the University of Texas MD Anderson Cancer Center campus in Houston and several cancer centers in Florida. But hardest hit this season — by far — was Puerto Rico. “The island is totally devastated,” Fernando Cabanillas, MD, medical director of the cancer center at Auxilio Mutuo Hospital in San Juan, told Cancer Therapy Advisor. “If you were not aware that a category 5 hurricane had crossed through the island, you would easily think a nuclear bomb had been dropped.” Oncologists and patients on the island have faced numerous challenges in Hurricane Maria’s “totally chaotic” aftermath, Dr Cabanillas said. “Patients are not able to come to their appointments for several reasons. Some are stuck in their towns with no way to get out. Some live in small towns in the mountains where bridges over rivers have been washed away. Others don’t have gasoline to drive to their appointments.” Without functioning cell towers in much of the island, furthermore, cancer centers and patients are unable to communicate.

Three powerful hurricanes battered Texas, Florida, and Puerto Rico in quick succession, and the ensuing floods disrupted cancer care in several affected locations.

“We don’t have a way of telling how many patients will show up for their appointments,” Dr Cabanillas noted. “Some drop in without an appointment while others never show up at all.” Before Hurricane Maria, approximately 600 patients a day were treated for cancer in Puerto Rico. Since the storm, more than 90% of patients have missed treatments or seen treatment delays. Drug supplies have been “problematic” because of delivery problems, causing additional treatment delays. “Many oncologists don’t have enough diesel fuel to run generators and are keeping chemotherapy drugs refrigerated at home,” said Michael Diaz, MD, of the Florida Cancer Specialists & Research Institute in St Petersburg. Chemotherapy drugs at other clinics among at least 75 facilities that offer cancer care on the island have been lost because of power and refrigeration failures, he added. Some cancer centers have not received replacement drug deliveries. “Radiotherapy cannot run off generators — they don’t provide the flat, continuous power needed,” Dr Diaz said. “Operating rooms are not usable because of flooding and damage — they’re not suitable, don’t meet the criteria for performing surgeries.” Pathology labs face similar challenges, with diesel tanks running low on fuel, endangering “months’ worth” of laboratory chemicals.

A22 CANCER THERAPY ADVISOR | NOVEMBER/DECEMBER 2017 | CancerTherapyAdvisor.com

Hurricane Aftermath Tests Cancer Centers in Puerto Rico, Florida, and Houston

FEATURE “Everybody is struggling just to get clean water,” Dr Diaz said. Pharmacies across the island have remained closed since the storm tore through the island on September 21. There has been some effort to evacuate individual patients to cancer centers in Florida. “We saw some patients from Puerto Rico who wanted to come here to continue their treatment,” said Jack Kolosky, CPA, MBA, chief operating officer at the Moffitt Cancer Center in Tampa, Florida. “The problem is logistics, frankly — getting them to the airport, booking a plane.” Puerto Rico has not formally requested evacuations of cancer patients to the mainland, a US Department of Health and Human Services official told Cancer Therapy Advisor. The Defense Department and Defense Logistics Agency did not respond to voice messages and e-mails requesting details about plans to move patients from Puerto Rico to the mainland. Some patients are getting themselves to the mainland for cancer treatment, Dr Cabanillas said. “Those who have the resources to hire private airplanes do so and leave the island,” he said. “I know of a good number of them who have left for the US, including at least 2 of my patients.” “It is going to be a long time before things are back to normal — 6 or 12 months before it’s business as usual,” Dr Diaz said. “This could prove to be a devastating catastrophe as far as cancer care is concerned, let alone everything else.” Possible Drug Shortages on the Mainland Hurricane Maria and flood waters could also affect patients on the mainland in the weeks ahead. The US Food and Drug Administration (FDA) has deployed more than 200 public health officers to the area and was flying additional teams to the island on Friday,

September 29, to inspect dozens of drug and medical device manufacturing plants on the island. FDA officials warned of possible nationwide and even global shortages of as-yet unspecified cancer drugs and other medications produced on the island. Baxter International has announced that damage to its facilities will disrupt shipments of IV saline solution, exacerbating a shortage predating the Hurricane.1,2 Shortages are possible for cancer drugs and immunosuppressants used in organ transplantation, FDA Commissioner Scott Gottlieb, MD, said in a press release.3 “These are products that are used daily in hospitals, outpatient clinics,

“It is going to be a long time before things are back to normal — 6 or 12 months before it’s business as usual.” and homes,” Dr Gottlieb said. “This is both a short- and long-term issue. We need to ensure access to these critical treatments for Americans who need them, but also recognize the important role that the medical product industry plays in helping Puerto Rico sustain its economy and help in its recovery.” Pharmaceutical and medical products represent 72% of Puerto Rico’s exports.4 MD Anderson in Houston and Florida Cancer Centers Fared Much Better Despite extensive and serious flooding in Houston following Hurricane Harvey, the University of Texas MD Anderson Cancer Center’s facilities were not inundated, thanks to an extensive system of more

than 75 floodgates built after Tropical Storm Allison in 2001, said interim chief medical officer Karen Lu, MD. “We’ve been through this before,” Dr Lu said. “There are a series of steps in place when a significant hurricane comes our way. We brought in enough food, cots. “We didn’t have any flooding. We had some water damage in the patient lobby because of back-up in a storm water drain.” That meant that no clinical, research, or lab facilities were damaged when Hurricane Harvey made landfall on Friday, August 25. “In addition to 540 in-patients, we had probably 1000 faculty and staff on site, clinicians, nurses, residents, lab techs, surgical techs, and housekeeping and security personnel,” Dr Lu told Cancer Therapy Advisor. “Nobody could really get in or out for about 36 hours. Different areas of Houston were flooding at different times, so nobody could get in all day that Sunday. “On Monday, those who were closer to the medical center could start getting to the hospital. By that afternoon, reinforcements had arrived to relieve the storm ride-out team.” Hurricane Harvey was a reminder that it takes many more people than oncologists and oncology nurses to run a cancer hospital, added Dr Lu, noting blood bank workers, pharmacy technicians, pharmacists, and support staff. Cancer centers across Florida similarly weathered Irma with minimal disruptions, officials told Cancer Therapy Advisor. Preparation meetings and incident command centers were established early and, unlike the situation in Puerto Rico, centers in Florida did not see communications or sustained power outages. Todd Schonherz, chief operating officer of Florida Cancer Specialists & Research Institute in Fort Myers, the largest medical oncology provider in the Continued on page A27

CancerTherapyAdvisor.com | NOVEMBER/DECEMBER 2017 | CANCER THERAPY ADVISOR A23

VIEWPOINT | LEAH LAWRENCE

Experts warn that the vitamin B3 supplement should not be taken for melanoma prevention unless an individual is at particularly high risk for the disease.

he risk of an invasive or in situ melanoma diagnosis is continuing to increase, with one recent study estimating the lifetime risk of developing either condition as 1 in 28.1 Nicotinamide, a form of vitamin B3 (niacin), is a “promising and well-tolerated” chemopreventive agent for patients at high risk for developing skin cancer, according to the results of a recent review of the agent.2 “Preclinical studies of nicotinamide have demonstrated important anticancer properties including DNA repair and the modulation of inflammation and immune suppression induced by damaging ultraviolet radiation,” Ahmad Tarhini, MD, PhD, of the Cleveland Clinic Taussig Cancer Institute in Ohio, told Cancer Therapy Advisor. ONTRAC was a phase 3 study that compared nicotinamide with placebo in 386 patients with at least 2 non-melanoma skin cancers in the previous 5 years.3 By 1 year, nicotinamide reduced the rate of new non-melanoma skin cancers by about 25% compared with placebo. “Nicotinamide can reduce the rate of non-melanoma skin cancer in high-risk patients who have already had numerous basal cell and squamous cell carcinomas,” said review author Diona L. Damian, PhD, professor of dermatology at the University of Sydney in Australia. To date, there have not been any adverse effects associated with the use of nicotinamide that cause concern, according

to Dr Damian. In the ONTRAC study, for example, there were no significant differences in adverse events between the 2 study arms after the 1-year intervention. The ONTRAC study did not, however, assess nicotinamide in melanoma and excluded anyone with a history of melanoma in the previous 5 years. “At this point in time we do not have clinical evidence from well-conducted studies that nicotinamide may affect the incidence or evolution of melanoma,” Dr Tarhini said. “Therefore, at best we can say that it is considered promising.” Dr Damian agreed, adding that “clinical trials would be needed to determine safety and effectiveness of nicotinamide in reducing melanoma risk in patients at high risk of [the disease].”

These trials would have to recruit patients at an increased risk for developing melanoma, not just skin cancer. These would be people with previous melanoma or those with genetic susceptibility. Dr Damian recommended the use of high-dose nicotinamide as a medical treatment only in those people at “extreme skin cancer risk,” like those with a history of multiple skin cancers. According to Dr Damian, anyone considering taking high-dose nicotinamide should discuss it with their dermatologist to check about drug interactions. ■ REFERENCES

1. Glazer AM, Winkelmann RR, Farberg AS, Rigel DS. Analysis of trends in US melanoma incidence and mortality. JAMA Dermatol. 2017;153(2):225-6. 2. Minocha R, Damian DL, Halliday GM. Melanoma and nonmelanoma skin cancer chemoprevention: a role for nicotinamide?

Photodermatol Photoimmunol Photomed. 2017 Jul 5. doi: 10.1111/phpp.12328 [Epub ahead of print] 3. Chen AC, Martin AJ, Choy B, et al. A phase

Nicotinamide molecule

A24 CANCER THERAPY ADVISOR | NOVEMBER/DECEMBER 2017 | CancerTherapyAdvisor.com

3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015;373:1618-26.

Should Nicotinamide Be Used for Melanoma Prevention?

Skin Cancer Advisor A section of Cancer Therapy Advisor that features exclusive news and clinical content for oncologists who specialize in the treatment of patients with skin cancer. Visit CancerTherapyAdvisor.com/SkinCancer to access the following and more:

• Articles on the latest news in skin cancer written by experts • • Skin Cancer Treatment Regimens adapted from NCCN Guidelines® • • An extensive range of current and concise drug information • • Videos of oncology experts speaking about key topics in the field of skin cancer management •

EXPERT PERSPECTIVE | MARIO SZNOL, MD

Long-term Survival From Ipilimumab/Nivolumab in Metastatic Melanoma Mario Sznol, MD, of the Yale University School of Medicine in New Haven, Connecticut, discusses data just published in the Journal of Clinical Oncology.

ccumulating data from longterm follow-up of patients with metastatic melanoma treated with the ipilimumab and nivolumab combination demonstrate unprecedented survival at 3 years. With at least 36 months of follow-up for all patients, Wolchok et al reported 58% overall 3-year survival in the ipilimumab/nivolumab combination arm for the 314 previously untreated patients enrolled in the CA209-067 randomized trial (ClinicalTrials.gov Identifier: NCT01844505).1 Among the 94 patients with metastatic disease treated on the first phase 1 trial of a ipilimumab/nivolumab combination (CA209-004; ClinicalTrials.gov Identifier: NCT01024231), Callahan et al reported a 3-year overall survival rate of 63%.2 Patients with poor prognostic features appeared to benefit from the combination; 3-year survival rates were 44% and 31% in patients with baseline LDH > ULN and > 2x ULN, respectively, in the CA209-067 trial, and were 61% and 28%, respectively, in the CA209-004 trial. The CA209-067 trial included arms for nivolumab alone and ipilimumab alone, but was not designed to directly compare the combination to nivolumab alone. The 3-year survival rate with nivolumab in this trial was 52%. In exploratory post-hoc subset analyses, higher survival for the

combination compared with nivolumab alone was most apparent in the subgroup of patients with tumor PD-L1 expression of less than 1% (3-year survival 54% vs 42%, respectively), and in the subgroup of patients with BRAF-mutated disease (3-year survival 68% vs 56%, respectively).

Patients with poor prognostic features appeared to benefit from the combination. Survival at 3 years was also numerically higher for the combination among patients with high and very high baseline LDH (44% vs 34%; 31% vs 14%, respectively). In an unexplained finding, patients treated in the United States appeared to have greater survival benefit from the combination than patients treated in Europe. In the CA209-004 trial, survival was not different among patients with or without a BRAF tumor mutation. For patients with a BR AF tumor mut at ion , a n on g oi n g E C O G trial (ClinicalTrials.gov Identifier: NCT02224781) is comparing first-line dabrafenib/trametinib treatment with ipilimumab/nivolumab, with a planned switch to the alternate combination at

progression. The primary endpoint is comparison of survival at 2 years. Using retrospective data, and in apparently similar patient populations, the ipilimumab/nivolumab combination appears to provide higher 3-year survival than targeted therapy. In the CA209-067 and CA209-004 trials, 3-year survival in patients with a tumor BRAF mutation was 68% and 63% respectively; 3-year survival for dabrafenib/trametinib in a pooled analysis of 563 patients was approximately 45%.3 Among the subset with LDH > ULN, dabrafenib-trametinib produced a 3-year survival of only 22%. While difficult to assess and report in trials, the approach to patient management may affect long-term survival rates in a small subset of patients. For example, patients developing severe toxicity before completion of the planned 4 cycles of the ipilimumab/nivolumab combination are not re-challenged with the combination. Although a substantial proportion of these patients may develop durable responses without additional therapy, nivolumab alone can be administered with caution after resolution of toxicity, and in a subset of patients may provide additional clinical benefit. Disease progression in patients during or after therapy completion may be limited to a few sites only; radiation or surgery for limited progression may produce longterm recurrence-free survival. Finally, a subset of patients developing disease progression after therapy discontinuation can respond again to re-induction with the combination â&#x20AC;&#x201D; possibly receiving additional survival benefit. Cumulative safety data from multiple trials of the ipilimumab/nivolumab combination and nivolumab alone in metastatic melanoma demonstrate substantially higher rates of grade 3 to 4 adverse events for the combination (in the range of 55% to 60%).4,5 While most

A26 CANCER THERAPY ADVISOR | NOVEMBER/DECEMBER 2017 | CancerTherapyAdvisor.com

EXPERT PERSPECTIVE severe adverse events can be managed with corticosteroids and, in some cases, secondary immune suppressive agents, a subset of patients will develop prolonged morbidity before resolution of toxicity, and in rare cases, deaths have been observed. The potential for improved survival with the combination must therefore be weighed against the potential for increased toxicity when choosing therapy for individual patients. Although not definitive, the post-hoc survival analyses in subgroups could be used to inform the risk-benefit calculation when making individual treatment decisions. It is unknown if administration of ipilimumab/nivolumab to patients with progression or suboptimal response to anti-PD-1 alone would produce equivalent overall survival compared with initial concurrent administration. Data from trials in other malignancies suggest

Feature Continued from page A23

state, said: “We already had a plan in place to consolidate offices throughout the state, moving physicians, nurses, and other staff to locations that had electrical power and were accessible to both patients and practice staff. That plan allowed us to make sure that patients were able to continue to be treated, just potentially at a different office in a different part of town.” “We had identified essential staff and backup teams well ahead of time,” Moffitt’s Jack Kolosky reported. “We had essential staff here by 5 am on the Sunday of the event. When people had questions or issues, they called the command center.” Moffitt had 160 inpatients during the storm — “slightly more” than an average weekend. “You have patients in the middle of bone marrow transplants or something

that the toxicity of the combination may be reduced by altering the dose ratio of ipilimumab and nivolumab. To test this question, a randomized trial (ClinicalTrials.gov Identifier: NCT02714218) comparing the approved dose and schedule to a regimen employing a higher dose of nivolumab with a lower dose of ipilimumab was initiated. If equal efficacy is achieved with lower toxicity, the addition of other promising agents to the ipilimumab/nivolumab combination may be possible to further improve overall survival. ■

advanced melanoma: updated survival, response, and safety data in a phase I dose-escalation study. J Clin Oncol. 2017 Oct 17. doi: 10.1200/JCO.2017.72.2850 [Epub ahead of print] 3. Schadendorf D, Long GV, Stroiakovski D, et al. Three-year pooled analysis of factors associated with clinical outcomes across dabrafenib and trametinib combination therapy phase 3 randomised trials. Eur

J Cancer. 2017;82:45-55. doi: 10.1016/j. ejca.2017.05.033 4. Weber JS, Hodi FS, Wolchok JD, et al. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melano-

REFERENCES

1. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab

ma. J Clin Oncol. 2017;35(7):785-92. doi: 10.1200/JCO.2015.66.1389 5. Sznol M, Ferrucci PF, Hogg D, et al. Pooled

and ipilimumab in advanced melanoma.

analysis safety profile of nivolumab and ipili-

N Engl J Med. 2017;377(14):1345-56. doi:

mumab combination therapy in patients with

10.1056/NEJMoa1709684 2. Callahan MK, Kluger H, Postow MA, et al. Nivolumab plus ipilimumab in patients with

like that, they can’t just go home,” Mr Kolosky said. Other patients with treatments already scheduled between Sunday and Tuesday were brought into the hospital ahead of the storm. Some patients were lost to follow-up in storm evacuations from the Houston area and in Florida, officials at MD Anderson and Florida centers acknowledged. But the vast majority of patients were rescheduled. By chance, when an office manager was evaluating a clinic in Deland, Florida, the day after the storm, an electrical contractor working to restore power to central Florida approached her about missing his Hodgkin lymphoma chemotherapy back home in Illinois, said Mr Schonherz. She had his paperwork sent from Illinois and he was scheduled for chemotherapy. Whether similarly uncomplicated solutions will be available to patients from Puerto Rico, however, remains to be seen. ■

advanced melanoma. J Clin Oncol. 2017 Sep 15. doi: 10.1200/JCO.2016.72.1167 [Epub ahead of print]

REFERENCES

1. Loftus P, Rockoff JD. Baxter says saline shipments disrupted in hurricane-wracked Puerto Rico. Wall Street Journal. http:// on.wsj.com/2guZCfl. Published September 27, 2017. Accessed September 2017. 2. Loftus P. Shortages of simple drugs thwart treatments: inexpensive medicines such as sterile talc and dextrose are in short supply, posing difficulties for doctors and patients.

Wall Street Journal website. http://on.wsj. com/2uBTeV3. Published July 1, 2017. Accessed September 2017. 3. FDA’s support of the hurricane relief effort [news release]. Silver Spring, MD: US Food and Drug Administration; September 28, 2017. http://bit.ly/2yCuVeX. 4. Keenan J, Palmer E. Hurricane Maria shutters much of Puerto Rico’s pharma manufacturing. FiercePharma website. http://bit. ly/2xRYpGi. Published September 26, 2017. Accessed September 2017.

CancerTherapyAdvisor.com | NOVEMBER/DECEMBER 2017 | CANCER THERAPY ADVISOR A27

REGIMEN & MONOGRAPH INDEX CANCER THERAPY REGIMENS & DRUG MONOGRAPHS 1 Bone Cancer 3 Brain Cancer 5 Breast Cancer

 Breast Cancer (Invasive)

17 Endocrine Cancer 21 Gastrointestinal Cancer 27 Genitourinary Cancer 37 Gynecologic Cancer 40 Head and Neck Cancer 42 Hematologic Cancer

 Hodgkin Lymphoma  Non-Hodgkin Lymphoma:

Adult T Cell Leukemia/Lymphoma

71 Lung Cancer

 Non–small Cell Lung Cancer

88 Sarcoma 89 Skin Cancer

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.

IMPORTANT INFORMATION FOR ALL READERS CANCER THERAPY ADVISOR 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 MPR is not necessarily reviewed by the supplier of a particular drug. If any questions arise about information in MPR, 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, MPR 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, MPR 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. MPR is offered to assist physicians in this area. © 2017 Haymarket Media, Inc.

A28 CANCER THERAPY ADVISOR | NOVEMBER/DECEMBER 2017 | CancerTherapyAdvisor.com

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 (Child-Pugh C): insufficient data. Embryofetal 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, nonabsorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin). Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome). How supplied: 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

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DRUG MONOGRAPHS

BONE CANCER 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

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. Embryofetal 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 life-threatening 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

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 ℞

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

℞

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 for 5 consecutive days if tolerated; continue until disease progression, discontinue if minimum dose not tolerated. Children: Not established.

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DRUG MONOGRAPHS

BRAIN CANCER 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-cisretinoic acid (RA), for the treatment of children with high-risk 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

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)

2–3

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

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%

INTERPRETATION OF CHILD-PUGH SCORES

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CANCER TREATMENT REGIMEN

BREAST CANCER Breast Cancer (Invasive) Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are 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 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.

Neoadjuvant/Adjuvant Chemotherapya,b,c,d,e Note: All recommendations are category 2A unless otherwise indicated.

REGIMEN

DOSING

Preferred Regimens for HER2-negative Disease1,f Dose-dense AC followed by paclitaxel Day 1: Doxorubicin 60mg/m2 IV (Category 1)2 Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 14 days for 4 cycles (all cycles are with myeloid growth factor support; refer to NCCN Guidelines for Myeloid Growth Factors), followed by: Day 1: Paclitaxel 175mg/m2 via 3-hour IV infusion. Repeat cycle every 14 days for 4 cycles (all cycles are with myeloid growth factor support). Dose-dense AC followed by weekly paclitaxel (Category 1)2

Day 1: Doxorubicin 60mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 14 days for 4 cycles, followed by: Day 1: Paclitaxel 80mg/m2 via 1-hour IV infusion weekly for 12 weeks.

TC (Category 1)3

Day 1: Docetaxel 75mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 21 days for 4 cycles (all cycles are with myeloid growth factor support).

Other Regimens for HER2-negative Disease1,f Dose-dense AC (Category 1)2

Day 1: Doxorubicin 60mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 14 days for 4 cycles (all cycles are with myeloid growth factor support).

AC (Category 2B)4

Day 1: Doxorubicin 60mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 21 days for 4 cycles.

TAC (Category 1)5

Day 1: Docetaxel 75mg/m2 IV Day 1: Doxorubicin 50mg/m2 IV Day 1: Cyclophosphamide 500mg/m2 IV. Repeat cycle every 21 days for 6 cycles (all cycles are with myeloid growth factor support).

CMF (Category 1)6

Days 1–14: Cyclophosphamide 100mg/m2 orally Days 1 and 8: Methotrexate 40mg/m2 IV Days 1 and 8: 5-fluorouracil 600mg/m2 IV. Repeat cycle every 28 days for 6 cycles.

AC followed by docetaxel (Category 1)7

Day 1: Doxorubicin 60mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 21 days for 4 cycles, followed by: Day 1: Docetaxel 100mg/m2 IV. Repeat cycle every 21 days for 4 cycles.

AC followed by weekly paclitaxel (Category 1)8

Day 1: Doxorubicin 60mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 21 days for 4 cycles, followed by: Day 1: Paclitaxel 80mg/m2 by 1-hour IV infusion weekly for 12 weeks.

EC (Category 1)9

Day 1: Epirubicin 100mg/m2 IV Day 1: Cyclophosphamide 830mg/m2 IV. Repeat cycle every 21 days for 8 cycles.

continued

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CANCER TREATMENT REGIMEN

BREAST CANCER Breast Cancer (Invasive) Treatment Regimens Preferred Regimens for HER2-positive Disease1,f,g,h,i REGIMEN

DOSING

AC followed by paclitaxel + trastuzumab10,j,k

Day 1: Doxorubicin 60mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 21 days for 4 cycles, followed by: Paclitaxel 80mg/m2 via 1-hour IV infusion weekly for 12 weeks, with: Trastuzumab 4mg/kg IV with first dose of paclitaxel, followed by: Trastuzumab 2mg/kg IV weekly to complete 1 year of treatment. As an alternative, trastuzumab 6mg/kg IV every 21 days may be used following the completion of paclitaxel, and given to complete 1 year of trastuzumab treatment.

AC followed by paclitaxel + trastuzumab + pertuzumab10,j,k

Day 1: Doxorubicin 60mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 21 days for 4 cycles, followed by: Day 1: Pertuzumab 840mg IV followed by 420mg IV Day 1: Trastuzumab 8mg/kg IV followed by 6mg/kg IV Days 1, 8, and 15: Paclitaxel 80mg/m2 IV. Repeat cycle every 21 days for 4 cycles. Day 1: Trastuzumab 6mg/kg IV. Repeat cycle every 21 days to complete 1 year of trastuzumab therapy.

Dose-dense AC followed by paclitaxel Day 1: Doxorubicin 60mg/m2 IV + trastuzumab11,j,k Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 14 days for 4 cycles, followed by: Day 1: Paclitaxel 175mg/m2 via 3-hour IV infusion. Repeat cycle every 14 days for 4 cycles, plus: Trastuzumab 4mg/kg IV with first dose of paclitaxel, followed by: Trastuzumab 2mg/kg IV weekly to complete 1 year of treatment. As an alternative, trastuzumab 6mg/kg IV every 21 days may be used following the completion of paclitaxel, and given to complete 1 year of trastuzumab treatment. TCH12,k

Day 1: Docetaxel 75mg/m2 IV Day 1: Carboplatin AUC 6mg • min/mL IV. Repeat cycle every 21 days for 6 cycles, with: Trastuzumab 4mg/kg IV week 1, followed by 2mg/kg IV for 17 weeks, followed by: Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. OR Trastuzumab 8mg/kg IV week 1, followed by: Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy.

TCH chemotherapy + pertuzumab13,k

Day 1: Trastuzumab 8mg/kg IV followed by 6mg/kg IV Day 1: Pertuzumab 840mg IV followed by 420mg IV Day 1: Docetaxel 75mg/m2 IV Day 1: Carboplatin AUC 6mg • min/mL IV. Repeat cycle every 21 days for 6 cycles, followed by: Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy.

Other Regimens for HER2-positive Disease1,f,g,h,i AC followed by docetaxel + trastuzumab12,j,k

Day 1: Doxorubicin 60mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 21 days for 4 cycles, followed by: Day 1: Docetaxel 100mg/m2 IV. Repeat cycle every 21 days for 4 cycles, with: Trastuzumab 4mg/kg IV week 1, followed by 2mg/kg IV weekly for 11 weeks, followed by: Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy.

AC followed by docetaxel + trastuzumab + pertuzumab13,j,k

Day 1: Doxorubicin 60mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 21 days for 4 cycles, followed by: Day 1: Pertuzumab 840mg IV followed by 420mg IV Day 1: Trastuzumab 8mg/kg IV followed by 6mg/kg IV Day 1: Docetaxel 75–100mg/m2 IV. Repeat cycle every 21 days for 4 cycles, followed by: Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy.

6 CANCER THERAPY ADVISOR | NOVEMBER/DECEMBER 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

BREAST CANCER Breast Cancer (Invasive) Treatment Regimens Other Regimens for HER2-positive Disease1,f,g,h,i (continued) REGIMEN

DOSING

Docetaxel + cyclophosphamide + trastuzumab14,k

Day 1: Docetaxel 75mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 21 days for 4 cycles, with: Trastuzumab 4mg/kg IV week 1, followed by: Trastuzumab 2mg/kg IV weekly for 11 weeks, followed by: Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. OR Trastuzumab 8mg/kg IV week 1, followed by: Trastuzumab 6mg/kg IV every 21 days to complete 1 year of treatment.

FEC followed by pertuzumab + trastuzumab + docetaxel13,j,k

Day 1: Fluorouracil 500mg/m2 IV Day 1: Epirubicin 100mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 21 days for 3 cycles, followed by: Day 1: Pertuzumab 840mg IV followed by 420mg IV Day 1: Trastuzumab 8mg/kg IV followed by 6mg/kg IV Day 1: Docetaxel 75–100mg/m2 IV. Repeat cycle every 21 days for 3 cycles, followed by: Day 1: Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy.

FEC followed by pertuzumab + trastuzumab + paclitaxel13,j,k

Day 1: Fluorouracil 500mg/m2 IV Day 1: Epirubicin 100mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV. Repeat cycle every 21 days for 3 cycles, followed by: Day 1: Pertuzumab 840mg IV followed by 420mg IV Day 1: Trastuzumab 8mg/kg IV followed by 6mg/kg IV Days 1, 8, and 15: Paclitaxel 80mg/m2 IV. Repeat cycle every 21 days for 3 cycles, followed by: Day 1: Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy.

Paclitaxel + trastuzumab15,k,l

Day 1: Paclitaxel 80mg/m2 IV weekly for 12 weeks, with Trastuzumab 4mg/kg IV with first dose of paclitaxel, followed by: Trastuzumab 2mg/kg IV weekly to complete 1 year of treatment. As an alternative, trastuzumab 6mg/kg IV every 21 days may be used following the completion of paclitaxel, and given to complete 1 year of trastuzumab therapy.

Pertuzumab + trastuzumab + docetaxel followed by FEC16,j,k

Day 1: Pertuzumab 840mg IV followed by 420mg IV Day 1: Trastuzumab 8mg/kg IV followed by 6mg/kg IV Day 1: Docetaxel 75–100mg/m2 IV. Repeat cycle every 21 days for 4 cycles, followed by adjuvant therapy: Day 1: Fluorouracil 600mg/m2 IV Day 1: Epirubicin 90mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV Day 1: Trastuzumab 6mg/kg IV Repeat cycle every 21 days for 3 cycles, followed by: Day 1: Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy.

Pertuzumab + trastuzumab + paclitaxel followed by FEC16,j,k

Day 1: Pertuzumab 840mg IV followed by 420mg IV Day 1: Trastuzumab 8mg/kg IV followed by 6mg/kg IV Days 1, 8, and 15: Paclitaxel 80mg/m2 IV. Repeat cycle every 21 days for 4 cycles, followed by adjuvant therapy: Day 1: Fluorouracil 600mg/m2 IV Day 1: Epirubicin 90mg/m2 IV Day 1: Cyclophosphamide 600mg/m2 IV Day 1: Trastuzumab 6mg/kg IV Repeat cycle every 21 days for 3 cycles, followed by: Day 1: Trastuzumab 6mg/kg IV every 21 days to complete 1 year of trastuzumab therapy.

continued

CancerTherapyAdvisor.com | NOVEMBER/DECEMBER 2017 | CANCER THERAPY ADVISOR 7

CANCER TREATMENT REGIMEN

BREAST CANCER Breast Cancer (Invasive) Treatment Regimens a The selection, dosing, and administration of anticancer agents and the management of associated toxicities are complex. Modifications of drug dose and schedule and initiation of supportive care interventions are often necessary because of expected toxicities and individual patient variability, prior treatment, and comorbidity. The optimal delivery of anticancer agents therefore requires a healthcare delivery team experienced in the use of anticancer agents and the management of associated toxicities in patients with cancer. b Retrospective evidence suggests that anthracycline-based chemotherapy regimens may be superior to nonanthracycline-based regimens in patients with HER2-positive tumors. c Randomized clinical trials demonstrate that the addition of a taxane to anthracycline-based chemotherapy provides an improved outcome. d CMF and radiation therapy may be given concurrently, or the CMF may be given first. All other chemotherapy regimens should be given prior to radiotherapy. e Chemotherapy and endocrine therapy used as adjuvant therapy should be given sequentially with endocrine therapy following chemotherapy. f Nab-paclitaxel may be substituted for paclitaxel or docetaxel due to medical necessity (ie, hypersensitivity reaction). If substituted for weekly paclitaxel or docetaxel, then the weekly dose of nab-paclitaxel should not exceed 125mg/m2. g In patients with HER2-positive and axillary node-positive breast cancer, trastuzumab should be incorporated into the adjuvant therapy (category 1). Trastuzumab should also be considered for patients with HER2-positive node-negative tumors ≥1cm (category 1). h Trastuzumab should optimally be given concurrently with paclitaxel as part of the AC followed by paclitaxel regimen, and should be given for 1 year total duration. i A pertuzumab-containing regimen can be administered to patients with ≥T2 or ≥N1, HER2-positive, early-stage breast cancer preoperatively. Patients who have not received a pertuzumab-containing regimen can receive adjuvant pertuzumab. j Trastuzumab given in combination with an anthracycline is associated with significant cardiac toxicity. Concurrent use of trastuzumab and pertuzumab with an anthracycline should be avoided. k Evaluate left ventricular ejection fraction (LVEF) before and during treatment. Although the optimal frequency of LVEF assessment during adjuvant trastuzumab therapy is not known, the FDA recommends LVEF measurements every 3 months during treatment. l Paclitaxel + trastuzumab may be considered for patients with low-risk, stage I, HER2-positive disease, particularly those not eligible for other standard adjuvant regimens due to comorbidities.

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.2.2017. Available at: http://www.nccn. org/professionals/physician_gls/pdf/breast.pdf. Accessed July 17, 2017. 2. Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21(8):1431–1439. Erratum in: J Clin Oncol. 2003;21(11):2226. 3. Jones S, Holmes F, O’Shaughnessey J, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research trial 9735. J Clin Oncol. 2009;27(8):1177–1183. 4. Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with six months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from NSABP B-15. J Clin Oncol. 1990;8(9):1483–1496. 5. Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005;352(22): 2302–2313. 6. Goldhirsch A, Colleoni M, Coates AS, et al. Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all CMFs alike? The International Breast Cancer Study Group (IBCSG). Ann Oncol. 1998;9(5):489–493. 7. von Minckwitz G, Raab G, Caputo A, et al. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol. 2005;23(12):2676–2685. 8. Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in adjuvant treatment of breast cancer. N Engl J Med. 2008; 358(16):1663–1671.

9. Piccart MJ, Di Leo A, Beauduin M, et al. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001;19(12): 3103–3110. 10. Romond EH, Perez EZ, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2 positive breast cancer. N Engl J Med. 2005;353(16):1673–1684. 11. Dang C, Fornier M, Sugarman S, et al. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer. J Clin Oncol. 2008;26(8):1216–1222. 12. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14): 1273–1283. 13. Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline–containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278–2284. 14. Jones SE, Collea R, Paul D, et al. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. Lancet Oncol. 2013;14(11): 1121–1128. 15. Tolaney S, Barry W, Dang C, et al. A phase II study of paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC). Abstract presented at: 36th Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 10-14, 2013; San Antonio, TX. Abstract S1-04. 16. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomized multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25–32.

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8 CANCER THERAPY ADVISOR | NOVEMBER/DECEMBER 2017 | CancerTherapyAdvisor.com

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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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 full labeling). 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 full labeling. 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: As monotherapy: for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast

cancer in postmenopausal women not previously treated with endocrine therapy, or HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. In combination therapy with palbociclib: HR-positive, 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. Adjuvant or extended adjuvant therapy: discontinue at tumor relapse; see full labeling. Advanced breast cancer: continue until tumor progression is evident. Severe hepatic impairment or cirrhosis: 2.5mg every other day. Children: Not established. Contraindications: Pregnancy. Warnings/Precautions: Monitor bone mineral density, serum cholesterol. Severe renal or hepatic impairment. Embryo-fetal toxicity; exclude pregnancy prior to initiation. Use effective contraception during and for ≥3wks after last

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DRUG MONOGRAPHS

BREAST CANCER dose. Nursing mothers: not recommended (during and for ≥3wks after last dose). Adverse reactions: Pain (bone, musculoskeletal, and others), hot flashes, arthralgia, flushing, asthenia, edema, headache, dizziness, hypercholesterolemia, sweating increased, GI upset, fatigue, somnolence, dyspnea, cough, insomnia, hypertension, anorexia, weight changes; thromboembolic or cardio- or cerebrovascular events (rare). How supplied: Tabs—30

Fluorouracil (various)

℞

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

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. Embryofetal 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 nodenegative 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

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DRUG MONOGRAPHS

BREAST CANCER inflammation, weight loss, nasopharyngitis, 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) ℞

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

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. Use effective contraception during therapy and for at least 3 weeks (females) or 3 months (males) after last dose. Pregnancy; exclude status prior to initiation. 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

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

IBRANCE Pfizer

IXEMPRA Bristol-Myers Squibb

℞

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

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DRUG MONOGRAPHS

BREAST CANCER with concomitant anticoagulation or antiplatelet therapy; monitor closely. 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 for toxicity: 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. Hepatic impairment. 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, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, voriconazole); consider alternatives; if unavoidable, reduce to Kisqali 400mg once daily. Avoid grapefruit, grapefruit juice, 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, ergots, 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

KISQALI FEMARA CO-PACK ℞ Novartis

Kinase inhibitor + aromatase inhibitor. Ribociclib 200mg; with letrozole 2.5mg; tabs. Indications: 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: Take together preferably in the AM. Swallow whole. Kisqali: initially 600mg once daily for 21 consecutive days, followed by 7 days off treatment for a complete 28-day cycle. Femara: 2.5mg once daily throughout the 28-day cycle. Concomitant strong CYP3A4 inhibitors: avoid; if coadmin necessary, reduce Kisqali to 400mg once daily. Hepatic impairment: initially Kisqali 400mg once daily (moderate and severe); Femara 2.5mg every other day (cirrhosis and severe dysfunction). Dose modifications for toxicity: see full labeling. 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. Hepatic impairment. 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, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, voriconazole); consider alternatives or see Adult. Avoid grapefruit, grapefruit juice, 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, ergots, 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. How supplied: Cartons—28 days of therapy (63 tabs × 200mg + 28 tabs); (42 tabs × 200mg + 28 tabs); (21 tabs × 200mg + 28 tabs)

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DRUG MONOGRAPHS

BREAST CANCER NERLYNX Puma Biotechnology

℞

Kinase inhibitor. Neratinib 40mg; tabs. Indications: Extended adjuvant treatment of early stage HER2-overexpressed/amplified breast cancer following adjuvant trastuzumab-based therapy. Adults: Initiate antidiarrheal prophylaxis (loperamide) with the first dose and continue during the first 2 treatment cycles (56 days); see full labeling. Swallow whole. Take with food. 240mg once daily for 1 year. Severe hepatic impairment (Child-Pugh C): reduce initial dose to 80mg. Dose modifications for adverse reactions: First dose reduction: 200mg/day; Second dose reduction: 160mg/day; Third dose reduction: 120mg/day; discontinue if unable to tolerate 120mg/day. Dose modifications for diarrhea, hepatotoxicity, or other general toxicities: see full labeling. Children: Not established. Warnings/Precautions: Monitor and treat diarrhea as needed; interrupt and reduce subsequent doses if severe diarrhea with dehydration occurs. Perform stool cultures as clinically indicated to exclude infectious causes of Grade 3/4 or any grade of diarrhea with complications. Measure total bilirubin, AST/ALT, alkaline phosphatase prior to initiation, monthly for the first 3 months, then every 3 months during treatment and as clinically indicated. Severe hepatic impairment: reduce dose. Embryo-fetal toxicity. Use effective contraception during therapy and for at least 1 month (females) or 3 months (males) after last dose. Pregnancy; exclude status prior to initiation. Nursing mothers: not recommended (during and for at least 1 month after last dose). Interactions: Avoid concomitant PPIs, H2receptor antagonists, strong or moderate CYP3A4 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, aprepitant, cimetidine, ciprofloxacin, clotrimazole, crizotinib, cyclosporine, dronedarone, erythromycin, fluconazole, fluvoxamine, imatinib, tofisopam, verapamil), and strong or moderate CYP3A4 inducers (eg, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John’s wort, bosentan, efavirenz, etravirine, modafinil). Separate dosing by 3hrs after antacids. Increased cardiotoxicity risk with digoxin. May inhibit transport of P-gp substrates (eg, dabigatran, fexofenadine). Adverse reactions: Diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST/ALT increase, nail disorder, dry skin, abdominal distention, weight decreased, urinary tract infection; hepatotoxicity. How supplied: Tabs—126, 180

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 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

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DRUG MONOGRAPHS

BREAST CANCER 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.

TEPADINA Adienne

℞

Children: Not established. Contraindications: Concomitant live or attenuated vaccines. Warnings/Precautions: For thalassemia: do not initiate if stem cell donor unavailable. Increased myelosuppression risk; monitor CBCs periodically and provide supportive care for infections, anemia, thrombocytopenia. Cutaneous toxicity risk with high-dose therapy (see full labeling). Discontinue and treat if anaphylactic or other significant allergic reaction occurs. Monitor serum transminases and bilirubin daily through BMT Day +28 and perform physical exam; provide supportive care if hepatic veno-occlusive disease develops. Do not exceed dose; discontinue if severe CNS toxicity occurs. Elderly. Moderateto-severe renal or hepatic impairment: monitor for toxicity. Embryo-fetal toxicity. Females of reproductive potential should use highly effective contraception during and for ≥6 months after last dose; and males should use effective contraception during and for ≥12 months after last dose. Pregnancy: verify status prior to initiation. Nursing mothers: not recommended. Interactions: See Contraindications. Avoid concomitant strong CYP3A4 inhibitors (eg, itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (eg, rifampin, phenytoin); consider alternatives; if use unavoidable, monitor closely. May potentiate CYP2B6 substrates. May reduce efficacy of cyclophosphamide. Adverse reactions: Neutropenia, anemia, thrombocytopenia, elevated ALT/AST, elevated bilirubin, mucositis, CMV infection, hemorrhage, diarrhea, hematuria, rash; carcinogenicity, secondary malignancy, CNS toxicity, possible infertility. How supplied: Single-dose vial—1

TREXALL Teva

℞

Visit OncologyNurseAdvisor.com for practical clinical information geared toward oncology nurses and other cancer care professionals.

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DRUG MONOGRAPHS

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

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: Risk of severe and fatal hepatotoxicity; discontinue if occurs; do not retreat. Monitor liver function tests before, every 4–6 weeks during therapy and as indicated. 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). Discontinue if severe skin reaction (eg, Stevens-Johnson syndrome, toxic epidural necrolysis) is suspected. 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), hand/foot syndrome, nausea, rash (may be

severe), vomiting, fatigue; hepatotoxicity, decreased LVEF, QT prolongation, interstitial lung disease, pneumonitis. 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 anthracyclinecontaining chemotherapy regimen or resistant to paclitaxel when further anthracycline therapy is not indicated (eg, prior cumulative doses of 400mg/m2 of doxorubicin or its equivalents). With docetaxel for metastatic breast cancer after failure of prior anthracycline-containing regimen. Adults: See 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 Sanofi 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

Access Cancer Therapy Advisor treatment regimens in a user-friendly format. CancerTherapyAdvisor.com/TreatmentRegimens.

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DRUG MONOGRAPHS

ENDOCRINE CANCER (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, 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-tomoderate 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 iodinerefractory 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 life-threatening 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. Embryo-fetal toxicity. Pregnancy: avoid. Use effective contraception during and for at least 2 weeks after treatment completion. Nursing mothers: not recommended.

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DRUG MONOGRAPHS

ENDOCRINE CANCER 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

diarrhea, anorexia, abdominal pain, hypertension, hemorrhage, electrolyte abnormalities; druginduced hepatitis, QT prolongation. How supplied: Tabs—120

ONIVYDE Ipsen ℞

Multikinase inhibitor. Sorafenib 200mg; tabs. Indications: Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment. Adults: Take on an empty stomach. 400mg twice daily. If toxicity occurs, may reduce dose to 400mg and 200mg 12hrs apart (either dose can come first); if second reduction is required, may reduce dose to 200mg twice daily; if third reduction is required, may reduce to 200mg once daily (see full labeling). Concomitant strong CYP3A4 inducers: consider increasing dose, monitor for toxicity. Children: Not established. Contraindications: Concomitant carboplatin/paclitaxel in patients with squamous cell lung cancer. Warnings/Precautions: Avoid in congenital long QT syndrome. Monitor patients with CHF, bradyarrhythmias, drugs known to prolong the QT interval, electrolyte abnormalities. Discontinue if severe dermatologic toxicity, hypertension, GI perforation, hemorrhage, cardiac ischemia, MI occurs. Suspend therapy before major surgery. Monitor BP weekly during the first 6 weeks and thereafter. Monitor hepatic function regularly; discontinue if transaminases significantly elevated. Severe hepatic impairment (ChildPugh C) or on dialysis. Monitor TSH levels monthly and adjust thyroid therapy. Use effective contraception during and for 2 weeks after stopping treatment. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: See Contraindications. Avoid strong CYP3A4 inducers (eg, St. John’s Wort, dexamethasone, phenytoin, carbamazepine, rifabutin, rifampin, phenobarbital) and neomycin; may decrease sorafenib levels. May potentiate warfarin (monitor PT & INR), other drugs metabolized by UGT1A1 or UGT1A9 pathway, or substrates of CYP2B6, CYP2C8, CYP2C9, P-gp. Concomitant Class Ia and III antiarrhythmics; may prolong QT interval. Adverse reactions: Dermatologic toxicity (eg, rash, hand-foot skin reaction, alopecia, pruritus, dry skin, Stevens-Johnson syndrome, toxic epidermal necrolysis), fatigue, weight loss,

℞

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; 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

SOMATULINE DEPOT Ipsen

℞

Somatostatin analogue. Lanreotide 60mg/0.2mL, 90mg/0.3mL, 120mg/0.5mL; 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. Renal or hepatic impairment. Monitor growth hormone (GH), IGF-1 levels, thyroid function, gallbladder, glucose. Pregnancy. 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, vomiting, inj site reactions, musculoskeletal pain, headache, dizziness, muscle spasm; gallbladder sludge, gallstones, hyperglycemia, hypoglycemia, sinus bradycardia, hypertension, anemia; rare: hypothyroidism. How supplied: Single-dose prefilled 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

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DRUG MONOGRAPHS

ENDOCRINE CANCER 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; 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

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, 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

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.

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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 infusionrelated 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; resume based on adequate healing; discontinue if complications develops during therapy until wound is fully healed. 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

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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 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 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. 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,

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER bi-weekly for 2nd month, then periodically (eg, every 2–3 months); liver function at baseline then monthly or as needed; renal function at baseline and during therapy; GI symptoms at baseline. Cardiovascular disease or risk factors; monitor. Diabetes. Hypertension. CHF. 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, 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 chemotherapyinduced 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. Monitor for severe skin reactions; permanently discontinue if SJS or TEN is confirmed. Permanently discontinue if any severe or Grade 3 immune-mediated

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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. Solid organ transplant recipients. 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

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

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: Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) in patients ≥12yrs who has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Hepatocellular carcinoma (HCC) in patients previously treated with sorafenib. 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 life-threatening (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 (non-HCC) or AST/ALT >10XULN (HCC) 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), immunemediated encephalitis, recurring Grade

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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 transplant-related complications (eg, hyperacute or Grade 3/4 acute GVHD, steroidrequiring 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

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 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. Embryofetal 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, handfoot 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,

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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 RAS (both KRAS and NRAS as determined by an FDA-approved test) metastatic colorectal carcinoma (mCRC) in combination with FOLFOX, or as monotherapy following disease progression after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. Limitation of use: not for treating RAS-mutant mCRC or for whom RAS mutation status is unknown. Adults: Confirm absence of a RAS mutation using an FDA-approved test prior to initiation. 6mg/kg by IV infusion over 60mins once every 14 days. If 1st infusion is tolerated, give subsequent infusions over 30–60mins. Doses >1000mg: infuse over 90mins. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: Monitor for dermatologic or soft tissue toxicities; withhold or discontinue if severe or life-threatening inflammatory or infectious complications occur. 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 8wks after completing therapy. Monitor for ocular toxicities (eg, keratitis); interrupt or discontinue if develop or worsen. Embryo-fetal toxicity; use effective contraception during and for 2mos after last dose. Pregnancy. Nursing mothers: not recommended during and for 2mos after last dose. Interactions: Concomitant bevacizumab and chemotherapy: increased mortality and toxicity may occur. Risk of acute renal failure with concomitant chemotherapy.

Adverse reactions: Rash, paronychia, fatigue, nausea, diarrhea; dermatologic or soft tissue toxicities (may be fatal), hypomagnesemia, hypocalcemia, hypokalemia, infusion reactions, ILD, pulmonary fibrosis, photosensitivity, keratitis. With FOLFOX: also stomatitis, mucosal inflammation, asthenia, anorexia. Testing considerations: EGFR amplification analysis, K-RAS mutation analysis. How supplied: Single-use vial (5mL, 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. 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; preservativefree. 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

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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 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)

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,

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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. 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 full labeling. 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)

EMCYT Pfizer

℞

Estramustine phosphate sodium (prodrug of estradiol) 140mg; caps. Indications: Palliative of metastatic, progressive prostate cancer.

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DRUG MONOGRAPHS

GENITOURINARY 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 full labeling. 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)

℞

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

IMFINZI AstraZeneca

℞

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,

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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 (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

℞

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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. Monitor for severe skin reactions; permanently discontinue if SJS or TEN is confirmed. 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. Solid organ transplant recipients. 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

LENVIMA Eisai

℞

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 life-threatening 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. Embryo-fetal 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

LUPRON DEPOT 7.5mg AbbVie ℞ GnRH analogue. Leuprolide acetate 7.5mg; depot susp for IM inj. Indications: Palliative treatment of advanced prostatic carcinoma. Adults: 7.5mg IM once a month. Rotate inj site.

Children: Not applicable. ℞ Also: LUPRON DEPOT-3 MONTH 22.5mg Leuprolide acetate 22.5mg; depot susp for IM inj. Adults: 22.5mg IM inj every 3 months (84 days). Do not split doses. Children: Not applicable. ℞ Also: LUPRON DEPOT-4 MONTH 30mg Leuprolide acetate 30mg; depot susp for IM inj; preservative-free. Adults: 30mg as single IM inj every 4 months (16 weeks). Do not split doses. Children: Not applicable. ℞ Also: LUPRON DEPOT-6 MONTH 45mg Leuprolide acetate 45mg; depot susp for IM inj. Adults: 45mg as single IM inj every 6 months (24 weeks). Do not split doses. Children: Not applicable. Contraindications: 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)

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

℞

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 life-threatening (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 (non-HCC) or AST/ALT >10XULN (HCC) 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), immunemediated 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 transplant-related 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: 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, estrogendependent carcinoma, gallbladder disease, thromboembolic disorders, hepatic tumors. GI upset, breakthrough bleeding, edema, weight changes, mastodynia, hypertension, depression, anaphylactic reactions, angioedema, intolerance to contact lenses. How supplied: Tabs 0.3mg, 0.625mg, 1.25mg— 100, 1000; 0.45mg, 0.9mg—100

PROLEUKIN Prometheus

℞

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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

TEPADINA Adienne

℞

Alkylating agent. Thiotepa 15mg, 100mg; per vial; lyophilized pwd for IV, intravesical, or intracavitary administration after reconstitution and dilution. Indications: Superficial papillary carcinoma of the urinary bladder. Intracavitary effusion due to neoplasm of serosal cavities. Adults: 60mg once weekly for 4 weeks; may repeat up to a total of 3 courses. Retain in bladder for 2hrs. Intracavitary administration: 0.6–0.8mg/kg every 1–4 weeks through same tube used to remove fluid from cavity. Maintenance doses: adjust no sooner than weekly based on blood counts. Children: Not established. Contraindications: Concomitant live or attenuated vaccines. Warnings/Precautions: For thalassemia: do not initiate if stem cell donor unavailable. Increased myelosuppression risk; monitor CBCs periodically and provide supportive care for infections, anemia, thrombocytopenia. Cutaneous toxicity risk with high-dose therapy (see full labeling). Discontinue and treat if anaphylactic or other significant allergic reaction occurs. Monitor serum transminases and bilirubin daily through BMT Day +28 and perform physical exam; provide supportive care if hepatic veno-occlusive disease develops. Do not exceed dose; discontinue if severe CNS toxicity occurs. Elderly. Moderateto-severe renal or hepatic impairment: monitor for toxicity. Embryo-fetal toxicity. Females of reproductive potential should use highly effective contraception during and for ≥6 months after last dose; and males should use effective contraception during and for ≥12 months after last dose. Pregnancy: verify status prior to initiation. Nursing mothers: not recommended. Interactions: See Contraindications. Avoid concomitant strong CYP3A4 inhibitors (eg, itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (eg, rifampin, phenytoin); consider alternatives; if use unavoidable, monitor closely. May potentiate CYP2B6 substrates. May reduce efficacy of cyclophosphamide. Adverse reactions: Neutropenia, anemia, thrombocytopenia, elevated ALT/AST, elevated bilirubin, mucositis, CMV infection, hemorrhage, diarrhea, hematuria, rash; carcinogenicity, secondary malignancy, CNS toxicity, possible infertility. How supplied: Single-dose vial—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

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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 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

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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. 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

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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 (platinumresistant): 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 (platinumresistant): 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); (platinumsensitive): 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. Cardiomyopathy (including left ventricular failure), acute infusion-related reactions, myelosuppression may occur. Have medications to treat infusion-related reactions and resuscitative equipment available. Hepatic impairment. Monitor blood (esp. CBC + platelets), hepatic (esp. SGOT/SGPT, alkaline phosphatase), and cardiac function (eg, MUGA, ECG). Monitor periodically for secondary oral cancers with long-term use. Avoid extravasation. Embryo-fetal toxicity. Use effective contraception during and for 6 months after last dose. 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.

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DRUG MONOGRAPHS

GYNECOLOGIC CANCER 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. Embryo-fetal toxicity. 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. 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. Concomitant strong or moderate CYP3A inhibitors: avoid; if co-admin unavoidable, reduce olaparib dose to 150mg twice daily (with strong inhibitors) or 200mg twice daily (with moderate inhibitors). Moderate renal impairment (CrCl 31–50mL/min): reduce to 300mg twice daily; max 600mg daily. Children: Not established. ℞ Also: LYNPARZA TABLETS Olaparib 100mg, 150mg.

Indications: Maintenance treatment of recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, in adults who are in complete or partial response to platinum-based chemotherapy. Treatment of deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer in adults who have been treated with ≥3 prior lines of chemotherapy. Adults: Swallow whole. 300mg twice daily; max 600mg daily. Continue until disease progression or unacceptable toxicity. Dose adjustments for adverse reactions: reduce to 250mg twice daily; may further reduce to 200mg twice daily. Concomitant strong or moderate CYP3A inhibitors: avoid; if co-admin unavoidable, reduce olaparib dose to 100mg twice daily (with strong inhibitors) or 150mg twice daily (with moderate inhibitors). Moderate renal impairment (CrCl 31–50mL/min): reduce to 200mg twice daily. Children: Not established. Warnings/Precautions: Caps and tabs are not interchangeable on a mg-to-mg basis. 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 (CrCl ≤30mL/min): 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; Tabs—60, 120

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

TEPADINA Adienne

℞

Alkylating agent. Thiotepa 15mg, 100mg; per vial; lyophilized pwd for IV, intravesical, or intracavitary administration after reconstitution and dilution. Indications: Adenocarcinoma of the ovary. Intracavitary effusion due to neoplasm of serosal cavities. Adults: Initially 0.3–0.4mg/kg IV given at 1–4 week intervals. Intracavitary administration: 0.6–0.8mg/kg every 1–4 weeks through same tube used to remove fluid from cavity. Maintenance doses: adjust no sooner than weekly based on blood counts. Children: Not established. Contraindications: Concomitant live or attenuated vaccines. Warnings/Precautions: For thalassemia: do not initiate if stem cell donor unavailable. Increased myelosuppression risk; monitor CBCs periodically

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DRUG MONOGRAPHS

GYNECOLOGIC CANCER and provide supportive care for infections, anemia, thrombocytopenia. Cutaneous toxicity risk with high-dose therapy (see full labeling). Discontinue and treat if anaphylactic or other significant allergic reaction occurs. Monitor serum transminases and bilirubin daily through BMT Day +28 and perform physical exam; provide supportive care if hepatic veno-occlusive disease develops. Do not exceed dose; discontinue if severe CNS toxicity occurs. Elderly. Moderate-to-severe renal or hepatic impairment: monitor for toxicity. Embryo-fetal toxicity. Females of reproductive potential should use highly effective contraception during and for ≥6 months after last dose; and males should use effective contraception during and for ≥12 months after last dose. Pregnancy: verify status prior to initiation. Nursing mothers: not recommended. Interactions: See Contraindications. Avoid concomitant strong CYP3A4 inhibitors (eg, itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (eg, rifampin, phenytoin); consider alternatives; if use unavoidable, monitor closely. May potentiate CYP2B6 substrates. May reduce efficacy of cyclophosphamide. Adverse reactions: Neutropenia, anemia, thrombocytopenia, elevated ALT/AST, elevated bilirubin, mucositis, CMV infection, hemorrhage, diarrhea, hematuria, rash; carcinogenicity, secondary malignancy, CNS toxicity, possible infertility. How supplied: Single-dose vial—1

TREXALL Teva

℞

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

ZEJULA Tesaro

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

HYPERSENSITIVITY to

a drug or its class is assumed to be a contraindication in all product monographs, although not explicitly stated.

℞

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.

ADVERSE REACTIONS Those adverse reactions listed within product monographs represent the potential for adverse effects based upon the active ingredient(s) and/or the drug class. It is not meant to be an inclusive list of responses.

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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 platinumbased 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 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. 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

℞

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. Monitor for severe skin reactions; permanently discontinue if SJS or TEN is confirmed. 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. Solid organ transplant recipients. 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

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: 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

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DRUG MONOGRAPHS

HEAD AND NECK CANCER 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

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 (non-HCC) or AST/ALT >10XULN (HCC) 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 transplant-related 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

TREXALL Teva

℞

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)

2–3

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 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

ABVD (Intent to treat with combined modality therapy)2-5

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

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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: CyclophosphaWmide 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

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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).

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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.

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Non-Hodgkin Lymphoma Treatment Regimens: Adult T Cell Leukemia/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 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.

Primary Therapy—Chronic Smoldering1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

Zidovudine + alpha-interferon2-6

Induction Therapy Zidovudine 1g orally daily + alpha-interferon 9 million units SC daily for at least 2 months, followed by Maintenance Therapy Zidovudine 600mg orally daily + alpha-interferon 4.5 million units SC daily for at least 1 year.

Primary Therapy—Acute1 Zidovudine + alpha-interferon2-6

CHOP7a

Day 1: Cyclophosphamide 750mg/m2 IV + doxorubicin 50mg/m2 IV + vincristine 1.4mg/m2 IV (max dose 2mg), plus Days 1–5: Prednisone 100mg orally daily. Repeat cycle every 3 weeks for 6–8 cycles.

CHOEP8,9a

Days 1–4: Etoposide 50mg/m2/day continuous IV infusion + doxorubicin 10mg/m2/day continuous IV infusion + vincristine 0.4mg/m2/day continuous IV infusion Days 1–5: Prednisone 60mg/m2 orally daily Day 5: Cyclophosphamide 750mg/m2 IV over 15 minutes. Repeat cycle every 3 weeks for 6–8 cycles.

Dose-adjusted EPOCH10a

HyperCVAD11a

Cycle 1, 3, 5, 7: Days 1–3: Cyclophosphamide 300mg/m2 IV over 2 hours every 12 hours for 6 doses + mesna 600mg/m2/day continuous IV infusion starting 1 hour before cyclophosphamide until 12 hours after completion Day 4: Doxorubicin 50mg/m2 IV over 24 hours Days 1–4 and Day 11–14: Dexamethasone 40mg IV or orally Days 4 and 11: Vincristine 2mg IV. Cycle 2, 4, 6, 8: Day 1: Methotrexate 200mg/m2 IV over 2 hours, then 800mg/m2 IV over 22 hours + leucovorin 50mg IV every 6 hours beginning 12 hours after completion of methotrexate Days 2 and 3: Cytarabine 3,000mg/m2 (1,000mg/m2 for patients ≥60 years old) IV over 2 hours every 12 hours. CNS Prophylaxis Day 2: Methotrexate 12mg intrathecally Day 7: Cytarabine 100mg intrathecally.

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CANCER TREATMENT REGIMEN

HEMATOLOGIC CANCER Primary Therapy—Lymphoma1 REGIMEN

DOSING

CHOP7a

CHOEP8,9a

Dose–adjusted EPOCH10a

HyperCVAD11a

There are no published data regarding the use of these regimens; however, they are used at NCCN Member Institutions for the treatment of adult T-cell leukemia/lymphoma.

References 1. NCCN Clinical Practice Guidelines in Oncology™. Non-Hodgkin’s Lymphomas. v 3.2016. Available at: http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf. Accessed December 15, 2016. 2. Bazarbachi A, Hermine O. Treatment with a combination of zidovudine and alpha-interferon in naïve and pretreated adult T-cell leukemia/lymphoma patients. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;13 Suppl 1:S186–190. 3. Bazarbachi A, Plumelle Y, Carlos Ramos J, et al. Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes. J Clin Oncol. 2010;28:4177–4183. 4. Hermine O, Allard I, Levy V, et al. A prospective phase II clinical trial with the use of zidovudine and interferon-alpha in the acute and lymphoma forms of adult T-cell leukemia/lymphoma. Hematol J. 2002;3:276–282. 5. Hodson A, Chrichton S, Monoto S, et al. Use of zidovudine and interferon alfa with chemotherapy improves survival in both acute and lymphoma subtypes of adult T-cell leukemia/lymphoma. J Clin Oncol. 2011;29:4696–4701. 6. White JD, Wharfe G, Stewart DM, et al. The combination of zidovudine and interferon al-

8. 9.

10.

11.

pha-2B in the treatment of adult T-cell leukemia/lymphoma. Leuk Lymphoma. 2001;40:287–294. Czuczman, MS, Weaver R, Alkuzweny B, et al. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin’s lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004;23:4711. Wilson WH, Bryant G, Bates S, et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin’s lymphoma. J Clin Oncol. 1993;11:1573. Gutierrez, M, Chabner BA, Pearson D, et al. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: An 8-year follow-up study of EPOCH. J Clin Oncol. 2000;18:3633. Wilson WH, Grossbard ML, Pittaluga S, et al. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002;99:2685. Thomas, DA, O’Brien S, Cortes J, et al. Outcome with the hyper-CVAD regimens in lymphoblastic lymphoma. Blood. 2004;104:1624.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER ADCETRIS Seattle Genetics

℞

CD30-directed antibody-drug conjugate. Brentuximab vedotin 50mg/vial; lyophilized pwd for IV infusion after reconstitution; preservativefree. 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 multiagent chemotherapy regimens in patients who are not auto-HSCT candidates or are at high risk of relapse or progression as post-autoHSCT 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 postauto-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 pre-existing neurological signs/symptoms; discontinue and evaluate if progressive multifocal leukoencephalopathy (PML) is suspected. 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), PML, 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.

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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; Non-hematologic 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; preservativefree. Indications: Non-Hodgkin’s lymphoma (CD20 antigen-expressing relapsed or refractory, low grade, follicular, transformed, or rituximabrefractory).

Adults: See full labeling. 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 full labeling on patient contact restrictions. Not for initial treatment. Have medical and supportive care available. Permanently discontinue if serious allergic reactions develop. >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, allergic 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

Access Cancer Therapy Advisor treatment regimens in a user-friendly format. CancerTherapyAdvisor.com/TreatmentRegimens.

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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; preservative-free. Indications: Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). 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). Treat up to 9 cycles (2 cycles for induction, followed by 3 cycles for consolidation, and up to 4 additional cycles of continued therapy). One single cycle = 28 days of continuous IV infusion followed by a 14-day treatment-free interval (during Cycles 1–5) or 56-day treatment-free interval (during Cycles 6–9). Hospitalization recommended for first 9 days of Cycle 1 and first 2 days of Cycle 2. Give by continuous IV infusion at a rate of 10mL/hr over 24hrs, 5mL/hr over 48hrs, or 0.6mL/hr over 7 days (not recommended for patients <22kg). <45kg (Cycle 1): 5mcg/m2/day (max 9mcg/day) on Days 1–7 and 15mcg/m2/day (max 28mcg/day) on Days 8–28; (Cycles 2–9): 15mcg/m2/day (max 28mcg/day) on Days 1–28. ≥45kg (Cycle 1): 9mcg/day on Days 1–7 and 28mcg/day on Days 8–28; (Cycles 2–9): 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: Infections, pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, neutropenia. How supplied: Pack—1 (single-use vial + IV solution stabilizer)

BOSULIF Pfizer

BUSULFEX Otsuka

℞

Tyrosine kinase inhibitor. Bosutinib 100mg, 500mg; tabs. Indications: Treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy. Adults: 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

℞

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 Sanofi Genzyme

℞

Monoclonal antibody, CD52 (recombinant, humanized). Alemtuzumab 30mg/mL; soln; for IV infusion after dilution; preservative-free. Indications: B-cell chronic lymphocytic leukemia (B-CLL). Adults: Premedicate with antihistamine and acetaminophen before 1st dose, and at dose escalations. Give by IV infusion over 2 hrs. Initially 3mg per day until infusion reactions are ≤ grade 2, then increase to 10mg per day until infusion reactions are ≤ grade 2, then to maintenance 30mg/day three times per week (on alternate days); duration of therapy (including escalation): 12 weeks. Do not exceed max single dose 30mg/dose or 90mg/week. Give prophylactic antibiotics and antivirals during treatment and for at least 2 months after completion or until CD4+ counts resolve (whichever occurs

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 full labeling. 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 Sanofi 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. Children: Not recommended. Warnings/Precautions: Renal or hepatic impairment. Obtain CBC and platelet counts

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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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; as combination therapy with pomalidomide and dexamethasone in patients who have received ≥2 prior therapies including lenalidomide and a proteasome inhibitor (PI); or as monotherapy in patients who have received ≥3 prior lines of therapy including a 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 or pomalidomide 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. Neonates/infants: defer live vaccines if exposed to drug in utero until hematology evaluation. Pregnancy. 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, constipation, vomiting, muscle spasms, arthralgia, back pain, pyrexia, chills, dizziness, insomnia, 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. Cardiomyopathy (including left ventricular failure), acute infusion-related reactions, myelosuppression may occur. Have medications to treat infusion-related reactions and resuscitative equipment available. Hepatic impairment. Monitor blood (esp. CBC + platelets), hepatic (esp. SGOT/SGPT, alkaline phosphatase), and cardiac function (eg, MUGA, ECG). Monitor periodically for secondary oral cancers with long-term use. Avoid extravasation. Embryo-fetal toxicity. Use effective contraception during and for 6 months after last dose. 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.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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). 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

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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 Sanofi 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; renal function at baseline and during therapy; GI symptoms at baseline. Cardiovascular disease or risk factors; monitor. Diabetes. Hypertension. CHF. 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. Testing considerations: BCR-Abl t(9;22) in Ph+CML patients How supplied: 100mg—90; 400mg—30

HYDREA Bristol-Myers Squibb

℞

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.

Adverse reactions: Leukopenia, thrombocytopenia, anemia, GI upset, anorexia; secondary malignancies, macrocytosis. Note: Wear disposable gloves when handling caps or bottle. How supplied: Caps—100

ICLUSIG ARIAD

℞

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 if suspected. Conduct eye exams at baseline and periodically during

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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

IDHIFA Celgene

℞

Isocitrate dehydrogenase-2 (IDH2) inhibitor. Enasidenib 50mg, 100mg; tabs. Indications: Treatment of adults with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test. Adults: Swallow whole. Take at same time each day. Initially 100mg once daily until disease progression or unacceptable toxicity; treat for a minimum of 6 months to allow time for response. Monitoring and dose modifications for toxicities: see full labeling. Children: Not established. Warnings/Precautions: Risk of differentiation syndrome (may be fatal if not treated). If differentiation syndrome is suspected, initiate oral or IV corticosteroids and hemodynamic monitoring until resolution; interrupt dose if severe pulmonary symptoms requiring intubation or ventilator support, and/or renal dysfunction persist >48hrs after corticosteroid initiation. Assess blood counts/chemistries for leukocytosis and tumor lysis syndrome prior to initiation; monitor at minimum of every 2 weeks for at least the first 3 months during therapy. Embryo-fetal toxicity. Females of reproductive potential and males (w. female partners) should use effective contraception during and for at least 1 month after final dose. Pregnancy: not recommended (exclude status prior to initiation). Nursing mothers: not recommended (during and for at least 1 month after final dose). Interactions: May increase or decrease concentrations of combined hormonal contraceptives. Adverse reactions: Nausea, vomiting, diarrhea, elevated bilirubin, decreased appetite; differentiation syndrome, leukocytosis, tumor lysis syndrome. How supplied: Tabs—30

IMBRUVICA

℞

Pharmacyclics and Janssen Biotech

Bruton’s tyrosine kinase (BTK) inhibitor. Ibrutinib 140mg; caps. Indications: Mantle cell lymphoma (MCL) in patients who have received at least one prior therapy. Chronic lymphocytic leukemia (CLL)/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, posaconazole (≤200mg twice daily), voriconazole: 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. Embryo-fetal toxicity. Pregnancy; avoid during and for 1 month after treatment cessation. Nursing mothers. Interactions: See Adult. Avoid concomitant strong CYP3A inhibitors (eg, boceprevir, clarithromycin, cobicistat, conivaptan, diltiazem, elvitegravir/ritonavir, idelalisib, indinavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, paritaprevir/ritonavir/ombitasvir ± dasabuvir, ritonavir, saquinavir/ritonavir, tipranavir/ritonavir, troleandomycin, posaconazole (at higher doses); if short-term use (eg, anti-infectives for ≤7days), consider interrupting ibrutinib therapy. Concomitant moderate CYP3A inhibitors (eg, aprepitant, cimetidine, ciprofloxacin, clotrimazole, crizotinib, cyclosporine, dronedarone, erythromycin, fluconazole, fluvoxamine, imatinib, verapamil): reduce ibrutinib dose (see Adult). Avoid grapefruit and Seville oranges during treatment. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, enzalutamide, mitotane, rifampin, phenytoin, St. John’s Wort). Increased risk of hemorrhage with concomitant antiplatelets or anticoagulants; monitor. Adverse reactions: Neutropenia, thrombocytopenia, diarrhea, anemia, musculoskeletal pain, rash, nausea, bruising, fatigue, hemorrhage, pyrexia, muscle spasms, stomatitis, pneumonia. How supplied: Caps—90, 120

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.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER ℞ 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: 18yrs: not established. 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. Cardiovascular disease (eg, MI, arrhythmias); monitor closely. Pulmonary disease (eg, COPD). Discontinue if severe psychiatric disorders (eg, suicidal behavior) or new/worsening ophthalmologic reactions develop. 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 CBCs, platelets, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Pwd: contains human albumin; monitor for possible viral disease and Creutzfeldt-Jakob disease transmission. Pre-existing psoriasis or sarcoidosis. Renal impairment. Transplant recipients. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Caution with myelosuppressive agents (eg, zidovudine), and drugs that can exacerbate depression. May potentiate theophylline. Increased risk of peripheral neuropathy with concomitant telbivudine. Dental/periodontal disorders, dry mouth with concomitant ribavirin. Adverse reactions: Flu-like symptoms (fever, headache, chills, myalgia, fatigue); abnormal LFTs, blood, cardiovascular, pulmonary, thyroid, and GU disorders, GI upset, abnormal vision,

skin reactions, CNS/psychiatric reactions, colitis, hypertriglyceridemia, pancreatitis; rare: autoimmune disorders, hypersensitivity. 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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 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. Monitor for severe skin reactions; permanently discontinue if SJS or TEN is confirmed. 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. Solid organ transplant recipients. 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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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, nausea, peripheral edema, vomiting, back pain; rash, hepatotoxicity, herpes zoster, eye disorders. How supplied: Caps—1, 3

ONCASPAR Baxalta

℞

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

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: Classical Hodgkin lymphoma (cHL) that relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, or after 3 or more lines of systemic therapy that includes autologous HSCT. 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 (non-HCC) or AST/ALT >10XULN (HCC) 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 transplant-related 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, 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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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. 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

℞

Antimetabolite. Mercaptopurine (6-MP) 50mg; scored tabs. Indications: Maintenance therapy of acute lymphatic leukemia as part of a combination regimen. Adults and Children: 1.5–2.5mg/kg per day as a single dose. Concomitant allopurinol: reduce dose of mercaptopurine to 1/3–1/4 of the usual dose. TPMT-deficient, renal or hepatic impairment: reduce dose, see literature. Contraindications: Prior resistance to mercaptopurine. Warnings/Precautions: Not effective in CNS leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, the lymphomas (including Hodgkin’s disease), or solid tumors. Renal impairment. Monitor liver function tests weekly at start of therapy, then monthly thereafter; discontinue if hepatotoxicity occurs. Preexisting liver disease (monitor more frequently). Obtain CBCs with differential, hemoglobin, hematocrit, platelets; discontinue if severe bone marrow suppression occurs. ThiopurineS-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

PURIXAN Rare Disease

℞

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 lymphoproliferative disorders and other malignancies (eg, skin cancers, sarcomas, uterine cervical cancer). Concomitant multiple immunosuppressants increase risk of EpsteinBarr virus (EBV)-associated lymphoproliferative disorders. Monitor and treat for EBV or cytomegalovirus; discontinue if macrophage activation syndrome occurs, or is suspected. Renal or hepatic impairment. Elderly. Embryofetal toxicity. 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, rash, urticaria, hyperuricemia, oral lesions, elevated transaminases, hyperbilirubinemia, hyperpigmentation, pancreatitis; hepatotoxicity. How supplied: Susp—100mL (w. oral syringes)

REVLIMID Celgene

℞

Immunomodulator. Lenalidomide 2.5mg, 5mg, 10mg, 15mg, 20mg, 25mg; caps; contains lactose. Indications: Multiple myeloma (MM): for combination treatment with dexamethasone; or for maintenance therapy following autologous hematopoietic stem cell transplantation (autoHSCT). Mantle cell lymphoma (MCL) in patients whose disease has relapsed or progressed after 2 prior therapies, one of which included bortezomib.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER Adults: Swallow whole with water. MM (combo therapy), MCL: 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. MM (post auto-HSCT): Ensure ANC ≥1000/mcL and/or platelets ≥75,000/mcL. Initially 10mg once daily on Days 1–28 of each 28-day cycle until disease progression or unacceptable toxicity; may increase to 15mg once daily after 3 cycles, if tolerated. Renal impairment: MM (combo therapy), MCL: (CrCl 30–60mL/min): initially 10mg/day; for MM, consider increasing to 15mg after 2 cycles, if tolerant; (CrCl <30mL/min without dialysis): initially 15mg every other day; (CrCl <30mL/min with dialysis): initially 5mg/day; administer after dialysis on dialysis days. MM (auto-HSCT): (CrCl 30–60mL/min): initially 5mg/day; (CrCl <30mL/min without dialysis): initially 2.5mg/day; (CrCl <30mL/min with dialysis): initially 2.5mg/day; administer after dialysis on dialysis days. Adjust dose based on patient tolerance. Auto-HSCT eligible: refer for hematopoietic cell mobilization within 4 cycles; if non-eligible, continue therapy until disease progression or unacceptable toxicity. Dose adjustments for hematologic toxicities: see full labeling. Children: Not established. Contraindications: Pregnancy. 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. Patients must not donate blood during and for 1 month after therapy; males must not donate sperm. Monitor for signs/symptoms of thromboembolic events; base thromboprophylaxis on patient’s risks. Monitor for signs of infection, bleeding, or bruising. 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), thyroid function before and during therapy. Monitor for second primary malignancies. Lactose intolerance. Max 28-day supply per ℞. Nursing mothers: not recommended. Interactions: Monitor digoxin. Concomitant warfarin; monitor PT, INR. May increase risk of

thrombosis with dexamethasone, erythropoietic agents, or estrogen-containing therapies. Adverse reactions: Diarrhea, fatigue, anemia, constipation, neutropenia, leukopenia, peripheral edema, insomnia, muscle cramp/spasms, abdominal pain, back pain, nausea, asthenia, pyrexia, upper RTI, bronchitis, nasopharyngitis, gastroenteritis, cough, rash, dyspnea, dizziness, decreased appetite, thrombocytopenia, tremor, pruritus; birth defects, thromboembolism, allergic reactions (discontinue if severe; do not resume), hepatotoxicity, tumor flare reaction (monitor; esp. in MCL), impaired stem cell mobilization, thyroid disorders. 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 and Biogen

℞

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 rituximab 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 concomitant 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

RITUXAN HYCELA

℞

Genentech and Biogen

CD20-directed cytolytic monoclonal antibody + endoglycosidase. Rituximab, hyaluronidase human 1400mg/23400 Units, 1600mg/26800 Units; soln for SC inj; preservative-free.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER Indications: Relapsed or refractory, follicular lymphoma (FL) as a single agent. Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy. Non-progressing (including stable disease) FL as a single agent after first-line CVP chemotherapy. Previously untreated diffuse large B-cell lymphoma (DLBCL) in combination with CHOP or other anthracycline-based chemotherapy regimens. Chronic lymphocytic leukemia (CLL) in combination with fludarabine and cyclophosphamide. Adults: Give by SC inj into abdomen. Premedicate with an antihistamine and acetaminophen prior to each dose; may consider glucocorticoids. Monitor for at least 15mins after each dose. Relapsed or refractory FL: 1400mg/23400 Units over 5mins once weekly for 3 or 7 weeks following a full dose of IV rituximab at Week 1. May give retreatment once weekly for 3 weeks following a full dose of IV rituximab at Week 1. Previously untreated FL: 1400mg/23400 Units over 5mins on Day 1 of Cycles 2–8 of chemotherapy (every 21 days) for up to 7 cycles following a full dose of IV rituximab on Day 1 of Cycle 1; if complete or partial response, initiate Rituxan Hycela maintenance 8 weeks following completion of Rituxan Hycela in combination with chemotherapy. Administer Rituxan Hycela as a single-agent every 8 weeks for 12 doses. Nonprogressing FL after first-line CVP chemotherapy: 1400mg/23400 Units over 5mins once weekly for 3 weeks at 6-month intervals following completion of 6–8 cycles of CVP and a full dose of IV rituximab at Week 1; max 16 doses. DLBCL: 1400mg/23400 Units over 5mins on Day 1 of Cycles 2–8 of CHOP chemotherapy for up to 7 cycles following a full dose of IV rituximab on Day 1 of Cycle 1. CLL: 1600mg/26800 Units over 7mins on Day 1 of Cycles 2–6 (every 28 days) for 5 cycles following a full dose of IV rituximab on Day 1 of Cycle 1. Give PCP and antiherpetic viral prophylaxis during and up to 12 months after CLL therapy. Children: Not established. Warnings/Precautions: Discontinue if severe injection or mucocutaneous reactions occur (eg, urticaria, hypotension, angioedema, hypoxia, pulmonary infiltrates, acute respiratory failure, 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 renal function, 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 cardiac or pulmonary conditions, prior cardiopulmonary adverse events, high malignant cell count; monitor during and after treatment. Elderly. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for at least 12 months after last dose. Pregnancy (monitor newborns/infants for infection). Nursing mothers: not recommended (during and for at least 6 months after last dose). Interactions: Live virus vaccines: not recommended. Renal toxicity with concomitant cisplatin. Adverse reactions: Infections, neutropenia, nausea, constipation, cough, fatigue, alopecia, anemia, thrombocytopenia, pyrexia, vomiting, injection site erythema, mucocutaneous reactions (may be fatal), hypersensitivity, PML, tumor lysis syndrome, renal toxicity, bowel obstruction/perforation (when concomitant chemotherapy), HBV reactivation, arrhythmias (discontinue if serious). How supplied: Single-dose vial—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 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. How supplied: Caps—56, 112

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.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 pwd for SC inj after reconstitution; contains mannitol; preservative-free. Indications: Treatment of 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 inj twice daily (approx. 12hrs apart) 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 inj 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) or hemorrhage (cerebral, GI). Monitor CBCs with platelets weekly during induction and initial maintenance cycles, then every 2wks during later cycles. Diabetes: monitor glucose levels frequently; if poorly controlled, avoid until glycemic control is established. Elderly. Embryo-fetal toxicity. Pregnancy (Cat. D); avoid. Nursing mothers: not recommended. Interactions: Avoid concomitant anticoagulants, aspirin, NSAIDs if platelets <50,000/microliters. 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 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.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 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-tosevere 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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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. Embryo-fetal 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

℞

tumor (stage I–II): 10–25mg per day orally for 4–8 days. Lymphosarcomas (stage III): 0.625– 2.5mg/kg daily. Mycosis fungoides (cutaneous T cell lymphoma): 5–50mg once weekly. Children: See literature. Contraindications: Pregnancy (Cat. X). Nursing mothers. Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration). Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity. Diabetes. Peptic ulcer. Ulcerative colitis. Infection. Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated. Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, nonabsorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin). Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome). How supplied: Tabs—30; soln (2mL, 4mL, 8mL, 10mL)—10 (single-use vials); pwd (1 gram)—1 (single-use vial)

TRISENOX Teva

℞

Antineoplastic. Arsenic trioxide 1mg/mL; soln for IV inj after dilution; preservative-free. Indications: Induction of remission and consolidation in acute promyelocytic leukemia (APL) refractory to or relapsed from retinoid and anthracycline chemotherapy, and whose APL has the t(15;17) translocation or PML/RAR-alpha gene expression. Adults: Give by IV infusion over 1–2 hours; may extend infusion up to 4 hours if acute vasomotor

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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, 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.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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: May be antagonized by concomitant strong CYP3A4 inducers (eg, rifampin, St. John’s Wort): not recommended. 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, peripheral neuropathy, fatigue, neuralgia, anemia, leukopenia, lymphopenia, rash, pyrexia, anorexia; hypotension, CHF, decreased LVEF, ARDS, diffuse infiltrative lung disease, 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 pre-existing 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), FrenchAmerican-British (FAB) classification M3 (including the M3 variant), characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene who are refractory to, or who have relapsed from, anthracycline chemotherapy, or for whom anthracycline-based chemotherapy is contraindicated. Adults: Use only for induction of remission. 45mg/m2 per day in two divided doses until complete remission is documented. Discontinue 30 days after complete remission or after 90 days of treatment, whichever occurs first. Children: See literature. Warnings/Precautions: Confirm APL diagnosis. Monitor for Retinoic Acid-APL (RA-APL) syndrome, leukocytosis, pseudotumor cerebri, or respiratory compromise. Consider temporarily interrupting therapy if moderate to severe RA-APL syndrome develops. Monitor blood counts, coagulation profile, lipids, liver function; consider temporary withdrawal if tests >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

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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER + 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

VYXEOS Jazz

℞

Anthracycline + antimetabolite. Daunorubicin, cytarabine 44mg/100mg (encapsulated in liposomes); per vial; lyophilized cake for IV infusion after reconstitution; contains copper; preservative-free. Indications: Treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). Adults: Calculate the prior cumulative anthracycline exposure before initiating each cycle. Give prophylactic antiemetics. Administer by IV infusion over 90mins. First induction: daunorubicin 44mg/m2 and cytarabine 100mg/m2 on Days 1, 3, and 5. Second induction (may give after 2–5 weeks if remission not achieved and no unacceptable toxicity): daunorubicin 44mg/m2 and cytarabine 100mg/m2 on Days 1 and 3. Consolidation (give 5–8 weeks after last induction): daunorubicin 29mg/m2 and cytarabine 65mg/m2 on Days 1 and 3. May give second consolidation 5–8 weeks after if no disease progression or unacceptable toxicity. Do not initiate consolidation until ANC recovers to >0.5Gi/L and platelet count >50Gi/L in the absence of unacceptable toxicity. Children: Not established.

Warnings/Precautions: Do not interchange with other daunorubicin and/or cytarabine-containing products. Prior anthracycline therapy, pre-existing cardiac disease, or radiotherapy to mediastinum: increased risk of cardiotoxicity. Assess CBCs, cardiac, liver, and renal function prior to initiation. Discontinue if impaired cardiac function unless benefit outweighs risk. If LVEF below normal or max lifetime cumulative anthracycline exposure limit reached: not recommended. Monitor for hypersensitivity reactions; interrupt and reduce infusion rate if mild or moderate symptoms; permanently discontinue if severe/life-threatening reactions occur. Wilson’s disease: use only if benefit outweighs risk. Monitor copper levels and serial neuropsychological exam; discontinue if signs/symptoms of acute copper toxicity develops. Avoid extravasation. Hepatic or severe renal impairment or ESRD: not studied. Embryofetal toxicity. Females of reproductive potential and males (with female partners) should use effective contraception during and for ≥6 months after last dose. Pregnancy; exclude status prior to initiation. Nursing mothers: not recommended (during and for ≥2 weeks after last dose). Interactions: Increased toxicity with concomitant cardiotoxic or hepatotoxic agents; monitor more frequently. Adverse reactions: Hemorrhagic events, febrile neutropenia, rash, edema, nausea, mucositis, diarrhea, constipation, musculoskeletal pain, fatigue, abdominal pain, dyspnea, headache, cough, decreased appetite, arrhythmia, pneumonia, bacteremia, chills, sleep disorders, vomiting; cardiotoxicity, copper overload, tissue necrosis. How supplied: Single-dose vials—2, 5

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 third-space accumulations prior to administration. Embryofetal 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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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. 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 non-Hodgkin 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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CANCER TREATMENT REGIMEN

LUNG CANCER Non–small Cell Lung Cancer (NSCLC) Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are 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 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.

Chemotherapy Regimens for Neoadjuvant and Adjuvant Therapy1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

Cisplatin + vinorelbine

Days 1 and 8: Cisplatin 50mg/m2 IV Days 1, 8, 15 and 22: Vinorelbine 25mg/m2 IV. Repeat cycle every 4 weeks for 4 cycles. OR Day 1: Cisplatin 100mg/m2 IV Days 1, 8, 15 and 22: Vinorelbine 30mg/m2 IV. Repeat cycle every 4 weeks for 4 cycles. OR Day 1: Cisplatin 75–80mg/m2 Days 1 and 8: Vinorelbine 25–30mg/m2. Repeat every 3 weeks for 4 cycles.

Cisplatin + etoposide3

Day 1: Cisplatin 100mg/m2 IV Days 1–3: Etoposide 100mg/m2 IV. Repeat cycle every 4 weeks for 4 cycles.

Cisplatin + gemcitabine5

Day 1: Cisplatin 75mg/m2 IV Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks.

Cisplatin + docetaxel6

Day 1: Docetaxel 75mg/m2 IV + cisplatin 75mg/m2 IV. Repeat every 3 weeks for 4 cycles.

Cisplatin + pemetrexed7

Day 1: Cisplatin 75mg/m2 IV + pemetrexed 500mg/m2 IV.* Repeat every 3 weeks for 4 cycles.

2–4

For patients with comorbidities or patients not able to tolerate cisplatin1 Paclitaxel + carboplatin8

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks for 4 cycles.

Chemotherapy Regimens Used With Radiation Therapy (RT)1 Concurrent Chemotherapy/RT1 Cisplatin + etoposide9,10,a,b

Days 1, 8, 29 and 36: Cisplatin 50mg/m2 IV Days 1–5 and 29–33: Etoposide 50mg/m2 IV Concurrent thoracic radiotherapy 1.8Gy/day for 5 days/week (total dose, 61Gy).

Cisplatin + vinblastine10,a,b

Days 1 and 29: Cisplatin 100mg/m2 IV Days 1, 8, 15, 22 and 29: Vinblastine 5mg/m2 IV with concurrent thoracic radiotherapy (total dose, 60Gy).

Carboplatin + pemetrexed (nonsquamous)11,a,b

Day 1: Carboplatin AUC 5mg • min/mL IV Day 1: Pemetrexed 500 mg/m2 IV with concurrent thoracic radiotherapy. Repeat every 3 weeks for 4 cycles.

Cisplatin + pemetrexed (nonsquamous)12,13

Day 1: Cisplatin 75 mg/m2 IV. Day 1: Pemetrexed 500 mg/m2 IV with concurrent thoracic radiotherapy.a,b Repeat every 3 weeks for 3 cycles ± additional 4 cycles of pemetrexed 500mg/m2.b

Paclitaxel + carboplatin14

Paclitaxel 45-50mg/m2 IV + carboplatin AUC 2mg • min/mL IV weekly with concurrent thoracic radiotherapy (total dose, 60Gy)a,b given 5 days per weeks in 2Gy fractionsa,b ± additional 2 cycles of paclitaxel 200mg/m2 and carboplatin AUC 6mg • min/mL IV.b continued

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LUNG CANCER NSCLC Treatment Regimens Chemotherapy Regimens Used With Radiation Therapy (RT)1 (continued) REGIMEN

DOSING

Sequential Chemotherapy/RT (Adjuvant)1 Cisplatin + vinblastine10

Days 1 and 29: Cisplatin 100mg/m2 IV. Days 1, 8, 15, 22 and 29: Vinblastine 5mg/m2 IV; followed by thoracic radiotherapy with 60Gy in 30 fractions beginning on Day 50.

Paclitaxel + carboplatin15

Day 1: Paclitaxel 200mg/m2 IV over 3 hours + carboplatin AUC 6mg • min/mL IV over 1 hour. Repeat every 3 weeks for 2 cycles; followed by thoracic radiotherapy 63Gy beginning on Day 42.

Consolidation Therapy1 Note: For patients with unresectable stage III NSCLC, PS 0-1, and no disease progression after 2 or more cycles of definitive chemoradiation

Durvalumab16

Day 1: Durvalumab 10mg/kg Repeat every 2 weeks for up to 12 months.

Systemic Therapy for Advanced & Metastatic Disease1 Principals of Therapy1 • The drug regimen with the highest likelihood of benefit, with toxicity deemed acceptable to both the physician and the patient, should be given as initial therapy for advanced lung cancer. • Stage, weight loss, performance status (PS), and gender predict survival. • Platinum-based chemotherapy prolongs survival, improves symptom control, and yields superior quality of life compared to best supportive care. • Histology of NSCLC is important in the selection of systemic therapy. • New agent/platinum combinations have generated a plateau in overall response rate ( 25%–35%), time to progression (4–6 months), median survival (8–10 months), 1-year survival rate (30%–40%), and 2-year survival rate (10%–15%) in fit patients. • Unfit patients of any age (PS 3–4) do not benefit from cytotoxic treatment, except erlotinib for those who are epidermal growth factor receptor (EGFR) mutation-positive. First-line Systemic Therapy Options1 Principals of Therapy1 • There is superior efficacy and reduced toxicity for cisplatin/pemetrexed in patients with nonsquamous histology compared with cisplatin/gemcitabine. • There is superior efficacy for cisplatin/gemcitabine in patients with squamous histology, in comparison to cisplatin/pemetrexed. • Two drug regimens are preferred; a third cytotoxic drug increases response rate but not survival. • Single-agent therapy may be appropriate in select patients. • Response assessment after 2 cycles, then every 2–4 cycles with CT of known sites of disease with or without contrast or when clinically indicated. Adenocarcinoma, Large Cell, NSCLC NOS (PS 0-1)1 Bevacizumab + carboplatin + paclitaxel (Category 1)17,c,d

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks for 6 cycles. Day 1: Bevacizumab 15mg/kg IV every 3 weeks until disease progression.

Bevacizumab + carboplatin + pemetrexed18,d

Day 1: Pemetrexed 500mg/m2 IV + carboplatin AUC 6mg • min/mL IV + bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks for up to 4 cycles, followed by: Day 1: Pemetrexed 500mg/m2 IV + bevacizumab 15mg/kg IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Bevacizumab + cisplatin + pemetrexed19,d

Day 1: Bevacizumab 7.5mg/kg IV + cisplatin 75mg/m2 IV + pemetrexed 500mg/m2 IV. Repeat cycle every 3 weeks for 4 cycles, followed by: Day 1: Bevacizumab 7.5mg/kg IV + pemetrexed 500mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + albumin-bound paclitaxel (Category 1)20

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1, 8, and 15: Nab-paclitaxel 100mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel (Category 1)21,c

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

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LUNG CANCER Systemic Therapy for Advanced & Metastatic Disease1 (continued) REGIMEN

DOSING

First-line Systemic Therapy Options1 (continued) Adenocarcinoma, Large Cell, NSCLC NOS (PS 0-1)1 (continued) Carboplatin + etoposide (Category 1)22,23

Day 1: Carboplatin 325mg/m2 IV Days 1, 2, and 3: Etoposide 100mg/m2 IV. Repeat cycle every 3 to 4 weeks until disease progression or unacceptable toxicity. OR First Course Day 1: Carboplatin AUC 4mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Second Course Day 1: Carboplatin AUC 5mg • min/mLIV Days 1–14: Etoposide 50mg orally twice daily Third Course Day 1: Carboplatin AUC 5mg • min/mLIV Days 1–21: Etoposide 50mg orally twice daily. Patients achieving a complete or partial response should receive an additional 3 courses at the same doses given in the third course.

Carboplatin + gemcitabine (Category 1)24

Day 1: Carboplatin AUC 5mg • min/mL IV Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel (Category 1)25,c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + pemetrexed (Category 1)26

Day 1: Pemetrexed 500mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + docetaxel (Category 1)21,c

Day 1: Cisplatin 75mg/m2 IV + docetaxel 75mg/m2 IV. Repeat cycle every 3 weeks.

Cisplatin + etoposide (Category 1)27

Day 1: Cisplatin 100mg/m2 IV Days 1–3: Etoposide 100mg/m2 IV. Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + gemcitabine (Category 1)25,28

Day 1: Cisplatin 80mg/m2 IV Days 1 and 8: Gemcitabine 1,000mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity. OR Day 1: Cisplatin 75mg/m2 IV Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + paclitaxel (Category 1)29,c

Day 1: Paclitaxel 135mg/m2 IV over 24 hours Day 2: Cisplatin 75mg/m2 IV. Repeat cycle every 3 weeks.

Cisplatin + pemetrexed (Category 1)28

Day 1: Pemetrexed 500mg/m2 IV + cisplatin 75mg/m2 IV. Repeat cycle every 3 weeks.

Gemcitabine + docetaxel (Category 1)30,c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV Day 8: Docetaxel 85mg/m2 IV. Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine (Category 1)31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV. Repeat cycle every 3 weeks.

Pembrolizumab + carboplatin + pemetrexed32, f

Days 1: Pembrolizumab 200mg IV + pemetrexed 500mg/m2 IV + carboplatin AUC 5mg • min/mL IV. Repeat cycle every 3 weeks for up to 4 cycles; followed by: Days 1: Pembrolizumab 200mg IV every 3 weeks for 24 months Days 1: Pemetrexed 500mg/m2 IV every 3 weeks (optional, indefinite) continued

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LUNG CANCER NSCLC Treatment Regimens Systemic Therapy for Advanced & Metastatic Disease1 (continued) REGIMEN

DOSING

First-line Systemic Therapy Options1 (continued) Adenocarcinoma, Large Cell, NSCLC NOS (PS 2)1 Albumin-bound paclitaxel33,c

Day 1: Albumin-bound paclitaxel 260mg/m2 IV. Repeat cycle every 3 weeks.

Carboplatin + albumin-bound paclitaxel34,35

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1, 8, and 15: Albumin-bound paclitaxel 100mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel21,c

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + etoposide22,23

Day 1: Carboplatin 325mg/m2 IV Days 1, 2, and 3: Etoposide 100mg/m2 IV. Repeat cycle every 3 to 4 weeks until disease progression or unacceptable toxicity. OR First Course Day 1: Carboplatin AUC 4mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Second Course Day 1: Carboplatin AUC 5mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Third Course Day 1: Carboplatin AUC 5mg • min/mL IV Days 1–21: Etoposide 50mg orally twice daily. Patients achieving a complete or partial response should receive an additional 3 courses at the same doses given in the third course.

Carboplatin + gemcitabine24

Day 1: Carboplatin AUC 5mg • min/mL IV Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel25,c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + pemetrexed26

Day 1: Pemetrexed 500mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks for up to 6 cycles.

Docetaxel36,37,c

Day 1: Docetaxel 75mg/m2 IV over 1 hour. Repeat cycle every 3 weeks.

Gemcitabine38-40

Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks.

Gemcitabine + docetaxel30,c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV Day 8: Docetaxel 85mg/m2 IV. Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV. Repeat cycle every 3 weeks.

Paclitaxel41-43,c

Days 1, 8, and 15: Paclitaxel 80mg/m2 IV. Repeat cycle every 4 weeks for up to 4 cycles.

Pemetrexed44

Day 1: Pemetrexed 500mg/m2 IV. Repeat cycle every 3 weeks.

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LUNG CANCER Systemic Therapy for Advanced & Metastatic Disease1 (continued) REGIMEN

DOSING

First-line Systemic Therapy Options1 (continued) Squamous Cell Carcinoma (PS 0-1)1 Carboplatin + albumin-bound paclitaxel (Category 1)20,c

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1, 8, and 15: Albumin-bound paclitaxel 100mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel (Category 1)21,c

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + gemcitabine (Category 1)24

Day 1: Carboplatin AUC 5mg • min/mL IV Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel (Category 1)25,c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat every 3 weeks until disease progression or unacceptable toxicity.

Cisplatin + docetaxel (Category 1)21,c

Day 1: Cisplatin 75mg/m2 IV + docetaxel 75mg/m2 IV. Repeat cycle every 3 weeks.

Cisplatin + etoposide (Category 1)27

Day 1: Cisplatin 100mg/m2 IV Days 1–3: Etoposide 100mg/m2 IV. Repeat cycle every 3 weeks for up to 6 cycles.

Cisplatin + gemcitabine (Category 1)25,28

Cisplatin + paclitaxel (Category 1)29,c

Day 1: Paclitaxel 135mg/m2 IV over 24 hours Day 2: Cisplatin 75mg/m2 IV. Repeat cycle every 3 weeks.

Gemcitabine + docetaxel (Category 1)30,c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV Day 8: Docetaxel 85mg/m2 IV. Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine (Category 1)31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV. Repeat cycle every 3 weeks.

Squamous Cell Carcinoma (PS 2)1 Albumin-bound paclitaxel33

Day 1: Albumin-bound paclitaxel 260mg/m2 IV. Repeat cycle every 3 weeks.

Carboplatin + albumin-bound paclitaxel34,35

Day 1: Carboplatin AUC 6mg • min/mL IV Days 1, 8, and 15: Albumin-bound paclitaxel 100mg/m2 IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Carboplatin + docetaxel21,c

Day 1: Docetaxel 75mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity. continued

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LUNG CANCER NSCLC Treatment Regimens Systemic Therapy for Advanced & Metastatic Disease1 (continued) REGIMEN

DOSING

First-line Systemic Therapy Options1 (continued) Squamous Cell Carcinoma (PS 2)1 (continued) Carboplatin + etoposide22,23

Day 1: Carboplatin 325mg/m2 IV Days 1, 2, and 3: Etoposide 100mg/m2 IV. Repeat cycle every 3 to 4 weeks until disease progression or unacceptable toxicity. OR First Course Day 1: Carboplatin AUC 4mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Second Course Day 1: Carboplatin AUC 5mg • min/mL IV Days 1–14: Etoposide 50mg orally twice daily Third Course Day 1: Carboplatin AUC 5mg • min/mL IV Days 1–21: Etoposide 50mg orally twice daily. Patients achieving a complete or partial response should receive an additional 3 courses at the same doses given in the third course.

Carboplatin + gemcitabine24

Day 1: Carboplatin AUC 5mg • min/mL IV Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV Repeat cycle every 4 weeks for 4 cycles.

Carboplatin + paclitaxel25,c

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC 6mg • min/mL IV. Repeat every 3 weeks until disease progression or unacceptable toxicity.

Docetaxel36,37c

Day 1: Docetaxel 75mg/m2 IV over 1 hour. Repeat cycle every 3 weeks.

Gemcitabine38-40

Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks.

Gemcitabine + docetaxel30,c

Days 1 and 8: Gemcitabine 1,000mg/m2 IV Day 8: Docetaxel 85mg/m2 IV. Repeat cycle every 3 weeks for 8 cycles.

Gemcitabine + vinorelbine31

Days 1 and 8: Vinorelbine 25mg/m2 IV + gemcitabine 1,000mg/m2 IV. Repeat cycle every 3 weeks.

Paclitaxel41-43

Days 1, 8, and 15: Paclitaxel 80mg/m2 IV. Repeat cycle every 4 weeks for up to 4 cycles.

Maintenance Therapy for Advanced & Metastatic Disease1 Principles of Maintenance Therapy1 Continuation maintenance refers to the use of at least one of the agents given in first line, beyond 4 to 6 cycles, in the absence of disease progression. Switch maintenance refers to the initiation of a different agent, not included as part of the first-line regimen, in the absence of disease progression, after 4 to 6 cycles of initial therapy. • Continuation Maintenance: Bevacizumab and cetuximab given in combination with chemotherapy should be continued until evidence of disease progression or unacceptable toxicity, as per the design of the clinical trials supporting their use. —— Continuation of bevacizumab after 4–6 cycles of platinum-doublet chemotherapy and bevacizumab (category 1). —— Continuation of cetuximab after 4–6 cycles of cisplatin, vinorelbine, and cetuximab (category 1). —— Continuation of pemetrexed after 4–6 cycles of cisplatin and pemetrexed chemotherapy, for patients with histologies other than squamous cell carcinoma (category 1). —— Continuation of bevacizumab + pemetrexed after 4–6 cycles of bevacizumab, pemetrexed, cisplatin/carboplatin, for patients with histologies other than squamous cell carcinoma. —— Continuation of gemcitabine after 4–6 cycles of platinum-doublet chemotherapy (category 2B). Switch Maintenance: Two studies have shown a benefit in progression-free and overall survival with the initiation of pemetrexed after first-line chemotherapy, in patients without disease progression after 4–6 cycles of therapy. —— Initiation of pemetrexed after 4–6 cycles of first-line platinum-doublet chemotherapy for patients with histologies other than squamous cell carcinoma (category 2B). —— Initiation of docetaxel after 4–6 cycles of first-line platinum-doublet chemotherapy in patients with squamous cell carcinoma (category 2B). • Close surveillance of patients without therapy is a reasonable alternative to maintenance.

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CANCER TREATMENT REGIMEN

LUNG CANCER Systemic Therapy for Advanced & Metastatic Disease1 (continued) REGIMEN

DOSING

Subsequent Therapy for Advanced & Metastatic Disease1 Principles of Subsequent Therapy1 • In patients who have experienced disease progression either during or after first-line therapy, single-agent docetaxel, or pemetrexed are established second-line agents. —— Nivolumab improves survival when compared with docetaxel —— Pembrolizumab improves overall survival in PD-L1 positive tumors when compared with docetaxel. —— Docetaxel is superior to vinorelbine or ifosfamide. —— Pemetrexed is considered equivalent to docetaxel with less toxicity in patients with adenocarcinoma and large cell carcinoma. —— Ramucirumab + docetaxel improves survival when compared to docetaxel alone. • If not already given, options for patients with PS 0–2 include docetaxel, pemetrexed (nonsquamous), erlotinib, or gemcitabine (category 2B for all options). • Response assessment with CT of known sites with or without contrast every 6–12 weeks. Nivolumab (Category 1)45,46

Day 1: Nivolumab 240mg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

Pembrolizumab (Category 1)47,57,e,f

Day 1: Pembrolizumab 2mg/kg IV. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Atezolizumab (Category 1)48,65,f

Day 1: Atezolizumab 1200mg IV over 1 hour. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity.

Docetaxel36,37

Day 1: Docetaxel 75mg/m2 IV over 1 hour. Repeat cycle every 3 weeks.

Pemetrexed44

Day 1: Pemetrexed 500mg/m2 IV. Repeat cycle every 3 weeks.

Gemcitabine38-40

Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks.

Ramucirumab + docetaxel49

Day 1: Ramucirumab 10mg/kg IV + docetaxel 75mg/m2 IV. Repeat cycle every 3 weeks.

First-line Targeted Therapy for Advanced & Metastatic Disease1 Sensitizing EGFR Mutation Positive1 Erlotinib (Category 1)58

Erlotinib 150mg orally once daily until disease progression or unacceptable toxicity.

Afatinib (Category 1)

Afatinib 40mg orally once daily until disease progression or unacceptable toxicity.

Gefitinib (Category 1)

Gefitinib 250mg orally once daily until disease progression or unacceptable toxicity.

ALK Positive1 Crizotinib (Category 1)56,61 Alectinib (Category 1) Preferred

Crizotinib 250mg orally twice daily until disease progression or unacceptable toxicity. 52,53,64

Ceritinib (Category 1)54,55,63

Day 1: Alectinib 600mg orally twice daily. Repeat until disease progression or unacceptable toxicity. Day 1: Ceritinib 750mg orally once daily. Repeat until disease progression or unacceptable toxicity.

ROS1 Rearrangement Positive1 Crizotinib56,61

Day 1: Crizotinib 250mg orally twice daily. Repeat until disease progression or unacceptable toxicity.

BRAF V600E Mutation Positive1 Dabrafenib + trametinib50,68,69,g

Day 1: Dabrafenib 150mg orally twice daily Day 1: Trametinib 2mg orally once daily Repeat until disease progression or unacceptable toxicity.

See First-line therapy options for adenocarcinoma/squamous cell carcinoma. PD-L1 Expression Positive1 Pembrolizumab (Category 1)51,e

Day 1: Pembrolizumab 200mg IV over 30 minutes. Repeat cycle every 3 weeks until disease progression or unacceptable toxicity continued

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CANCER TREATMENT REGIMEN

LUNG CANCER NSCLC Treatment Regimens Subsequent Targeted Therapy for Advanced & Metastatic Disease1 REGIMEN

DOSING

Sensitizing EGFR Mutation Positive1,h Osimertinib (Category 1)62i

Osimertinib 80mg orally once daily until disease progression or unacceptable toxicity.

Erlotinib58

Erlotinib 150mg orally once daily until disease progression or unacceptable toxicity.

Afatinib

Afatinib 40mg orally once daily until disease progression or unacceptable toxicity.

Gefitinib 250mg orally once daily until disease progression or unacceptable toxicity.

Gefitinib60 ALK Positive

Crizotinib56,61

Crizotinib 250mg orally twice daily until disease progression or unacceptable toxicity.

Ceritinib54,55,63

Ceritinib 750mg orally once daily until disease progression or unacceptable toxicity.

Alectinib

Alectinib 600mg orally twice daily until disease progression or unacceptable toxicity.

52,53,64

Brigatinib

Days 1–7: Brigatinib 90mg orally once daily followed by: Day 1: Brigatinib 180mg orally once daily Repeat until disease progression or unacceptable toxicity. Refer to guidelines.

ROS1 Rearrangement Positive1 See first-line therapy options for adenocarcinoma, squamous cell carcinoma, or PD-L1 expression positive (>50%) BRAF V600E Mutation Positive1 If progression occurs after dabrafenib + trametinib, recommendation is first-line therapy options for adenocarcinoma/squamous cell carcinoma. If progression occurs after first-line therapy options for adenocarcinoma/squamous cell carcinoma, recommendation is dabrafenib + trametinib. PD-L1 Expression Positive1 See first-line therapy options for adenocarcinoma or squamous cell carcinoma Regimens can be used as neoadjuvant/preoperative/induction chemoradiotherapy. Regimens can be used as adjuvant or definitive concurrent chemotherapy/RT. c Albumin-bound paclitaxel may be substituted for either paclitaxel or docetaxel in patients who have experienced hypersensitivity reactions after receiving paclitaxel or docetaxel despite premedication, or for patients where the standard premedications (ie. Dexamethasone, H2 blockers, H1 blockers) are contraindicated. d Bevacizumab should be given until progression. e Pembrolizumab is approved for patients with NSCLC with PD-L1 expression levels >1%, as determined by an FDA-approved test. f If pembrolizumab not previously given. g Single-agent vemurafenib or dabrafenib are treatment options if the combination of dabrafenib + trametinib is not tolerated. h T790M testing should be performed upon progression. i Osimertinib if T790M(+) disease, if T790M(-) refer to first line therapy options for adenocarcinoma, squamous cell carcinoma, or PD-L1 expression positive (>50%). Refer to Treatment Guidelines. a

References 1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™ Non-Small Cell Lung Cancer. v 8.2017. Available at: http://www.nccn.org/ professionals/physician_gls/pdf/nscl.pdf. Accessed August 14, 2017. 2. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-lung cancer. N Engl J Med. 2005;352:2589–2597. 3. Arriagada R, Bergman B, Dunant A, et al. The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med. 2004;350:351–360. 4. Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006;7:719–727. 5. Pérol M, Chouaid C, Pérol D, et al. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced nonsmall-cell lung cancer. J Clin Oncol. 2012;30:3516–3524. 6. Fossella F, Pereira JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003;21:3016–3024. 7. Kreuter M, Vansteenkiste J, Fishcer JR, et al. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013;24:986–992.

8. Strauss GM, Herndon III JE, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008;26:5043–5051. 9. Albain KS, Crowley JJ, Turrisi AT III, et al. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: A Southwest Oncology Group Phase II Study, SWOG 9019. J Clin Oncol. 2002;20:3454–3460. 10. Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103:1452–1460. 11. Govindan R, Bogart J, Stinchcombe T, et al. Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: Cancer and Leukemia Group B trial 30407. J Clin Oncol. 2011;29: 3120–3125. 12. Choy H, Gerber DE, Bradley JD, et al. Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: a e systematic review of completed and ongoing studies. Lung Cancer. 2015;87:232–240. 13. Senan S, Brade A, Wang LH, et al. PROCLAIM: randomized phase III trial of pemetrexed-cisplatin or etoposide-cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous nonsmall-cell lung cancer. J Clin Oncol. 2016;34:953–962.

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LUNG CANCER References (continued) 14. Bradley JD, Paulus R, Komaki R, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16:187–199. 15. Belani CP, Choy H, Bonomi P, et al. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005;23:5883–5891. 16. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non-small cell lung cancer [article and supplementary appendix published online ahead of print September 8, 2017]. N Engl J Med. 2017. 17. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small cell lung cancer. N Engl J Med. 2006;355:2542–2550. 18. Patel JD, Socinski MA, Garon EB, et al. Pointbreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small cell lung cancer. J Clin Oncol. 2013;31:4349–4357. 19. Barlesi F, Scherpereel A, Rittmeywr A, et al. Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small cell lung cancer: AVAPERL. J Clin Oncol. 2013;31:3004–3011. 20. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012:30:2055–2062. 21. Fossella F, Periera JR, von Pawel J, et al. Randomized, multinational, phase III study ofdocetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003;21(16): 3016–3024. 22. Klastersky J, Sculier JP, Lacroix H, et al. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. J Clin Oncol. 1990;8:1556–1562. 23. Frasci G, Comella P, Panza N, eta l. Carboplatin-oral etoposide personalized dosing in elderly non-small cell lung cancer patients. Gruppo Oncologico Cooperativo Sud-Italia. Eur J Cancer. 1998;34:1710–1714. 24. Danson S, Middleton MR, O’Byrne KJ, et al. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and ciplatin in patients with advanced non-small-cell lung carcinoma. Cancer. 2003;98:542–553. 25. Ohe Y, Ohashi Y, Kubota K, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol. 2007;18:317–323. 26. Scagliotti GV, Kortsik C, Dark GG, et al. Pemetrexed combined with oxaliplatin or carboplatin as first-line treatment in advanced non-small cell lung cancer: a multicenter, randomized, phase II trial. Clin Cancer Res. 2005;11:690–696. 27. Cardenal F, Lopez-Cabrerizo MP, Anton A, et al. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small cell lung cancer. J Clin Oncol. 1999;17:12–18. 28. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage NSCLC. J Clin Oncol. 2008;26:3543–3551. 29. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Engl J Med. 2002;346:92–98. 30. Pujol JL, Breton JL, Gervais R, et al. Gemcitabine-docetaxel versus cisplatinvinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin. Ann Oncol. 2005;16:602–610. 31. Tan EH, Szczesna A, Krzakowski M, et al. Randomized study of vinorelbine— gemcitabine versus vinorelbine—carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2005;49:233–240. 32 . Langer CJ, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17:1497–1508. 33. Green M, Manikhas G, Orlov S, et al. Abraxane®, a novel Cremophor®-free, albuminbound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Ann Oncol. 2006;17:1263–1268. 34. Rizvi N, Riely G, Azzoli, C, et al. Phase I/II Trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non– small-cell lung cancer. J Clin Oncol. 2008;26:639–643. 35. Socinski MA, Bondarenko I, Karaseva NA, et al. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012:30:2055–2062. 36. Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320

Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000;18:2354–2362. 37. Fidias PM, Dakhil SR, Lyss AP, et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small cell lung cancer. J Clin Oncol. 2009;27:591–598. 38. Zatloukal P, Kanitz E, Magyar P, et al Gemcitabine in locally advanced and metastatic non-small cell lung cancer: the Central European phase II study. Lung Cancer. 1998;22:243–250. 39. Sederholm C, Hillerdal G, Lamberg K, et al. Phase III trial of gemcitabine plus carboplatin versus single agent gemcitabine in the treatment of locally advanced or metastatic non-small cell lung cancer: the Swedish Lung Cancer Study group. J Clin Oncol. 2005;23:8380–8288. 40. Perol M, Chouaid C, Perol D, et al. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced nonsmall cell lung cancer. J Clin Oncol. 2012;30:3516–3524. 41. Lilenbaum RC, Herndon JE, List MA, et al. Single-agent versus combination chemotherapy in advanced non-small cell lung cancer: the cancer and leukemia group B (study 9730). J Clin Oncol. 2005;23:190–196. 42. Ceresoli GL, Gregorc V, Cordio S, et al. Phase II study of weekly paclitaxel as second-line therapy in patients with advanced non-small cell lung cancer. Lung Cancer. 2004;44:231–239. 43. Yasuda K, Igishi T, Kawasaki Y, et al. Phase II study of weekly paclitaxel in patients with nonsmall cell lung cancer who have failed previous treatments. Oncology. 2004;66:347–352. 44. Hanna NH, Sheperd FA, Fossella FV, et al. Randomized phase III study of pemetrexed versus docetaxel in patients with non-small cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22:1589–1597. 45. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–1639. 46. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–135. 47. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2015. 48. Barlesi F, Park K, Ciardiello F, et al. Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC [abstract]. ESMO Congress; Copenhagen. ESMO 2016: LBA44. 49. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384:665–673. 50. Planchard D, Besse B, Groen HJM, et al. An open-label phase 2 trial of dabrafenib plus trametinib in patients with previously treated BRAF V600E-mutant metastatic non-small cell lung cancer. Lancet Oncol. 2016;17:984–993. 51. Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823–1833. 52. Ou SH, Ahn JS, De Petris L, et al. Alectinib in Crizotinib-Refractory ALK-Rearranged NonSmall-Cell Lung Cancer: A Phase II Global Study. J Clin Oncol. 2016;34(7):661–668. 53. Shaw AT, Gandhi L, Gadgeel S, et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016;17(2):234-242. 54. Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-Rearranged Non–Small-Cell Lung Cancer. N Engl J Med. 2014;370(13):1189–97. 55. Soria JC, Tan DSW, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017;389(10072):917–929. 56. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–703. 57. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the Treatment of Non–SmallCell Lung Cancer, N Engl J Med. 2015;372(21):2018–28. 58. Tarceva [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2016 59. Gilotrif [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2016. 60. Iressa [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2015. 61. Xalkori [prescribing information]. New York, NY: Pfizer Inc.; 2016. 62. Tagrisso [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2016. 63. Zykadia [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; 2016. 64. Alecensa [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2016. 65. Tecentriq [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2017. 66. Keytruda [prescribing information]. Whitehouse Station, NJ: Merck & Co, Inc.; 2017. 67. Alunbrig [prescribing information]. Cambridge, MA: Ariad Pharmaceuticals, Inc.; 2017. 68. Tafinlar [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2015. 69. Mekinist [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2015.

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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; 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

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DRUG MONOGRAPHS

LUNG CANCER 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 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

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

CYRAMZA Lilly

℞

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 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; resume based on adequate healing; discontinue if complications develops during therapy until wound is fully healed. 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

GILOTRIF Boehringer Ingelheim

℞

Tyrosine kinase inhibitor. Afatinib 20mg, 30mg, 40mg; tabs. Indications: First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitutions as detected by an FDAapproved test. Limitations of use: safety and efficacy 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

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DRUG MONOGRAPHS

LUNG CANCER

℞

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. Embryo-fetal toxicity. 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

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.

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

disease progression or not tolerated. Severe renal 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

IRESSA AstraZeneca

℞

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

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DRUG MONOGRAPHS

LUNG CANCER in patients without disease progression. In 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. Monitor for severe skin reactions; permanently discontinue if SJS or TEN is confirmed. 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. Solid organ transplant recipients. 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 Novartis

℞

Kinase inhibitor. Trametinib 0.5mg, 2mg; tabs. Indications: In combination with dabrafenib for the treatment of metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation, as detected by an FDA-approved test. Adults: Confirm presence of BRAF V600E mutation prior to initiation. Take at same time each day, 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. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: See full labeling for dabrafenib 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. Monitor for non-cutaneous malignancies, pulmonary embolism (permanently discontinue if life-threatening), colitis, GI perforations, skin toxicities and secondary infections. Permanently discontinue for all Grade 4 hemorrhagic events or any Grade 3 events that do not improve. 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 baseline and is less than the lower limit of normal; permanently discontinue if symptomatic cardiomyopathy or persistent asymptomatic LV dysfunction is unresolved within 4wks. Perform eye exam periodically and at any time for visual disturbances; permanently discontinue if retinal vein occlusion develops or retinal pigment epithelial detachment persists. Permanently discontinue if interstitial lung disease or pneumonitis occurs. Withhold if fever >104°F or any serious febrile reaction occurs and evaluate for infection; prophylaxis with antipyretics may be needed when resuming. Pre-existing diabetes or hyperglycemia; monitor serum glucose levels. Severe renal or moderate-to-severe hepatic impairment. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for 4 months after treatment. Pregnancy. Nursing mothers: not recommended (during and for 4 months after last dose).

Adverse reactions: Rash, diarrhea, lymphedema. In combination with dabrafenib: also pyrexia, chills, fatigue, nausea, vomiting, hypertension, peripheral edema, dry skin, decreased appetite, hemorrhage, cough, dyspnea. How supplied: Tabs—30

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

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DRUG MONOGRAPHS

LUNG CANCER 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

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 transplant-related complications (eg, hyperacute or Grade 3/4 acute GVHD, steroidrequiring 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 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 life-threatening (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 (non-HCC) or AST/ALT >10XULN (HCC) 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), immunemediated encephalitis, recurring Grade

℞

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

TAFINLAR Novartis

℞

Kinase inhibitor. Dabrafenib 50mg, 75mg; caps. Indications: In combination with trametinib for the treatment of metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation, as detected by an FDA-approved test. Limitation of use: not indicated for the treatment of wild-type BRAF NSCLC. Adults: Confirm presence of BRAF V600E 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 (approx. 12hrs apart); continue until disease progression or unacceptable toxicity. Dose modifications: 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. Monitor for non-cutaneous malignancies; permanently discontinue if RAS mutationpositive malignancy occurs. Permanently discontinue for all Grade 4 hemorrhagic events or any persistent Grade 3 events. Risk of cardiomyopathy with trametinib; assess LVEF prior to initiation, after one month, and then at every 2–3 month intervals during treatment; withhold for symptomatic cardiomyopathy or asymptomatic LV dysfunction of >20% from baseline that is below institutional lower limit of normal. Withhold if fever ≥101.3°F or any serious febrile 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; permanently discontinue for persistent Grade ≥2 lasting >6wks. G6PD deficiency: monitor for hemolytic anemia. Severe renal or moderate-to-severe hepatic impairment. Embryo-fetal toxicity. Females of reproductive potential should use highly effective nonhormonal contraception during and for 2wks after last dose. Pregnancy. Nursing mothers: not recommended (during and for 2wks after last dose). Interactions: Avoid concomitant strong CYP3A4 or CYP2C8 inhibitors (eg, ketoconazole,

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DRUG MONOGRAPHS

LUNG CANCER nefazodone, clarithromycin, gemfibrozil); if unavoidable, monitor closely. May antagonize effects of CYP3A4, CYP2C8, CYP2C9, CYP2C19, CYP2B6 substrates (eg, midazolam, warfarin, dexamethasone, hormonal contraceptives); consider alternatives or monitor. Adverse reactions: Hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, palmar-plantar erythrodysesthesia syndrome; skin toxicity (may be serious). In combination with trametinib: also chills, fatigue, rash, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, hemorrhage, cough, dyspnea. How supplied: Caps—120

TAGRISSO AstraZeneca

℞

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 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

TARCEVA Astellas and Genentech

℞

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. 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),

Access Cancer Therapy Advisor treatment regimens in a user-friendly format. CancerTherapyAdvisor.com/TreatmentRegimens.

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DRUG MONOGRAPHS

LUNG CANCER 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 infusion-related 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)

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 nonhematologic 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

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DRUG MONOGRAPHS

LUNG CANCER 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. Moderateto-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, betablockers, non-dihydropyridine 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

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.

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

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DRUG MONOGRAPHS

SARCOMA DOXIL Janssen Biotech

℞

Anthracycline. Doxorubicin HCl (liposomal) 2mg/mL; dispersion for IV infusion after dilution; preservative-free. Indications: AIDS-related Kaposi’s sarcoma refractory to combination chemotherapy. Adults: Give by IV infusion at initial rate of 1mg/min; may increase rate to complete infusion over 1hr if no infusion reactions occur; may premedicate with antiemetics. 20mg/m2 once every 3 weeks. Hepatic dysfunction (serum bilirubin ≥1.2mg/dL), hand-foot syndrome, hematologic toxicity (esp. ANC, platelets), or stomatitis: reduce dose. Consider total anthracycline and anthracenedione doses and irradiation when calculating total cumulative dose. See full labeling. Children: Not established. Warnings/Precautions: Not substitutable on a mg/mg basis with other doxorubicin products. Cardiomyopathy (including left ventricular failure), acute infusion-related reactions, myelosuppression may occur. Have medications to treat infusion-related reactions and resuscitative equipment available. Hepatic impairment. Monitor blood (esp. CBC + platelets), hepatic (esp. SGOT/SGPT, alkaline phosphatase), and cardiac function (eg, MUGA, ECG). Monitor periodically for secondary oral cancers with long-term use. Avoid extravasation. Embryo-fetal toxicity. Use effective contraception during and for 6 months after last dose. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Caution with cyclosporine, phenobarbital, phenytoin, streptozocin, digoxin, myelosuppressants, others. Previous mediastinal irradiation, cyclophosphamide, other cardiotoxic drugs: monitor for cardiotoxicity and hepatotoxicity. Adverse reactions: Asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand and foot syndrome, rash, neutropenia, thrombocytopenia, anemia; infusion reactions, cardiovascular events (eg, cardiomyopathy, CHF, acute LV failure), recall of skin reaction from prior radiation therapy, toxoplasmosis, urine discoloration (red/orange). How supplied: Single-use vials (10mL, 25mL)—1

INTRON A Merck

30 million IU/m2 IM or SC three times weekly; continue until 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: 18yrs: not established. 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. Cardiovascular disease (eg, MI, arrhythmias); monitor closely. Pulmonary disease (eg, COPD). Discontinue if severe psychiatric disorders (eg, suicidal behavior) or new/worsening ophthalmologic reactions develop. 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 CBCs, platelets, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Pwd: contains human albumin; monitor for possible viral disease and Creutzfeldt-Jakob disease transmission. Pre-existing psoriasis or sarcoidosis. Renal impairment. Transplant recipients. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Caution with myelosuppressive agents (eg, zidovudine), and drugs that can exacerbate depression. May potentiate theophylline. Increased risk of peripheral neuropathy with concomitant telbivudine. Dental/periodontal disorders, dry mouth with concomitant ribavirin. Adverse reactions: Flu-like symptoms (fever, headache, chills, myalgia, fatigue); abnormal LFTs, blood, cardiovascular, pulmonary, thyroid, and GU disorders, GI upset, abnormal vision, skin reactions, CNS/psychiatric reactions, colitis, hypertriglyceridemia, pancreatitis; rare: autoimmune disorders, hypersensitivity. See full labeling. How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial—1; Soln (multidose vials): 18million, 25million IU/vial—1

℞

PANRETIN Eisai

℞

Retinoid. Alitretinoin 0.1%; gel. Indications: Cutaneous lesions of AIDS-related Kaposi’s sarcoma (KS). Adults: Apply twice daily to lesions (avoid mucous membranes and normal skin); do not occlude; may increase to 3–4 times daily as tolerated. Reduce frequency or suspend treatment if local toxicity occurs. Children: Not recommended. Warnings/Precautions: Not for use when systemic KS therapy required. Avoid sun, UV light.

Flammable. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Increases DEET toxicity (avoid). Adverse reactions: Photosensitivity, rash, pruritus, pain, exfoliative dermatitis, paresthesia, edema. How supplied: Gel—60g

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

SEE LITERATURE Consult the manufacturer’s labeling for full prescribing information.

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

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 noncutaneous); 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

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DRUG MONOGRAPHS

SKIN CANCER 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 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; renal function at baseline and during therapy; GI symptoms at baseline. Cardiovascular disease or risk factors; monitor. Diabetes. Hypertension. CHF. 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, 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

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, as adjuvant to surgical treatment in patients who are free of disease but at high risk for systemic recurrence, within 56 days of surgery. Adults: Use appropriate preparation and route: see full labeling. Induction: use pwd form only. 20million IU/m2 IV over 20mins, 5 consecutive days per week, for 4wks. Maintenance: 10 million IU/m2 SC 3 times per week for 48wks. Dose adjustments for toxicity: see full labeling. Children: 18yrs: not established. 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. Cardiovascular disease (eg,

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DRUG MONOGRAPHS

SKIN CANCER MI, arrhythmias); monitor closely. Pulmonary disease (eg, COPD). Discontinue if severe psychiatric disorders (eg, suicidal behavior) or new/worsening ophthalmologic reactions develop. 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 CBCs, platelets, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Pwd: contains human albumin; monitor for possible viral disease and Creutzfeldt-Jakob disease transmission. Pre-existing psoriasis or sarcoidosis. Renal impairment. Transplant recipients. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Caution with myelosuppressive agents (eg, zidovudine), and drugs that can exacerbate depression. May potentiate theophylline. Increased risk of peripheral neuropathy with concomitant telbivudine. Dental/periodontal disorders, dry mouth with concomitant ribavirin. Adverse reactions: Flu-like symptoms (fever, headache, chills, myalgia, fatigue); abnormal LFTs, blood, cardiovascular, pulmonary, thyroid, and GU disorders, GI upset, abnormal vision, skin reactions, CNS/psychiatric reactions, colitis, hypertriglyceridemia, pancreatitis; rare: autoimmune disorders, hypersensitivity. See full labeling. How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial—1; Soln (multidose vials): 18million, 25million IU/vial—1

KEYTRUDA Merck

℞

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. Monitor for severe skin reactions; permanently discontinue if SJS or TEN is confirmed. 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. Solid organ transplant recipients. 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 Novartis

℞

Kinase inhibitor. Trametinib 0.5mg, 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: not indicated for treatment of patients who have progressed on prior BRAF-inhibitor therapy. Adults: Confirm presence of BRAF V600E or V600K mutation prior to initiation. Take at same time each day, 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. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: See full labeling for dabrafenib 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. Monitor for non-cutaneous malignancies, pulmonary embolism (permanently discontinue if life-threatening), colitis, GI perforations, skin toxicities and secondary infections. Permanently discontinue for all Grade 4 hemorrhagic events or any Grade 3 events that do not improve. 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 baseline and is less than the lower limit of normal; permanently discontinue if symptomatic cardiomyopathy or persistent asymptomatic LV dysfunction is unresolved within 4wks. Perform eye exam periodically and at any time for visual disturbances; permanently discontinue if retinal vein occlusion develops or retinal pigment epithelial detachment persists. Permanently discontinue if interstitial lung disease or pneumonitis occurs. Withhold if fever >104°F or any serious febrile reaction occurs and evaluate for infection; prophylaxis with antipyretics may be needed when resuming. Pre-existing diabetes or hyperglycemia; monitor serum glucose levels. Severe renal or moderateto-severe hepatic impairment. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for 4 months after treatment. Pregnancy. Nursing mothers: not recommended (during and for 4 months after last dose). Adverse reactions: Rash, diarrhea, lymphedema. In combination with dabrafenib: also pyrexia, chills, fatigue, nausea, vomiting, hypertension, peripheral edema, dry skin, decreased appetite, hemorrhage, cough, dyspnea. How supplied: Tabs—30

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DRUG MONOGRAPHS

SKIN CANCER 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 embryo-fetal 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 >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

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

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 (non-HCC) or AST/ALT >10XULN (HCC) 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, 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

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SKIN CANCER 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]). 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 nonhematologic 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 Novartis

℞

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 (approx. 12hrs apart); continue until disease progression or unacceptable toxicity. Dose modifications: 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. Monitor for non-cutaneous malignancies; permanently discontinue if RAS mutation-positive malignancy occurs. Permanently discontinue for all Grade 4 hemorrhagic events or any persistent Grade 3 events. Risk of cardiomyopathy with trametinib; assess LVEF prior to initiation, after one month, and then at every 2–3 month intervals during treatment; withhold for symptomatic cardiomyopathy or

asymptomatic LV dysfunction of >20% from baseline that is below institutional lower limit of normal. Withhold if fever ≥101.3°F or any serious febrile 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; permanently discontinue for persistent Grade ≥2 lasting >6wks. G6PD deficiency: monitor for hemolytic anemia. Severe renal or moderate-to-severe hepatic impairment. Embryo-fetal toxicity. Females of reproductive potential should use highly effective non-hormonal contraception during and for 2wks after last dose. Pregnancy. Nursing mothers: not recommended (during and for 2wks after last dose). Interactions: Avoid concomitant strong CYP3A4 or CYP2C8 inhibitors (eg, ketoconazole, nefazodone, clarithromycin, gemfibrozil); if unavoidable, monitor closely. May antagonize effects of CYP3A4, CYP2C8, CYP2C9, CYP2C19, CYP2B6 substrates (eg, midazolam, warfarin, dexamethasone, hormonal contraceptives); consider alternatives or monitor. Adverse reactions: Hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, palmarplantar erythrodysesthesia syndrome; skin toxicity (may be serious). In combination with trametinib: also chills, fatigue, rash, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, hemorrhage, cough, dyspnea. How supplied: Caps—120

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DRUG MONOGRAPHS

SKIN CANCER 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 in patients ≥12yrs. 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. Embryo-fetal toxicity. Females of reproductive potential should use

effective contraception during and for 3 months after final dose. Pregnancy. Nursing mothers: not recommended (during and for 3 months after final dose). Adverse reactions: Fatigue, diarrhea, pruritus, rash, colitis, headache, weight loss, nausea, pyrexia, decreased appetite, vomiting, insomnia; immune-mediated reactions. Note: To enroll pregnant patients in the Pregnancy Safety Surveillance Study, call (844) 593-7869. How supplied: Single-use vial (50mg, 200mg)—1

ZELBORAF Genentech

℞

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; continue until disease progression or unacceptable toxicity. Concomitant strong CYP3A4 inducer: avoid; if unavoidable, increase dose by 240mg as tolerated. 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, ketoconazole, itraconazole, voriconazole, clarithromycin, saquinavir, ritonavir, indinavir, nelfinavir); consider alternatives. Avoid concomitant strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin); consider alternatives, or increase dose (see Adult). 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, Dupuytren’s contracture (may be severe), plantar fascial fibromatosis. How supplied: Tabs—112, 120

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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Brand name–bold type Generic name–light type Medical condition–red type *-product contains other active ingredients ext-external inj-injectable.

A Abiraterone Zytiga

Abraxane (inj) cancer, breast cancer, pancreatic non-small cell lung cancer

9 17 80

Actinic keratoses

Adcetris (inj)

Ado-trastuzumab Kadcyla

Afatinib Gilotrif

Afinitor cancer, breast cancer, renal progressive neuroendocrine tumors of pancreatic origin (pNET) progressive non-functional neuroendocrine tumors (NET) of gastrointestinal or lung origin subependymal giant cell astrocytoma (SEGA) Aldesleukin Proleukin (inj) Alecensa Alectinib Alecensa

cancer, renal glioblastoma non-small cell lung cancer Avelumab Bavencio (inj)

ALPHABETICAL INDEX 3, 21, 27, 37, 81 3, 21, 27, 37, 81 3, 21, 27, 37, 81

27, 89

Axitinib Inlyta

Azacitidine Vidaza (inj)

B Basal cell carcinoma

89, 92

C Cabazitaxel Jevtana (inj)

Cabometyx

Cabozantinib Cabometyx Cometriq

28 18

Campath (inj)

Cancer, bladder

27, 29–30, 34–35, 86

Cancer, breast

1, 9–16, 18, 22–23, 26, 29, 39, 41, 66, 86

Cancer, cervical

3, 21, 27, 37, 81–82

Cancer, colorectal

3, 11, 16, 18, 21–22, 24–27, 37, 40, 81

9 27 17

Bavencio (inj) cancer, bladder cancer, renal melanoma

27 27 89

Cancer, GI

Beleodaq (inj)

Cancer, liver

24, 32

Cancer, lung

1, 15, 37, 39, 41, 59, 66, 80–86

Belinostat Beleodaq (inj)

32, 92

Bendamustine Bendeka (inj) Treanda (inj)

Bendeka (inj)

Bevacizumab Avastin (inj)

Alemtuzumab Campath (inj)

Alimta (inj)

11, 21, 23

Cancer, head and neck

Cancer, ovarian

3, 21, 37–39, 52, 81–82, 88

Cancer, pancreatic 49 66

Cancer, prostate

Cancer, renal

3, 21, 27, 37, 81

1, 4, 15, 22, 39–41, 66, 86

11, 17–20, 22, 25, 33, 85 10, 28–33, 35–36 3, 21, 24, 27–28, 30–32, 34–35, 37, 81, 86, 92

Cancer, sarcoma

1–2

Cancer, stomach

11, 18, 22

Bexarotene Targretin Targretin (ext)

64 65

Cancer, testicular

Bexxar

Capecitabine Xeloda

Cancer, thyroid

29 17–19, 24, 32

Alitretinoin Panretin (ext)

Altretamine Hexalen

Bicalutamide Casodex

Caprelsa

Alunbrig

Blinatumomab Blincyto (inj)

Carfilzomib Kyprolis (inj)

Blincyto (inj)

Casodex

Ceritinib Zykadia

Cerubidine (inj)

Anaplastic astrocytoma

Anastrozole Arimidex

Arimidex

Aromasin

Arranon

Arsenic trioxide Trisenox (inj)

Arzerra (inj)

Asparaginase Erwinia chrysanthemi Erwinaze (inj)

Atezolizumab Tecentriq (inj) Avastin (inj) cancer, cervical cancer, colorectal cancer, ovarian

34, 86 3, 21, 27, 37, 81 3, 21, 27, 37, 81 3, 21, 37, 81

Bone metastases

2, 70

Bortezomib Velcade (inj)

Bosulif

Bosutinib Bosulif

Cetuximab Erbitux (inj)

Chlorambucil Leukeran

Breast cancer

14–15

Chorioadenoma destruens

16, 26

22, 40 59 1, 15, 39, 41, 66, 86

Brentuximab vedotin Adcetris (inj)

Choriocarcinoma, gestational

Brigatinib Alunbrig

Clofarabine Clolar (inj)

Clolar (inj)

Cobimetinib Cotellic

Busulfan Busulfex (inj) Myleran

50 59

Busulfex (inj)

1, 15, 39, 41, 66, 86

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ALPHABETICAL INDEX Colorectal cancer

22–23

Brand name–bold type Generic name–light type Medical condition–red type *-product contains other active ingredients ext-external inj-injectable.

Elotuzumab Empliciti (inj)

Cotellic

Eloxatin (inj)

Crizotinib Xalkori

Emcyt

Empliciti (inj)

Cometriq

Cyramza (inj) cancer, GI cancer, lung

21 81

Cytarabine DepoCyt (inj) Vyxeos (inj)*

52 69

D Dabrafenib Tafinlar Dacogen (inj) Daratumumab Darzalex (inj)

Enasidenib Idhifa

Enzalutamide Xtandi

Erbitux (inj) cancer, colorectal cancer, head and neck Eribulin Halaven (inj)

84, 93 51

Erivedge Erlotinib Tarceva

22, 40 22, 40 1, 11 89 20, 85

Erwinaze (inj)

Darzalex (inj)

Erythema nodosum leprosum

Dasatinib Sprycel

Daunorubicin Cerubidine (inj) Vyxeos (inj)*

Estrace cancer, breast cancer, prostate

10, 29 10, 29

51 69

Estradiol Estrace

10, 29 28 28

Decitabine Dacogen (inj)

Estradiol valerate Delestrogen (inj)

Degarelix Firmagon (inj)

Estramustine Emcyt

Delatestryl

Delestrogen (inj)

Estrogens, conjugated Premarin

Estrogens, esterified Menest

Denileukin diftitox Ontak (inj) Denosumab Xgeva (inj)

DepoCyt (inj)

Dermatofibrosarcoma protuberans Dinutuximab Unituxin (inj) Doxil (inj) cancer, ovarian kaposi sarcoma multiple myeloma Doxorubicin, liposomal Doxil (inj) Durvalumab Imfinzi (inj)

22, 54, 90

4 37, 52, 88 37, 52, 88 37, 52, 88 37, 52, 88 29

E Efudex (ext)

Eligard (inj)

Everolimus Afinitor

14, 32 31 3, 9, 17, 27

Evista

Evomela (inj)

Exemestane Aromasin

F

Fluorouracil cancer, breast cancer, colorectal cancer, pancreatic cancer, stomach Flutamide

Fulvestrant Faslodex (inj) Fusilev (inj)

10 22

G Gazyva (inj)

Gefitinib Iressa

GI stromal tumors

Gleevec dermatofibrosarcoma protuberans GI stromal tumors hypereosinophilic syndrome leukemia, acute myeloid leukemia, chronic eosinophilic leukemia, chronic myelogenous mastocytosis myelodysplastic syndromes Glioblastoma

Halaven (inj) cancer, breast cancer, sarcoma

11, 23 11, 23 37

Histrelin Vantas

Femara

10 29

Fludarabine Fludara (inj)

54 89 11, 18, 22

22, 54, 90 22, 54, 90

Hexalen

Faslodex (inj)

22, 54, 90 22, 54, 90 22, 54, 90

11 1

Herceptin (inj) cancer, breast cancer, GI

Hyaluronidase human Rituxan Hycela (inj)*

Fludara (inj)

22, 54, 90 22, 54, 90

3, 21, 27, 37, 81

Hodgkin lymphoma

Firmagon (inj)

22, 54, 90

H

Fluorouracil Efudex (ext) Fluorouracil

19, 22, 25, 33, 54, 90

Gilotrif

Hodgkin disease

Farydak

11, 18, 22 11, 18, 22 11, 18, 22 11, 18, 22

48, 58, 60 59, 83 62

Hycamtin cancer, cervical cancer, lung cancer, ovarian Hydatidiform mole

37, 82 37, 82 37, 82 1, 15, 39, 41, 66, 86

Hydrea cancer, head and neck leukemia, chronic myeloid

40 55

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ALPHABETICAL INDEX

Brand name–bold type Generic name–light type Medical condition–red type *-product contains other active ingredients ext-external inj-injectable. Hydroxyurea Hydrea Hypercalcemia Hypereosinophilic syndrome

40, 55 70 22, 54, 90

I Ibrance

Ibritumomab Zevalin (inj)

Ibrutinib Imbruvica

Iclusig

Idamycin (inj)

Idarubicin Idamycin (inj) Idelalisib Zydelig

56 70

Idhifa

Ifex (inj)

Ifosfamide Ifex (inj)

Imatinib Gleevec

22, 54, 90

Imbruvica

Imfinzi (inj)

Imlygic (inj)

Inlyta

Interferon alfa-2b Intron A (inj) Intron A (inj) kaposi sarcoma leukemia, hairy cell lymphoma, follicular melanoma

56, 88, 90 56, 88 56 56 56, 90

K Kadcyla

Kaposi sarcoma

37, 52, 56, 88

22 24

Lonsurf

Kisqali

Lymphoma, malignant

13 58

Lymphoma, mantle cell

Kisqali Femara Co-Pack

Kyprolis (inj)

L Lanreotide Somatuline Depot (inj)

Lapatinib Tykerb

Lartruvo (inj)

Lenalidomide Revlimid

Lenvatinib Lenvima

18, 31

Lenvima cancer, renal cancer, thyroid

31 18

Letrozole Femara Kisqali Femara Co-Pack*

10 13

Leucovorin

Leukemia

59, 83

Leukemia, acute lymphoblastic 50–51, 53, 55, 59–61, 63, 68–69

Ipilimumab Yervoy (inj)

Iressa

Irinotecan Onivyde (inj)

Leukemia, acute nonlymphocytic

51, 64

Leukemia, acute promyelocytic

66, 68

Istodax

Leukemia, B-cell chronic lymphocytic 50, 54

Ixabepilone Ixempra (inj)

Ixazomib Ninlaro Ixempra (inj)

60 12

Leukemia, acute lymphocytic Leukemia, acute myeloid

51, 61 22, 54, 56, 63, 69, 90

Leukemia, chronic eosinophilic

22, 54, 90

Leukemia, chronic lymphocytic

48–49, 54, 56, 62, 66, 68, 70

Leukemia, chronic myelogenous

22, 50, 54, 59, 63–65, 90

Leukemia, chronic myeloid 57 30

Levoleucovorin Fusilev (inj)

30 40 30 23 58 91 82

J

28 31

Keytruda (inj) cancer, bladder cancer, head and neck cancer, renal colorectal cancer hodgkin lymphoma melanoma non-small cell lung cancer

Iodine I 131 Tositumomab Bexxar*

Jakafi Jevtana (inj)

Leuprolide Eligard (inj) Lupron Depot 7.5mg (inj)

Leukemia, hairy cell

Leukemia, T-cell acute lymphoblastic

Leukeran

Lupron Depot 7.5mg (inj)

Lymphoma, cutaneous T-cell

57, 60, 64–65, 67, 70

Lymphoma, follicular

56, 62, 70

Lymphoma, lymphocytic

62 59 56, 67

Lymphoma, marginal zone

Lymphoma, peripheral T-cell

48, 57

Lymphoma, small lymphocytic

56, 70

Lymphoma, T-cell lymphoblastic

Lymphomatous meningitis

Lymphosarcoma Lynparza

59, 83 38

M Malignant pleural mesothelioma

Mantle cell lymphoma

Marqibo (inj)

Mastocytosis

22, 54, 63, 90

Mechlorethamine Mustargen (inj) Valchlor (ext)

59, 83 67

Mekinist melanoma non-small cell lung cancer Melanoma Melanoma, metastatic

91 83 56, 89–94 32, 92

Melphalan Evomela (inj)

Menest

Mercaptopurine Purinethol Purixan

61 61

Methotrexate Trexall Xatmep

1, 15, 39, 41, 66, 86 69

Methoxsalen Uvadex

Midostaurin Rydapt Multiple myeloma Mustargen (inj) cancer, lung

63 37, 52–53, 58, 60–61, 65, 67, 70, 88 59, 83

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ALPHABETICAL INDEX hodgkin disease leukemia lymphosarcoma mycosis fungoides polycythemia vera

59, 83 59, 83 59, 83 59, 83 59, 83

Mycosis fungoides

1, 15, 39, 41, 59, 66, 83, 86

Mycosis fungoides-type cutaneous T-cell lymphoma Myelodysplastic syndromes

Myleran

67 22, 51, 54, 68, 90 59

N Navelbine (inj)

Necitumumab Portrazza (inj)

Nelarabine Arranon

Neoplasms

28, 35

Neratinib Nerlynx

Nerlynx

Neuroblastoma

Neuroendocrine tumors

19, 25, 33

Nexavar cancer, liver cancer, renal cancer, thyroid

24, 32 24, 32 19, 24, 32

Nivolumab Opdivo (inj)

Non-small cell lung cancer

Onivyde (inj)

Ontak (inj)

Opdivo (inj) cancer, colorectal cancer, head and neck cancer, lung cancer, renal hodgkin lymphoma melanoma

24 40 84 32 60 92

Osimertinib Tagrisso

Radium Ra 223 dichloride Xofigo (inj)

Raloxifene Evista

Oxaliplatin Eloxatin (inj)

P Paclitaxel, protein-bound Abraxane (inj)

9, 17, 80

Revlimid

Ribociclib Kisqali Kisqali Femara Co-Pack*

13 13

Rituxan (inj)

62 62

Rituximab Rituxan (inj) Rituxan Hycela (inj)*

62 62

Panretin (ext) Pazopanib Votrient

1, 35

Romidepsin Istodax

Rubraca

Rucaparib Rubraca

23, 30, 40, 58, 82, 91

Ruxolitinib Jakafi

Pemetrexed Alimta (inj)

Perjeta (inj)

Pertuzumab Perjeta (inj)

14 57, 59, 83

Pomalyst

Odomzo

Ponatinib Iclusig Portrazza (inj)

21, 81

Regorafenib Stivarga

Rituxan Hycela (inj)

Obinutuzumab Gazyva (inj)

Olaratumab Lartruvo (inj)

R

61 61

Purixan

Pomalidomide Pomalyst

Olaparib Lynparza

Purinethol

Panobinostat Farydak

O

Polycythemia vera

Ofatumumab Arzerra (inj)

Provenge (inj)

Panitumumab Vectibix (inj)

3, 20–21, 27, 37, 80–87

32, 92 32, 92

Palbociclib Ibrance

Pembrolizumab Keytruda (inj)

1, 15, 39, 41, 49, 62, 66, 69, 86

Proleukin (inj) cancer, renal melanoma, metastatic

Ramucirumab Cyramza (inj)

Peginterferon alfa-2b Sylatron (inj)

24, 32, 40, 60, 84, 92

Non-Hodgkin lymphoma

Oncaspar (inj)

Ninlaro

Progressive non-functional neuroendocrine tumors (NET) of gastrointestinal or lung origin

Omacetaxine mepesuccinate Synribo (inj)

Pegaspargase Oncaspar (inj)

Nilotinib Tasigna Niraparib Zejula

Brand name–bold type Generic name–light type Medical condition–red type *-product contains other active ingredients ext-external inj-injectable.

Premarin cancer, breast cancer, prostate Progressive neuroendocrine tumors of pancreatic origin (pNET)

Rydapt

57 63

S Sarcoma, soft tissue Sipuleucel-T Provenge (inj) Skeletal-related events

1 33 2

Soltamox

Somatuline Depot (inj)

Sonidegib Odomzo

14 32

Sorafenib Nexavar

19, 24, 32

Sprycel

Stivarga

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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. Subependymal giant cell astrocytoma (SEGA) Sunitinib Sutent Superficial basal cell carcinoma Sutent cancer, pancreatic GI stromal tumors neuroendocrine tumors Sylatron (inj)

19, 25, 33 89 19, 25, 33 19, 25, 33 19, 25, 33 93

Synribo (inj)

Systemic anaplastic large cell lymphoma (sALCL)

Tafinlar melanoma non-small cell lung cancer

93 84

Tagrisso

Talimogene laherparepvec Imlygic (inj)

Tamoxifen Soltamox Tamoxifen Tarceva cancer, pancreatic non-small cell lung cancer Targretin

14 15 20, 85 20, 85 64

Targretin (ext)

Tasigna

Tecentriq (inj) cancer, bladder cancer, renal

34, 86 34, 86

Temodar

Temozolomide Temodar

Temsirolimus Torisel (inj)

15, 34, 38

Tipiracil Lonsurf*

Topotecan Hycamtin

37, 82

Vemurafenib Zelboraf

Venclexta

Venetoclax Venclexta

Vesanoid

Torisel (inj)

Vidaza (inj)

Tositumomab Bexxar*

Vincristine sulfate liposome Marqibo (inj)

Vinorelbine Navelbine (inj)

83, 91

Vismodegib Erivedge

11, 23

Vorinostat Zolinza

Votrient cancer, renal cancer, sarcoma

35 1

Vumon (inj) Vyxeos (inj)

68 69

Trabectedin Yondelis (inj) Trametinib Mekinist Trastuzumab Herceptin (inj)

T Tabloid

Thiotepa Tepadina (inj)

ALPHABETICAL INDEX

Treanda (inj)

Trelstar (inj)

Tretinoin Vesanoid

Trexall cancer, breast 1, 15, 39, 41, 66, 86 cancer, head and neck 1, 15, 39, 41, 66, 86 cancer, lung 1, 15, 39, 41, 66, 86 chorioadenoma destruens 1, 15, 39, 41, 66, 86 choriocarcinoma, gestational 1, 15, 39, 41, 66, 86 hydatidiform mole 1, 15, 39, 41, 66, 86 mycosis fungoides 1, 15, 39, 41, 66, 86 non-hodgkin lymphoma 1, 15, 39, 41, 66, 86 Trifluridine Lonsurf*

Triptorelin Trelstar (inj)

Trisenox (inj) Tykerb

66 16

U Unituxin (inj) Uvadex

4 67

X Xalkori

Xatmep

Xeloda cancer, breast cancer, colorectal

16, 26 16, 26

Xgeva (inj)

Xofigo (inj) Xtandi

36 36

Y Yervoy (inj) Yondelis (inj)

94 2

Z Zaltrap (inj)

Zejula

Zelboraf

Zevalin (inj)

Teniposide Vumon (inj)

Tepadina (inj) breast cancer cancer, bladder cancer, breast cancer, ovarian

15 34 15 38

Valchlor (ext)

Testosterone enanthate Delatestryl

Valrubicin Valstar

Ziv-aflibercept Zaltrap (inj)

Valstar

Zoledronic acid Zometa

Thalidomide Thalomid

Vandetanib Caprelsa

Zolinza

Zometa

Thalomid

Vantas

Zydelig

Thioguanine Tabloid

Vectibix (inj)

Zykadia

Velcade (inj)

Zytiga

V

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MANUFACTURERS INDEX AbbVie (800) 633-9110 AbbVie and Genentech (800) 633-9110; (800) 821-8590 Actelion Pharmaceuticals (866) 228-3546 Adienne Pharma & Biotech +41 (0)91 210 47 26 Allergan (800) 433-8871; (714) 246-4500 Amgen, Inc. (800) 772-6436; (805) 447-1000 ARIAD Pharmaceuticals, Inc. (855) 552-7423 Astellas Pharma US, Inc. (800) 727-7003; (800) 888-7704 Astellas Pharma US, Inc. and Genentech, Inc. (888) 827-2382 AstraZeneca Pharmaceuticals (800) 237-8898; (800) 236-9933 Baxalta (866) 424-6724 Baxter (800) 422-9837 Bayer and Onyx (866) 639-2827 Bayer Healthcare Pharmaceuticals Inc. (800) 288-8371; (800) 468-0894 Bedford Laboratories (800) 521-5169; (800) 562-4797 Boehringer Ingelheim Pharmaceuticals (800) 542-6257; (800) 236-4248 Bristol-Myers Squibb (800) 321-1335 Celgene Corp (908) 673-9000 Clovis Oncology (844) 258-7662 DARA BioSciences, Inc. (919) 872-5578 Dendreon (877) 256-4545

Eisai Pharmaceuticals (888) 422-4743; (201) 692-1100 EMD Serono, Inc. (888) 275-7376 Endo Pharmaceuticals (800) 462-3636; (610) 558-9800 Exelixis, Inc. (650) 837-7000 Ferring Pharmaceuticals, Inc. (888) 337-7464 Genentech and Biogen (800) 821-8590; (866) 633-4636 Genentech, Inc. (800) 821-8590; (650) 225-1000 Gilead Sciences, Inc. (800) 445-3235; (650) 574-3000 GlaxoSmithKline (888) 825-5249 Incyte Corporation (855) 463-3463 Ipsen Biopharmaceuticals, Inc. (866) 837-2422 Janssen Biotech, Inc. (800) 526-7736 Janssen Pharmaceuticals, Inc. (800) 526-7736 Jazz Pharmaceuticals plc (650) 496-3777 JHP Pharmaceuticals (866) 923-2547 Lilly, Eli and Company (800) 545-5979; (317) 276-2000 Merck & Co., Inc. (800) 672-6372; (800) 609-4618 Millennium Pharmaceuticals, Inc. (866) 835-2233 Novartis Pharmaceuticals Corp (800) 693-9993; (973) 503-8300 Otsuka America Pharmaceutical, Inc. (800) 441-6763; (301) 990-0030 Pfizer Inc. (800) 438-1985; (212) 573-2323

Pharmacyclics and Janssen Biotech (877) 877-3536 Pierre Fabre Pharmaceuticals, Inc. (973) 355-8000 Prometheus Labs, Inc. (888) 423-5227 Puma Biotechnology (424) 248-6500 Rare Disease Therapeutics, Inc. (615) 399-0700 Recordati Rare Diseases, Inc. (908) 236-0888 Roche Diagnostics Corp. (317) 521-2000 Sanofi Aventis (800) 446-6267; (800) 633-1610 Sanofi Genzyme Company (800) 745-4447; (617) 252-7500 Sanofi US and Regeneron (800) 633-1610 Seattle Genetics, Inc. (855) 473-2436 Sigma-Tau Pharmaceuticals, Inc. (800) 447- 0169 Silvergate Pharmaceuticals (855) 379-0382 Spectrum Pharmaceuticals, Inc. (877) 387-4538 Taiho Oncology (609) 750-5300 Takeda Pharmaceuticals North America, Inc. (877) 825-3327; (847) 383-3000 Tesaro, Inc. (844) 483-7276 Teva Pharmaceuticals (215) 591-3000 Therakos, Inc. (877) 865-6850; (610) 280-1000 Tolmar Inc. (877) 986-5627 United Therapeutics Corp. (877) 864-8437 Valeant Pharmaceuticals, Inc (877) 361-2719

100 CANCER THERAPY ADVISOR | NOVEMBER/DECEMBER 2017 | CancerTherapyAdvisor.com

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