Cancer Therapy Advisor September/October 2017 Issue by Haymarket Media

SEPTEMBER/OCTOBER 2017 | VOL 4, ISSUE 1

CancerTherapyAdvisor.com

CancerTherapyAdvisor

A31 FEATURE

Malware in Medicine: Prevention Is Key to Protection There is an ongoing battle between hackers and security experts, and it’s not at all clear who is winning.

FEATURING Cancer Therapy Regimens and Oncology Drug Monographs from

1 Bone Cancer

3 Brain Cancer 14 Breast Cancer 22 Endocrine Cancer

A16 LATEST NEWS

Headlines in oncology research, including gastrointestinal cancer and renal cell carcinoma

26 Gastrointestinal Cancer 33 Genitourinary Cancer 53 Gynecologic Cancer 58 Head and Neck Cancer

A30 IN THE CLINIC SEPTEMBER/OCTOBER 2017 | VOL 4, ISSUE 1

60 Hematologic Cancer

Telotristat for Diarrhea in Patients With Carcinoid Syndrome

83 Lung Cancer 91 Sarcoma

A36 EXPERT PERSPECTIVE

CAR T Cell Therapy for ALL: An Evolutionary Perspective A34 FACT SHEET Answering Questions About Low-fat Diet and Breast Cancer

92 Skin Cancer

Regimen included

A6 FEATURED PRODUCTS

A38 REGIMEN & MONOGRAPH INDEX

Drug Descriptions of Rydapt and Zejula

A15 IN THE PIPELINE The Latest on Oncology Drugs

A16

A30 IN THE CLINIC

A34

A36

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

LATEST NEWS Headlines in Oncology Research and Practice

A31

–97 CANCER THERAPY REGIMENS & 1 DRUG MONOGRAPHS

1 Bone Cancer

 3 Brain Cancer

Telotristat for Diarrhea in Patients With Carcinoid Syndrome

14 Breast Cancer

C. ANDREW KISTLER, MD, PharmD, RPh

22 Endocrine Cancer

FEATURE

 26 Gastrointestinal Cancer

Malware in Medicine: Prevention Is Key to Protection

 33 Genitourinary Cancer

WENDY ORENT, PhD

 53 Gynecologic Cancer

FACT SHEET

58 Head and Neck Cancer

Answering Questions About Low-fat Diet and Breast Cancer

60 Hematologic Cancer

ANDREA S. BLEVINS PRIMEAU, PhD, MBA

83 Lung Cancer

EXPERT PERSPECTIVE

91 Sarcoma

CAR T Cell Therapy for ALL: An Evolutionary Perspective

92 Skin Cancer

HOLLY A. SWAIN EWALD, PhD, AND PAUL W. EWALD, PhD

98 ALPHABETICAL INDEX

Cancer Therapy Advisor (ISSN 2375-558X), September/October 2017, Volume 4, Number 1. 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.

A4 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

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Yale Cancer Center  New Haven, CT

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Thomas Jefferson University Hospital  Philadelphia, PA

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CancerTherapyAdvisor.com | SEPTEMBER/OCTOBER 2017 | CANCER THERAPY ADVISOR A5

LATEST NEWS | RENAL CELL CARCINOMA

According to a study published in the Journal of Clinical Oncology, combining nivolumab with ipilimumab is safe, efficacious, and potentially improves overall survival (OS) among patients with metastatic renal cell carcinoma (mRCC). In the phase 1, dose-escalation CheckMate-016 study, investigators randomly assigned patients into 3 arms: nivolumab 3 mg/kg plus ipilimumab 1mg/kg (N3I1), nivolumab 1 mg/ kg plus ipilimumab 3 mg/kg (N1I3), or nivolumab 3 mg/kg plus ipilimumab 3 mg/kg (N3I3). Each treatment was administered every 3 weeks for up to 4 doses intravenously (IV) followed by nivolumab 3 mg/kg IV monotherapy every 2 weeks until disease progression or intolerable toxicity. The N3I1 and N1I3 arms had a 40.4% overall response rates (ORR), with ongoing responses in 42.1% of patients in the N3I1 arm vs 36.8% in the N1I3 arm. The 2-year OS was 67.3% in the N3I1 arm vs 69.9% in the N1I3 arm. Grade 3 or 4 adverse events were reported in 38.3% in the N3I1 arm vs 61.7% of patients in the N1I3 arm. There were no confirmed responses in the N3I3 arm due to a high censoring percentage. The study authors concluded that “the encouraging safety results in patients treated with the N3I1 combination regimen support the additional clinical investigation of N3I1 in a phase [3] study for patients with mRCC.”

Savolitinib Shows Promise for MET-driven Papillary Renal Cell Carcinoma Savolitinib, a potent and selective small-molecule MET kinase inhibitor, was tolerable, was safe, and may have treatment potential for patients with MET-driven papillary renal cell carcinoma (PRCC), according to a trial published in the Journal of Clinical Oncology. Metastasis, angiogenesis, tumor growth, and treatment resistance are each associated with MET activation and lead to a poor prognosis in many cancers. The primary objective of this study was to determine savolitinib activity in PRCC tumors by MET status. The single arm, phase 2 study enrolled 109 patients and assessed the safety and efficacy of savolitinib in patients with histologically confirmed locally advanced or metastatic PRCC. Forty percent of patients had

MET-driven PRCC, 42% were MET-independent, and 17% had unknown MET status. Patients received savolitinib 600 mg once daily. The overall response rate (ORR) was 7% in the treatment population, but MET-driven patients had a significantly higher response rate of 18% partial response vs METindependent PRCC (0%). Patients with MET-driven PRCC had a median progression-free survival (mPFS) of 6.2 months (95% CI, 4.1–7.0) vs 1.4 months in MET-independent PRCC (95% CI, 1.4–2.7), (hazard ratio [HR], 0.33; 95% CI, 0.20-0.52; log-rank P < .001). The most frequently observed adverse effects in patients were nausea, vomiting, fatigue, and peripheral edema. Study authors concluded that “these results confirm that savolitinib, a potent and selective small-molecule MET kinase inhibitor, holds promise as a personalized treatment for patients with metastatic MET-driven PRCC.”

Restoring ASPP1 May Improve Outcomes in Clear Cell RCC Downregulation of apoptosis stimulating of p53 protein1 (ASPP1) confers drug resistance and permits tumor growth in clear cell renal cell carcinoma (ccRCC), according to an article published in the International Journal of Cancer. p53 mutation correlates with cancer drug resistance, though this gene is rarely inactivated in ccRCC and chemotherapy resistance is a hallmark of this disease. Non-genetic means of inactivating p53 may be responsible. For this study, researchers evaluated the role of ASPP1 in p53-related tumor cell apoptosis by comparing ccRCC tissue samples from 20 patients against normal tissue samples. Compared with normal tissue, the average ASPP1 microRNA transcripts were downregulated 3.9-fold and the protein level was downregulated by 4.9-fold. More than 95% with ccRCC had “remarkably” decreased ASPP1 levels, regardless of age and sex. ASPP1 downregulation was also directly associated with worse disease stage and prognosis. Restoring ASPP1 expression suppressed ccRCC growth and conferred sensitivity to fluorouracil. The authors concluded that “further investigation is warranted to ascertain if ASPP1 could be a useful prognostic factor or therapeutic target in ccRCC and many others.”

A28 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

Nivolumab and Ipilimumab Welltolerated, Active in Metastatic Renal Cell Carcinoma

RENAL CELL CARCINOMA

| LATEST NEWS

Toxicity-driven Sunitinib Dosing Improves Outcomes in RCC

Plasma HGF Levels During Treatment Prognostic for Survival in RCC

Toxicity-driven dosing of sunitinib improved response rates and survival compared with historical standard dosing among patients with metastatic renal cell carcinoma (RCC), according to researchers who presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. Better outcomes are associated with higher sunitinib exposure. The aim of this study was to determine if individualized toxicity-driven dosing of sunitinib would improve progression-free survival (PFS) compared with standard dosing. The multicenter phase 2 trial enrolled 117 patients with metastatic RCC to receive 50 mg per day of sunitinib for 28 days with treatment breaks of 7 days. Patients who developed grade 2 toxicity prior to the completion of the first cycle remained taking 50 mg per day during the next cycle. Patients who were unable to tolerate 50 mg received a dose reduction to 37.5 mg then 25 mg for at least 7 days. Patients who experienced minimum toxicity during the 28 days received dose escalation to 62.5 mg, then 75 mg during the next cycle. Dose escalation occurred among 18.5% of patients, with 12 patients receiving 62.5 mg and 8 patients receiving 75 mg. Dose reduction occurred in 45.4% of patients. The dose was reduced to 37.5 mg in 20.4% of patients and to 25 mg in 9.3% of patients. Toxicity resulted in sunitinib discontinuation in 9.3% of patients. The overall response rate (ORR) was 90.7%, with complete response occurring in 2.8% of patients, partial response in 47.2%, and stable disease in 40.7%. The median PFS was 11.9 months (95% CI, 9.3–16.5 months) and the median overall survival (OS) was 35.9 months (95% CI, 27.4 months–not reached). According to the authors, historical data from the EFFECT trial, which used a 4 week on, 2 week off dosing schedule, demonstrated an ORR of 75%, with complete response, partial response, and stable disease rates of 0%, 32%, and 43%, respectively. The median PFS was 8.5 months (95% CI, 6.9–11.1 months) and the median OS was 23.1 months (95% CI, 17.4–25.4 months). The authors went on to state that these results suggest that “individualized dosing is safe and feasible in a multicenter setting and associated with improved dose intensity and one of the best ORR, PFS, and OS reported for a [tyrosine kinase inhibitor].”

Plasma hepatocyte growth factor (HGF) levels during treatment are prognostic for overall survival among patients with renal cell carcinoma (RCC) being treated with interferon alpha with or without bevacizumab, according to researchers. Elevated HGF levels, which are linked to a high rate of angiogenesis, are linked to worse survival rated among patients with RCC treated with interferon alpha and bevacizumab. For this analysis of the phase 3 ALLIANCE study, researchers determined the link between changes of HGF levels during treatment and survival. Of 310 patients, 148 of whom were treated with interferon alpha only and 162 of whom were treated with interferon alpha plus bevacizumab, the baseline HGF level was 161.4 pg/mL. HGF levels greater than the median at 4 weeks of treatment were associated with worse overall survival (14 months vs 27 months for median or lower levels). While only 9 patients with baseline median or lower HGF levels had elevated levels by 4 weeks, 66 patients with baseline elevated HGF levels had median or lower levels at 4 weeks. Patients with a decline in HGF levels had longer overall survival than those with high levels at baseline and at 4 weeks (19 months vs 13 months). The authors concluded that “HGF predicts for therapeutic benefit and represents a potential mechanism of resistance.”

Sunitinib is conventionally given 4 weeks on and 2 weeks off (4/2), but many patients experience adverse events during the weeks 3 and 4. Researchers sought to determine if 2 weeks on and 1 week off (2/1) would reduce toxicities without compromising efficacy. The trial treated 59 patients with metastatic renal cell carinoma with 50 mg sunitinib on a 2/1 schedule. Grade 3+ fatigue, diarrhea, or hand-foot syndrome (HFS) occurred in 24% of patients, which is similar to the historical rates of 25%-30% with the 4/2 schedule. The rate of any grade diarrhea was 75%, fatigue was 71%, and HFS was 54%. Dose reduction was required in 59% of patients. The response rate to sunitinib was 37% (95% CI, 25.0%-50.9%), and the median progression-free survival was 19.3 months (95% CI, 8.2 months-not reached). The investigators stated that the “efficacy data [was] suggestive of long-term tolerability in patients receiving sunitinib on a 2/1 schedule.”

CancerTherapyAdvisor.com | SEPTEMBER/OCTOBER 2017 | CANCER THERAPY ADVISOR A29

Two-to-One Sunitinib Schedule Fails to Reduce Toxicity

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

harmD,

RPh

Telotristat for Diarrhea in Patients With Carcinoid Syndrome A new treatment option may decrease diarrhea incidence with a relatively safe side effect profile. Recently, a new medication, telotristat, was developed as combination therapy with octreotide for patients with carcinoid syndrome–related diarrhea. Telotristat inhibits the conversion of tryptophan to serotonin, which is one of the primary mediators of diarrhea in carcinoid syndrome.4,5 Telotristat is an oral medication; the US Food and Drug Administration (FDA)-approved dose is 250 mg 3 times daily with food.5,6 The FDA indication for telotristat is for combination therapy with a somatostatin analog (such as octreotide) when a patient’s carcinoid syndrome–related diarrhea

Continued on page A37

arcinoid syndrome is the collection of symptoms generally caused by factors secreted by neuroendocrine tumors (NETs). NETs are typically found in the gastrointestinal (GI) tract and lungs and secrete a myriad of compounds including serotonin, histamine, and dopamine.1-3 As up to 40 compounds are secreted by NETs, the clinical presentation varies depending on the secreted hormone. Carcinoid syndrome is most frequently seen in patients with liver metastases at time of presentation. Patients with carcinoid syndrome frequently experience flushing, hypotension, and diarrhea. Excess serotonin is implicated in diarrhea by causing increased GI secretions and motility; histamine and kallikrein contribute to the significant flushing experienced by these patients. Diarrhea occurs in close to 80% of patients with carcinoid syndrome. The diarrhea is typically secretory in nature, where patients will experience over one liter of watery (non-bloody) stool per day, nocturnal symptoms, and continuation of diarrhea despite fasting. If stool studies are collected, these patients will typically have an osmotic gap of less than 50 mOsm/kg. Somatostatin analogs such as octreotide are used to treat these patients experiencing significant diarrhea. Octreotide acts as an anti-secretory agent that inhibits the secretion of multiple hormones by NETs.

is inadequately controlled on a somatostatin analog alone. When using the short-acting formulation of octreotide, octreotide should be given 30 minutes after telotristat to avoid decreased concentrations of telotristat. The most common adverse reactions include headache and nausea. Although less common, patients should be monitored closely for constipation, as this rarely caused colonic perforation or obstruction in clinical studies. Patients should be counseled on this rare side effect and should stop telotristat and contact their physician if they develop worsening or severe abdominal pain or constipation. In the clinical studies, a decrease in daily bowel movements was seen as early as 1 to 3 weeks and persisted to the end of the 12-week study period in patients receiving telotristat. Over the 12-week time period, patients in the telotristat group had approximately 1 fewer bowel movement per day compared with placebo. Near half of patients receiving telotristat were considered responders

Telotristat is an oral medication; the US Food and Drug Administration (FDA)-approved dose is 250 mg 3 times daily with food,

A30 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

FEATURE

BY WENDY ORENT, PhD

omputer malware is called a virus for a reason. Like pathogens and cancer cells, the danger of malware lies in persistence and spread. Shut it down, as the WannaCry ransomware program infecting Great Britain’s National Health Service (NHS) was in May 2017, and that particular disease is eradicated. But cancer cells in the body may develop resistance to treatments, and pathogens often develop resistance to antibiotics and antivirals, or learn, in other ways, to overcome immunity. Infections and cancers may be thought of as an arms race between agents or rogue cells and the host. The race against malware is much the same: it’s a battle between hackers and security experts, though it’s not at all clear who is winning. The health care sector, considered low-hanging fruit by hackers, is particularly vulnerable to attack. In May 2017, WannaCry, which seems to have originated in North Korea but used software developed at the United States National Security Agency (NSA) and was sold on the dark web by a group called the Shadow Brokers, had a nearly catastrophic effect on the NHS.1 The ransomware locked computer systems and threatened to delete files unless ransom was paid in bitcoin. The ransomware exploited some older Windows systems that were either no longer supported by Microsoft or never had their security weaknesses patched.

The race against malware is much the same as a war between an infectious agent and a host: it’s a battle between hackers and security experts, and it’s not at all clear who is winning.

But fixing the technology alone will not address the most basic problem. As Niam Yaraghi, PhD, a fellow at the Brookings Institution Center for Technology Innovation, puts it, “you can fix the technology part, you can encrypt [your data], but how are you going to fix the stupidity? If you use the most advanced technology in the world, if people click on phishing links, [hackers] will still have access to user names and passwords.” Physicians and nurses under stress, says Dr Yaraghi, can easily make such mistakes. Much of the discussion of health care systems’ vulnerability focuses on the potential theft of patient data. But according to Dr Yaraghi, medical information “really isn’t all that valuable. I think [the risk of hacking] is very serious but at the same time not very serious. If you’re a patient, it’s likely you’re being hacked, but unlikely you’re being affected by the hacking.” It is, relatively speaking, easy for a hacker to steal the identity of one person. But to steal the identity of thousands would require a conspiracy. Furthermore, says Dr Yaraghi, foreign attackers probably wouldn’t be able to make much use of the data, implying that an identity theft conspiracy would have to be based in the United States, where cybercriminals can more easily be caught. This has not yet happened, and it is unlikely to occur in the future. The massive cyberattack launched against the Anthem health insurance company in 2015, in which hackers stole the protected personal information

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Malware in Medicine: Prevention Is Key to Protection

FEATURE — including names, addresses, birth dates, and Social Security numbers — of 78.8 million members and employees, does not appear to have caused any personal damage. The reason for the breach remains unclear.2 The theft of personal data is not, therefore, the major threat in this age of cyber insecurity. More dangerous are ransomware attacks like WannaCry, which can shut down hospital services and destroy patient records. According to Dr Yaraghi, some hospitals are laying in stocks of bitcoin to pay off attackers in the case of a ransomware attack, implying that encrypting and backing up patient data are understood within the health care community to be insufficient. Elliott Frantz, founder of the cybersecurity firm, Virtue Security, agrees that ransomware is easier to monetize than the theft of medical records. The WannaCry hackers demanded bitcoin for ransom, but sometimes extortion is not the attack’s objective. The so-called Petya or Goldeneye attack, which may have originated in Russia and attacked many nations, including the Ukraine, could have been designed and executed out of malice: the sites designed to receive the ransom payments were not functional. W hat was interesting about the Petya attack was the sophisticated way it infected and spread, says Mr Frantz. “The people who were attacked were not necessarily at fault. [Petya] could spread to systems that are fully patched,” unlike the NHS WannaCry breach last May. Pet ya “digs ver y deep into the Windows system internals to extract passwords and uses those passwords to log into other computers,” explains Mr Frantz. “It targets institutions. It’s designed to spread laterally. That’s one of the key things about this that

makes Petya new and interesting. The WannaCry ransomware was primitive by comparison.” One effective way to prevent such attacks, whether their aim is ransom or disruption, is to practice what security experts call “hygiene,” or safe and secure computer habits that prevent the virus from entering a system. Yet computer hygiene is only as strong as its weakest link: Mr Frantz points out that “there’s always going to be someone who falls for the age-old trick of opening attachments.” Phishing emails are designed to appear as if they came from a known person. And if one person clicks on the link, the malware burns like pandemic influenza through an entire system. “Hackers go to significant lengths to learn about their victims,” he added.

More dangerous than personal data theft are ransomware attacks that can shut down hospital services. What then? According to Jon Neiditz, a partner in the Atlanta-based law firm Kilpatrick, Townsend & Stockton and an expert in privacy and health security law, “you can’t rule out needing bitcoin at some point,” though he acknowledges that the FBI in 2016 advised institutions never to pay ransom.3 He points out, however, that in 2015 an FBI expert admitted that sometimes bitcoin is the only recourse.4 In one instance, Mr Neiditz says, a company paid a ransom fee that the hackers promised would keep them safe for a year. Six months later, the hackers came back for more. The company objected that they had

been promised a full year. The hackers agreed, apologized, and disappeared again for another 6 months. “Honor among thieves,” says Mr Neiditz. “In the information security world, no one would ever say ‘I’ll never need bitcoin.’” But relying on bitcoin — and acceding to blackmail — is hardly a long-term solution to the threat of ransomware. Willingness to pay perpetuates a corrupt and dangerous system. In Mr Frantz’s opinion, the key to fending off ransomware is, instead, building in many layers of protection for each system. Hospitals must ensure adequate employee training, which starts with teaching the entire staff to recognize and avoid phishing attacks. But even a highly trained team is never going to be impenetrable. So, of necessity, there are a number of second-line defenses every hospital or medical system should employ. Antimalware — some level of protection against ransomware using antivirus software — is important, and so is the use of more complex passwords. General security testing provides another level of protection. “Penetration testing — hiring people to try to break into the system — shows how ransomware can spread easily [through a particular system] and [identifies] where to close loopholes,” says Mr Frantz. Network monitoring represents yet another level of protection. This involves developing ways to block attacks from spreading laterally within a system. With network monitoring, hospitals can learn quickly if there is a systems breach. “You’ll never be able to stop all attacks. But you need enough insight and enough capability to respond in a timely manner,” says Mr Frantz. In the event of a ransomware attack on a medical institution or office, regularly scheduled back-up and remote storage of medical records can help to

A32 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

FEATURE mitigate damage. Even if a hospital is temporarily shut down, records that document recent patient care and hospital scheduling can help quickly restart the system. Mr Neiditz warns that as back-up systems have to connect to a network, they also can be contaminated. Mr Frantz notes, however, that such a scenario is unlikely to occur if the back-ups are kept offl ine and stored in a safe remote location. No strategies are perfect for completely protecting hospital systems from ransomware attacks, says Mr Frantz. “There’s no magic solution against this

line of attack. But if you do your due diligence, follow best practices, and don’t be negligent, you’ll be in a lot better shape.” ■

modernhealthcare.com/article/20160330/ NEWS/160339997. Published March 30, 2016. Accessed July 2017. 3. Incidents of ransomware on the rise: protect yourself and your organization [news

References

release]. Washington, DC: Federal Bureau of

1. Burgess M. Hacking the hackers: everything

Investigation; April 29, 2016. https://www.

you need to know about Shadow Brokers’

fbi.gov/news/stories/incidents-of-ransom-

attack on the NSA. Wired website. http:// www.wired.co.uk/article/nsa-hacking-tools-

ware-on-the-rise. Accessed July 2017. 4. Paul. FBI’s advice on ransomware? Just pay

stolen-hackers. Published April 18, 2017.

the ransom. The Security Ledger website.

Accessed July 2017.

https://securityledger.com/2015/10/fbis-

2. Herman B. Details of Anthem’s massive

advice-on-cryptolocker-just-pay-the-ran-

cyberattack remain in the dark a year later.

som. Published October 22, 2015. Accessed

Modern Healthcare website. http://www.

July 2017.

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FACT SHEET | BY ANDREA S. BLEVINS PRIMEAU, P D, MBA h

Answering Questions About Low-fat Diet and Breast Cancer Data suggest that a low-fat diet with an increase in vegetable and fruit intake may lower the risk of allcause mortality among women with breast cancer.

question many patients with cancer ask is if diet can improve their prognosis or prevent recurrence. A low-fat diet has been shown to prevent or improve many conditions, including breast cancer. This fact sheet explores the data from studies evaluating the effect of a low-fat diet on breast cancer outcomes.

Supportive Data The WINS trial (ClinicalTrials.gov Identifier: NCT00002564) randomly assigned 2437 women with early-stage breast cancer to an intervention or control group. The intervention group received intensive dietary intervention with a target of 15% of energy from fat, whereas the control group received minimal counseling. The counselors did not discuss weight reduction.1,2 The baseline energy from fat was 29.6% and 29.2% in the intervention and control groups, respectively, and was 20.3% and 29.2%, respectively, at 12 months. This change was maintained for at least 5 years. Fruit intake increased in the intervention group, and serum fatty acid analysis suggested that the fatty acid profiles were improved. Relapse-free survival (RFS), the primary endpoint, was 24% higher in the intervention group (events, 9.8%) compared with the control group (events, 12.4%; hazard ratio [HR], 0.76; 95% CI, 0.60– 0.98; P = .077 log-rank, P = .034). Women with hormone receptor–negative disease

experienced an even greater benefit, with a 42% higher RFS at 8 years (RFS, 9.5%) with the intervention compared with the control counseling. The authors noted, however, that body weight was significantly lower in the intervention group (P = .005) after 60 months and could have influenced the results.

A low-fat diet has been shown to prevent or improve many conditions, including breast cancer. In the prospective Collaborative Women’s Longevity Study (CWLS) population study, 4441 women with breast cancer aged 20 to 79 completed a food frequency questionnaire and were followed for a mean of 5.5 years for all-cause and breast cancer–related mortality.3 There was a significantly greater risk of all-cause mortality among women with the highest intake of saturated fat (HR, 1.41; 95% CI, 1.06–1.87; Ptrend = .03) and trans fat (HR, 1.78; 95% CI, 1.35– 2.32; Ptrend = .01) intake compared with those with the lowest intakes. There was a trend toward higher saturated and trans fats intake and increased breast cancer–related mortality, but this

association was not significant. Total fat intake was not associated with all-cause or breast c ancer–related mortality. A meta-analysis of 3 of the studies described in this fact sheet,1,3,7 which included 9966 women with breast cancer, concluded that a low-fat diet reduced the risk of breast cancer recurrence by 23% (HR, 0.77; 95% CI, 0.63–0,94; P = .009) and all-cause mortality by 17% (HR, 0.83; 95% CI, 0.69–1.00; P = .05).4 More recently, an analysis of the Women’s Health Initiative (WHI) trial evaluated the role of dietary intervention with breast cancer outcomes. This trial randomly assigned 48,835 postmenopausal women without breast cancer to dietary intervention with a goal of fat intake of 20% of energy and increased fruits, vegetables, and grains, or the usual diet. This analysis identified 1764 women in the cohort who developed breast cancer.5 Though there was a trend of fewer breast cancer–related deaths among the women during the 8.5-year intervention compared with the usual dietary group, the finding was not significant (0.016% vs 0.024% per year; HR, 0.67; 95% CI, 0.43–1.06; P = .08). All-cause mortality after breast cancer, however, was significantly less in the intervention group vs the usual diet group (0.025% vs 0.038% per year; HR, 0.65; 95% CI, 0.45–0.94; P = .02). During the 16-year follow-up period, breast cancer–related mortality was significantly less in the intervention group (0.085% per year) compared with the usual diet group (0.11% per year; HR, 0.82; 95% CI, 0.70–0.96; P = .01). Unsupportive Data A prospective cohort of 1982 women with breast cancer diagnosed between 1976 and 1990 were followed for 18 years. The cohort completed biennial

A34 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

FACT SHEET questionnaires that included food frequency. The primary endpoint was time to all-cause mortality.6 Dietary fat intake was not associated with mortality, nor was there an association with red meat intake. High protein intake, however, was associated with reduced risk of mortality (relative risk high quintile vs low quintile, 0.65; 95% CI, 0.47–0.88). In the multicenter Women’s Healthy Eating and Living (WHEL) trial, 3088 women with early-stage breast cancer aged 18 to 70 enrolled between 1995 and 2000 were randomly assigned to an intervention group or a control group. The intervention group received telephone counseling, cooking classes, and newsletters to encourage daily targets of vegetable, fruit, fiber, and fat intake, whereas the control group received print materials with the 5-A-Day dietary guidelines. The mean follow-up was 7.3 and the primary endpoint was an invasive breast cancer event or all-cause mortality.7 There was no significant difference in the rates of breast cancer events or all-cause mortality, though the women in the intervention group successfully maintained significantly higher vegetable (+65%), fruit (25%), and fiber (+30%) intake and lower fat intake (−13%; P < .001 for all).

Changes in dietary intake were confirmed using biomarkers such as plasma carotenoids, triacylglycerol, and high-density lipoprotein cholesterol. Baseline energy from fat was 28.5% and 28.7% in the intervention and control groups, respectively, and 28.9% and 32.4%, respectively at 72 months, indicating that although there were differences between the 2 groups, the intervention group did not lower their fat intake compared with baseline. A secondary analysis of the WHEL t rial t hat included 2967 women evaluated the effect of greater vegetable, fruit, and fiber intake and lower fat intake on the prognosis of women with and without hot flashes.8 Women without hot flashes had 31% fewer events than women without hot flashes in the intervention group (HR, 0.69; 95% CI, 0.51–0.93; P = .02) and in the control group (HR, 0.65; 95% CI, 0.49–0.85; P = .002), which suggests that the presence of hot flashes, but not diet, may be associated with breast cancer prognosis.

low-fat diet on breast cancer outcomes. Several trials demonstrate a decrease in all-cause mortality among women with breast cancer who adopt a lowfat diet. Yet other important factors, such as weight loss and the types of fats ingested, must be considered. The data overall suggest that a lowfat diet with an increase in vegetable and fruit intake may lower the risk of all-cause mortality among women with breast cancer, but more studies are needed to provide patients with a definitive recommendation. ■ References 1. Chlebowski RT, et al. Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women’s Intervention Nutrition Study. J Natl Cancer Inst. 2006;98:1767-76. 2. Blackburn GL, et al. Dietary fat reduction and breast cancer outcome: results from the Women’s Intervention Nutrition Study (WINS). Am J Clin Nutr. 2007;86(3):s878-81. 3. Beasley JM, et al. Post-diagnosis dietary factors and survival after invasive breast cancer. Breast Cancer Res Treat.

Conclusion Differences in trial design, populations, and levels of energy intake from fat renders it difficult to achieve a definitive conclusion regarding the effect of a

2011;128:229-36. 4. Xing MY, et al. Effect of low-fat diet on breast cancer survival: a meta-analysis. Asian Pac J

Cancer Prev. 2014;15:1141-4. 5. Chlebowski RT, et al. Low-fat dietary pattern and breast cancer mortality in the Women’s Health Initiative randomized controlled trial.

J Clin Oncol. 2017;35(25):2919-26. 6. Holmes MD, et al, Willett WC. Dietary factors © HINTERHAUS PRODUCTIONS / GETTY IMAGES

and the survival of women with breast carcinoma. Cancer. 1999;86:826-35. 7. Pierce JP, et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the WHEL Randomized Trial. JAMA. 2007;298:289-98. 8. Gold EB, et al. Dietary pattern influences breast cancer prognosis in women without hot flashes: the Women’s Healthy Eating and Living trial. J Clin Oncol. 2009;27:352-9.

CancerTherapyAdvisor.com | SEPTEMBER/OCTOBER 2017 | CANCER THERAPY ADVISOR A35

EXPERT PERSPECTIVE | HOLLY A. SWAIN EWALD, P D, AND PAUL W. EWALD, P D h

CAR T Cell Therapy for ALL: An Evolutionary Perspective Enthusiasm for the CAR T cell approach may redirect rather than augment other possibly safer, more effective, approaches to cancer therapy.

US Food and Drug Adminis tration (FDA) panel recently recommended the approval of CTL019 chimeric antigen receptor (CAR) T cell therapy for acute lympho blastic leukemia (ALL). This first-ever recommendation for a CAR T therapy was based on evidence that the treat ment’s clinical benefits outweighed considerable safety concerns.1,2 The population eligible for this therapy is restricted to children through young adults with relapsed or refractory B cell ALL, among whom the survival rate can be less than 30%.3 CAR T cells have engineered receptors composed of a cell-surface component that binds to a tumor antigen and is attached to one or more internal signal initiators. CTL019 CAR T cells are designed to identify ALL B cells by the CD19 cell surface protein also expressed on normal B cells. By design, CAR T cells circumvent major histocompatibility complex (MHC) presentation and thus the pathways to this mechanism of immunological activation. The genetically modified receptor aboard these cytotoxic T cells binds directly with a tumor antigen to initiate cell killing. This approach necessitates CAR T cell interaction with a specific surface mol ecule, which will often be a self-antigen found on normal and cancer cells. In childhood ALL that does not respond to standard therapy, the risk of CAR T killing normal cells must be

weighed against the probability of death from the cancer itself. For ALL, an alter native therapy is life-long immune sup pression following hematopoietic stem cell transplant (HSCT). The potential for destruction of normal B cell popula tions by CAR T cells may therefore be considered an acceptable risk.

The risk of CAR T killing normal cells must be weighed against the probability of death from the cancer itself. It is, however, important to recog nize that years of experience titrating immune suppressive drugs to prevent graft-versus-host disease after HSCT may minimize the risk to the surviving patient, whereas, at this time, CAR T cells cannot be withdrawn, and deleteri ous effects of B cell depletion may differ from patient to patient. CAR T cells are sometimes referred to as a “living drug” because their action directs a therapeutic molecule against a cellular target. From an evolutionary perspective, this term is apt because, like an antimicrobial drug favoring the evo lution of antimicrobial resistance, CAR T cells can favor evolution of resistance

through selective pressure on an antigen. This evolutionary effect has already been noted in response to CTL019: subpopulations of tumor cells altered by CD19 have emerged during treatment, resulting in patient relapse.4 There are additional concerns regard ing CTL019 CAR T cell therapy in par ticular and engineered T cell therapies in general. In the relatively few CAR T trials, there have been numerous deaths directly attributable to the therapy. In one CTL019 CAR T cell study, further more, severe to life-threatening cases of cytokine release syndrome occurred in almost half of the patients.5 Other adverse events can include lethal T cell cross-reactivity and cerebral edema. Despite early positive results, a phase 2 trial using an alternative CD19-targeted CAR T cell therapy was discontinued after multiple deaths. Trade secret pro tection restricts public access to infor mation that might clarify why the trial was unsuccessful.6 CAR T cells are representative of the engineered arm of adoptive cell therapy (ACT). The other arm, which uses nat ural variation in T cell receptors, also requires that T cells be obtained from the patient, but then selects and expands the subpopulations of T cells that interact with tumor antigens ex vivo. These cells are then returned to the patient as in CAR T therapy.7 This non-engineered arm uses the versatility of the immune system, which has been molded by natu ral selection to kill cells with foreign and abnormal antigens and has a low avidity for self-antigens. The selective amplifica tion of the normal repertoire can produce a T cell population capable of interacting with multiple tumor antigens. In the patient, these already-existing T cells have, by definition, failed at tumor destruction—a fact that may lend more credence to engineering receptors than warranted, as the failure may not be

A36 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

EXPERT PERSPECTIVE due to the activity of the receptor but because of a suppressive tumor microenvironment. Checkpoint inhibitors have been used to augment ACT, and careful analyses of these results may help parse out the relative value of ACT approaches. The promise of CAR T cells is attractive to researchers because of, rather than in spite of, the need to use self-antigens like CD19 given their presence in virtually the entire population. Patients that receive CTL019 therapy will have their normal B cell population depleted and therefore require immunoglobulin therapy. This is not a trivial effect of therapy, as B cells are essential for protection from infection and immunoglobulin replacement therapy is not always well-tolerated.8 Because CAR T cells interact directly with cancer cell surface antigens, they appear to be limited to the risky use of self-antigens or to rare universal neoantigens. On the other hand, CAR T cells are not subject to problems with isolating or expanding subpopulations of patient-derived T cells capable of tumor-killing, a process that is sometimes unsuccessful and protracted in a clinical contextâ&#x20AC;&#x201D; where time is a scarce resource. Evolution has had a tremendous head start on generating effective and safe cytotoxic T cells. Efforts to improve engineered T cell components include

In The Clinic

multi-antigen binding and suicide switches, which, while promising, may solve one problem and introduce others. Developing therapies that apply the versatile sophistication of the immune system to fight cancer is likely the best long-term strategy. The FDA recommendation to move forward with ALL CAR T cell therapy for relapsed or refractory disease appears appropriate. Nonetheless, engineering a self-antigen-targeted T cell, which necessitates immunoglobulin replacement therapy, makes sense only in the context of a likely cancer-related death due to a paucity of alternative therapies. Targeting self-antigens is a potential weakness in CAR designs that might constrain it to a final-effort therapy as opposed to a universal cancer treatment. Ultimately, we are concerned that enthusiasm for the CAR T cell approach will redirect rather than augment other possibly safer, more effective, evolutionarily informed approaches to cancer therapy. â&#x2013;

2017. https://www.novartis.com/news/ media-releases/novartis-car-t-cell-therapyctl019-unanimously-10-0-recommendedapproval-fda. Accessed August 2017. 3. Bhojwani D, Pui CH. Relapsed childhood acute lymphoblastic leukaemia. Lancet

Oncol. 2013;14(6):e205-17. doi: 10.1016/ S1470-2045(12)70580-6 4. Ruella M, Maus MV. Catch me if you can: leukemia escape after CD19-directed T cell immunotherapies. Comput Struct

Biotechnol J. 2016;14:357-62. doi: 10.1016/j. csbj.2016.09.003 5. Fitzgerald JC, Weiss SL, Maude SL, et al. Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia. Crit Care Med. 2017;45(2):e12431. doi: 10.1097/CCM.0000000000002053 6. Hey SP, Kesselheim AS. The FDA, Juno Therapeutics, and the ethical imperative of transparency. BMJ. 2016;354:i4435. doi: 10.1136/bmj.i4435

References

transfer as personalized immunotherapy for

1. Maude SL, Frey N, Shaw PA, et al. Chimeric anti-

human cancer. Science. 2015;348(6230):62-

gen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507-17. doi: 10.1056/NEJMoa1407222 2. Novartis CAR-T cell therapy CTL019 unani-

8. doi: 10.1126/science.aaa4967 8. Cherin P, Marie I, Michallet M, et al. Management of adverse events in the treatment of patients with immunoglobulin ther-

mously (10-0) recommended for approval by

apy: a review of evidence. Autoimmun Rev.

FDA advisory committee to treat pediatric,

2016;15(1):71-81. doi: 10.1016/j.rev.2015.09.002

1. Mota JM, Sousa LG, Riechelmann RP. Complications from carcinoid syn-

compared with 20% of patients receiving placebo; telotristat also reduced serotonin metabolites compared with placebo. The management of diarrhea in patients with carcinoid syndrome can be extremely challenging. Telotristat represents a new treatment option that may decrease diarrhea incidence with a relatively safe side effect profile. n

Basel, Switzerland: Novartis; July 13,

7. Rosenberg SA, Restifo NP. Adoptive cell

References

Continued from page A30

young adult r/r B-cell ALL [news release].

drome: review of the current evidence.

Ecancermedicalscience. 2016;10:662. 2. Kunz PL. Carcinoid and neuroendocrine tumors: building on success. J Clin Oncol. 2015;33(16):1855-63. doi: 10.1200/ JCO.2014.60.2532 3. Modlin IM, Kidd M, Latich I, Zikusoka MN,

4. Pavel M, Horsch D, Caplin M, et al. Telotristat etiprate for carcinoid syndrome: a single-arm, multicenter trial. J Clin

Endocrinol Metab. 2015;100(4):1511-9. 5. Kulke MH, Horsch D, Caplin ME, et al. Telotristat ethyl, a tryptophan hydroxylase inhibitors for the treatment of carcinoid syndrome. J Clin Oncol. 2017;35(1):14-23. 6. Xermelo package insert. Xermelo website. https://www.xermelo.com/Media/

Shapiro MD. Current status of gastroin-

Default/pdfs/Product_Info_telotri-

testinal carcinoids. Gastroenterology.

stat_etiprate.pdf. Updated February 2017.

2005;128(6):1717-1751.

Accessed August 2017.

CancerTherapyAdvisor.com | SEPTEMBER/OCTOBER 2017 | CANCER THERAPY ADVISOR A37

REGIMEN & MONOGRAPH INDEX CANCER THERAPY REGIMENS & DRUG MONOGRAPHS 1

Bone Cancer

Brain Cancer

 Brain Cancer

Breast Cancer

Endocrine Cancer

Gastrointestinal Cancer

 Anal Carcinoma

Genitourinary Cancer

 Bladder Cancer

 Prostate Cancer  Renal Cell Carcinoma

Gynecologic Cancer

 Uterine Sarcoma

Head and Neck Cancer

Hematologic Cancer

Lung Cancer

Sarcoma

92 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 (CTA) is an up-to-date guide to commonly prescribed pharmaceuticals, as well as certain OTC products. It has been produced to provide an easily accessible reminder of basic information useful to review when prescribing medications, such as specific indications for use, dosage, and a checklist of precautions, interactions, and adverse drug reactions. Reference should always be made to each drug being coadmin istered. The information it contains is intended solely for use by the medical profession. IT IS NOT INTENDED FOR LAY READERS. This reference has been assembled and edited by an experienced staff of pharmacists uti lizing information available from FDA-approved labeling. Distinctions have not necessarily been made between those reactions that are well-documented and/or clinically significant, and those that carry only a theoretical risk. A renowned board of consulting medical specialists has also independently reviewed the product references. However, although every effort is made to assure accuracy, the information in CTA is not necessarily reviewed by the supplier of a particular drug. If any questions arise about information in CTA, the physician should verify it against labeling or by contacting the company marketing the drug. The publisher and editors do not warrant or guarantee any of the products described or the information describing them. THE PUBLISHER AND EDITORS DO NOT ASSUME, AND HEREBY EXPRESSLY DISCLAIM ANY LIABILITY WHATSOEVER FOR ANY ERRORS OR OMISSIONS IN SUCH INFORMATION OR FOR ANY USE OF ANY OF THE PRODUCTS LISTED. No prescription drug should be used except on the advice of, and as directed by, a physician. The training and experience of a physician are essential to forming any opinion on the appropriateness of a specific drug for a specific patient. The information in this publication is not by itself sufficient for a lay person—or even a physician—to evaluate the risks and benefits of taking any particular drug. In reaching professional judgments on whether to prescribe a pharmaceutical, which to prescribe, and under what regimen, the physician should thoroughly understand the options available for any clinical application, the potential effectiveness of each product, and the associated risks and side effects. This knowledge should be considered in light of the special circumstances of the patient, for each patient is unique. No single reference can substitute for medical training and experience. The physician must be familiar with the full product labeling, provided by the manufacturer or distributor of the drug, of every product he or she prescribes, as well as the relevant medical literature. Certain additional qualifications are important in using this book. First, CTA has been deliberately kept concise, with a standardized format, so that it could be a convenient reference tool. This means that lengthy and detailed explanations about certain aspects of drugs commonly found in labeling are omitted or condensed. Second, by revising and reprinting quarterly, CTA should be one of the most up-to-date guides to prescription drugs now available in print. Only the current issue should be used. The prescribing decision is ultimately the responsibility of the physician. CTA is offered to assist physicians in this area. © 2017 Haymarket Media, Inc.

A38 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 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, non-absorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin). Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome). How supplied: Soln (2mL, 4mL, 8mL, 10mL)—10 (single-use vials); pwd (1 gram)—1 (single-use vial)

VOTRIENT GlaxoSmithKline

℞

Tyrosine kinase inhibitor. Pazopanib 200mg; tabs. Indications: Advanced soft tissue sarcoma in patients who have received prior chemotherapy. Limitation of use: not for treating adipocytic soft tissue sarcoma or gastrointestinal stromal tumors. Adults: Take on an empty stomach. Swallow whole. 800mg once daily. Dose adjustments: see full labeling. Hepatic impairment: moderate: 200mg once daily; severe: not recommended. Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir, clarithromycin): avoid and consider alternate drug; if warranted, reduce dose of pazopanib to 400mg; may reduce further if toxicity

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DRUG MONOGRAPHS

BONE CANCER 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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CANCER TREATMENT REGIMEN

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

Systemic Therapy for Adult Low-Grade Infiltrative Supratentorial Astrocytoma/Oligodendroglioma1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

Adjuvant Treatment Combination PCV (lomustine + procarbazine + vincristine) (Category 1)2

Day 1: Lomustine 110mg/m2 orally. Days 8–21: Procarbazine 60mg/m2 orally once daily. Days 8 and 29: Vincristine 1.4mg/m2 (maximum 2mg) IV. Repeat every 6 weeks.

Temozolomide3–5

Days 1–49: Temozolomide 75mg/m2 orally. Repeat cycle every 11 weeks (7 weeks on/4 weeks off) for 6 cycles. OR For children/adolescents: Temozolomide monthly 5-day courses at doses of 200mg/m2/day (patients with no prior craniospinal irradiation [CSI]) or 180mg/m2/day (prior CSI). OR Days 1–21: Temozolomide 75mg/m2/day orally. Repeat cycle every 28 days.

Recurrent or Progressive, Low Grade Disease Temozolomide3,6a

Days 1–49: Temozolomide 75mg/m2 orally. Repeat cycle every 11 weeks (7 weeks on/4 weeks off) for 6 cycles. OR Days 1–5: Temozolomide 150mg/m2 to 200mg/m2; when patients progress during conventional temozolomide treatment, change temozolomide to a 50mg/m2 daily regimen. Repeat cycle every 28 days.

Combination PCV regimens (lomustine + procarbazine + vincristine)7

Day 1: Lomustine 110mg/m2 orally. Days 8–21: Procarbazine 60mg/m2 orally once daily. Days 8 and 29: Vincristine 1.4mg/m2 (maximum 2mg) IV. Repeat every 6 weeks.

Platinum-based regimen: Carboplatin8

Day 1: Carboplatin 350mg/m2 IV Days 1–3: Teniposide 50mg/m2 IV. Repeat cycle every 4 weeks.

Platinum-based regimen: Carboplatin9

Carboplatin 560mg/m2 IV at 4-week intervals; continued until disease progression, unacceptable toxicity, or for 12 additional courses after achieving maximal response.

Platinum-based regimen: Cisplatin10

Days 1–3: Cisplatin 25mg/m2/day IV + etoposide 100mg/m2/day IV. Repeat cycle every 4 weeks for first 3 cycles, then repeat every 5 weeks for next 3 cycles, then repeat every 6 weeks for the last 3 cycles; total 10 cycles over approximately 10–11 months (total dose 750mg/m2 cisplatin and 3,000mg/m2 etoposide).

Lomustine11

Lomustine 130mg/m2 orally every 6 weeks.

Carmustine12

Carmustine 150–200mg/m2 IV as a single dose or divided over 2 days given every 6 weeks OR 75–100mg/m2/day IV for 2 days every 6 weeks. continued

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CANCER TREATMENT REGIMEN

BRAIN CANCER Brain Cancer Treatment Regimens Systemic Therapy for Anaplastic Gliomas1 REGIMEN

DOSING

Adjuvant Treatment Temozolomide13,14

Days 1–5: Temozolomide 200mg/m2/day orally. Repeat cycle every 4 weeks until disease progression or for up to 24 cycles.

PCV with deferred RT13

Day 1: Lomustine 110mg/m2 orally Days 8–21: Procarbazine 60mg/m2 orally once daily Days 8 and 29: Vincristine 1.4mg/m2 (maximum 2mg) IV. Repeat every 6 weeks.

Concurrent temozolomide (with RT)15

2 Gy given 5 days/week for 6 weeks plus continuous daily oral temozolomide (75mg/m2/day, 7 days per week from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant temozolomide 150–200mg/m2/day for 5 days. Repeat cycle every 28 days.

Recurrence Therapy Temozolomide4,6,16

Temozolomide 50mg/m2 daily for up to 1 year or until disease progression. OR For children/adolescents: Temozolomide monthly 5-day courses at doses of 200mg/m2/day (patients with no prior CSI) or 180mg/m2/day (prior CSI). OR Days 1–5: Temozolomide 150mg/m2 to 200mg/m2 5 days of each 28-day cycle; when patients progress during conventional temozolomide treatment, change temozolomide to a 50mg/m2 daily regimen. OR Days 1–5: Temozolomide 150mg/m2 to 200mg/m2. Repeat cycle every 28 days.

Lomustine or carmustine11,12,17

Day 1: Lomustine 100–130mg/m2/day orally. Repeat cycle every 6 weeks. OR Carmustine 150–200mg/m2 IV as a single dose or divided over 2 days given every 6 weeks OR 75–100mg/m2/day IV for 2 days every 6 weeks.

Combination PCV regimens (lomustine + procarbazine + vincristine)7

Day 1: Lomustine 110mg/m2 orally Days 8–21: Procarbazine 60mg/m2 orally once daily Days 8 and 29: Vincristine 1.4mg/m2 (maximum 2mg) IV. Repeat every 6 weeks.

Bevacizumab18–20b

Day 1: Bevacizumab 10mg/kg IV. Repeat cycle every 14 days.

Bevacizumab + irinotecan21,22c

Day 1: Bevacizumab 10mg/kg IV plus irinotecan 125mg/m2 IV. Repeat cycle every 2 weeks. OR Bevacizumab 10mg/mg2 IV plus irinotecan 340mg/m2 IV in patients receiving enzyme-inducing antiepileptic drugs (EIAED). Repeat cycle every 14 days.

Bevacizumab + nitrosurea23

Days 1 and 15: Bevacizumab 10mg/kg IV Days 1 and 8: Fotemustine 75mg/m2 IV Followed after a 3-week interval by a maintenance phase of bevacizumab 10mg/kg IV plus fotemustine 75mg/m2 IV. Repeat cycle every 3 weeks.

Bevacizumab + carboplatin (Category 2B)24,25

Day 1: Bevacizumab 10mg/kg IV plus carboplatin AUC 4–6mg •min/mL, depending on the patient’s prior treatment history and bone marrow reserves; cycle 2 doses of carboplatin (every 28 days) and 3 doses of bevacizumab (every 14 days) and lasted 6 weeks.

Irinotecan26,27

Day 1: Irinotecan 350mg/m2 IV to patients on non-enzyme-inducing antiepileptic drugs (NEIAED) or 600mg/m2 to patients on EIAED. Repeat cycle every 21 days. OR Day 1: Irinotecan 350mg/m2 IV. Repeat cycle every 21 days.

Platinum-based regimen: Carboplatin8

Day 1: Carboplatin 350mg/m2 IV Days 1–3: Teniposide 50mg/m2 IV. Repeat cycle every 4 weeks.

Platinum-based regimen: Carboplatin9

Carboplatin 560mg/m2 IV at 4-week intervals; continued until disease progression, unacceptable toxicity, or for 12 additional courses after achieving maximal response.

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BRAIN CANCER Systemic Therapy for Anaplastic Gliomas1 (continued) REGIMEN

DOSING

Recurrence Therapy (continued) Platinum-based regimen: Cisplatin10

Cyclophosphamide (Category 2B)28,29

Days 1–2: Cyclophosphamide 750mg/m2 IV. Repeat cycle every 28 days.

Etoposide30

Etoposide 50mg/day IV given until the neutrophil count dropped to < 1.0 × 109/L or the platelets fell to < 75 × 109/L and resumed when the counts rose to normal levels.

Systemic Therapy for Anaplastic Oligoastrocytoma1 Adjuvant Treatment Radiotherapy + PCV for 1p19q co-deleted (Category 1)31

59.6 4 Gy of RT, followed by 6 cycles of standard PCV: Day 1: Lomustine 110mg/m2 orally Days 8–21: Procarbazine 60mg/m2 orally once daily Days 8 and 29: Vincristine 1.4mg/m2 (maximum 2mg) IV. Repeat every 6 weeks.

Systemic Therapy for Glioblastoma1 Adjuvant Treatment Concurrent temozolomide (with RT)15

Post-RT temozolomide32

Days 1–5: Temozolomide 150–200mg/m2/day orally for 5 days. Repeat cycle every 28 days.

Temozolomide + standard RT33

Days 1–5: Temozolomide 200mg/m2, orally plus: Standard RT: 60.0 Gy administered in 2.0 Gy fractions over 6 weeks.

Recurrence Therapy Bevacizumab34–36b

Day 1: Bevacizumab 10mg/kg IV. Repeat cycle every 14 days.

Bevacizumab + irinotecan22,34–36c

Day 1: Bevacizumab 10mg/kg IV. Repeat cycle every 14 days. After tumor progression, immediately treat with bevacizumab 10mg/kg IV plus irinotecan 340mg/m2 or 125mg/m2 IV every 14 days, depending on use of EIAEDs.

Bevacizumab + nitrosurea23c

Bevacizumab + carboplatin (Category 2B)24,25c

Day 1: Bevacizumab 10mg/kg IV plus carboplatin AUC 4–6mg • min/mL, depending on the patient’s prior treatment history and bone marrow reserves; cycle 2 doses of carboplatin (every 28 days) and 3 doses of bevacizumab (every 14 days) for 6 weeks.

Temozolomide6,32,37

Days 1–5: Temozolomide 150mg/m2 to 200mg/m2; when patients progress during conventional temozolomide treatment, change temozolomide to a 50mg/m2 daily regimen. Repeat cycle every 28 days. OR 2 Gy given 5 days/ week for 6 weeks plus continuous daily oral temozolomide (75mg/m2/day, 7 days per week from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant temozolomide 150–200mg/m2/day for 5 days. Repeat cycle every 28 days. OR Chemotherapy-naive patients: Days 1–5: Temozolomide 200mg/m2/day. Chemotherapy-experienced patients: Days 1–5: Temozolomide 150mg/m2/day, increasing to 200mg/m2/day in the absence of grade 3/4 toxicity. Repeat cycle every 28 days. continued

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CANCER TREATMENT REGIMEN

BRAIN CANCER Brain Cancer Treatment Regimens Systemic Therapy for Glioblastoma1 (continued) REGIMEN

DOSING

Recurrence Therapy (continued) Lomustine or carmustine11,12,17

Combination PCV regimens (lomustine + procarbazine + vincristine)7

Day 1: Lomustine 110mg/m2 orally Days 8–21: Procarbazine 60mg/m2 orally once daily Days 8 and 29: Vincristine 1.4mg/m2 (maximum 2mg) IV. Repeat every 6 weeks.

Cyclophosphamide (category 2B)28

Days 1–2: Cyclophosphamide 750mg/m2 IV. Repeat cycle every 28 days.

Platinum-based regimen: Carboplatin8

Day 1: Carboplatin 350mg/m2 IV Days 1–3: Teniposide 50mg/m2 IV. Repeat cycle every 4 weeks.

Platinum-based regimen: Carboplatin9

Carboplatin 560mg/m2 IV at 4-week intervals; continued until disease progression, unacceptable toxicity, or for 12 additional courses after achieving maximal response.

Platinum-based regimen: Cisplatin10

Systemic Therapy for Intracranial and Spinal Ependymoma (Excluding Supependymoma)1 Recurrence Therapy Platinum-based regimen: Carboplatin8

Day 1: Carboplatin 350mg/m2 Days 1–3: Teniposide 50mg/m2. Repeat cycle every 4 weeks.

Platinum-based regimen: Carboplatin9

Carboplatin 560mg/m2 IV at 4-week intervals; continued until disease progression, unacceptable toxicity, or for 12 additional courses after achieving maximal response.

Platinum-based regimen: Cisplatin10

Etoposide30

Etoposide 50mg/day given until the neutrophil count dropped to <1.0 × 109/L or the platelets fell to <75 × 109/L and resumed when the counts rose to normal levels.

Bevacizumab34–37b

Day 1: Bevacizumab 10mg/kg IV. Repeat cycle every 14 days.

Temozolomide3–5

Days 1–49: Temozolomide 75mg/m2 orally. Repeat cycle every 11 weeks (7 weeks on/4 weeks off) for 6 cycles. OR Days 1–21: Temozolomide 75mg/m2/day orally. Repeat cycle every 28 days.

Systemic Therapy for Adult Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumor (PNET)1 Adjuvant Treatment Weekly vincristine during craniospinal radiation therapy followed by either of the following regimens. Note that omission of vincristine during radiation therapy phase of therapy or dose modification may be required for adults because they do not tolerate this regimen as well. Data supporting the use of vincristine has been found in pediatric trials only. Patients should be closely monitored for neurologic toxicity with periodic exams. Vincristine + cisplatin + lomustine38

During craniospinal radiotherapy (RT) Day 1: Lomustine 75mg/m2 orally Day 2: Cisplatin 75mg/m2 IV Days 2, 8 and 15: Vincristine 1.5mg/m2 IV bolus, max 2mg bolus; up to max 8 doses.

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BRAIN CANCER Systemic Therapy for Adult Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumor (PNET)1 (continued) REGIMEN

DOSING

Adjuvant Treatment (continued) Vincristine + cisplatin + cyclophosphamide39

Day 1: Cisplatin 75mg/m2 IV Days 2, 8 and 15: Vincristine 1.5mg/m2 IV bolus, max 2mg bolus Days 22, 23: Cyclophosphamide 1,000mg/m2 IV.

Recurrence Therapy No prior chemotherapy: Consider high-dose chemotherapy with autologous stem cell reinfusion in patients who achieve a complete remission with conventional doses of salvage chemotherapy or have no residual disease after re-resection.35 High dose cyclophosphamide ± etoposide Carboplatin + etoposide + cyclophosphamide Cisplatin + etoposide + cyclophosphamide Prior chemotherapy: Consider high-dose chemotherapy with autologous stem cell reinfusion in patients who achieve a complete remission with conventional doses of salvage chemotherapy or have no residual disease after re-resection.35 High dose cyclophosphamide ± etoposide Temozolomide3

Temozolomide 75mg/m2 orally in 11-week cycles of 7 weeks on followed by 4 weeks off.

Oral etoposide40,41

Days 1–21: Etoposide 50mg orally daily. Repeat cycle every 4 weeks.

Primary CNS Lymphoma1 Primary Treatment High dose methotrexate + chemotherapy42–44

High dose methotrexate combined with the following plus radiation therapy: Weeks 1, 3, 5, 7, and 9: MTX 2.5g/m2 + vincristine 1.4mg/m2 with a cap of 2.8mg (2m2) Weeks 1, 5, and 9: Procarbazine 100mg/m2/day orally for 7 days Weeks, 2, 4, 6, 8, and 10: Methotrexate 12mg intraventicularly Weeks 1, 3, 5, 7, and 9: Leucovorin 20mg every 6 hours orally for 12 doses Weeks, 2, 4, 6, 8, and 10: Leucovorin 10mg orally twice daily for 8 doses Weeks 11–15: Whole-brain RT in 1.80-Gy fractions for a total dose of 45 Gy Weeks 16 and 19: Cytarabine 3mg/m2/day IV for 2 days. Repeat for 5 cycles. OR Day 1: MTX 3.5g/m2 Days 2–3: Cytarabine 2g/m2 IV twice a day. OR Day 1: MTX 4gm/m2 IV, followed by leucovorin 20–25mg IV every 6 hours starting 24 hours after MTX for 72 hours or until serum MTX level <1 × 10–8mg/dL. Increase leucovorin to 40mg every 4 hours if MTX level >1 × 10–5mg/dL at 48 hours or >1 × 10–8mg/dL at 72 hours. Days 3–5: Ifosfamide 1.5gm/m2 IV + mesna 400mg IV before ifosfamide, then 4 hours and 8 hours after.

High dose methotrexate (MTX 2.5–4.0mg/m2) + chemotherapy ± monoclonal antibody45

Day 1: Rituximab 500mg/m2 IV Day 2: MTX 3.5mg/m2 IV plus vincristine 1.4mg/m2 Procarbazine 100mg/m2/day was administered for 7 days with odd-numbered cycles.

High dose methotrexate (MTX 8.0mg/m2) + chemotherapy ± monoclonal antibody46–47

High dose methotrexate combined with the following plus radiation therapy deferred radiation therapy: Induction therapy MTX 8g/m2 IV administered every 2 weeks until complete response achieved or max of 8 cycles reached. Consolidation MTX 8g/m2 IV administered every 2 weeks for 2 cycles. Maintenance therapy MTX 8g/m2 IV administered every 4 weeks for 11 cycles. Plus Day 1: Rituximab 375mg/m2 IV. Repeat cycle every 4 weeks for 4 cycles. OR Induction therapy Day 1: Rituximab 375mg/m2 IV, followed by Days 1–5: Temozolomide 150–200mg/m2 orally daily, after rituximab infusion. Repeat cycle every 4 weeks for 4 cycles. Maintenance therapy Days 1–5: Temozolomide 150–200mg/m2 orally daily. Repeat cycle every 4 weeks for 8 cycles. continued

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BRAIN CANCER Brain Cancer Treatment Regimens Primary CNS Lymphoma1 (continued) REGIMEN

DOSING

Primary Treatment (continued) Consider urgent glucarpidase (carboypeptidase G2) for prolonged MTX clearance due to MTX-induced renal toxicity48

Glucarpidase, one 50U/kg dose IV, 2 doses 24 hours apart, or 3 doses every 4 hours; thymidine 8 g/m2/day IV administered as continuous IV infusion for ≥48 hours after the last dose of glucarpidase; leucovorin 1g/m2 IV every 6 hours before administration of glucarpidase and at a dose of 250mg/m2 IV every 6 hours for 48 hours after administration of the last dose of glucarpidase.

Recurrent or Progressive Disease Consider high-dose chemotherapy with autologous stem cell reinfusion in patients who achieve a complete remission with conventional doses of salvage chemotherapy or have no residual disease after re-resection.35 Re-treat with high-dose methotrexate46

Induction therapy MTX 8g/m2 IV administered every 2 weeks until complete response achieved or max of 8 cycles reached. Consolidation MTX 8g/m2 IV administered every 2 weeks for 2 cycles. Maintenance therapy MTX 8g/m2 IV administered every 4 weeks for 11 cycles.

Rituximab ± temozolomide49

Induction therapy Day 1: Rituximab 375mg/m2 IV,  Days 1–5: Temozolomide 150–200mg/m2 orally daily, administered after rituximab infusion. Repeat cycle every 4 weeks for 4 cycles. Maintenance therapy Days 1–5: Temozolomide 150–200mg/m2 orally daily, administered after rituximab infusion. Repeat cycle every 4 weeks for 8 cycles.

Topotecan50

Days 1–5: Topotecan 1.5mg/m2 IV. Repeat cycle every 21 days.

High-dose cytarabine51

Cytarabine 3g/m2 IV.

Dexamethasone + high-dose cytarabine + cisplatin52

Day 1: Cisplatin 100mg/m2 continuous IV infusion over 24 hours, followed by 2 pulses each of cytarabine at a dose of 2g/m2 given 12 hours apart. Days 1–4: Dexamethasone 40mg PO or IV. Repeat cycle every 3–4 weeks for 6–10 courses.

Pemetrexed53

Pemetrexed 900mg/m2 IV every 21 days for 6 weeks.

Meningioma1 Interferon-alfa (Category 2B)54

α-IFN 106 units/m2 SC every other day for 4 weeks. Repeat cycle every 4 weeks.

Somatostatin analog55

Sandostatin LAR Depot 10–30mg IM every 4 weeks.

Sunitinib (Category 2B)56

Days 1–28: Sunitinib 50mg orally daily. Repeat cycle every 42 days.

Systemic Therapy for Limited (1–3) Metastatic or Multiple (>3) Metastatic Lesions1 Recurrent disease—Treatment as per the regimens of the primary tumor (‡ Bevacizumab + chemotherapy can be considered for patients who have failed monotherapy with bevacizumab) Carmustine wafer57

8 wafers (7.7mg) for a total of 61.6mg implanted intracranially.

High-dose methotrexate (MTX; breast Breast: MTX 3.5g/m2 IV. Lymphoma: Treatment based on weekly high-dose MTX 3.5g/m2 and weekly intra-CSF cytarabine; oral procarbazine and lymphoma)58,59 100mg/m2 days 2–15 was added to patients whose bone marrow reserve could tolerate this drug.

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BRAIN CANCER Systemic Therapy for Limited (1–3) Metastatic or Multiple (>3) Metastatic Lesions1 (continued) REGIMEN

DOSING

Capecitabine ± lapatinib, cisplatin, etoposide60–68

Days 1–14: lapatinib 1,250mg orally plus capecitabine 1,000mg/m2 orally twice per day. Repeat cycle every 21 days. OR Days 1–14: Capecitabine 2,000mg/m2/day in 2 divided doses for 14 days, followed by a 7-day rest and lapatinib 1,250mg once daily continuously. OR Day 1: Cisplatin 100mg/m2 IV Days 4, 6, and 8: Etoposide 100mg/m2. Repeat cycle every 21 days. OR Day 1: Cisplatin 100mg/m2 IV Days 1, 3, and 5 OR Days 4, 6, and 8: Etoposide 100mg/m2 IV. Repeat cycle every 21 days. OR (breast) Capecitabine orally starting at a dose of 1,800mg/m2/day (up to 2,000mg/m2/day) in 2 divided doses, and temozolomide given orally once daily at a starting dose of 75mg/m2/day. Concomitant daily doses given on days 1–5 and days 8–12, with cycles repeated every 21 days until disease progression. OR (breast) Days 1–14: Capecitabine 2,000mg/m2/day orally once daily. Repeat cycle every 21 days. OR (breast) Days 1–21: Capecitabine 2,400mg/m2/day orally once daily. Repeat cycle every 28 days.

Ipilimumab (melanoma)69

Day 1: Ipilimumab 10mg/kg IV. Repeat cycle every 21 days for a maximum 4 cycles. Individuals who were clinically stable at week 24 were eligible to receive ipilimumab 10mg/kg every 12 weeks.

BRAF inhibitors (melanoma): Dabrafenib70

Dabrafenib 150mg orally twice daily.

BRAF inhibitors (melanoma): Vemurafenib71

Vemurafenib 960mg orally twice daily.

Topotecan (small cell lung)50

Days 1–5: Topotecan 1.5mg/m2 IV over 30 minutes. Repeat cycle every 21 days.

Systemic Therapy for Leptomeningeal Metastases1 Organ-specific Systemic Chemotherapy; Emphasizing Drugs with Good CNS Penetration Intra-CSF chemotherapy: Liposomal (slow-release) cytarabine (lymphoma/leukemias)72,73

Induction Liposomal cytarabine 50mg intrathecally once every 14 days for 2 doses. Maintenance Liposomal cytarabine 50mg every 14 days for 2 doses, followed by 50mg every 28 days for 2 doses. OR Induction Liposomal cytarabine 50mg intraventricularly every 14 days for 3 doses plus rituximab 25mg intraventricularly twice per week for 8 doses. Maintenance Liposomal cytarabine 50mg intraventricularly once weekly plus rituximab 25mg intraventricularly twice weekly for 4 weeks. Repeat cycle every 4 weeks until disease progression

Intra-CSF chemotherapy: topotecan74

Topotecan 400 μg intraventrically twice weekly for 6 weeks.

Intra-CSF chemotherapy: etoposide75 Induction Days 1–5: Etoposide 0.5mg/day intra-CSF every other week for 8 weeks. Maintenance Days 1–5: Etoposide 0.5mg/day every 4 weeks. Intra-CSF chemotherapy: trastuzumab76

Cumulative dose of intrathecal trastuzumab given in clinical studies was 1,040mg (SD 697.9, median 1,215, range 55–1,675)

Intra-CSF chemotherapy: Interferon-alfa (category 2B)77

IFN-α 1 × 106 IU subcutaneously every other day 3 times per week for 4 weeks by induction. continued

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CANCER TREATMENT REGIMEN

BRAIN CANCER Brain Cancer Treatment Regimens Systemic Therapy for Leptomeningeal Metastases1 (continued) REGIMEN

DOSING

Organ-specific Systemic Chemotherapy; Emphasizing Drugs with Good CNS Penetration (continued) High-dose methotrexate for lymphoma and breast58

Breast: MTX 3.5g/m2 IV.

Erlotinib (Category 2B)78

Weekly pulse erlotinib for EGFR exon 19 or exon 21 L858R mutation non-small cell lung cancer; trial demonstrates that a new schedule of erlotnib administration may overcome acquired resistance to erlotinib. Pulsatile high-dose erlotinib was found to be effective against brain metastases in patients who had progressed while on treatment with standard-dose erlotinib. Pulsatile high-dose erlotinib 1,500mg (median dose with range of 900–1,500mg) once weekly.

Systemic Therapy for Metastatic Spine Tumors1 Use regimen for disease specific site. a For patients not previously treated b Patients who have good performance status but evidence of radiographic progression may benefit from continuation of bevacizumab to prevent rapid

neurologic deterioration

c Bevacizumab + chemotherapy can be considered for patients who have failed monotherapy with bevacizumab

References 1. NCCN Clinical Practice Guidelines in Oncology™. Central Nervous System Cancers. v 1.2016. Available at http://www.nccn.org/professionals/physician_gls/pdf/cns. pdf. Accessed October 18, 2016. 2. Shaw EG, Wang M, Coons SW, et al. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult lowgrade glioma: initial results of RTOG 902. J Clin Oncol. 2012;30:3065–3070. 3. Kesari S, Schiff D, Drappatz J, et al. Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res. 2009;15:330–337. 4. Nicholson HS, Kretschmar CS, Krailo M, et al. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children’s Oncology Group. Cancer. 2007;110:1542–1550. 5. Pouratian N, Gasco J, Sherman JH, Shaffrey ME, Schiff D. Toxicity and efficacy of protracted low dose temozolomide for the treatment of low grade gliomas. J Neurooncol. 2007;82: 281–288. 6. Perry JR, Rizek P, Cashman R, Morrison M, Morrison T. Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule: the “rescue” approach. Cancer. 2008;113:2152–2157. 7. Triebels VH, Taphoorn MJ, Brandes AA, et al. Salvage PCV chemotherapy for temozolomide-resistant oligodendrogliomas. Neurology. 2004;63:904–906. 8. Brandes AA, Basso U, Vastola F, et al. Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study. Ann Oncol. 2003;14:1727–1731. 9. Moghrabi A, Friedman HS, Ashley DM, et al. Phase II study of carboplatin (CBDCA) in progressive low-grade gliomas. Neurosurg Focus. 1998;4:e3. 10. Massimino M, Spreafico F, Riva D, et al. A lower-dose, lowertoxicity cisplatinetoposide regimen for childhood progressive low-grade glioma. J Neurooncol. 2010;100:65–71. 11. Lomustine (CeeNU) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company. 2012. 12. Carmustine (BiCNU) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company. 2011. 13. Wick W, Hartmann C, Engel C, et al. NOA-04 randomized phased III trials of sequential radiochemotherapy of ana plastic glioma with procarbazine, lomustine, and vincristine or temozolamide. J Clin Oncol. 2009;27:5874–5880. 14. Taliansky-Aronov A, Bokstein F, Lavon I, Siegal T. Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial. J Neurooncol. 2006;79:153–157. 15. Stupp R, Mason WP, van den Bent MJ, et al. European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352:987–996.

16. Perry JR, Bélanger K, Mason WP, et al. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol. 2010;28:2051–2057. 17. Wick W, Puduvalli VK, Chamberlain MC, et al. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol. 2010;28: 1168–1174. 18. Chamberlain MC, Johnston S. Bevacizumab for recurrent alkylator-refractory anaplastic oligodendroglioma. Cancer. 2009;115:1734–1743. 19. Chamberlain MC, Johnston S. Salvage chemotherapy with bevacizumab for recurrent alkylator-refractory anaplastic astrocytoma. J Neurooncol. 2009;91:359–367. 20. Norden AD, Young GS, Setayesh K, et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology. 2008;70:779–787. 21. Taillibert S, Vincent LA, Granger B, et al. Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology. 2009;72:1601–1606. 22. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007;13:1253–1259. 23. Soffietti R, Rudà R, Trevisan E, et al. Phase II study of bevacizumab and nitrosourea in patients with recurrent malignant glioma: a multicenter Italian study [abstract 2012] J Clin Oncol. 2009;27(Suppl 15):90s. 24. Mrugala MM, Crew LK, Fink JR, Spence AM. Carboplatin and bevacizumab for recurrent malignant glioma. Oncol Lett. 2012;4:1082–1086. 25. Thompson EM, Dosa E, Kraemer DF, Neuwelt EA. Treatment with bevacizumab plus carboplatin for recurrent malignant glioma. Neurosurgery. 2010;67:87–93. 26. Chamberlain MC, Wei-Tsao DD, Blumenthal DT, Glantz MJ. Salvage chemotherapy with CPT-11 for recurrent temozolomiderefractory anaplastic astrocytoma. Cancer. 2008;112: 2038–2045. 27. Chamberlain MC. Salvage chemotherapy with CPT-11 for recurrent oligodendrogliomas. J Neurooncol. 2002;59: 157–163. 28. Chamberlain MC, Tsao-Wei DD. Salvage chemotherapy with cyclophosphamide for recurrent, temozolomide-refractory glioblastoma multiforme. Cancer. 2004;100:1213–1220. 29. Chamberlain MC, Tsao-Wei DD, Groshen S. Salvage chemotherapy with cyclophosphamide for recurrent temozolomiderefractory anaplastic astrocytoma. Cancer. 2006;106: 172–179. 30. Fulton D, Urtasun R, Forsyth P. Phase II study of prolonged oral therapy with etoposide (VP16) for patients with recurrent malignant glioma. J Neurooncol. 1996;27:149–155. 31. van den Bent MJ, Brandes AA, Taphoorn MJ, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013;31:344–350.

10 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

BRAIN CANCER References (continued) 32. Malmström A, Grønberg BH, Marosi C, et al ; Nordic Clinical Brain Tumour Study Group (NCBTSG). Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol. 2012; 13:916–926. 33. Cloughesy TF, Prados MD, Wen PY. A phase II randomized noncomparative clinical trial of the effect of bevacizumab alone or in combination with irinotecan on 6 month progression free survival (PFS6) in recurrent treatment-refractory glioblastoma (GBM) [abstract]. J Clin Oncol. 2008;26(suppl 15):2010b. 34. Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27:4733–4740. 35. Kreisl TN, Kim L, Moore K, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009;27:740–745. 36. Yung WK, Prados MD, Yaya-Tur R, et al. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol. 1999;17:2762–2771. 37. Packer RJ, Gajjar A, Vezina G, et al. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006;24:4202–4208. 38. Dunkel IJ, Gardner SL, Garvin JH Jr, Goldman S, Shi W, Finlay JL. High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma. Neuro Oncol. 2010; 12:297–303. 39. Ashley DM, Meier L, Kerby T, et al. Response of recurrent medulloblastoma to lowdose oral etoposide. J Clin Oncol. 1996;14:1922–1927. 40. Chamberlain MC, Kormanik PA. Chronic oral VP-16 for recurrent medulloblastoma. Pediatr Neurol. 1997;17:230–234. 41. DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol. 2002;20:4643–4648. 42. Ferreri AJ, Reni M, Foppoli M, et al; International Extranodal Lymphoma Study Group (IELSG). High-dose cytarabine plus high-dose methotrexate versus highdose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009;374:1512–1520. 43. Thiel E, Korfel A, Martus P, et al. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010;11:1036–1047. 44. Shah GD, Yahalom J, Correa DD, et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007; 25:4730–4735. 45. Batchelor T, Carson K, O’Neill A, Grossman SA, Alavi J, New P, Hochberg F, Priet R. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96–07. J Clin Oncol. 2003;21:1044–1049. 46. Chamberlain MC, Johnson SK. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neuro Oncol. 2010;12: 736–744. 47. Wieduwilt MJ, Valles F, Issa S, et al. Immunotherapy with intensive consolidation for primary central nervous system lymphoma: a pilot study and prognostic assessment by diffusion-weighted MRI. Clin Cancer Res. 2012 Jan 6. [Epub ahead of print] 48. Widemann BC, Balis FM, Kim A, et al. Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome. J Clin Oncol. 2010;28:3979–3986. 49. Enting RH, Demopoulos A, DeAngelis LM, Abrey LE. Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide. Neurology. 2004;63:901–903. 50. Topotecan (Hycamtin) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline. 2015. 51. De Angelis L, Kreis W, Chan K, et al. Pharmacokinetics of ara-C and ara-U in plasma and CSF after high-dose administration of cytosine arabinoside. Cancer Chemother Pharmacol. 1992; 29:173–177. 52. McLaughlin P, Velasquez WS, Redman JR, et al. Chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin for parenchymal brain lymphoma. J Natl Cancer Inst. 1988;80: 1408–1412. 53. Raizer JJ, Rademaker A, Evens AM, et al. Pemetrexed in the treatment of relapsed/ refractory primary central nervous system lymphoma. Cancer. 2012;118:3743–3748. 54. Chamberlain MC, Glantz MJ. Interferon-alpha for recurrent World Health Organization grade 1 intracranial meningiomas. Cancer. 2008;113:2146–2151.

55. Chamberlain MC, Glantz MJ, Fadul CE. Recurrent meningioma: salvage therapy with long-acting somatostatin analogue. Neurology. 2007;69:969–973. 56. Kaley TJ, Wen P, Schiff D, et al. Phase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma. Neuro Oncology. 2014;17:116–121. 57. Ewend MG, Brem S, Gilbert M, et al. Treatment of single brain metastasis with resection, intracavity carmustine polymer wafers, and radiation therapy is safe and provides excellent local control. Clin Cancer Res. 2007;13:3637–3641. 58. Lassman AB, Abrey LE, Shah GD, et al. Systemic high-dose intravenous methotrexate for central nervous system metastases. J Neurooncol. 2006;78:255–260. 59. Bokstein F, Lossos A, Lossos IS, et al. Central nervous system relapse of systemic non-Hodgkin’s lymphoma: Results of treatment based on high-dose methotrexate combination chemotherapy. Leuk Lymphoma. 2002;43:587–593. 60. Metro G, Foglietta J, Russillo M, et al. Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine. Ann Oncol. 2011;22:625–630. 61. Sutherland S, Ashley S, Miles D, et al. Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases--the UK experience. Br J Cancer. 2010; 102:995–1002. 62. Cocconi G, Lottici R, Gisagni G et al, Combination therapy with platinum and etoposide in brain metastases from breast carcinoma. Cancer Invest. 1990;8:327–334. 63. Franciosi V, Cocconi G, Michiara M, et al. Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma. Cancer. 1999;85:1599–1605. 64. Rivera E, Meyers C, Groves M, et al. Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma. Cancer. 2006;107:1348–1354. 65. Fabi A, Vidiri A, Ferretti G, et al. Dramatic regression of multiple brain metastases from breast cancer with Capecitabine: another arrow at the bow? Cancer Invest. 2006;24:466-8. 66. Siegelmann-Danieli N, Stein M, Bar-Ziv J. Complete response of brain metastases originating in breast cancer to capecitabine therapy. Isr Med Assoc J. 2003;5: 833–834. 67. Wang MLH, Yung AWK, Royce ME, et al. Capecitabine for 5-fluorouracil-resistant brain metastases from breast cancer. Am J Clin Oncol. 2001;24:421–424. 68. Hikino H, Yamada T, Johbara K, et al. Potential role of chemo-radiation with oral capecitabine in a breast cancer patient with central nervous system relapse. Breast. 2006;15:97–99. 69. Margolin K, Ernstoff MS, Hamid O, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13:459–465. 70. Long GV, Trefzer U, Davies MA, et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:1087–1095. 71. Dummer R, Goldinger SM, Turtschi CP, et al. Vemurafenib in patients with BRAF(V600) mutation-positive melanoma with symptomatic brain metastases: final results of an open-label pilot study. Eur J Cancer. 2014;50:611–621. 72. Jaeckle KA, Phuphanich S, Bent MJ, et al Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine. Br J Cancer. 2001; 84:157–163. 73. Chamberlain MC, Johnston S, Van Horn A, Glantz MJ. Recurrent lymphomatous meningitis treated with intra-CSF rituximab and liposomal ara-C. J Neurooncol. 2009;91: 271–277. 74. Groves MD, Glantz MJ, Chamberlain MC, et al. A multicenter phase II trial of intrathecal topotecan in patients with meningeal malignancies. Neuro Oncol. 2008;10:208-215. 75. Chamberlain MC, Tsao-Wei DD, Groshen S. Phase II trial of intracerebrospinal fluid etoposide in the treatment of neoplastic meningitis. Cancer. 2006;106:2021–2027. 76. Zagouri F, Sergentanis TN, Bartsch R, et al. Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis. Breast Cancer Res Treat. 2013;139:13–22. 77. Chamberlain MC. A phase II trial of intra-cerebrospinal fluid alpha interferon in the treatment of neoplastic meningitis. Cancer. 2002; 94:2675–2680. 78. Grommes C, Oxnard GR, Kris MG et al. ‘Pulsatile’ highdose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. Neuro Oncol. 2011;13:1364–1369. (Revised 12/2016) © 2017 Haymarket Media, Inc.

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DRUG MONOGRAPHS

BRAIN CANCER AFINITOR Novartis

℞

mTOR kinase inhibitor. Everolimus 2.5mg, 5mg, 7.5mg, 10mg; tabs. ℞ Also: AFINITOR DISPERZ Everolimus 2mg, 3mg, 5mg; tabs for oral susp. Indications: In adults and children with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. Adults and Children: <1yr: not recommended. Swallow tabs whole with water or use Disperz tabs administered as a suspension only. Take at the same time each day either consistently with or without food. Prepare suspension using 5mL of water in an oral syringe or 25mL of water in a drinking glass; max 10mg dose per syringe or glass. ≥1yrs: initially 4.5mg/m2 once daily. Do not combine the 2 dosage forms to achieve the desired total dose. Use therapeutic drug monitoring to guide subsequent dosing. Adjust dose at 2 week intervals as needed to achieve and maintain trough concentrations of 5–15ng/mL (see full labeling). Severe hepatic impairment: initiate at 2.5mg/m2 once daily. Concomitant strong CYP3A4/PgP inhibitors: avoid; moderate CYP3A4/PgP inhibitors: initiate at 2.5mg/m2 once daily, if CYP3A4/PgP inhibitor discontinued, after 2–3 days, return to dose used prior to initiating moderate inhibitor. Concomitant strong CYP3A4 inducers: avoid, if required, then initiate at 9mg/m2 once daily; if discontinued, then return to dose used prior to initiating strong inducer. Continue therapy until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions, or others: see full labeling. Contraindications: Allergy to other rapamycin derivatives. Warnings/Precautions: Monitor for new or worsening respiratory symptoms. Increased risk of infections; some may be severe or fatal; monitor and treat promptly if occur. Pre-existing invasive fungal infections: treat before starting. Monitor for signs of woundrelated complications. Peri-surgical period. Hepatic impairment (see Adult dose). Monitor CBCs, renal function, lipids, and blood glucose prior to starting and periodically thereafter. Avoid close contact with those who have received live vaccines. Pediatrics: complete childhood vaccination series according to ACIP guidelines prior to initiation. Elderly. Females of reproductive potential must use effective contraception during therapy and for 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Avoid live vaccines. Potentiated by strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), grapefruit or grapefruit juice;

avoid. Caution with moderate CYP3A4/PgP inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem); reduce everolimus dose if used. Antagonized by strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s Wort; avoid. Adverse reactions: Pneumonitis (interrupt, reduce dose and/or manage with corticosteroids; if severe, discontinue; may reintroduce daily dose at approx. 50% lower than previously administered), infections (discontinue if invasive systemic fungal infection develops), stomatitis (treat with non-alcoholic, non-peroxide mouthwash), diarrhea, nausea, abdominal pain, rash, fatigue, edema, fever, asthenia, cough, headache, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see full labeling). How supplied: Tabs, Disperz—28 (4 blister cards × 7 tabs)

AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free. Indications: Glioblastoma, as a single agent for patients with progressive disease following prior therapy. Adults: Give by IV infusion. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins. 10mg/kg every 2 weeks. Children: Not established. Warnings/Precautions: Risk of GI perforations, surgery and wound healing complications, and hemorrhage. Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). Do not administer if recent history of hemoptysis of ≥ ½-teaspoon of red blood. Permanently discontinue if GI perforation, tracheoesophageal fistula, any grade 4 fistula, or grade 4 venous thromboembolic event. Discontinue if fistula involving internal organ, wound healing complications, hemorrhage, severe arterial thromboembolic event (ATE), hypertensive crisis or encephalopathy, posterior reversible encephalopathy syndrome (PRES), or nephrotic syndrome occurs; suspend therapy if severe hypertension, moderate-to-severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Avoid in ovarian cancer if evidence of recto-sigmoid involvement by pelvic exam, bowel involvement on CT scan, or symptoms of bowel obstruction. History of arterial thromboembolism. Diabetes. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis; if ≥2+, do further assessment with a 24-hour urine collection.

Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy: may cause fetal harm; use effective contraception during and for 6 months after last dose. Nursing mothers: not recommended. Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation and fistulae, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, PRES, infusion reactions, ovarian failure, neutropenia, infection. How supplied: Single-use vial—1

TEMODAR Merck

℞

Alkylating agent. Temozolomide 5mg, 20mg, 100mg, 140mg, 180mg, 250mg; caps. ℞ Also: TEMODAR INJECTION Temozolomide 100mg; per vial; lyophilized pwd for IV infusion after reconstitution; contains mannitol. Indications: Newly diagnosed glioblastoma multiforme. Refractory anaplastic astrocytoma. Adults: See full labeling for monitoring and dose adjustment guidelines. IV: Infuse over 90 mins. Oral caps: Swallow whole with water; take on empty stomach at bedtime to reduce nausea, pretreat with antiemetics. Glioma: Concomitant phase, for newly diagnosed: 75mg/m2 daily for 42 days with focal radiotherapy; Maintenance phase, Cycle 1: 150mg/m2 once daily for 5 consecutive days, then 23 days off; for Cycles 2 through 6: increase to 200mg/m2 once daily for 5 consecutive days if tolerated, then 23 days off. Anaplastic astrocytoma: 150mg/m2 once daily for 5 consecutive days per 28-day treatment cycle; increase dose in subsequent cycles to 200mg/m2 for 5 consecutive days if tolerated; continue until disease progression, discontinue if minimum dose not tolerated. Children: Not established. Contraindications: Hypersensitivity to dacarbazine. Warnings/Precautions: Myelosuppression (higher risk in women or elderly, esp. in 1st cycle). Do not begin therapy unless hematology (ANC and platelets) is acceptable. Do CBC prior to treatment initiation and on Day 22 of each cycle or within 48 hours of that day; repeat weekly until recovery if ANC or platelets fall below acceptable limits. Perform LFTs at baseline, midway through Cycle 1, prior to each subsequent cycle, and 2–4wks after last dose. Screen for HBV infection prior to initiation. Monitor for signs of hepatitis or HBV reactivation during and several months after treatment; discontinue if occurs. Glioblastoma: monitor for and provide prophylaxis against P. carinii pneumonia (PCP). Severe renal or hepatic impairment. Avoid inhalation, and skin/mucous

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DRUG MONOGRAPHS

BRAIN CANCER 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

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

℞

GD2-binding monoclonal antibody. Dinutuximab 3.5mg/mL; soln for IV infusion after dilution; preservative-free. Indications: In combination with granulocytemacrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2) and 13-cis-retinoic acid (RA), for the treatment of children with highrisk neuroblastoma who achieve at least a

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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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 woundrelated complications. Peri-surgical period. Hepatic impairment (see Adult dose). Monitor CBCs, renal function, lipids, and blood glucose prior to starting and periodically thereafter. Avoid close contact with those who have received live vaccines. Pediatrics: complete childhood vaccination series according to ACIP guidelines prior to initiation. Elderly. Females of reproductive potential must use effective contraception during therapy and for 8 weeks after treatment. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Avoid live vaccines. Potentiated by strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole), grapefruit or grapefruit juice; avoid. Caution with moderate CYP3A4/PgP inhibitors (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem); reduce everolimus dose if used. Antagonized by strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital), St. John’s Wort; avoid. Adverse reactions: Pneumonitis (interrupt, reduce dose and/or manage with corticosteroids; if severe, discontinue; may reintroduce daily dose at approx. 50% lower than previously administered), infections (discontinue if invasive systemic fungal infection develops),

stomatitis (treat with non-alcoholic, non-peroxide mouthwash), diarrhea, nausea, abdominal pain, rash, fatigue, edema, fever, asthenia, cough, headache, decreased appetite; increased serum creatinine, blood glucose, lipids; decreased hemoglobin, platelets, neutrophils, serum phosphate; proteinuria, renal failure, others (see full labeling). How supplied: Tabs—28 (4 blister cards × 7 tabs)

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 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

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DRUG MONOGRAPHS

BREAST CANCER final dose. Nursing mothers: not recommended (during and for 1 month after final dose). Interactions: Antagonized by strong CYP3A4 inducers (eg, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John’s wort). Adverse reactions: Hot flashes, fatigue, arthralgia, headache, insomnia, increased sweating, nausea, increased appetite; reductions in BMD. How supplied: Tabs—30

DELATESTRYL Endo

CIII

Androgen. Testosterone enanthate 200mg/mL; IM inj; in sesame oil; contains chlorobutanol. Indications: Advancing inoperable metastatic mammary cancer in females who are 1–5 years postmenopausal. Adults: Give by deep IM inj into gluteal muscle. 200–400mg once every 2–4 weeks. Max 400mg/month. Monitor closely. Children: Not established. Contraindications: Male breast or prostate cancer. Pregnancy (Cat.X). Warnings/Precautions: Discontinue if jaundice, abnormal liver function, hypercalcemia, or edema occurs. Monitor liver function, hemoglobin, hematocrit, cholesterol, urine and serum calcium. Preexisting cardiac, renal or hepatic disease (discontinue if edema occurs). History of MI or coronary artery disease. Monitor for venous thromboembolism; discontinue if suspected. Elderly. Nursing mothers: not recommended. Interactions: May potentiate oral anticoagulants, oxyphenbutazone. May alter insulin requirements. Increased risk of edema with ACTH, corticosteroids. May affect thyroid levels. Adverse reactions: Amenorrhea, menstrual irregularities, inhibition of gonadotropin secretion, virilization; others: inj site reactions, peliosis hepatis, edema, hepatic carcinoma, nausea, jaundice, hirsutism, acne, polycythemia, headache, anxiety, depression, paresthesia, altered libido, fluid and electrolyte disturbances, suppression of clotting factors, increased serum cholesterol. How supplied: Multidose vial (5mL)—1

ESTRACE Allergan

℞

Estrogen. Estradiol 0.5mg, 1mg, 2mg+; scored tabs; +contains tartrazine. Indications: Palliative treatment of metastatic breast cancer in select patients (see literature). Adults: 10mg 3 times daily for at least 3 months. Children: Not applicable. Contraindications: Thrombophlebitis. Thromboembolic disorders. Cerebrovascular

disorders. Abnormal undiagnosed genital bleeding. Estrogen-depended neoplasias. Liver dysfunction or disease. Pregnancy (Cat. X). Warnings/Precautions: Asthma (2mg tabs). Hepatic dysfunction. Conditions aggravated by fluid retention. Cardiovascular disorders, arterial vascular disease, and risks factors (eg, hypertension, diabetes, obesity, SLE). Familial hyperlipoprotenemia. Monitor BP. Discontinue if jaundice occurs and before prolonged immobilization (eg, surgery). Nursing mothers. Adverse reactions: See literature. GI upset, headache, hypertension, edema, hypercalcemia, gallbladder or thromboembolic disease, gynecomastia, impotence, impaired glucose tolerance. How supplied: Tabs—100

EVISTA Lilly

℞

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

FASLODEX AstraZeneca Estrogen receptor antagonist. Fulvestrant 50mg/mL; soln for IM inj. Indications: Hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression following

℞

antiestrogen therapy. In combination with palbociclib: HR-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in women with disease progression after endocrine therapy. Adults: Give by IM inj slowly (1–2 mins/injection). 500mg (as two 5mL injections, one in each buttock) on Days 1, 15, 29, then once per month thereafter. For combination therapy: give with palbociclib 125mg daily with food for 21 days, followed by 7 days off; in pre/perimenopausal women: also treat with LHRH agonists. Moderate hepatic impairment: 250mg (as one 5mL injection) on Days 1, 15, 29, then once per month thereafter. Other dose modification: see full labeling. Children: Not established. Warnings/Precautions: Bleeding diatheses, thrombocytopenia, or anticoagulant use. Moderate-to-severe hepatic impairment. When administering at the dorsogluteal inj site due to proximity of the sciatic nerve. Embryo-fetal toxicity. Pregnancy: do testing within 7 days prior to initiating; use effective contraception during therapy and for 1 year after last dose. Nursing mothers: not recommended (during therapy and for 1 year after last dose). Interactions: May interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels. Adverse reactions: Inj site pain (including sciatica, neuralgia, neuropathic pain, peripheral neuropathy), nausea, vomiting, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, constipation; increased hepatic enzymes, hypersensitivity reactions. How supplied: Prefilled syringe kit (2 × 5mL)—1

FEMARA Novartis

℞

Aromatase inhibitor. Letrozole 2.5mg; tabs. Indications: In postmenopausal women: Adjuvant treatment of hormone receptor positive early breast cancer; Extended adjuvant treatment of early breast cancer after 5 years of adjuvant tamoxifen therapy; First-line treatment of hormone receptor positive or unknown, locally advanced or metastatic breast cancer; Treatment of advanced breast cancer with disease progression following antiestrogen therapy. Adults: 2.5mg once daily. Continue until tumor progression is evident. Adjuvant or extended adjuvant therapy: treat for at least 24 months (see literature). Severe hepatic impairment or cirrhosis: 2.5mg every other day.

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DRUG MONOGRAPHS

BREAST CANCER Children: Not applicable. Contraindications: Women of premenopausal endocrine status. Pregnancy (Cat.X). Warnings/Precautions: Severe renal or hepatic impairment. Monitor bone mineral density, serum cholesterol. Nursing mothers. Adverse reactions: Pain (bone, musculoskeletal, and others), hot flashes, arthralgia, flushing, asthenia, edema, headache, dizziness, hypercholesterolemia, sweating increased, GI upset, fatigue, dyspnea, cough, insomnia, hypertension, alopecia, anorexia, weight changes, hypercalcemia, pleural effusion, vertigo; thromboembolic or cardioor cerebrovascular events (rare). How supplied: Tabs—30

Fluorouracil (various)

℞

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

HALAVEN Eisai Non-taxane microtubule dynamics inhibitor. Eribulin mesylate 0.5mg/mL, soln for IV inj. Indications: Treatment of metastatic breast cancer in patients who have previously received

℞

at least two chemotherapeutic regimens for metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. Adults: Give by IV inj over 2–5mins. 1.4mg/m² on Days 1 and 8 of a 21-day cycle. Mild hepatic impairment (Child-Pugh A) or moderate-to-severe renal impairment (CrCl 15–49mL/min): 1.1mg/m² on Days 1 and 8 of a 21-day cycle. Moderate hepatic impairment (Child-Pugh B): 0.7mg/m² on Days 1 and 8 of a 21-day cycle. Hold dose for ANC <1000/mm³, platelets <75000/mm³, or grade 3 or 4 non-hematological toxicities. Delay or reduce dose according to toxicities; see full labeling. Do not re-escalate dose after it is reduced. Children: <18yrs: not established. Warnings/Precautions: Monitor CBCs prior to each dose; increase frequency of monitoring if grade 3 or 4 cytopenias develop, delay and reduce subsequent doses if febrile neutropenia or grade 4 neutropenia lasting >7 days develops. Monitor for peripheral neuropathy; withhold dose if grade 3 or 4 peripheral neuropathy develops until resolution to grade 2 or less. Congenital long QT syndrome: avoid. CHF, bradyarrhythmias, electrolyte abnormalities: monitor ECG for prolonged QT interval. Correct electrolyte abnormalities (K+, Mg+) before treatment; monitor. Severe hepatic impairment (Child-Pugh C): insufficient data. Embryo-fetal toxicity. Pregnancy (avoid). Use effective contraception during treatment and for ≥2 weeks (females) or 3.5 months (male partners) after final dose. Nursing mothers: not recommended (during and for 2 weeks after final dose). Interactions: Caution with other drugs that prolong QT interval (eg, Class IA and III antiarrhythmics); monitor. Adverse reactions: Neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, constipation, abdominal pain, pyrexia, hypokalemia, hypocalcemia; febrile neutropenia, possible QT prolongation, elevated liver enzymes. Note: Do not mix with dextrose-containing solutions. Do not administer in same line as other drugs or fluids. How supplied: Single-use vial (2mL)—1

HERCEPTIN Genentech

℞

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

with doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; or in combination with docetaxel and carboplatin). Adults: Do not substitute for or with adotrastuzumab emtansine. Give as IV infusion. Initially 4mg/kg over 90 mins, followed by 2mg/kg over 30 mins weekly; administer until tumor progression. Adjuvant treatment (administer trastuzumab weekly for 52 weeks; therapy >52 weeks: not recommended); In combination therapy: with doxorubicin and cyclophosphamide, followed by either paclitaxel or docetaxel; or with docetaxel/carboplatin: initially 4mg/kg over 90 mins, followed by 2mg/kg over 30 mins once weekly for the 1st 12 weeks (concurrently w. paclitaxel or docetaxel) or 1st 18 weeks (concurrently w. docetaxel/carboplatin). One week after the last trastuzumab weekly dose, give trastuzumab 6mg/kg over 30–90 mins every 3 weeks. Following multi-modality anthracycline based therapy: initially 8mg/kg over 90 mins, then 6mg/kg over 30–90 mins every 3 weeks. Infusion reactions or cardiomyopathy: see full labeling. Children: Not established. Warnings/Precautions: Increased risk of cardiomyopathy. Conduct cardiac assessment (eg, history, physical exam, LVEF) at baseline, every 3 months during and after therapy or every 6 months for ≥2yrs after therapy (if adjuvant); repeat LVEF at 4 week intervals if dose is withheld due to significant left ventricular cardiac dysfunction. Interrupt therapy if dyspnea or significant hypotension occurs; consider discontinuing permanently if severe infusion reactions, CHF, pulmonary toxicity, or significant left ventricular myocardial dysfunction develops. Symptomatic intrinsic lung disease. Extensive tumor involvement of the lungs. Test for HER2 protein overexpression and HER2 gene amplification using 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: Fever, diarrhea, nausea, chills, infections, increased cough, headache, CHF, insomnia, fatigue, dyspnea, rash, neutropenia, anemia, thrombocytopenia, stomatitis, mucosal 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).

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DRUG MONOGRAPHS

BREAST CANCER Note: Enroll pregnant women with breast cancer who are using trastuzumab in the MotHER-the Herceptin Pregnancy Registry (800) 690-6720. Testing considerations: HER2 protein overexpression How supplied: Vial—1 (w. diluent)

IBRANCE Pfizer

℞

Kinase inhibitor. Palbociclib 75mg, 100mg, 125mg; caps. Indications: Treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women; or fulvestrant in women with disease progression following endocrine therapy. Adults: Swallow whole. Take with food. 125mg once daily for 21 consecutive days followed by 7 days off to complete a 28-day cycle, in combination with an aromatase inhibitor or with fulvestrant 500mg on Days 1, 15, 29, and once monthly thereafter (see each drug’s full labeling for dosing/duration). In the combination with fulvestrant therapy: pre/perimenopausal women should be treated with LHRH agonists according to clinical practice standards. Dose modification for adverse reactions: First reduction: 100mg/day; Second dose reduction: 75mg/day; discontinue if <75mg/day required. Dose modification for hematologic or non-hematologic toxicities: see full labeling. Concomitant strong CYP3A inhibitors: avoid and consider alternative drug; if use necessary, reduce palbociclib dose to 75mg/day. Children: Not established. Warnings/Precautions: Monitor CBCs prior to initiation and at start of each cycle, as well as on Day 15 of first 2 cycles, and as clinically indicated. Interrupt, reduce dose, or delay starting treatment cycles if Grade 3 or 4 neutropenia develops. If maximum of Grade 1–2 neutropenia develops in first 6 cycles, monitor CBCs for subsequent cycles every 3 months, at start of each cycle, and as clinically indicated. Monitor for fever. Moderate or severe hepatic impairment. Severe renal impairment. Embryo-fetal toxicity. 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 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 ℞

Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Potentiated by strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, certain macrolides, nefazodone, grapefruit juice); avoid. Caution with mild or moderate CYP3A4 inhibitors; consider alternative agents. Antagonized by strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, dexamethasone, phenobarbital); avoid. Avoid St. John’s wort. Adverse reactions: Peripheral sensory neuropathy, fatigue, asthenia, myalgia, arthralgia, alopecia, GI upset, stomatitis, mucositis, musculoskeletal pain, palmarplantar erythrodysesthesia syndrome, anorexia, abdominal pain, nail disorder, constipation; myelosuppression (neutropenia, leukopenia, anemia, thrombocytopenia); hypersensitivity reactions; others. How supplied: Kit—1 vial (w. diluent)

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.

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,

IXEMPRA Bristol-Myers Squibb

KADCYLA Genentech

℞

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DRUG MONOGRAPHS

BREAST CANCER infusion-related or hypersensitivity reactions; if significant, slow or interrupt infusion; discontinue if life-threatening. Monitor platelets at baseline and prior to each dose; if platelets <50,000/mm3, delay dose until recovery to ≥75,000/mm3; if platelets <25,000/mm3, delay until recovery to ≥75,000/mm3 and reduce dose. If thrombocytopenia occurs <100,000/mm3 and concomitant anticoagulants, monitor closely. Monitor for neurotoxicity; withhold temporarily if Grade 3 or 4 peripheral neuropathy occurs. Test for HER2 protein overexpression or gene amplification using FDA-approved tests by labs with demonstrated proficiency. Pregnancy: avoid. Use effective contraception during therapy and for 7 months (females) or 4 months (males) after last dose. Nursing mothers: not recommended (during and for 7 months after last dose). Interactions: Avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, clarithromycin, atazanavir, indinavir, ritonavir, nefazodone, nelfinavir, saquinavir, telithromycin); if unavoidable, consider delaying therapy. Caution with concomitant anticoagulation or antiplatelet therapy; monitor closely. Adverse reactions: Fatigue, nausea, musculoskeletal pain, hemorrhage, thrombocytopenia, headache; increased transaminases, constipation, epistaxis, oligohydramnios (do fetal testing if occurs), infertility. Note: Enroll pregnant women who were exposed to Kadcyla in the MotHER Pregnancy Registry (800) 690-6720. How supplied: Single-use vial—1

KISQALI Novartis

℞

Kinase inhibitor. Ribociclib 200mg; tabs. Indications: In combination with an aromatase inhibitor, as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)negative advanced or metastatic breast cancer. Adults: Swallow whole. 600mg once daily for 21 consecutive days followed by 7 days off treatment for a complete 28-day cycle. Take preferably in the AM with letrozole 2.5mg once daily throughout the 28-day cycle (see full labeling of letrozole or for dosing/administration with other aromatase inhibitors). Dose modifications: see full labeling. Moderate and severe hepatic impairment: initially 400mg once daily. Children: Not established. Warnings/Precautions: Avoid in patients with long QT syndrome, uncontrolled or significant cardiac disease including recent MI, CHF, unstable angina and bradyarrhythmias, electrolyte abnormalities. Assess ECG prior to initiation; start therapy only if QTcF values <450 msec. Repeat ECG at Day 14 of Cycle 1, beginning of Cycle 2, and as clinically

indicated; monitor more frequently if any QTcF prolongation occurs. Monitor serum electrolytes prior to initiation, at the beginning of the first 6 cycles, and as clinically indicated; correct any abnormality before starting. Permanently discontinue if QTcF >500msec or >60msec change from baseline and associated with any of the following: Torsades de Pointes, polymorphic ventricular tachycardia, unexplained syncope, or serious arrhythmia. Perform LFTs prior to initiation; monitor every 2 weeks for first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated; monitor more frequently if Grade ≥2 abnormalities noted. Discontinue if AST/ALT >20XULN, Grade 3 (AST/ALT >5 to 20XULN) recurs, or AST/ALT >3XULN with total bilirubin >2XULN. Perform CBCs prior to initiation; monitor every 2 weeks for first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. Discontinue if any other Grade 4 toxicities occur. Embryo-fetal toxicity. Pregnancy: avoid; exclude status prior to initiation. Females of reproductive potential should use effective contraception during and for ≥3 weeks after last dose. Nursing mothers: not recommended (during and for ≥3 weeks after last dose). Interactions: Avoid concomitant with strong CYP3A inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, voriconazole); consider alternatives; if unavoidable, reduce to Kisqali 400mg once daily. Avoid grapefruit, pomegranates, pomegranate juice. Avoid concomitant with strong CYP3A inducers (eg, phenytoin, rifampin, carbamazepine, St. John’s wort); consider alternatives. Caution with concomitant CYP3A substrates with a narrow therapeutic index (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, midazolam, pimozide, quinidine, sirolimus, tacrolimus); may need to reduce these doses. Avoid concomitant with drugs known to prolong QT interval (eg, amiodarone, bepridil, chloroquine, clarithromycin, disopyramide, halofantrine, haloperidol, methadone, moxifloxacin, IV ondansetron, pimozide, procainamide, quinidine, sotalol). Adverse reactions: Neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, back pain; QT prolongation, hepatobiliary toxicity, possible infertility. How supplied: Blister pack—14, 21

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; preservativefree.

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DRUG MONOGRAPHS

BREAST CANCER Indications: In combination with trastuzumab and docetaxel: to treat patients with HER2positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease; for 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 embryofetal 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, 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

SOLTAMOX ORAL

℞

SOLUTION DARA BioSciences

Antiestrogen. Tamoxifen (as citrate) 10mg/5mL; licorice and aniseed flavors; sugar-free; contains alcohol. Indications: Treatment of metastatic breast cancer in men and women. Axillary node-positive breast cancer in postmenopausal women after surgery + irradiation. Axillary node-negative breast cancer in women after surgery + irradiation. Reduction in risk of invasive breast cancer in women with ductal carcinoma in situ (DCIS) after surgery + radiation. Reduction in breast cancer incidence in high-risk women. Adults: Treatment: 20–40mg/day; give doses >20mg in divided doses (AM and PM). Reduction of incidence in high-risk women or DCIS: 20mg once daily for 5 years. Children: Not recommended. Contraindications: For reduction in incidence in high-risk women and women with DCIS: concomitant coumarin anticoagulants, history of deep vein thrombosis or pulmonary embolism. Warnings/Precautions: See literature. Do gynecological exam at least annually. DCIS and risk reduction: consider increased risk of uterine cancer (endometrial adenocarcinoma, uterine sarcoma), stroke and pulmonary embolism. Women with advanced disease: discontinue if severe hypercalcemia occurs. Monitor blood, lipids, liver function, for thromboembolism symptoms (eg, leg swelling, unexplained shortness of breath), and for uterine changes/cancer (eg, pelvic pain or pressure); promptly investigate any abnormal vaginal bleeding. Breast cancer treatment: history of thromboembolic events. Pregnancy (Cat.D); avoid. Premenopausal: use effective non-hormonal contraception during and within 2 months of discontinuing therapy; begin therapy during menses or, if irregular menses, obtain (–) B-hCG pregnancy test first. Nursing mothers: not recommended. Interactions: See Contraindications. May potentiate oral anticoagulants; if co-administered, monitor PT. Concomitant anastrozole: not recommended. Antagonizes letrozole. Plasma levels reduced by CYP3A4 inducers (eg, rifampin, aminoglutethimide). Cytotoxic drugs increase risk of thrombotic events. Potentiated by bromocriptine. Adverse reactions: Hot flashes, vaginal discharge, altered menses, oligomenorrhea, nausea, cough, edema, fatigue, abdominal cramps, bone and tumor pain (in advanced disease), local disease flare, hypercalcemia,

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DRUG MONOGRAPHS

BREAST CANCER 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

℞

Alkylating agent. Thiotepa 15mg, 100mg; per vial; lyophilized pwd for IV, intravesical, or intracavitary administration after reconstitution and dilution. Indications: Adenocarcinoma of the breast. 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 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

℞

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

TYKERB GlaxoSmithKline

℞

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

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DRUG MONOGRAPHS

BREAST CANCER 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

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

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DRUG MONOGRAPHS

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 (Cat. D) (may cause fetal harm; use appropriate effective contraception during and for 4 months after stopping therapy), nursing mothers: not recommended. Interactions: Avoid strong CYP3A4 inducers (eg, rifampicin, St. John’s Wort). Avoid other drugs that can prolong QT interval (eg, amiodarone, disopyramide, procainamide, sotalol, dofetilide, chloroquine, clarithromycin, dolasetron, granisetron, haloperidol, pimozide, methadone, moxifloxacin). Potentiates OCT2 transporters (eg, metformin), digoxin; monitor. Adverse reactions: Diarrhea/colitis (suspend if severe), rash, acneiform dermatitis, nausea, hypertension, headache, upper respiratory tract infections, decreased appetite, abdominal pain, hypocalcemia, hypoglycemia, increased ALT; QT prolongation, torsades de pointes, sudden death, severe skin reactions (eg,

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DRUG MONOGRAPHS

ENDOCRINE CANCER toxic epidermal necrolysis, Stevens-Johnson syndrome; permanently discontinue if occurs), photosensitivity. Note: Prescribers and pharmacies must enroll in the Caprelsa REMS program by calling (800) 236-9933 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

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

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DRUG MONOGRAPHS

ENDOCRINE CANCER 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

NEXAVAR Bayer and Onyx

℞

Multikinase inhibitor. Sorafenib 200mg; tabs. Indications: Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment. Adults: Take on an empty stomach. 400mg twice daily. If toxicity occurs, may reduce dose to 400mg and 200mg 12hrs apart (either dose can come first); if second reduction is required, may reduce dose to 200mg twice daily; if third reduction is required, may reduce to 200mg once daily (see full labeling). Concomitant strong CYP3A4 inducers: consider increasing dose, monitor for toxicity. Children: Not established. Contraindications: Concomitant carboplatin/paclitaxel in patients with squamous cell lung cancer. Warnings/Precautions: Avoid in congenital long QT syndrome. Monitor patients with CHF, bradyarrhythmias, drugs known to prolong the QT interval, electrolyte abnormalities. Discontinue if severe dermatologic toxicity, hypertension, GI perforation, hemorrhage, cardiac ischemia, MI occurs. Suspend therapy before major surgery. Monitor BP weekly during the first 6 weeks and thereafter. Monitor hepatic function regularly; discontinue if transaminases significantly elevated. Severe hepatic impairment (Child-Pugh C) or on dialysis. Monitor TSH levels monthly and adjust thyroid therapy. Use effective contraception during and for 2 weeks after stopping treatment. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: See Contraindications. Avoid strong CYP3A4 inducers (eg, St. John’s Wort, dexamethasone, phenytoin, carbamazepine, rifabutin, rifampin, phenobarbital) and neomycin; may decrease sorafenib levels. May potentiate warfarin (monitor PT & INR), other drugs metabolized by UGT1A1 or UGT1A9 pathway, or substrates of CYP2B6, CYP2C8, CYP2C9, P-gp. Concomitant Class Ia and III antiarrhythmics; may prolong QT interval. Adverse reactions: Dermatologic toxicity (eg, rash, hand-foot skin reaction, alopecia, pruritus, dry skin, Stevens-Johnson syndrome, toxic epidermal necrolysis), fatigue, weight loss, diarrhea, anorexia, abdominal pain, hypertension, hemorrhage, electrolyte abnormalities; druginduced hepatitis, QT prolongation. How supplied: Tabs—120

ONIVYDE Ipsen

℞

Topoisomerase inhibitor. Irinotecan 43mg/10mL; liposomal dispersion for IV infusion after dilution. Indications: In combination with fluorouracil and leucovorin, for treatment of metastatic adenocarcincoma of the pancreas after disease progression following gemcitabine-based therapy. Limitations of use: as a single agent, not for the treatment of metastatic adenocarcinoma of the pancreas. Adults: Do not substitute for other irinotecan HCl-containing drugs. Give by IV infusion over 90 mins prior to fluorouracil and leucovorin. 70mg/m2 every 2 weeks. If homozygous UGT1A1*28 allele: initially 50mg/m2; may increase to 70mg/m2 as tolerated in subsequent cycles. If serum bilirubin >ULN: no dose recommended. Premedicate with corticosteroid and antiemetic 30 mins prior to infusion. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: Severe and lifethreatening neutropenia, neutropenic sepsis, diarrhea can occur. Monitor CBCs on Days 1 and 8 of every cycle and more frequently if indicated; withhold if ANC <1500/mm3 or neutropenic fever occurs; reduce dose in subsequent cycles for Grade 3–4 neutropenia or neutropenic fever after recovery. Bowel obstruction: do not administer. Withhold for Grade 2–4 diarrhea; initiate loperamide if late onset or atropine IV/SC (unless contraindicated) if early onset; resume at reduced dose after recovery to Grade 1. Withhold if new or progressive dyspnea, cough, and fever occurs, pending evaluation; discontinue if interstitial lung disease confirmed. Permanently discontinue if severe hypersensitivity reaction occurs. Females of reproductive potential should use effective contraception during therapy and for 1 month after final dose; males should use condoms during and for 4 months after final dose. Pregnancy. Nursing mothers: not recommended (during therapy and for 1 month after final dose). Interactions: Avoid concomitant strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, St. John’s wort) if possible; substitute non-enzyme inducing therapies at least 2 weeks before initiating irinotecan. Avoid concomitant strong CYP3A4 (eg, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) or UGT1A1 inhibitors (eg, atazanavir, gemfibrozil, indinavir) if possible; 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, 90mg, 120mg; prolonged-release soln for SC inj. Indications: Treatment of unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival. Adults: Give by deep SC inj into the superior external quadrant of the buttock. Rotate inj site. 120mg every 4 weeks. Children: Not established. Warnings/Precautions: Diabetes. Hypothyroidism. Cardiovascular disease. Hepatic or severe renal impairment. Monitor thyroid function, gallbladder, glucose. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Potentiates bromocriptine, CYP450 substrates (eg, quinidine, terfenadine), bradycardia-inducing drugs (eg, β-blockers); adjust doses. Antagonizes cyclosporine; adjust dose. May need to adjust antidiabetic agents. Adverse reactions: Diarrhea, cholelithiasis, abdominal pain, nausea, inj site reactions; gallbladder sludge, gallstones, hyperglycemia, hypoglycemia, sinus bradycardia, hypertension, anemia; rare: hypothyroidism. How supplied: Single-use pre-filled syringe—1

SUTENT Pfizer

℞

Multikinase inhibitor. Sunitinib (as malate) 12.5mg, 25mg, 37.5mg, 50mg; gelatin caps. Indications: Progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with unresectable locally advanced or metastatic disease. Adults: 37.5mg once daily continuously without a scheduled off-treatment period. May adjust dose in increments or decrements of 12.5mg. Concomitant strong CYP3A4 inhibitors (see Interactions): may reduce dose to 25mg daily. Concomitant strong CYP3A4 inducers (see Interactions): may increase to max 62.5mg daily. Children: Not established. Warnings/Precautions: Hepatotoxicity; may be severe or fatal. Monitor liver function tests before starting, during each cycle of treatment and as clinically needed; interrupt if Grade 3 or 4 hepatic adverse events occur and discontinue if no resolution; if severe liver function changes or signs/symptoms of failure, do not restart. Cardiovascular events: monitor for CHF during therapy, and LVEF at baseline and periodically; 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

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DRUG MONOGRAPHS

ENDOCRINE CANCER 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

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

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

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CANCER TREATMENT REGIMEN

GASTROINTESTINAL CANCER Anal Carcinoma Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The 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.

Localized Cancer1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

5-fluorouracil (5-FU) + mitomycin + radiotherapy2,3a

Days 1–4 and 29–32: 5-FU 1,000mg/m2/day continuous infusion Days 1 and 29: Mitomycin 10mg/m2 IV bolus (maximum 20mg per course), plus Concurrent radiotherapy. OR Days 1–4 and 29–32: 5-FU 1,000mg/m2/day continuous IV infusion Day 1: Mitomycin 12mg/m2 (capped at 20mg), plus Concurrent radiotherapy.

Capecitabine + mitomycin + radiotherapy4,5

Capecitabine 825mg/m2 orally twice daily, Monday–Friday, on each day that radiotherapy is given, throughout the duration of radiotherapy (typically 28 treatment days), plus Days 1 and 29: Mitomycin 10mg/m2 IV bolus, plus Concurrent radiotherapy. OR Days 1–5: Capecitabine 825mg/m2 orally twice daily weekly for 6 weeks, plus Day 1: Mitomycin 12mg/m2 IV bolus, plus Concurrent radiotherapy.

5-FU + cisplatin6 (category 2B)

Days 1–5: 5-FU 1,000mg/m2/day continuous IV infusion Day 2: Cisplatin 100mg/m2 IV Repeat cycle every 4 weeks, plus Concurrent radiotherapy.

Metastatic Cancer1 5-FU + cisplatin6

Days 1–5: 5-FU 1,000mg/m2/day continuous infusion Day 2: Cisplatin 100mg/m2 IV over 1 hour. Repeat cycle every 4 weeks.

OTE: Patients with anal cancer as the first manifestation of HIV may be treated with the same regimen as non-HIV patients. Patients with active HIV/AIDS-related complications or a history of N complications (eg, malignancies, opportunistic infections) may not tolerate full-dose therapy or may not tolerate mitomycin and require dosage adjustment or treatment without mitomycin. a For radiotherapy dosing, please see NCCN Anal Carcinoma Guidelines v 2.2017 “Principles of radiation therapy.”

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Anal Carcinoma. v 2.2017. Available at: http://www.nccn.org/ professionals/physician_gls/pdf/anal.pdf. Accessed June 1, 2017. 2. Ajani JA, Winter KA, Gunderson LL, et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008;299(16):1914–1921. 3. James RD, Glynne-Jones R, Meadows HM, et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2×2 factorial trial. Lancet Oncol. 2013;14(6):516–524.

4. Goodman KA, Rothenstein D, Cambridge L, et al. Capecitabine plus mitomycin in patients undergoing definitive chemoradiation for anal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2014;90(1):S32–S33. 5. Thind G, Johal B, Follwell M, Kennecke HF. Chemoradiation with capecitabine and mitomycin-C for stage I-III anal squamous cell carcinoma. Radiation Oncology. 2014;9:124. 6. Faivre C, Rougier P, Ducreux M, et al. 5-fluorouracil and cisplatin combination chemotherapy for metastatic squamous-cell anal cancer. Bull Cancer. 1999;86(10):861–865.

26 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

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 gastroesophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. In combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), for the treatment of metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Adults: Give by IV infusion over 60 mins. Premedicate with IV histamine H1-antagonist (eg, diphenhydramine) prior to each infusion; or with dexamethasone and acetaminophen in those who have experienced Grade 1 or 2 infusion reaction. Gastric cancer: 8mg/kg every 2 weeks. When given in combination: administer prior to paclitaxel. mCRC: 8mg/kg every 2 weeks prior to FOLFIRI. Continue until disease progression or unacceptable toxicity. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: Increased risk of hemorrhage; permanently discontinue if severe bleeding occurs. Control hypertension prior to initiating. Monitor blood pressure every 2 weeks or more frequently as indicated; if severe hypertension develops, temporarily suspend until medically controlled. Monitor for infusion-related reactions during therapy. Have emergency resuscitative equipment available. Permanently discontinue if severe arterial thromboembolic events, severe uncontrolled hypertension (despite antihypertensives), hypertensive crisis or encephalopathy, Grade 3 or 4 infusion-related reactions, urine protein >3g/24hrs, nephrotic syndrome, or GI perforation occurs. Impaired wound healing: withhold Cyramza prior to surgery. Clinical deterioration in patients with Child-Pugh B or C cirrhosis (eg, new or worsening encephalopathy, ascites, hepatorenal syndrome). Discontinue if reversible

posterior leukoencephalopathy syndrome develops. Monitor proteinuria by urine dipstick and/or urinary protein creatinine ratio. Monitor thyroid function. Pregnancy: avoid. Use effective contraception during therapy and for ≥3 months after last ramucirumab dose. Nursing mothers: not recommended. Adverse reactions: Hypertension, diarrhea, headache, fatigue, asthenia, hyponatremia, anemia, intestinal obstruction, neutropenia, epistaxis, stomatitis/mucosal inflammation, rash, decreased appetite; arterial thromboembolic events, proteinuria, GI perforation, infusionrelated reactions. How supplied: Single-dose vial (10mL, 50mL)—1

ELOXATIN Sanofi Aventis

℞

Alkylating agent (organoplatinum complex). Oxaliplatin 5mg/mL; soln for IV infusion after dilution; preservative-free. Indications: Adjuvant treatment for Stage III colon cancer in patients who have undergone complete resection of the primary tumor (in combination with infusional 5-FU/LV). Treatment of advanced colorectal cancer (in combination with infusional 5-FU/LV). Adults: See full labeling. Premedicate with antiemetics. Give by IV infusion every two weeks for a total of 6 months (12 cycles) for adjuvant use or until disease progression or unacceptable toxicity for advanced disease. Day 1: 85mg/m2 + leucovorin, followed by 5-FU. Day 2: Leucovorin followed by 5-FU. Severe renal impairment: initially 65mg/m2. Neuropathy, other toxicities: see full labeling for dose adjustments. Children: Not established. Contraindications: Known allergy to other platinum compounds. Warnings/Precautions: Monitor for allergic reactions; discontinue if occurs; do not rechallenge. Have epinephrine, corticosteroids, antihistamines available during infusion. Monitor for neuropathy; reduce dose or discontinue if needed. Severe neutropenia: delay therapy until neutrophils ≥1.5 × 109/L; withhold for sepsis or septic shock; reduce dose after recovery. Monitor WBCs with differential, hemogloblin, platelets, blood chemistries (including ALT, AST, bilirubin, creatinine) before each cycle. Discontinue if interstitial lung disease or pulmonary fibrosis is suspected. Patients with CHF, bradyarrhythmias, concomitant drugs known to prolong the QT interval, and electrolyte abnormalities: monitor ECG. Correct hypokalemia or hypomagnesemia prior to

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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.

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER Warnings/Precautions: Hepatic or renal impairment. Monitor weight and for fluid retention regularly; CBCs weekly for 1st month, bi-weekly for 2nd month, then periodically (eg, every 2–3 months); liver function at baseline then monthly or as needed; GI symptoms at baseline. Cardiovascular disease or risk factors; monitor. Immunosuppression and potential toxicities (liver, kidney, cardiac) from long-term use. Monitor for tumor lysis syndrome; correct clinically significant dehydration and treat high uric acid levels before initiating therapy. Monitor growth in children. Possible cardiogenic shock/LV dysfunction in conditions with high eosinophil levels (eg, HES/CEL, MDS/MPD, ASM); consider concomitant systemic steroid prophylaxis (1–2mg/kg) for 1 or 2 wks if abnormal ECG or serum troponin. Monitor TSH levels in thyroidectomy patients undergoing levothyroxine replacement. Embryo-fetal toxicity. Pregnancy (avoid); exclude status prior to initiation. Females of reproductive potential should use highly effective contraception during treatment and for 14 days after cessation. Nursing mothers: not recommended (during and for 1 month after final dose). Interactions: Avoid grapefruit juice. Potentiated by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by strong CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin, rifabutin, rifampicin); consider alternatives. May potentiate drugs metabolized by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain statins, sirolimus, tacrolimus) or CYP2C9 (use heparin instead of warfarin). Caution with concomitant CYP2D6 substrates that have a narrow therapeutic window. Adverse reactions: Edema (may be severe), nausea, vomiting, musculoskeletal pain, diarrhea, muscle cramps, rash (may be severe; eg, erythema multiforme, 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 adverse reaction recurs, for any life-threatening

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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; preservativefree. 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 irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. Adults: Take within 1 hour after completion of AM & PM meals. Initially 35mg/m2 twice daily on Days 1–5 and 8–12 of each 28-day cycle until disease progression or unacceptable toxicity; max 80mg per dose (based on trifluridine component). Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: Obtain CBC prior to and on Day 15 of each cycle, and as clinically indicated. Do not initiate cycle until ANC ≥1,500/mm3 or febrile neutropenia is resolved, platelets ≥75,000/mm3 or Grade 3/4 nonhematological adverse reactions resolved to Grade 0/1. Withhold dose if ANC <500/mm3 or febrile neutropenia, platelets <50,000/mm3, or Grade 3/4 non-hematological adverse reactions occur; upon recovery, resume at a reduced dose (see full labeling). Moderate or severe hepatic impairment: do not initiate. Moderate renal impairment: may require dose modification; severe (CrCl <30mL/min) or ESRD: not studied. Elderly. Pregnancy. Females of reproductive potential must use effective contraception during treatment; males must use condoms during and for ≥3 months after final dose. Nursing mothers: not recommended (during treatment and for 1 day after final dose). Adverse reactions: Anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, pyrexia. How supplied: Tabs—20, 40, 60

NEXAVAR Bayer and Onyx

℞

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

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

STIVARGA Bayer

℞

Kinase inhibitor. Regorafenib 40mg; tabs. Indications: Metastatic colorectal cancer in patients who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecanbased chemotherapy, an anti-VEGF therapy, and, if RAS wild type, an anti-EGFR therapy. Locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) in patients who have been previously treated with imatinib mesylate or sunitinib malate. Hepatocellular carcinoma (HCC) in patients previously treated with sorafenib. Adults: Swallow whole with water after a lowfat meal (contains <600 calories and <30% fat). 160mg once daily for the first 21 days of each 28-day cycle; until disease progression or unacceptable toxicity. Dose modifications: reduce by 40mg increments (see full labeling). Children: <18yrs: not established. Warnings/Precautions: Risk of severe liver injury (may be fatal). Obtain LFTs before starting and at least every 2 weeks during first 2 months of treatment; interrupt and reduce or discontinue if persistent hepatotoxicity or hepatocellular necrosis occurs. Severe hepatic impairment: not recommended. Increased risk of infections; withhold if Grade 3/4 occurs or infection of any grade worsens; resume when resolved. Permanently discontinue if severe or life-threatening hemorrhage occurs. Interrupt and reduce or permanently discontinue if dermatological toxicity occurs (eg, hand-foot skin reaction [a.k.a. palmar-plantar erythrodysesthesia],

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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. Embryo-fetal toxicity. Females and males of reproductive potential should use effective contraception during treatment and up to 2 months after completion. Pregnancy. Nursing mothers: not recommended (during and for 2 weeks after final dose). Interactions: Potentiated by strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, voriconazole); avoid. Antagonized by strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, St. John’s Wort); avoid. Potentiates BCRP substrates (eg, methotrexate, fluvastatin, atorvastatin); monitor closely. Monitor INR levels with concomitant warfarin. Adverse reactions: Asthenia/fatigue, decreased appetite and food intake, 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, 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

Read the latest oncology headlines, including practice-changing research and practical commentary from experts by visiting CancerTherapyAdvisor.com.

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DRUG MONOGRAPHS

GASTROINTESTINAL CANCER 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; preservative-free. Indications: In combination with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) for patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen. Adults: Start ziv-aflibercept prior to any component of the FOLFIRI regimen on treatment day. Give 4mg/kg as an IV infusion over 1hr every 2 weeks; continue until disease progression or unacceptable toxicity. For recurrent or severe hypertension, suspend until controlled. Upon resumption, permanently reduce to 2mg/kg. For recurrent proteinuria, suspend until proteinuria <2g per 24hrs, then permanently reduce to 2mg/kg.

Children: Not established. Warnings/Precautions: Increased risk of hemorrhage; monitor for signs/symptoms. Do not start in patients with severe hemorrhage; discontinue if develops. Monitor for GI perforation, fistula formation, compromised wound healing; discontinue if occurs. Suspend therapy at least 4 weeks prior to elective surgery; do not resume for at least 4 weeks following major surgery and until wound is fully healed. Monitor BP every 2 weeks and treat appropriately if hypertension occurs; temporarily suspend until controlled; discontinue if hypertensive crisis/encephalopathy occurs. Discontinue if arterial thromboembolic events (eg, transient ischemic attack, cerebrovascular accident, angina pectoris) occur. Monitor for proteinuria; suspend if proteinuria ≥2g per 24hrs; discontinue if nephrotic syndrome or thrombotic microangiopathy occurs. Monitor CBC with differential at baseline and prior to start of each cycle; delay until neutrophils ≥1.5x109/L. Risk of severe diarrhea and dehydration esp. in elderly (monitor). Discontinue if reversible posterior leukoencephalopathy syndrome occurs. Pregnancy (Cat. C). Use effective contraception during and up to 3 months after the last dose. Nursing mothers: not recommended. Adverse reactions: Leukopenia, diarrhea, neutropenia, proteinuria, AST/ALT increased, stomatitis, fatigue, thrombocytopenia, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, headache. How supplied: Single-use vials (100mg/4mL)—1, 3; (200mg/8mL)—1

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

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

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CANCER TREATMENT REGIMEN

GENITOURINARY CANCER Bladder Cancer Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The 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.

Perioperative Chemotherapy (Neoadjuvant or Adjuvant)1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

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

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

Gemcitabine + cisplatin4–6

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

Cisplatin + methotrexate + vinblastine (CMV)7

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

Principles of Chemotherapy Management • For patients who are not candidates for cisplatin, there are no data to support a recommendation for perioperative chemotherapy. • Randomized trials and meta-analyses show a survival benefit for cisplatin-based neoadjuvant chemotherapy (3 or 4 cycles) in patients with muscleinvasive bladder cancer.2,8,9 • Meta-analysis suggests a survival benefit to adjuvant therapy for pathologic T3, T4, or N+ disease at cystectomy.9 • Neoadjuvant chemotherapy is preferred over adjuvant-based chemotherapy on a higher level of evidence data. • DDMVAC is preferred over standard MVAC based on category I evidence showing DDMVAC to be better tolerated and more effective than conventional MVAC in advanced disease.3,10 Based on these data, the traditional dose and schedule for MVAC is no longer recommended. • Perioperative gemcitabine and cisplatin is a reasonable alternative to DDMVAC based on category I evidence showing equivalence to conventional MVAC in the setting of advanced disease.5,6 • For gemcitabine/cisplatin, both 21- and 28-day regimens are acceptable. Better dose compliance may be achieved with fewer delays in dosing using the 21-day schedule.11 • Neoadjuvant chemotherapy may be considered for select patients with upper tract urothelial carcinoma, particularly for higher stage and/or grade tumors, as renal function will decline after nephroureterectomy and may preclude adjuvant therapy. • Carboplatin should not be substituted for cisplatin in the perioperative setting. —— For patients with borderline renal function or minimal dysfunction, a split-dose administration of cisplatin may be considered (such as 35mg/m2 on days 1 and 2 or days 1 and 8; category 2B). Although safer, the relative efficacy of the cisplatin-containing combination administered with such modifications remains undefined. • For patients with borderline renal function, estimate glomerular filtration rate to assess eligibility for cisplatin.

First-line Chemotherapy for Locally Advanced or Metastatic Disease 1,a Cisplatin Eligible (Standard Regimens) Gemcitabine + cisplatin (Category 1)6

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

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CANCER TREATMENT REGIMEN

GENITOURINARY CANCER Bladder Cancer Treatment Regimens First-line Chemotherapy for Locally Advanced or Metastatic Disease 1,a (continued) REGIMEN

DOSING

Cisplatin Eligible (Standard Regimens) (continued) DDMVAC with growth factor support (Category 1)3,10

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

Principles of Chemotherapy Management • The presence of both visceral metastases and Eastern Cooperative Oncology Group performance score ≥ 2 strongly predict poor outcome with chemotherapy. Patients without these adverse prognostic factors have the greatest benefit from chemotherapy. • For most patients, the risks of adding paclitaxel to gemcitabine and cisplatin outweigh the limited benefit seen in the randomized trial.18 • A substantial proportion of patients cannot receive cisplatin-based chemotherapy due to renal impairment or other comorbidities. —— Participation in clinical trials of new or more tolerable therapy is recommended. Cisplatin Ineligible (Alternative Regimens) Gemcitabine15

Gemcitabine 1200mg/m2 administered weekly x3 on a 4-week cycle.

Gemcitabine + paclitaxel16

Gemcitabine 2500mg/m2 over 30 minutes, plus paclitaxel 150mg/m2 over 3 hours given every 2 weeks.

Ifosfamide + doxorubicin + gemcitabine17 (For patients with good kidney function and good performance status)

Days 1–4: Ifosfamide 1500mg/m2 infused over 3 hours daily, plus mesna 225mg/m2 over 15 minutes at hours 0, 3, 7, and 11 Day 3: Doxorubicin 45mg/m2 over 15 minutes via peripheral IV or up to 12–18 hours via central line on day 3 only Days 2 and 4: Gemcitabine 150mg/m2 over 30 minutes.

Subsequent Systemic Therapy for Locally Advanced or Metastatic Disease1,a Standard Regimens Pembrolizumab (Category 1)19

Pembrolizumab 200mg every 3 weeks.

Atezolizumab20

Atezolizumab 1200mg IV infusion over 60 minutes every 3 weeks.

Nivolumab21

Nivolumab 3mg/kg IV every 2 weeks.

Durvalumab22

Durvalumab 10mg/kg once every 2 weeks up to 12 months, unacceptable toxicity, or confirmed progressive disease.

Avelumab23,24

Avelumab 10mg/kg IV over 1 hour every 2 weeks.

Paclitaxel or docetaxel25,26

Paclitaxel 80mg/m2 every week OR Docetaxel 100mg/m2 over 1 hour every 21 days.

Gemcitabine15

Gemcitabine 1200mg/m2 administered weekly ×3 on a 4-week cycle.

Pemetrexed27

Day 1: Pemetrexed 500mg/m2 IV every 21 days, plus vitamin B12, folic acid, and dexamethasone prophylaxis.

34 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

GENITOURINARY CANCER Subsequent Systemic Therapy for Locally Advanced or Metastatic Disease1,a (continued) Alternate Regimens for Select Patients Nab-paclitaxel28

Nab-paclitaxel at 260mg/m2 IV every 3 weeks.

Ifosfamide29

Ifosfamide to 1,500mg/m2 IV with mesna 750 mg/m2 IV for 5 days every 3 weeks, with doses modified for hematologic, renal, and central nervous system toxicity.

Methotrexate

Follow usual protocols.

Ifosfamide + doxorubicin + gemcitabine17

Gemcitabine + paclitaxel16

Gemcitabine 2500mg/m2 over 30 minutes, plus paclitaxel 150mg/m2 over 3 hours given every 2 weeks.

Gemcitabine + cisplatin5

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

DDMVAC3

Day 1: Methotrexate 30mg/m2 IV Day 2: Vinblastine 3mg/m2 IV, plus doxorubicin 30mg/m2 IV, plus cisplatin 70mg/m2 IV Repeat every 2 weeks for 3–4 cycles.

First-line Radiosensitizing Chemotherapy Regimens1,a,b First-line Standard Chemotherapy Regimens (Doublet Preferred) Cisplatinc + 5-FU30

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

Cisplatinc + paclitaxel30,31

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

5-FU + mitomycin32

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

Alternate Regimens Cisplatinc alone33

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

Low-dose gemcitabine (Category 2B)34,35

Gemcitabine 75mg/m2 IV weekly given concurrently with radiotherapy.

Radiosensitizing Chemotherapy With Conventionally Fractionated Radiation1,a,e • Cisplatinc • Taxane (docetaxel or paclitaxel; Category 2B)

• 5-FU ± mitomycin (both Category 2B) • Capecitabine (Category 3)

• Low-dose gemcitabine (Category 2B)

c d

Participation in clinical trials of new agents is recommended. For bladder-preserving chemoradiation following a maximal transurethral resection of bladder tumor. Carboplatin in not an effective radiation sensitizer and should not be substituted for cisplatin with radiation. On days 1, 3, 15, and 17, radiation was given immediately following the chemotherapy using twice-a-day 3 Gy per fraction cores to the pelvis for a total radiation dose of 24 Gy (with at least a 4-hour interfraction interval). e For palliation of metastases or for pelvic recurrence after cystectomy. f Upon complete or near complete response, patients received consolidation chemoradiation consisting of 1.5 Gy pelvic radiotherapy twice a day for 8 days to 24 Gy (total dose: 64.3 Gy to the tumor and 44.8 Gy to the pelvic lymph nodes) and paclitaxel 50mg/m2 days 1 and 8 and cisplatin 15mg/m2 on days 1, 2, 8, and 9. a

continued

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CANCER TREATMENT REGIMEN

GENITOURINARY CANCER Bladder Cancer Treatment Regimens References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Bladder Cancer. v 5.2017. Available at: http://www.nccn.org/professionals/ physician_gls/PDF/bladder.pdf. Accessed February 19, 2016. 2. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349(9):859–866. 3. Sternberg CN, de Mulder PH, Schornagel JH, et al. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for R esearch and Treatment of Cancer Protocol no. 30924. J Clin Oncol. 2001;19(10):2638–2646. 4. Dash A, Pettus JA, Herr HW, et al. A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer. 2008;113(9):2471–2477. 5. von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18(17):3068–3077. 6. von der Maase H, Sengelov L, Roberts JT, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602–4608. 7. Griffiths G, Hall R, Sylvester R, et al. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscleinvasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011;29(16): 2171–2177. 8. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol. 2005;48(2):202–205. 9. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration.Adjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis of individual patient data. Eur Urol. 2005;48(2):189–199. 10. Sternberg CN, de Mulder P, Schornagel JH, et al. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006;42(1):50–54. 11. Soto Parra H, Cavina R, Latteri F, et al. Three-week versus four-week schedule of cisplatin and gemcitabine: results of a randomized phase II study. Ann Oncol. 2002;13(7): 1080–1086. 12. De Santis M, Bellmunt J, Mead G, et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012; 30(2):191–199. 13. Balar AV, Galsky MD, Rosenberg JE, et al; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67–76. 14. Balar AV, Castellano DE, O’Donnell PH, et al. Pembrolizumab as first-line therapy in cisplatin-ineligible advanced urothelial cancer: results from the total KEYNOTE-052 study population. J Clin Oncol. 2017;35(suppl 6):284–285. 15. Stadler WM, Kuzel T, Roth B, Raghavan D, Dorr FA. Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer. J Clin Oncol. 1997;15(11):3394–3398. 16. Calabrò F, Lorusso V, Rosati G, et al. Gemcitabine and paclitaxel every 2 weeks in patients with previously untreated urothelial carcinoma. Cancer. 2009;115(12):2652–2659. 17. Siefker-Radtke A, Dinney C, Shen Y, et al. A phase II clinical trial of sequential neoadjuvant chemotherapy with ifosfamide, doxorubicin, and gemcitabine, followed by

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35.

cisplatin, gemcitabine, and ifosfamide in locally advanced urothelial cancer: final results. Cancer. 2013;119(3):10.1002/cncr.27751. Bellmunt J, von der Maase H, Mead GM, et al. Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC Intergroup Study 30987. J Clin Oncol. 2012;30(10):1107–1113. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376 (11):1015–1026. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387(10031):1909–1920. Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18(3):312–322. Powles T, O’Donnell PH, Massard C, et al. Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma. J Clin Oncol. 2017;35(suppl 6):286. Apolo AB, Infante JR, Balmanoukian A, et al. Avelumab, an anti–programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter, phase 1b study. J Clin Oncol. 2017 Apr 4: JCO2016716795. doi: 10.1200/JCO.2016.71.6795. Patel MR, Ellerton JA, Infante JR, et al. Avelumab in patients with metastatic urothelial carcinoma: Pooled results from two cohorts of the phase 1b JAVELIN Solid Tumor trial. J Clin Oncol. 2017;35(suppl 6):330. Sideris S, Aoun F, Zanaty M, et al. Efficacy of weekly paclitaxel treatment as a single agent chemotherapy following first-line cisplatin treatment in urothelial bladder cancer. Mol Clin Oncol. 2016;4(6):1063–1067. doi:10.3892/mco.2016.821. McCaffrey JA, Hilton S, Mazumdar M, et al. Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol. 1997;15(5):1853–1857. Sweeney CJ, Roth BJ, Kabbinavar FF, et al. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006;24(21):3451–3457. Ko YJ, Canil CM, Mukherjee SD, et al. Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study. Lancet Oncol. 2013;14(8):769–776. Witte RS, Elson P, Bono B, et al. Eastern Cooperative Oncology Group phase II trial of ifosfamide in the treatment of previously treated advanced urothelial carcinoma. J Clin Oncol. 1997;15(2):589–593. Mitin T, Hunt D, Shipley WU, et al. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013;14(9):863–872. Efstathiou JA, Spiegel DY, Shipley WU, et al. Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol. 2012;61(4):705–711. James ND, Hussain SA, Hall E, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012;366:1477–1488. Coppin CM, Gospodarowicz MK, James K, et al. Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. J Clin Oncol. 1996; 14:2901–2907. Kent E, Sandler H, Montie J, et al. Combined-modality therapy with gemcitabine and radiotherapy as a bladder preservation strategy: results of a phase I trial. J Clin Oncol. 2004;22(13):2540–2545. Choudhury A, Swindell R, Logue JP, et al. Phase II study of conformal hypofractionated radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer. J Clin Oncol. 2011;29(6):733–738. (Revised 7/2017) © 2017 by Haymarket Media, Inc.

36 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

GENITOURINARY CANCER Prostate Cancer Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The 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.

Castration-recurrent Prostate Cancer1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

First-line Therapy1 No Visceral Metastases Enzalutamide (Category 1)2-4

Enzalutamide 160mg (four 40mg capsules) orally daily with or without food; prednisone can be given concurrently but is not required.

Abiraterone acetate + prednisone (Category 1)5-8

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

Docetaxel + prednisone (Category 1)9,10

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

Radium-223 (for symptomatic bone metastases) (Category 1)11,12

Radium-223 50kBq/kg every 4 weeks for 6 injections.

Visceral Metastases Docetaxel + prednisone (Category 1)9,10

Day 1: Docetaxel 75mg/m2 IV once every 3 weeks + prednisone 5mg orally twice daily. Repeat for up to 10 cycles if tolerated. Addition of estramustine to this regimen is not recommended.

Enzalutamide (Category 1)2-4

Enzalutamide 160mg (four 40mg capsules) orally daily with or without food; prednisone can be given concurrently but is not required.

Abiraterone acetate + prednisone5-8

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

Mitoxantrone + prednisone

Day 1: Mitoxantrone 12–14mg/m2 IV every 3 weeks + prednisone 10mg orally daily or 5mg twice daily. Repeat for up to 10 cycles if tolerated.

9,10

Subsequent Therapy1 No Visceral Metastases Prior Therapy Enzalutamide/Abiraterone Docetaxel + prednisone (Category 1)9,10

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

Abiraterone acetate + prednisone5-8

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

Enzalutamide

Enzalutamide 160mg (four 40mg capsules) orally daily with or without food; prednisone can be given concurrently but is not required.

2-4

Radium-223 (for symptomatic bone metastases) (Category 1)11,12

Radium-223 50kBq/kg every 4 weeks for 6 injections.

Sipuleucel-T (if no or minimal symptoms, no liver metastases, life expectancy >6 months, and an ECOG score of 0–1)13,14*

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

continued

CancerTherapyAdvisor.com | SEPTEMBER/OCTOBER 2017 | CANCER THERAPY ADVISOR 37

CANCER TREATMENT REGIMEN

GENITOURINARY CANCER Prostate Cancer Treatment Regimens Castration-recurrent Prostate Cancer1 (continued) REGIMEN

DOSING

Subsequent Therapy (continued) 1

No Visceral Metastases (continued) Prior Therapy Docetaxel Enzalutamide (Category 1)2-4

Enzalutamide 160mg (four 40mg capsules) orally daily with or without food; prednisone can be given concurrently but is not required.

Abiraterone acetate + prednisone (Category 1)5-8

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

Radium-223 (for symptomatic bone metastases) (Category 1)11,12

Radium-223 50kBq/kg every 4 weeks for 6 injections.

Cabazitaxel + prednisone (Category 1)15-17

Day 1: Cabazitaxel 25mg/m2 IV every 3 weeks + prednisone 10mg orally daily or 5mg twice daily throughout cabazitaxel treatment (starting doses are reduced by 5 mg/m2 and 10 mg/m2 for mild and moderate hepatic impairment, respectively). Repeat for up to 10 cycles if tolerated.

Sipuleucel-T (if no or minimal symptoms, no liver metastases, life expectancy >6 months, and an ECOG score of 0–1)13, 14*

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

Docetaxel rechallenge9,10

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

Mitoxantrone + prednisone9,10

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

Visceral Metastases Prior Therapy Enzalutamide/Abiraterone Docetaxel + prednisone (Category 1)9,10

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

Abiraterone acetate + prednisone5-8

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

Enzalutamide2-4

Enzalutamide 160mg (four 40mg capsules) orally daily with or without food; prednisone can be given concurrently but is not required.

Prior Therapy Docetaxel Enzalutamide (Category 1)2-4

Enzalutamide 160mg (four 40mg capsules) orally daily with or without food; prednisone can be given concurrently but is not required.

Abiraterone acetate + prednisone (Category 1)5-8

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

Cabazitaxel + prednisone (Category 1)15-17

Docetaxel rechallenge9,10

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

Mitoxantrone + prednisone9,10

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

38 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

GENITOURINARY CANCER Castration-Recurrent Prostate Cancer1 (continued) General treatment notes: • Encourage men with advanced prostate cancer to participate in clinical trials and refer early to a medical oncologist. • Reserve systemic chemotherapy for men with castration-resistant metastatic prostate cancer except when enrolled in a clinical trial. • Secondary hormone therapy (eg, antiandrogens, antiandrogen withdrawal, ketoconazole, corticosteroids) is also an option for patients with castration-resistant prostate cancer. • Many variables should be considered when tailoring prostate cancer therapy for the individual patient, including adjusted life expectancy, disease characteristics, predicated outcomes, and patient preferences. • All prostate cancer patients should receive best supportive care throughout treatment. *The maximum dosing interval has not been established.13

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Prostate Cancer. v 2.2017. Available at: http://www.nccn.org/professionals/ physician_gls/pdf/prostate.pdf. Accessed May 9, 2017. 2. Xtandi [prescribing information]. Northbrook, IL: Astellas Pharma US, Inc.; 2016. 3. Scher HI, Fizazi K, Saad F, et al; AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367(13):1187–1197. 4. Beer TM, Armstrong AJ, Rathkopf DE, et al; PREVAIL Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371(5):424–433. 5. Zytiga [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; 2017. 6. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995–2005. 7. Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COUAA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13(10):983–992. 8. Logothetis CJ, Basch E, Molina A, et al. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 2012;13(12):1210–1217.

9. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–1512. 10. Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 2008;26:242–245. 11. Xofigo [prescribing information]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2016. 12. Parker C, Nilsson S, Heinrich D, et al; ALSYMPCA Investigators. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013(3);369:213–223. 13. Provenge [prescribing information]. Seattle, WA: Dandreon Corp.; 2014. 14. Kantoff PW, Higano CS, Shore ND, et al; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–422. 15. Jevtana [prescribing information] Bridgewater, NJ: sanofi-aventis U.S. LLC; 2016. 16. de Bono JS, Oudard S, Ozguroglu M, et al; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010;376(9747):1147–1154. 17. Bahl A, Oudard S, Tombal B, et al; TROPIC Investigators. Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial. Ann Oncol. 2013;24(9):2402–2408.

Prostate 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 prostate cancer. Visit CancerTherapyAdvisor.com/Prostate to gain access to the following and more: • Articles on the latest news in prostate cancer written by experts • Prostate 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 prostate cancer management

CancerTherapyAdvisor.com | SEPTEMBER/OCTOBER 2017 | CANCER THERAPY ADVISOR 39

CANCER TREATMENT REGIMEN

GENITOURINARY CANCER Renal Cell Carcinoma Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced 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.

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

First-line Therapy for Patients with Predominantly Clear Cell Histology1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

Pazopanib (Category 1; preferred)2,3

Pazopanib 800mg orally once daily without food.

Sunitinib (Category 1; preferred)4,5

Sunitinib 50mg orally daily with or without food for 4 weeks, followed by 2 weeks off.

Bevacizumab + IFN-α (Category 1)6-8

Bevacizumab 10mg/kg IV every 2 weeks + IFN-α.

Temsirolimus (Category 1: poor-prognosis patients; Category 2B: selected patients of other risk groups)9,10

Temsirolimus 25mg IV over 30–60 minutes once weekly until disease progression or unacceptable toxicity.

Axitinib11,12a

Axitinib 5mg orally every 12 hours.

High-dose IL-2 (for selected patients with excellent performance status and normal organ function)13,14b

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

Sorafenib (for selected patients)15c

Sorafenib 400mg orally twice daily without food.

Subsequent Therapy for Patients with Predominantly Clear Cell Carcinoma1 Cabozantinib (Category 1; preferred)16d

Cabozantinib 60mg orally once daily without food until disease progression or unacceptable toxicity.

Nivolumab (Category 1; preferred)17,18d

Nivolumab 240mg IV every 2 weeks until disease progression or unacceptable toxicity.

Axitinib (Category 1)11,12a

Axitinib 5mg orally every 12 hours.

Lenvatinib + everolimus (Category 1)19

Lenvatinib 18 mg orally once daily + everolimus 5 mg orally once daily with or without food until disease progression or unacceptable toxicity.

40 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

CANCER TREATMENT REGIMEN

GENITOURINARY CANCER Subsequent Therapy for Patients with Predominantly Clear Cell Carcinoma1 (continued) REGIMEN

DOSING

Everolimus20,21

Everolimus 10mg orally once daily with or without food.

Pazopanib2,3

Pazopanib 800mg orally once daily without food.

Sorafenib22-25

Sorafenib 400mg orally twice daily without food.

Sunitinib4,26,27

Sunitinib 50mg orally daily with or without food for 4 weeks, followed by 2 weeks off.

Bevacizumab (Category 2B)28

Bevacizumab 10mg/kg IV every 2 weeks.

High-dose IL-2 (for selected patients) (Category 2B)13,14b

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

Temsirolimus (Category 2B)29,30

Temsirolimus 25mg IV over 30-60 minutes weekly until disease progression or unacceptable toxicity.

Systemic Therapy for Patients with Non-clear Cell Histology1 Sunitinib (preferred)4,26,27

Sunitinib 50mg orally daily with or without food for 4 weeks, followed by 2 weeks off.

Axitinib11,12a

Axitinib 5mg orally every 12 hours.

Bevacizumab28

Bevacizumab 10mg/kg IV every 2 weeks.

Cabozantinib16d

Cabozantinib 60mg orally once daily without food until disease progression or unacceptable toxicity.

Erlotinib31e

Erlotinib 150mg orally once daily without food.

Everolimus20,21

Everolimus 10mg orally once daily with or without food.

Lenvatinib + everolimus19

Lenvatinib 18 mg orally once daily + everolimus 5 mg orally once daily with or without food until disease progression or unacceptable toxicity.

Nivolumab17,18d

Nivolumab 240mg IV every 2 weeks until disease progression or unacceptable toxicity.

Pazopanib2,3

Pazopanib 800mg orally once daily without food.

Sorafenib22-25

Sorafenib 400mg orally twice daily without food.

Temsirolimus (Category 1: poor-prognosis patients; Category 2A: selected patients of other risk groups)27,28

Temsirolimus 25mg IV over 30–60 minutes weekly until disease progression or unacceptable toxicity.

a May increase to 7mg every 12 hours after 2 weeks based on criteria; may increase to 10mg every 12 hours after 2 weeks based on criteria. b Treatments divided into 60-day courses, with each IV treatment course consisting of 2 cycles of therapy, separated by approximately 7–10 days of rest with no other therapy during the remainder of the 60 days. c Patients who progressed were dose-escalated to 600 mg twice daily. d Based on the results of phase III trials, eligible patients should preferentially receive this agent over everolimus. e Erlotinib is used off-label for RCC. The NCCN guidelines include it as an optional first-line therapy for patients with relapsed or medically unresectable stage IV non-clear cell carcinoma.

continued

CancerTherapyAdvisor.com | SEPTEMBER/OCTOBER 2017 | CANCER THERAPY ADVISOR 41

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GENITOURINARY CANCER Renal Cell Carcinoma Treatment Regimens References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology™. Kidney. v 2.2017. Available at: http://www.nccn.org/professionals/physician_ gls/pdf/kidney.pdf. Accessed December 16, 2016. 2. Votrient [package insert]. Research Triangle Park, NC: GSK; 2016. 3. Sternberg CN, Davis ID, Mardiak J et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28:1061–1068. 4. Sutent [package insert]. New York, NY: Pfizer Labs; 2016. 5. Gore ME, Szczylik C, Porta C, et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009;10:757–763. 6. Avastin [package insert]. San Francisco, CA: Genentech; 2016. 7. Escudier B, Pluzanska A, Koralewski P, et al; AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370:2103–2111. 8. Rini BI, Halabi S, Rosenberg JE, et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol. 2010;28:2137–2143. 9. Torisel [package insert]. Philadelphia, PA: Wyeth; 2016. 10. Hudes G, Carducci M, Tomczak P, et al; Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271–2281. 11. Inlyta [package insert]. New York, NY: Pfizer Inc; 2016. 12. Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomized phase 3 trial. Lancet. 2011;378:1931–1939. 13. Proleukin [package insert]. San Diego, CA: Prometheus Laboratories; 2016. 14. McDermott DF, Regan MM, Clark JI, et al. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol. 2005;23:133–141. 15. Escudier B, Szczylik C, Hutson TE, et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(8):1280–1289. 16. Choueiri TK, Escudier B, Powles T, et al; METEOR Investigators. Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1814–1823.

17. Motzer RJ, Escudier B, McDermott DF, et al; CheckMate 025 Investigators. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–1813. 18. Opdivo [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2016. 19. Lenvima [package insert]. Woodcliff Lake, NJ: Eisai Inc.; 2016. 20. Afinitor [package insert]. East Hanover, NJ: Novartis; 2016. 21. Motzer RJ, Escudier B, Oudard S, et al; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008;372:449–456. 22. Nexavar [package insert]. Wayne, NJ: Bayer HealthCare; 2016. 23. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear cell renal-cell carcinoma. N Engl J Med. 2007;356: 125–134. 24. Di Lorenzo G, Carteni G, Autorino R, et al. Phase II study of sorafenib in patients with sunitinib-refractory metastatic renal cell cancer. J Clin Oncol. 2009;27:4469–4474. 25. Garcia JA, Hutson TE, Elson P, et al. Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab. Cancer. 2010;116:5383–5390. 26. Motzer RJ, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24:16–24. 27. Motzer RJ, Rini BI, Bukowski RM, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA. 2006;295: 2516–2524. 28. Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody,for metastatic renal cancer. N Engl J Med. 2003;349:427–434. 29. Atkins MB, Hidalgo M, Stadler WM, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol. 2004;22:909–918. 30. Hutson TE, Escudier B, Esteban E, et al. Temsirolimus vs Sorafenib as Second Line Therapy in Metastatic Renal Cell Carcinoma: Results from the INTORSECT Trial [abstract]. Ann Oncol. 2012;23:Abstract: LBA22. 31. Gordon MS, Hussey M, Nagle RB, et al. Phase II study of erlotinib in patients with locally advanced or metastatic papillary histology renal cell cancer: SWOG S0317. J Clin Oncol. 2009;27:5788–5793. (Revised 1/2017) © 2017 by Haymarket Media, Inc.

Renal Cell Carcinoma Advisor A section of Cancer Therapy Advisor that features exclusive news and clinical content for oncologists who specialize in the treatment of patients with RCC. Visit CancerTherapyAdvisor.com/RCC to gain access to the following and more: • Articles on the latest news in RCC written by experts • RCC 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 RCC management

42 CANCER THERAPY ADVISOR | SEPTEMBER/OCTOBER 2017 | CancerTherapyAdvisor.com

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 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)

AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free. Indications: Metastatic renal cell carcinoma (mRCC) in combination with interferon alfa. Adults: Give by IV infusion. Infuse 1st dose over 90 mins; if tolerated, infuse 2nd dose over 60 mins, and subsequent doses over 30 mins. 10mg/kg every 2 weeks with interferon alfa. Children: Not established. Warnings/Precautions: Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). History of hemoptysis of ≥ ½-teaspoon of red blood: do not administer. Discontinue if GI perforation, non-GI fistula formation, wound healing complications, serious hemorrhage, severe arterial or Grade 4 venous thromboembolic events, hypertensive crisis, nephrotic syndrome, or posterior reversible encephalopathy syndrome occurs; suspend therapy if severe hypertension, moderate to severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Cardiovascular disease. Diabetes. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis. Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy (Cat.C). Nursing mothers: not recommended.

Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, posterior reversible encephalopathy syndrome, infusion reactions, ovarian failure. How supplied: Single-use vial—1

BAVENCIO EMD Serono

℞

Programmed death-ligand 1 (PD-L1) blocking antibody. Avelumab 20mg/mL; soln for IV infusion after dilution; preservative-free; contains mannitol. Indications: Treatment of locally advanced or metastatic urothelial carcinoma (UC) in patients who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinumcontaining chemotherapy. Adults: Premedicate with an antihistamine and acetaminophen prior to the first 4 infusions; then subsequent doses as clinically indicated. Give as IV infusion over 60mins. 10mg/kg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling. Children: <12yrs: not established. Warnings/Precautions: See full labeling. Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for Grade 3/4 pneumonitis or recurrent Grade 2 pneumonitis, Grade 4 diarrhea or colitis or recurrent Grade 3 diarrhea or colitis, AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, any life-threatening (Grade 4) or recurrent severe (Grade 3) immune-mediated adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2/3 immune-mediated adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2/3 diarrhea or colitis, Grade 3/4 adrenal insufficiency, Grade 3/4 thyroid disorders, Grade 3/4 hyperglycemia, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN; withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if Grade 1/2 infusion reactions occur; permanently discontinue if Grade 3/4. Monitor for abnormal liver tests, adrenal insufficiency, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give

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DRUG MONOGRAPHS

GENITOURINARY CANCER replacement therapy for hypothyroidism. Embryofetal 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 literature. GI upset, headache, hypertension, edema, hypercalcemia, gallbladder or thromboembolic disease, gynecomastia, impotence, impaired glucose tolerance. How supplied: Multi-dose vials (5mL)—1

ELIGARD Tolmar

℞

GnRH analogue. Leuprolide acetate 7.5mg, 22.5mg, 30mg, 45mg; per inj; ext-rel susp for SC inj. Indications: Palliative treatment of advanced prostate cancer. Adults: Allow product to reach room temperature before using; inject within 30 minutes of mixing. Use correct formulation. Rotate inj sites. 7.5mg SC once per month; or 22.5mg SC once every 3 months; or 30mg SC once every 4 months; or 45mg SC once every 6 months. Children: Not established. Contraindications: Pregnancy (Cat.X). Warnings/Precautions: May worsen metastatic vertebral lesions and/or urinary tract obstruction; monitor closely during first few weeks. Increased risk of diabetes, MI, sudden cardiac death, stroke; monitor blood glucose, HbA1c, and for signs/symptoms of CVD during therapy. Risk of QT prolongation in patients with congenital long QT syndrome, CHF, or frequent electrolyte abnormalities. Correct and monitor electrolyte abnormalities; consider monitoring ECGs. Monitor serum testosterone, PSA periodically. Nursing mothers: not recommended. Interactions: Caution with concomitant drugs known to prolong the QT interval. May interfere with pituitary-gonadal diagnostic tests. Adverse reactions: Malaise, fatigue, hot flashes/sweats, testicular atrophy, local reactions (eg, burning/stinging, pain, erythema, bruising, pruritus); transient worsening of signs/symptoms (eg, bone pain, neuropathy, hematuria, bladder outlet obstruction), spinal cord compression, hyperglycemia, decreased bone density; rare: pituitary apoplexy. How supplied: Single-use kit—1 (with sterile or sterile safety needle)

EMCYT Pfizer

℞

Estramustine phosphate sodium (prodrug of estradiol) 140mg; caps. Indications: Palliative of metastatic, progressive prostate cancer. Adults: Take 1 hour before or 2 hours after meals. 14mg/kg in 3 or 4 divided doses; reevaluate after 30 to 90 days. Continue as long as favorable response maintained.

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DRUG MONOGRAPHS

GENITOURINARY CANCER Children: Not applicable. Contraindications: Active thrombophlebitis or thromboembolic disorders (except when tumor mass caused by thromboembolic phenomenon). Allergy to estradiol, nitrogen mustard. Warnings/Precautions: History of thrombophlebitis, thrombosis, thromboembolic disorders. Cerebro- or cardiovascular disease. Diabetes. Hypertension. Conditions aggravated by fluid retention. Renal or hepatic dysfunction. Monitor bilirubin and hepatic enzymes during and for 2 months after treatment is discontinued. Metabolic bone diseases associated with hypercalcemia. Use effective contraception. Interactions: Absorption impaired by calcium. Adverse reactions: Edema, dyspnea, leg cramps; nausea, diarrhea, GI upset; pruritus, dry skin, easy bruising; breast tenderness and enlargement; lethargy, emotional lability, insomnia; leucopenia; abnormal bilirubin, LDH, SGOT. Thrombosis, MI. How supplied: Caps—100

ESTRACE Allergan

℞

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

FIRMAGON Ferring GnRH antagonist. Degarelix 80mg/vial, 120mg/vial; pwd for SC inj after reconstitution. Indications: Advanced prostate cancer. Adults: Give by SC inj in abdomen once every 28 days; avoid waist and rib areas. Two 120mg

injections once, then one 80mg inj once every 28 days. Children: Not established. Contraindications: Pregnancy (Cat.X). Warnings/Precautions: Congenital long QT syndrome. CHF. Correct electrolyte abnormalities. Monitor electrolytes and ECG periodically. Monitor serum PSA. Discontinue if serious hypersensitivity reaction occurs; do not rechallenge. Moderate or severe renal impairment (CrCl <50mL/min). Severe hepatic impairment. Nursing mothers: not recommended. Interactions: Caution with concomitant drugs known to prolong the QT interval. Adverse reactions: Inj site reactions (eg, pain, erythema, swelling, induration), hot flashes, increased weight, fatigue, increased transaminases, increased gamma-glutamyltransferase; 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, 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

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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 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 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

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DRUG MONOGRAPHS

GENITOURINARY CANCER NEXAVAR Bayer and Onyx

℞

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

OPDIVO Bristol-Myers Squibb

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol. Indications: Advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy. Locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinumcontaining chemotherapy.

Adults: Give as IV infusion over 60mins. 240mg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: See full labeling. Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderate-to-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or lifethreatening. Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Monitor for transplant-related complications (eg, hyperacute or Grade 3/4 acute GVHD, steroid-requiring febrile syndrome, hepatic venoocclusive disease) and treat promptly. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥5 months after final dose. Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended. Adverse reactions: Asthenia/fatigue, musculoskeletal pain, decreased appetite, nausea, cough, rash, dyspnea, diarrhea, constipation, back pain, arthralgia; immunemediated reactions (may be fatal). How supplied: Single-use vial (4mL, 10mL)—1

PREMARIN Pfizer

℞

Estrogen. Conjugated estrogens 0.3mg, 0.45mg, 0.625mg, 0.9mg, 1.25mg; tabs. Indications: Treatment of advanced androgendependent carcinoma of the prostate (for palliation only). Adults: 1.25mg—2.5mg 3 times daily. Children: Not applicable.

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

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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 platinumcontaining 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

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.

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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 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

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DRUG MONOGRAPHS

GENITOURINARY CANCER 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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CANCER TREATMENT REGIMEN

GYNECOLOGIC CANCER Uterine Sarcoma Treatment Regimens Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The 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.

Systemic Therapy for Uterine Sarcoma1 Note: All recommendations are Category 2A unless otherwise indicated.

REGIMEN

DOSING

Combination Regimens Docetaxel + gemcitabine2ab (Preferred for leiomyosarcoma)

Days 1 and 8: Gemcitabine 900mg/m2 IV over 90 minutes followed by docetaxel 100mg/m2 IV over 60 minutes on day 8 followed by Days 9–15: Granulocyte colony-stimulating factor (G-CSF) 150μ/m2 SQ OR Pegfilgrastim 6mg SQ on day 9 or 10. Repeat cycle every 3 weeks until disease progression or toxicity occurs.

Doxorubicin + ifosfamide3

Day 1: Doxorubicin 50mg/m2 over 15 minutes followed by ifosfamide 5g/m2 via 24-hour continuous IV admixed with mesna 6g/m2 36-hour continuous IV. Repeat cycle every 3 weeks if counts allow.

Doxorubicin + dacarbazine4

Day 1: Doxorubicin 60mg/m2 IV. Days 1–4: Dacarbazine 750mg/m2 IV via continuous infusion for 96 hours. Repeat cycle every 3 weeks.

Gemcitabine + dacarbazine5

Day 1: Gemcitabine 10mg/m2/min IV over 180 minutes followed by dacarbazine 500mg/m2 IV over 20 minutes. Repeat every 2 weeks for a total of 12 cycles.

Gemcitabine + vinorelbine6

Days 1 and 8: Vinorelbine 25mg/m2 IV over 10 minutes followed by gemcitabine 800mg/m2 IV over 90 minutes. Repeat cycle every 21 days.

Single-agent Regimens Dacarbazine5

Day 1: Dacarbazine 1200mg/m2 IV over 20 minutes. Repeat cycle every 3 weeks for total of 8 cycles.

Doxorubicin7

Day 1: Doxorubicin 75mg/m2 IV bolus. Repeat every 3 weeks.

Epirubicin8

Day 1: Epirubicin 75mg/m2 IV bolus. Repeat every 3 weeks.

Eribulin9 (Category 2B)

Days 1 and 8: Eribulin 1.4mg/m2 IV. Repeat every 21 days until disease progression or unacceptable toxicity.

Gemcitabine10

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

Ifosfamide11

Days 1–5: Ifosfamide 1.5gm/m2 IV daily with mesna.

Liposomal doxorubicin12

Day 1: Liposomal doxorubicin 50mg/m2. Repeat every 4 weeks.

Pazopanib13

Pazopanib 800mg orally once daily until disease progression or unacceptable toxicity.

Temozolomide

Trabectedin14-17c

Temozolomide 50–75mg/m2 daily for 6 of 8 weeks. Trabectedin 1.5mg/m2 via 24-hour continuous IV infusion. Repeat once every 3 weeks. continued

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CANCER TREATMENT REGIMEN

GYNECOLOGIC CANCER Uterine Sarcoma Treatment Regimens Systemic Therapy for Uterine Sarcoma1 (continued) Single-agent Regimens (continued) Vinorelbine (Category 2B)18

Days 1 and 8: Vinorelbine 30mg/m2. Repeat every 21 days.

Docetaxel (Category 3)19

Days 1, 8, and 15: Docetaxel 36mg/m2 IV over 1 hour. Repeat every 28 days until disease progression or unacceptable toxicity.

Hormone Therapy1d REGIMEN

DOSING

Medroxyprogesterone acetate (Category 2B for ER/PR-positive uLMS), megestrol acetate (Category 2B for ER/PR-positive uLMS), aromatase inhibitors, gonadotropin-releasing hormone analogs (Category 2B for low-grade ESS and ER/PR-positive uLMS) Abbreviations: ER = estrogen receptor; ESS = endometrial stromal sarcoma; PR = progesterone receptor; SQ = subcutaneous; uLMS = uterine leiomyosarcoma; UUS = undifferentiated uterine sarcoma. a Preferred for uLMS. b Patients with prior pelvic irradiation received gemcitabine 675mg/m2 IV and docetaxel 75mg/m2 IV. c For uLMS that has been treated with a prior anthracycline-containing regimen. d For low-grade ESS or hormone-receptor positive (ER/PR) uLMS; preferably there is small tumor volume or an indolent growth pace.

References 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Uterine Neoplasms V.2.2017. Available at: http://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed June 1, 2017. 2. Hensley ML, Blessing JA, Mannel R, Rose PG. Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 2008;109(3):329–334. 3. Sutton G, Blessing JA, Malfetano JH. Ifosfamide and doxorubicin in the treatment of advanced leiomyosarcomas of the uterus: a Gynecologic Oncology Group study. Gynecol Oncol. 1996; 62(2): 226–229. 4. Zalupski M, Metch B, Balcerzak S, et al. Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study. J Natl Cancer Inst. 1991;83(13):926–932. 5. Garcia-Del-Muro X, Lopez-Pousa A, Maurel J, et al. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011;29(18):2528–2533. 6. Dileo P, Morgan J, Zahrieh D, et al. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas. Cancer. 2007;109(9):1863–1869. 7. Judson I, Radford JA, Harris M, et al. Randomized phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2001;37(7):870–877. 8. Mouridsen HT, Bastholt L, Somers R, et al. Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987;23(10): 1477–1483. 9. Schöffski P, Maki RG, Italiano A, et al. Randomized, open-label, multicenter, phase III study of eribulin versus dacarbazine in patients (pts) with leiomyosarcoma (LMS) and adipocytic sarcoma (ADI). J Clin Oncol. 2015;33(18_suppl):LBA10502.

10. Look KY, Sandler A, Blessing JA, et al. Phase II trial of gemcitabine as second-line chemotherapy of uterine leiomyosarcoma: a Gynecologic Oncology Group (GOG) Study. Gynecol Oncol. 2004;92(2):644–647. 11. Sutton GP, Blessing JA, Barrett RJ, et al. Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Am J Obstet Gynecol. 1992;166(2):556–559. 12. Amant F, Coosemans A, Debiec-Rychter M, et al. Clinical management of uterine sarcomas. Lancet Oncol. 2009;10(12): 1188–1198. 13. van der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379(9829):1879–1886. 14. Gajdos C, Elias A. Trabectedin: safety and efficacy in the treatment of advanced sarcoma. Clin Med Insights Oncol. 2011;5:35–43. 15. Demetri GD, Chawla SP, von Mehren M, et al. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009;27(25): 4188–4196. 16. Fayette J, Boyle H, Chabaud S, et al. Efficacy of trabectedin for advanced sarcomas in clinical trials versus compassionate use programs: analysis of 92 patients treated in a single institution. Anticancer Drugs. 2010;21(1):113–119. 17. Pautier P, Floquet A, Chevreau C, et al; French Sarcoma Group. Trabectedin in combination with doxorubicin for first-line treatment of advanced uterine or soft-tissue leiomyosarcoma (LMS-02): a non-randomised, multicentre, phase 2 trial. Lancet Oncol. 2015;16(4):457–464. 18. Muggia F, Blessing JA, Method M. Evaluation of vinorelbine in persistent or recurrent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 2004;92(2):639–643. 19. Garcia AA, Blessing JA, Nolte S, Mannel RS. A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: a study by the Gynecologic Oncology Group. Gynecol Oncol. 2008;111(1):22–26. (Revised 6/2017) © 2017 by Haymarket Media, Inc.

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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 (platinum-resistant): 10mg/kg every 2 weeks with either paclitaxel, pegylated liposomal doxorubicin, or topotecan (weekly); or, 15mg/kg every 3 weeks with topotecan (every 3 weeks); (platinum-sensitive): 15mg/kg every 3 weeks with carboplatin/paclitaxel for 6 cycles and up to 8 cycles or carboplatin/gemcitabine for 6 cycles and up to 10 cycles; followed by Avastin 15mg/kg every 3 weeks as a single agent until disease progression. Children: Not established. Warnings/Precautions: Risk of GI perforations, surgery and wound healing complications, and hemorrhage. Do not start therapy before or for at least 28 days after surgery; allow surgical incisions to completely heal (see full labeling). Do not administer if recent history of hemoptysis of ≥ ½-teaspoon of red blood. Permanently discontinue if GI perforation, tracheoesophageal fistula, any grade 4 fistula, or grade 4 venous thromboembolic event. Discontinue if fistula involving internal organ, wound healing complications, hemorrhage, severe arterial thromboembolic event (ATE), hypertensive crisis or encephalopathy, posterior reversible encephalopathy syndrome (PRES), or nephrotic syndrome occurs; suspend therapy if severe hypertension, moderate-to-severe proteinuria (resume when <2g/24hrs), or severe infusion reaction occurs. Avoid in ovarian cancer if evidence of recto-sigmoid involvement by pelvic exam, bowel involvement on CT scan, or symptoms of bowel obstruction. History of

arterial thromboembolism. Diabetes. Monitor BP every 2–3 weeks. Monitor proteinuria by dipstick urine analysis; if ≥2+, do further assessment with a 24-hour urine collection. Elderly. Increased risk of ovarian failure; inform females of reproductive potential prior to starting therapy. Pregnancy: may cause fetal harm; use effective contraception during and for 6 months after last dose. Nursing mothers: not recommended. Adverse reactions: Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis; GI perforation and fistulae, wound dehiscence/impaired healing, necrotizing fasciitis (discontinue if occurs), hemorrhage, non-GI fistula formation, arterial or venous thromboembolic events, PRES, infusion reactions, ovarian failure, neutropenia, infection. How supplied: Single-use vial—1

DOXIL Janssen Biotech

℞

Anthracycline. Doxorubicin HCl (liposomal) 2mg/mL; dispersion for IV infusion after dilution; preservative-free. Indications: Ovarian cancer refractory to platinum-based chemotherapy. Adults: Give by IV infusion at initial rate of 1mg/min; may increase rate to complete infusion over 1hr if no infusion reactions occur; may premedicate with antiemetics. 50mg/m2 once every 4 weeks; continue for at least 4 cycles as tolerated. Hepatic dysfunction (serum bilirubin ≥1.2mg/dL), hand-foot syndrome, hematologic toxicity (esp. ANC, platelets), or stomatitis: reduce dose. Consider total anthracycline and anthracenedione doses and irradiation when calculating total cumulative dose. See full labeling. Children: Not established. Warnings/Precautions: Not substitutable on a mg/mg basis with other doxorubicin products. Cardiotoxicity, acute infusion-related reactions, myelosuppression may occur. Have resuscitative/antiallergic equipment and expertise available. Hepatic impairment. Monitor blood (esp. CBC + platelets), hepatic (esp. SGOT/SGPT, alkaline phosphatase), and cardiac function (esp. myocardial biopsy). Monitor periodically for secondary oral cancers with longterm use. Avoid extravasation. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Caution with cyclosporine, phenobarbital, phenytoin, streptozocin, digoxin, myelosuppressants, others. Previous mediastinal irradiation, cyclophosphamide, other

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

HEXALEN Eisai

℞

S-triazine derivative. Altretamine 50mg; caps. Indications: Palliative treatment of persistent or recurrent ovarian cancer following first-line therapy with a cisplatin and/or alkylating agentbased combination. Adults: 260mg/m2 daily in four divided doses (after meals and at bedtime), for either 14 or 21 consecutive days in a 28-day cycle. Discontinue for >14 days if GI intolerance is unresponsive to treatment, WBC count <2000/mm3 or granulocyte count <1000/mm3, platelet count <75000/mm3, or progressive neurotoxicity occurs. Restart at 200mg/m2 daily. Discontinue indefinitely if neurologic symptoms fail to stabilize. Children: Not recommended. Contraindications: Severe myelosuppression or neurologic toxicity, except cisplatin-related neuropathy. Warnings/Precautions: Monitor for myelosuppression (do monthly CBCs) and neurotoxicity. Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Avoid pyridoxine. Severe orthostatic hypotension with MAOIs. Adverse reactions: Nausea, vomiting, peripheral neuropathy, CNS symptoms (eg, mood disorders, ataxia, dizziness), myelosuppression, renal dysfunction, increased alkaline phosphatase. How supplied: Caps—100

HYCAMTIN GlaxoSmithKline

℞

Topoisomerase inhibitor. Topotecan (as HCl) 4mg/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol; preservative-free. Indications: Metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy. Stage IV-B, recurrent or persistent carcinoma of the cervix in combination with cisplatin. Adults: Verify dose using BSA. Usual max dose 4mg IV. Confirm baseline

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DRUG MONOGRAPHS

GYNECOLOGIC CANCER neutrophils ≥1,500cells/mm3 and platelets ≥100,000cells/mm3 prior to 1st course of therapy. Give by IV infusion over 30 mins. Ovarian cancer: 1.5mg/m2 daily for 5 consecutive days starting on Day 1 of a 21-day cycle. Cervical cancer: 0.75mg/m2 on Days 1 (with cisplatin), 2, and 3, repeated every 21 days. Dose adjustments, renal impairment: see full labeling. Children: Not established. Warnings/Precautions: Monitor peripheral blood cell counts during therapy; hold subsequent doses until neutrophils >1,000cells/mm3, platelets >100,000cells/mm3, and hemoglobin ≥9g/dL. History of interstitial lung disease, pulmonary fibrosis, lung cancer, thoracic exposure to radiation, use of pneumotoxic drugs and/or colony stimulating factors: increased risk of interstitial lung disease; monitor, discontinue if occurs. Moderate to severe renal impairment. Avoid extravasation. Elderly. Use effective contraception during and for ≥1 month after last dose (in females), or during and for ≥3 months (in males with female partners). Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: Myelosuppression potentiated with platinum agents. Neutropenia potentiated by G-CSF; administer ≥24hrs after last topotecan dose. 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

℞

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DRUG MONOGRAPHS

GYNECOLOGIC CANCER 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

℞

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)

ZEJULA Tesaro Poly (ADP-ribose) polymerase (PARP) inhibitor. Niraparib 100mg; caps. Indications: Maintenance treatment in adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Adults: Start treatment within 8 weeks after most recent platinum-containing regimen. Swallow whole. 300mg once daily until disease progression or unacceptable toxicity. Dose adjustments for adverse reactions: see full labeling.

℞

Children: Not established. Warnings/Precautions: Discontinue if myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) is confirmed. Monitor CBC weekly for the first month, monthly for the next 11 months then periodically thereafter; do not start therapy until recovery from hematological toxicity due to previous chemotherapy (CTCAE Grade ≤1); discontinue if toxicities unresolved within 28 days after interruption (see full labeling). Monitor BP and heart rate monthly for the first year then periodically thereafter. Cardiovascular disorders (eg, coronary insufficiency, arrhythmias, hypertension); monitor closely. Embryo-fetal toxicity. Pregnancy; exclude status prior to initiating therapy. Females of reproductive potential should use effective contraception during therapy and for ≥6 months after last dose. Nursing mothers: not recommended (during and for 1 month after last dose). Interactions: Concomitant antihypertensives; dose adjustments of Zejula may be needed. Adverse reactions: Thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue/asthenia, decreased appetite, urinary tract infection, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, hypertension. How supplied: Caps—90

HYPERSENSITIVITY to

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

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.

Oncology Nurse Advisor provides important clinical information, including a CE activity in each issue. Go to OncologyNurseAdvisor.com/Subscribe to sign up for a free subscription.

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DRUG MONOGRAPHS

HEAD AND NECK CANCER ERBITUX Lilly

℞

Epidermal growth factor receptor blocker. Cetuximab 100mg/vial, 200mg/vial; soln for IV infusion; preservative-free. Indications: In combination with radiation therapy for treating locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN). In combination with platinum-based therapy with 5-fluorouracil (5-FU) for first-line treatment of recurrent locoregional disease or metastatic SCCHN. As a single agent for recurrent or metastatic SCCHN after failure of prior platinum-based therapy. Adults: Pretreat with H1 blocker. Give by IV infusion (use filter); max rate: 10mg/min. Initial dose: 400mg/m2 once over 2hrs; then 250mg/m2 once weekly over 1 hour. Combination therapy: Give initial dose 1 week prior to initiation of radiation therapy. Complete administration 1 hour prior to platinum-based therapy with 5-FU. Give subsequent weekly dose for duration of radiation therapy (6–7 weeks) or until disease progression or unacceptable toxicity. Permanently reduce infusion rate by 50% if Grade 1 or 2 and nonserious 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

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DRUG MONOGRAPHS

HEAD AND NECK CANCER prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderate-to-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or life-threatening. Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Monitor for 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, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea; immune-mediated reactions (may be fatal). How supplied: Single-use vial (4mL, 10mL)—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: Epidermoid cancers of the head and neck. Adults: See literature. Children: Not established. Contraindications: Pregnancy (Cat. X). Nursing mothers. Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration). Discontinue immediately if blood counts drop

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

LIVER FUNCTION ASSESSMENT Child-Pugh Score is used to assess residual liver function and injury severity in cirrhosis patients.

CHILD-PUGH SCORES Criteria

1 point

2 points

3 points

Total serum bilirubin (mg/dL)

2–3

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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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; preservative-free. Indications: Non-Hodgkin’s lymphoma (CD20 antigen-expressing relapsed or refractory, low

℞

grade, follicular, transformed, or rituximabrefractory). Adults: See literature. Pretreat with acetaminophen 650mg and oral diphenhydramine 50mg and thyroid blockers; continue thyroid blockers 2 weeks after therapeutic dose. Give by IV infusion. Dosimetric step: Tositumomab 450mg over 1hr, then Iodine I131 tositumomab (containing 5mCi I131 and 35mg tositumomab) over 20 minutes. Therapeutic step (7–14 days after dosimetric step if biodistribution acceptable): tositumomab 450mg over 1hr, then calculated therapeutic dose of Iodine I131 tositumomab over 20 minutes. Reduce infusion rate by 50% if infusional toxicity occurs; stop if severe; may continue at 50% rate if severe symptoms resolve. Children: Not recommended. Contraindications: Hypersensitivity to murine proteins. Pregnancy (Cat.X). Warnings/Precautions: Use only by physicians trained in radionuclide therapy. Handle and dispose of properly. See literature on patient contact restrictions. Not for initial treatment. >25% lymphoma marrow involvement and/or impaired bone marrow reserve, platelet count <100000cells/mm3, neutrophil count <1500cells/mm3, or intolerant to thyroid blockers: not recommended. High tumor burden. Splenomegaly. Renal impairment. Screen for human anti-mouse antibodies (increases anaphylaxis risk). Obtain CBCs and platelet counts before and for up to 12 weeks after therapy. Monitor TSH (before and annually), serum creatinine (before). Use adequate contraception during and for 12 months after therapy. Elderly. Nursing mothers: not recommended. Interactions: Concomitant other forms of irradiation or chemotherapy: not recommended. Caution with live viral vaccines, anticoagulants, platelet aggregation inhibitors. Adverse reactions: Thrombocytopenia, neutropenia, anemia, headache, asthenia, fever, chills, pain, GI upset, cough, pneumonia, pleural effusion, dehydration, rash, infection, hemorrhage, hypersensitivity reactions (may be fatal), myelodysplastic syndrome, secondary malignancies, antibody formation. Note: For technical questions call (877) 423-9927. How supplied: Dosimetric pack (tositumomab 2 × 225mg/vial + 1 × 35mg/vial and Iodine I131 tositumomab 1 × 20mL single-use vial)—1; Therapeutic pack (tositumomab 2 × 225mg/vial + 1 × 35mg/vial and Iodine I131 tositumomab 1 or 2 × 20mL single-use vial)—1

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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER BLINCYTO Amgen

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Bispecific CD19-directed CD3 T-cell engager. Blinatumomab 35mcg; per vial; lyophilized pwd for IV infusion after reconstitution; preservativefree. Indications: Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Adults and Children: Strictly follow preparation and administration instructions. Pre-medicate with dexamethasone 20mg (adults) or 5mg/m2 to max 20mg (pediatrics) 1 hour prior to 1st dose of each cycle, prior to a step dose, or when restarting infusion after interruption (≥4 hours). Hospitalization recommended for first 9 days of Cycle 1 and first 2 days of Cycle 2. One single cycle = 28 days of continuous IV infusion followed by a 14-day treatment-free interval. Treat up to a total of 5 cycles. ≥45kg: can give by continuous IV infusion at a rate of 10mL/hr over 24 hours, 5mL/hr over 48 hours, or 0.6mL/hr over 7 days (not recommended for patients <22kg). Cycle 1: 9mcg/day on Days 1–7 and 28mcg/day on Days 8–28. Subsequent cycles: 28mcg/day on Days 1–28. <45kg: Cycle 1: 5mcg/m2/day (max 9mcg/day) on Days 1–7 and 15mcg/m2/day (max 28mcg/day) on Days 8–28. Subsequent cycles: 15mcg/m2/day (max 28mcg/day) on Days 1–28. Dose adjustments or using 7-day infusion of Blincyto (with preservative): see full labeling. Warnings/Precautions: Monitor for signs/symptoms of cytokine release syndrome or neurological toxicities; interrupt or discontinue as recommended (see full labeling). Monitor for infections; give antibiotic prophylaxis as appropriate. Monitor for tumor lysis syndrome; interrupt or discontinue as needed. Obtain lab tests (including WBC, ANC) during infusion; interrupt if prolonged neutropenia occurs. Monitor ALT, AST, GGT, and total bilirubin prior to and during treatment; interrupt if transaminases rise >5XULN or if bilirubin rises >3XULN. Evaluate if signs/symptoms of pancreatitis develop; interrupt or discontinue as appropriate. Risk of leukoencephalopathy, esp. in those with prior treatment with cranial irradiation and antileukemic chemotherapy (including high-dose methotrexate or intrathecal cytarabine). Elderly. Neonates/infants: risk of gasping syndrome (due to benzyl alcohol preservative). Pregnancy; verify status prior to initiation. Females of reproductive potential should use effective contraception during and for at least 48hrs after last dose. Nursing mothers: not recommended (during and for at least 48hrs after last dose). Interactions: Concomitant live vaccines: not recommended (for at least 2 weeks prior to initiation, during treatment, and until immune recovery after last cycle). Caution with concomitant CYP450 substrates esp. drugs with narrow therapeutic index (eg, warfarin, cyclosporine); monitor and adjust dose as needed.

Adverse reactions: Pyrexia, headache, nausea, vomiting, edema, hypokalemia, anemia, febrile neutropenia, neutropenia, thrombocytopenia, abdominal pain, infections; pneumonia, sepsis, device-related infection, tremor, overdose, encephalopathy, confusion. How supplied: Pack—1 (single-use vial + IV solution stabilizer)

BOSULIF Pfizer

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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 shortacting antacids or H2 blockers instead; separate dosing by ≥2hrs. Adverse reactions: Diarrhea, nausea, thrombocytopenia, rash, vomiting, abdominal

pain, RTI, anemia, pyrexia, abnormal LFTs, fatigue, cough, headache; fluid retention, hepatic or renal toxicity. How supplied: Tabs 100mg—120; 500mg—30

BUSULFEX Otsuka

℞

Alkylating agent. Busulfan 6mg/mL; soln for IV administration after dilution. Indications: In combination with cyclophosphamide, as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia. Adults: See full labeling. Premedicate with anticonvulsants and antiemetics. Give by IV infusion over 2 hours. 0.8mg/kg of ideal body weight or actual body weight, whichever is lower, every 6 hours for 4 days for total of 16 doses (on Days -7, -6, -5, and -4). Give cyclophosphamide after the 16th dose of busulfan (Days -3 and -2). Give hematopoietic progenitor cells on Day 0. Obese: base dose on adjusted ideal body weight. Children: See full labeling. Warnings/Precautions: Risk of severe and prolonged myelosuppression; requires hematopoietic progenitor cell transplantation. Seizure disorder. Head trauma. Renal or hepatic impairment. Monitor CBCs with differential, platelet counts, liver enzymes, bilirubin during treatment and until recovery. Monitor for infection and bleeding. Embryo-fetal toxicity. Pregnancy. Use effective contraception during and after treatment. Nursing mothers: not recommended. Interactions: Potentiated by itraconazole and acetaminophen. May be antagonized by phenytoin. Caution with potentially epileptogenic drugs. Adverse reactions: Myelosuppression, nausea, stomatitis, vomiting, anorexia, diarrhea, insomnia, fever, hypomagnesemia, abdominal pain, anxiety, headache, hyperglycemia, hypokalemia; seizures (with higher doses), hepatic veno-occlusive disease (with high AUC), cardiac tamponade (in pediatric patients with thalassemia), cellular dysplasia; rare: bronchopulmonary dysplasia with pulmonary fibrosis. How supplied: Single-use vials (10mL)—8

CAMPATH 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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER antibiotics and antivirals during treatment and for at least 2 months after completion or until CD4+ counts resolve (whichever occurs later). Dose adjustments for neutropenia and thrombocytopenia: see literature. Retitrate if therapy interrupted for ≥7 days. Children: Not recommended. Warnings/Precautions: Discontinue dose for autoimmune or recurrent/persistent severe cytopenias (except lymphopenia). Withhold dose for severe cytopenias (except lymphopenia), grade 3 or 4 infusion reactions, serious infections, or during antiviral treatment for cytomegalovirus (CMV) infection or confirmed CMV viremia. Obtain CBCs, platelet counts weekly, assess CD4+ counts after treatment until recovery to ≥200cells/μL. Monitor for infusion reactions; CMV infection (continue for 2 months after therapy ends). Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Avoid live virus vaccines (after recent therapy). May interfere with tests using antibodies. Irradiate any blood products given (GVHD may occur). Adverse reactions: See literature; may be fatal. Infusion reactions, cytopenias (eg, neutropenia, lymphopenia, thrombocytopenia, anemia), infections (eg, CMV), GI upset, insomnia, anxiety; others. How supplied: Single-use vials—1, 3

CERUBIDINE Bedford

℞

Anthracycline. Daunorubicin HCl 20mg/vial; lyophilized pwd for IV infusion after reconstitution; contains mannitol. Indications: In combination with other chemotherapy for remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults. Adults: Give by IV infusion. Acute nonlymphocytic leukemia (in combination with cytosine arabinoside): <60yrs: 45mg/m2 daily on days 1, 2 and 3 of the first course and on days 1, 2 of subsequent courses; ≥60yrs: 30mg/m2 daily on days 1, 2 and 3 of the first course and on days 1, 2 of subsequent courses. Acute lymphocytic leukemia (in combination with vincristine, prednisone, L-asparaginase): 45mg/m2 daily on days 1, 2 and 3. Hepatic or renal impairment: reduce dose (see literature). Children: Give by IV infusion. <2yrs or BSA<0.5m2: use weight (mg/kg) to calculate dose. 25mg/m2 on day 1 every week (in combination with vincristine and prednisone).

Warnings/Precautions: Treat if any systemic infections 1st. Pre-existing drug-induced bone marrow suppression. Cardiovascular disease, thoracic irradiation, previous doxorubicin therapy (cumulative doses >550mg/m2): increased risk of cardiotoxicity. Monitor blood counts, cardiac, hepatic and renal function prior to each treatment. Renal or hepatic impairment. Hyperuricemia; monitor blood uric acid levels and give allopurinol prophylatically. Avoid extravasation. Children. Elderly. Pregnancy (Cat. D); avoid use. Nursing mothers: not recommended. Interactions: Do not use if previously received max cumulative doxorubicin dose; or if concomitant with cyclophosphamide: increased cardiotoxicity. Concomitant myelosuppressives: consider dose reduction. Increased risk of liver toxicity with hepatotoxic agents (eg, high-dose methotrexate). Adverse reactions: Myelosuppression, cardiotoxicity, alopecia, rash, inj site reactions, GI upset, mucositis, abdominal pain, hyperuricemia; rare: anaphylaxis. How supplied: Single-dose vials—10

CLOLAR 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.

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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER Children: Not recommended. Warnings/Precautions: Renal or hepatic impairment. Obtain CBC and platelet counts before each dosing cycle and as needed. Monitor hepatic function (do baseline liver chemistries and serum creatinine). Pregnancy (Cat.D); use appropriate contraception (both men and women). Nursing mothers: not recommended. Adverse reactions: Neutropenia, thrombocytopenia, anemia, leukopenia, fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, hyperglycemia. How supplied: Single-use vial—1

DARZALEX Janssen Biotech

℞

CD38-directed monoclonal antibody. Daratumumab 100mg/5mL, 400mg/20mL; per vial; soln for IV infusion after dilution; contains mannitol; preservative-free. Indications: Treatment of multiple myeloma: as combination therapy with lenalidomide and dexamethasone, or bortezomib and dexamethasone, in patients who have received ≥1 prior therapy; 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. Cardiotoxicity, acute infusion-related reactions, myelosuppression may occur. Have resuscitative/antiallergic equipment and expertise available. Hepatic impairment. Monitor blood (esp. CBC + platelets), hepatic (esp. SGOT/SGPT, alkaline phosphatase), and cardiac function (esp. myocardial biopsy). Monitor periodically for secondary oral cancers with longterm use. Avoid extravasation. Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: Caution with cyclosporine, phenobarbital, phenytoin, streptozocin, digoxin, myelosuppressants, others. Previous mediastinal irradiation, cyclophosphamide, other cardiotoxic drugs: monitor for cardiotoxicity and hepatotoxicity. Adverse reactions: Asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand and foot syndrome, rash, neutropenia, thrombocytopenia, anemia; infusion reactions, cardiovascular events (eg, cardiomyopathy, CHF, acute LV failure), recall of skin reaction from prior radiation therapy, toxoplasmosis, urine discoloration (red/orange). How supplied: Single-use vials (10mL, 25mL)—1

EMPLICITI Bristol-Myers Squibb

℞

SLAMF7-directed immunostimulatory antibody. Elotuzumab 300mg, 400mg; per vial; lyophilized pwd for IV infusion after reconstitution; preservative-free. Indications: In combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma who have received 1–3 prior therapies. Adults: Give by IV infusion at initial rate of 0.5mL/min; may increase stepwise if no reactions develop; max rate 2mL/min (see full labeling).

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER After 4 cycles, infusion rate may be increased up to max 5mL/min. Administer with lenalidomide and dexamethasone (see full labeling for dosing schedule). 10mg/kg every week for the first 2 cycles then every 2 weeks thereafter; continue until disease progression or unacceptable toxicity. Premedicate with dexamethasone, H1 blocker, H2 blocker, and acetaminophen before each infusion. Dose modifications: see full labeling. Children: Not established. Contraindications: Consult lenalidomide and dexamethasone prescribing information for contraindications before starting therapy. Warnings/Precautions: Interrupt infusion if Grade ≥2 infusion reactions occur and manage appropriately. Monitor for development of infections and treat promptly. Monitor for second primary malignancies. Monitor liver function periodically; discontinue if Grade ≥3 elevation of liver enzymes occur; consider resuming after return to baseline values. Pregnancy: not studied. Nursing mothers: not recommended. Interactions: May interfere with correct response classification in SPEP and serum immunofixation assays. Adverse reactions: Fatigue, diarrhea, pyrexia, constipation, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, pneumonia. Note: For lenalidomide and dexamethasone specific dosing and safety information, refer to the respective full prescribing labels. How supplied: Single-dose vial—1

ERWINAZE Jazz

℞

Asparagine-specific enzyme. Asparaginase Erwinia chrysanthemi 10,000 IU; per vial; lyophilized pwd for IM or IV inj after reconstitution. Indications: As a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coliderived asparaginase. Adults and Children: Give by IM inj (max 2mL/inj site) or IV (infuse over 1hr). To substitute for a pegaspargase dose: 25,000 IU/m2 three times weekly (M/W/F) for 6 doses for each planned pegaspargase dose. To substitute for a native E. coli asparaginase dose: 25,000 IU/m2 for each scheduled native E. coli asparaginase dose within a treatment. When IV use: consider monitoring nadir serum asparaginase activity (NSAA) levels; switch to IM inj if levels are inadequate.

Contraindications: History of serious pancreatitis, thrombosis, hemorrhagic events with prior L-asparaginase therapy. Warnings/Precautions: Have resuscitation equipment available and other agents necessary to treat anaphylaxis. Discontinue if serious hypersensitivity reactions occur. Monitor for pancreatitis; discontinue if severe or hemorrhagic pancreatitis manifested by abdominal pain >72hrs and amylase elevation ≥2XULN occurs. Withhold therapy if mild pancreatitis; may resume after resolution. Monitor glucose levels at baseline and during therapy. Discontinue if thrombotic or hemorrhagic event occurs; may resume after resolution. Pregnancy (Cat.C). Nursing mothers: not recommended. Adverse reactions: Systemic hypersensitivity, hyperglycemia, abnormal transaminases, fever, pancreatitis, local reactions, vomiting, nausea, thrombosis, hyperbilirubinemia, abdominal pain/discomfort, diarrhea. How supplied: Vials (3mL)—5

EVOMELA Spectrum Alkylating agent. Melphalan HCl 50mg/vial; lyophilized pwd; for IV infusion after reconstitution. Indications: High-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma. Palliative treatment of multiple myeloma when oral therapy is not appropriate. Adults: Give prophylactic antiemetics. Conditioning treatment: Give by IV infusion over 30 minutes. 100mg/m2 daily for 2 consecutive days (Days -3 and -2) prior to transplantation (Day 0). If patient weighs >130% of their ideal body weight, use adjusted ideal body weight. Palliative treatment: Give by IV infusion over 15–20 minutes. 16mg/m2 as a single infusion at 2-week intervals for 4 doses, then at 4-week intervals after recovery from toxicity. Renal impairment (BUN ≥30mg/dL): consider up to 50% dose reduction for palliative treatment. Children: Not established. Warnings/Precautions: Prior irradiation or chemotherapy. Severe bone marrow suppression. Monitor CBCs during treatment; provide supportive care for infections, anemia, thrombocytopenia until adequate recovery. GI toxicity; provide supportive care. Monitor LFTs. Renal impairment. Embryo-fetal toxicity; use effective contraception during and after treatment. Pregnancy, nursing mothers: not recommended.

℞

Interactions: Caution with cyclosporine, BCNU, nalidixic acid. Adverse reactions: Decreased neutrophil, WBC, lymphocyte, and platelet counts, diarrhea, nausea, fatigue, hypokalemia, anemia, vomiting; hypersensitivity reactions, hepatic disorders, secondary malignancies, infertility. How supplied: Single-dose vial (20mL)—1

FARYDAK Novartis

℞

Histone deacetylase inhibitor. Panobinostat 10mg, 15mg, 20mg; caps. Indications: Multiple myeloma, in patients who have received at least two prior therapies (including bortezomib and an immunomodulatory agent), in combination with bortezomib and dexamethasone. Adults: Swallow whole with water. Take at same time on scheduled days. Initially 20mg once every other day for 3 doses/wk in Weeks 1 and 2 of each 21-day cycle for up to 8 cycles. Consider 8 more cycles for patients with clinical benefit if no severe or significant toxicity; max 16 cycles (48 wks). Give with bortezomib inj and oral dexamethasone per scheduled day. Hepatic impairment: mild: initially 15mg; moderate: initially 10mg; severe: avoid. Concomitant strong CYP3A inhibitors: initially 10mg. Dose adjustments and modifications for toxicity: see full labeling. Children: Not established. Warnings/Precautions: Risk of severe diarrhea and cardiac toxicities. Monitor hydration and electrolytes at baseline, weekly during therapy, or more as indicated. Initiate antidiarrheals at onset of diarrhea; interrupt dose if 4–6 stools/day. Do not initiate if history of recent MI or unstable angina, QTcF >450msec, significant baseline ST-segment or T-wave abnormalities, active infections. Perform ECG prior to initiation and repeat during treatment as indicated. Correct electrolyte abnormalities prior to initiation and monitor; interrupt if QTcF ≥480msec; discontinue if QT prolongation does not resolve. Serious hemorrhage. Obtain CBC prior to initiation; monitor weekly during therapy or more as indicated. Monitor for infections; treat and consider interruption or discontinuation if diagnosed. Monitor liver function prior to and during treatment; consider dose adjustments if abnormal tests observed. ESRD or dialysis: not studied. Elderly: monitor for toxicity more frequently (esp. GI, myelosuppression, cardiac). Embryo-fetal toxicity. Pregnancy: avoid. Obtain pregnancy test prior to and during treatment. Use effective contraception during and for ≥3 months after last dose; males: use condoms during and

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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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HEMATOLOGIC CANCER reduce dose by 25%. Renal or hematologic reactions: see full labeling. Avoid concomitant strong CYP3A4 inducers (eg, rifampin): if needed, increase imatinib dose by at least 50%. Children: Take with food and water in 1 or 2 divided doses; may disperse tab in water or apple juice and take promptly. <1yrs: not recommended. ≥1yrs: Newly diagnosed Ph+CML: 340mg/m2 per day (max 600mg). Newly diagnosed Ph+ALL: 340mg/m2 per day (max 600mg); give with chemotherapy. If severe nonhematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction. Renal or hematologic reactions: see full labeling. Avoid concomitant strong CYP3A4 inducers (eg, phenytoin): if needed, increase imatinib dose by at least 50%; monitor closely. Warnings/Precautions: Hepatic or renal impairment. Monitor weight and for fluid retention regularly; CBCs weekly for 1st month, bi-weekly for 2nd month, then periodically (eg, every 2–3 months); liver function at baseline then monthly or as needed; GI symptoms at baseline. Cardiovascular disease or risk factors; monitor. Immunosuppression and potential toxicities (liver, kidney, cardiac) from long-term use. Monitor for tumor lysis syndrome; correct clinically significant dehydration and treat high uric acid levels before initiating therapy. Monitor growth in children. Possible cardiogenic shock/LV dysfunction in conditions with high eosinophil levels (eg, HES/CEL, MDS/MPD, ASM); consider concomitant systemic steroid prophylaxis (1–2mg/kg) for 1 or 2 wks if abnormal ECG or serum troponin. Monitor TSH levels in thyroidectomy patients undergoing levothyroxine replacement. Embryo-fetal toxicity. Pregnancy (avoid); exclude status prior to initiation. Females of reproductive potential should use highly effective contraception during treatment and for 14 days after cessation. Nursing mothers: not recommended (during and for 1 month after final dose). Interactions: Avoid grapefruit juice. Potentiated by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by strong CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin, rifabutin, rifampicin); consider alternatives. May potentiate drugs metabolized by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain statins, sirolimus, tacrolimus) or CYP2C9 (use heparin instead of warfarin). Caution with

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

concomitant CYP2D6 substrates that have a narrow therapeutic window. Adverse reactions: Edema (may be severe), nausea, vomiting, musculoskeletal pain, diarrhea, muscle cramps, rash (may be severe; eg, erythema multiforme, StevensJohnson syndrome), fatigue, abdominal pain, dizziness, blurred vision, somnolence, fever, headache, cough, arthralgia/myalgia, dyspnea, hypokalemia, night sweats, anorexia, pruritus, hemorrhage, anemia, neutropenia, thrombocytopenia, weight gain, renal or hepatotoxicity, immunosuppression, hypothyroidism; rare: severe CHF, LV dysfunction. Testing considerations: BCR-Abl t(9;22) in Ph+CML patients How supplied: 100mg—90; 400mg—30

HYDREA Bristol-Myers Squibb

ICLUSIG ARIAD

℞

Antimetabolite. Hydroxyurea 500mg; caps. Indications: Resistant chronic myeloid leukemia. Adults: Base dose on ideal or actual weight, whichever is less. Individualize. Initially 15mg/kg/day. Renal impairment (CrCl <60mL/min or ESRD): initially 7.5mg/kg/day; give dose following dialysis (monitor). Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: Risk of severe myelosuppression; reduce dose or discontinue if necessary. Monitor blood counts at baseline and at least once a week during therapy. Correct severe anemia before starting. Markedly depressed bone marrow function: do not initiate. Monitor for malignancies. Avoid sun exposure. Previous irradiation therapy (monitor for skin erythema) or chemotherapy. Macrocytosis may mask folic acid deficiency; prophylactic folic acid is recommended. Myeloproliferative disorders; discontinue if cutaneous vasculitic ulcerations occur. Renal or hepatic impairment. Elderly. Embryo-fetal toxicity. Pregnancy; avoid. Exclude pregnancy prior to initiating; use effective contraception during and for ≥6 months (females) or ≥1 year (males) after therapy. Nursing mothers: not recommended. Interactions: Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [monitor], fatal hepatotoxicity, peripheral neuropathy). Avoid live vaccines. Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated results in urea, uric acid, and lactic acid assays.

℞

Kinase inhibitor. Ponatinib 15mg, 30mg, 45mg; tabs; contains lactose. Indications: Treatment of adults with chronic, accelerated, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated. Treatment of adults with T315I-positive CML (chronic, accelerated, or blast phase) or T315I-positive Ph+ ALL. Limitations of use: not for treating patients with newly diagnosed chronic phase CML. Adults: Swallow whole. ≥18yrs: initially 45mg once daily; consider reducing dose in chronic and accelerated phase CML if major cytogenic response achieved. Consider discontinuing if no response occurred by 3 months. Concomitant strong CYP3A inhibitors or hepatic impairment: reduce to 30mg once daily. Dose modification for hematologic and non-hematologic toxicity: see full labeling. Children: <18yrs: not established. Warnings/Precautions: Risk of venous thromboembolism and arterial occlusion (including fatal MI, stroke, stenosis of arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures) in patients with or without CV risk factors (including ≤50yrs old, or increasing age, history of ischemia, HTN, diabetes, hyperlipidemia); monitor and interrupt or discontinue if occurs. Monitor for signs/symptoms of heart failure; interrupt or consider discontinuing if develops or worsens. Monitor hepatic function at baseline, then at least monthly or as needed; interrupt, reduce or discontinue as clinically indicated. Monitor and manage BP elevations; interrupt, reduce dose or discontinue if not controlled; evaluate for renal artery stenosis if significant worsening, labile or treatment-resistant hypertension occurs. Risk of pancreatitis; check serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated; do not restart until complete resolution and lipase levels <1.5XULN. Increased toxicity in newly diagnosed chronic phase CML: not recommended. Monitor for neuropathy; consider interrupting and evaluate

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HEMATOLOGIC CANCER if suspected. Conduct eye exams at baseline and periodically during treatment. Interrupt therapy and evaluate for serious/severe hemorrhage or cardiac arrhythmias. Monitor for fluid retention; interrupt, reduce, or discontinue as indicated. Obtain CBCs every 2 weeks for the first 3 months, then monthly or as indicated. Tumor lysis syndrome; ensure adequate hydration and treat uric levels prior to therapy. Compromised wound healing (withhold for 1 week prior to major surgery) and GI perforation. Interrupt therapy if reversible posterior leukoencephalopathy syndrome occurs; resume only when resolved and if the benefit outweighs the risk. Elderly. Embryo-fetal toxicity. Pregnancy (avoid). Females of reproductive potential should use effective contraception during and for 3 weeks after last dose. Nursing mothers: not recommended. Interactions: Potentiated by strong CYP3A inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole); see Adult dose. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, rifampin, phenytoin, St. John’s Wort). Caution with concomitant drugs that elevate gastric pH (eg, PPIs), P-gp and ABCG2 substrates. Adverse reactions: Hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, pyrexia, diarrhea, increased lipase, vomiting, myalgia, extremity pain; myelosuppression. How supplied: Tabs 15mg—30, 60, 180; 30mg— 30; 45mg—30, 90

IDAMYCIN Pfizer

℞

Anthracycline. Idarubicin HCl 20mg/vial; lyophilized pwd for IV infusion after reconstitution. ℞ Also: IDAMYCIN PFS Idarubicin 1mg/mL; soln for IV infusion; preservative-free. Indications: Acute myeloid leukemia. Adults: Give by slow IV infusion (over 10–15 mins). 12mg/m2 daily for 3 days (in combination with cytarabine). May give 2nd course if needed; if toxicity develops after 1st course, delay until resolved; reduce dose by 25%. Hepatic and renal impairment: consider reduce dose. Children: Not established. Warnings/Precautions: Pre-existing bone marrow suppression. Cardiovascular disease. Thoracic irradiation. Previous anthracycline therapy at high cumulative doses. Renal or hepatic impairment. Monitor CBCs, cardiac, renal and hepatic function prior to and during treatment. Avoid extravasation. Elderly. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended. Interactions: Concomitant drugs that suppress cardiac contractility or cardiotoxic drugs (eg, trastuzumab, cyclophosphamide, paclitaxel): not

recommended; avoid use for 5 half-lives after discontinuing cardiotoxic drug. Adverse reactions: Myelosuppression, GI upset, mucositis, abdominal pain, alopecia, rash, inj site reactions, hepatotoxicity, renal toxicity, cardiotoxicity (eg, CHF, arrhythmias, chest pain, MI, asymptomatic declines in LVEF), hyperuricemia. How supplied: Single-dose vials—1; PFS: Singledose vials (5mL, 10mL, 20mL)—1

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. ℞ Also: INTRON A SOLN Interferon alfa-2b, recombinant; 10 million IU, 18 million IU, 25 million IU; per vial; for inj; contains m-cresol. Indications: Hairy cell leukemia. Initial treatment of clinically aggressive follicular Non-Hodgkin’s lymphoma in conjunction with anthracycline-containing combination chemotherapy. Adults: Use SC route if platelets <50,000/mm3. Hairy cell leukemia: 2 million IU/m2 IM or SC 3 times a week for up to 6 months. Follicular lymphoma: 5 million IU SC 3 times a week for up to 18 months in conjunction with anthracyclinecontaining chemotherapy regimen and following completion of the chemotherapy regimen. See literature for appropriate preparation and route and for dose adjustments. Children: Not recommended. Contraindications: Decompensated liver disease. Autoimmune hepatitis. Warnings/Precautions: May cause or exacerbate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders: monitor closely, discontinue if they worsen. Severe psychiatric disorders (esp. depression). Cardiovascular or pulmonary disease. Severe myelosuppression; discontinue if neutrophil count <0.5 X109/L or platelets 25X109/L. Permanently discontinue if severe (Grade 3) hepatic injury or decompensation (Child-Pugh score >6 [Class B and C]) develop. Thyroid abnormalities; discontinue if uncontrolled by medication. Diabetes. Coagulation disorders. Maintain adequate hydration. Monitor blood, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Psoriasis. Renal dysfunction. Transplant recipients. Elderly. Debilitated.

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HEMATOLOGIC CANCER Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Caution with myelosuppressives, and drugs that can exacerbate depression. May potentiate theophylline (may double its levels). Adverse reactions: Flu-like symptoms (fever, headache, myalgia, fatigue); hepatic, hematologic, respiratory, skin, genitourinary system, CNS, cardiovascular, endocrine (esp. thyroid), GI, or visual disorders; colitis, hypertriglyceridemia, pancreatitis, infections, injection site reactions, dental and periodontal disorders; others (see full labeling). How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial—1; Soln (multidose vials): 18million, 25million IU/vial—1

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 highrisk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. Treatment of polycythemia vera (PV) in patients with inadequate response to, or intolerant of, hydroxyurea. Adults: Doses may be given by NG tube if unable to swallow tabs. Myelofibrosis: Platelets >200X109/L: initially 20mg twice daily. Platelets 100–200X109/L: initially 15mg twice daily. Platelets 50–<100X109/L: initially 5mg twice daily. May increase doses by 5mg twice daily to a max of 25mg twice daily; do not increase during the first 4 weeks of therapy and not more frequently than every 2 weeks. Discontinue treatment after 6 months if no reduction in spleen size or symptom improvement. Interrupt treatment if platelets <50X109/L or ANC <0.5X109/L. May restart after recovery of platelets or ANC (see full labeling for max allowable restarting doses). Consider dose reductions if platelets decrease but remain ≥50X109/L (see full labeling). Dose modifications for patients starting treatment with platelets 50–<100X109/L: see full labeling. PV: initially 10mg twice daily. May increase doses by 5mg twice daily to a max of 25mg twice daily; do not increase during the first 4 weeks of therapy and not more frequently than every 2 weeks. Consider dose reductions for Hgb and/or platelet decreases (see full labeling). Interrupt treatment if Hgb <8g/dL, platelets <50X109/L, or ANC <1.0X109/L. May restart after recovery of hematologic parameters (see full labeling for max allowable restarting doses). Concomitant strong CYP3A4 inhibitors (see Interactions) or fluconazole ≤200mg (Myelofibrosis): initially 10mg twice daily if platelets ≥100X109/L; if platelets 50–<100X109/L: initially 5mg once daily; (PV): initially 5mg twice daily. Other reductions, hepatic or renal impairment, ESRD: see full labeling.

Children: Not established. Warnings/Precautions: Monitor for thrombocytopenia, anemia, neutropenia; manage by reducing dose, interrupt, or transfusion if occur. Obtain CBC and platelets before initiating therapy, every 2–4 weeks until doses are stabilized, and then as clinically indicated. Risk of serious bacterial, mycobacterial, fungal, and viral infections; evaluate and treat if signs/symptoms occur. Confirm resolution of active infections before starting. May exacerbate myelofibrosis following treatment interruption or discontinuation. Risk of non-melanoma skin cancer; perform periodic skin exams. Increases in lipid parameters including total-C, LDL, triglycerides; assess 8–12 weeks after starting and treat if hyperlipidemia develops. Avoid abrupt cessation. Renal or hepatic impairment. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Avoid concomitant fluconazole doses >200mg daily. Potentiated by strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and mild or moderate CYP3A4 inhibitors (eg, erythromycin). Antagonized by strong CYP3A4 inducers (eg, rifampin). Adverse reactions: Thrombocytopenia, anemia, bruising, dizziness, headache; herpes zoster, tuberculosis (monitor promptly and test for latent infection), progressive multifocal leukoencephalopathy (discontinue if occurs), Hepatitis B. How supplied: Tabs—60

KEYTRUDA Merck

℞

Human programmed death receptor-1 (PD-1)-blocking antibody. Pembrolizumab 50mg/vial; lyophilized pwd for IV infusion after reconstitution; 25mg/mL; per vial; soln for IV infusion after dilution; both: preservative-free. Indications: Refractory classical Hodgkin lymphoma (cHL) or in patients who have relapsed after ≥3 prior lines of therapy. Adults: Give as IV infusion over 30mins. 200mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions. Children: Give as IV infusion over 30mins. 2mg/kg (max 200mg) every 3 weeks until

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HEMATOLOGIC CANCER 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, infusion-related reactions. How supplied: Single-use vial 50mg—1; Singleuse vial 25mg/mL—1

KYPROLIS Amgen Proteasome inhibitor. Carfilzomib 30mg/vial, 60mg/vial; lyophilized pwd for IV inj after reconstitution; preservative-free. Indications: In combination with dexamethasone or lenalidomide plus dexamethasone for the treatment of patients

℞

with relapsed or refractory multiple myeloma who have received 1–3 lines of therapy. As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received ≥1 lines of therapy. Adults: See full labeling. Hydrate prior to and following administration as needed. Premedicate with dexamethasone prior to all Cycle 1 doses, during subsequent cycles, and if infusion reactions occur. Give by IV on two consecutive days each week for 3 weeks (Days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest period (Days 17–28). Lenalidomide/dexamethasone combination: Infuse over 10 mins. In Cycle 1: initially 20mg/m2 per dose on Days 1 and 2; if tolerated increase to 27mg/m2 on Day 8 and subsequent cycles. From Cycle 13, omit the Day 8 and 9 doses. Discontinue carfilzomib after Cycle 18. See full labeling for lenalidomide and dexamethasone dosing. Dexamethasone combination: Infuse over 30 mins. In Cycle 1: initially 20mg/m2 per dose on Days 1 and 2; if tolerated increase to 56mg/m2 on Day 8 and subsequent cycles. Monotherapy: initially 20mg/m2 per dose in Cycle 1 on Days 1 and 2; if tolerated increase to 27mg/m2 on Day 8 (by 10-min infusion regimen) or 56mg/m2 on Day 8 (by 30-min infusion regimen) and continue same dose for subsequent cycles. From Cycle 13, omit the Day 8 and 9 doses. All: continue until disease progression or unacceptable toxicity occurs. Toxicity dose modification: see full labeling. Mild or moderate hepatic impairment: reduce dose by 25%. ESRD on dialysis: give dose after session. Children: Not established. Warnings/Precautions: Monitor for signs/symptoms of cardiac failure or ischemia; evaluate promptly if toxicity is suspected. Increased risk of cardiac complications in patients with NYHA Class III and IV heart failure, recent MI, conduction abnormalities, angina, uncontrolled arrhythmias; do full medical assessment prior to starting. Pulmonary hypertension; if suspected, withhold therapy until resolved; may consider restarting after reevaluation. Discontinue if pulmonary toxicity occurs. Monitor for dyspnea or tumor lysis syndrome (TLS), and manage promptly if occurs; interrupt therapy until resolved. Maintain adequate hydration. Monitor for volume overload. Monitor platelets frequently during therapy. Evaluate signs/symptoms of blood loss; reduce or withhold dose as appropriate. Monitor for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS); discontinue and evaluate if suspected. Discontinue and evaluate if posterior reversible encephalopathy syndrome (PRES) is suspected. Monitor BP, renal function, liver enzymes, electrolytes (eg, potassium) regularly; reduce or withhold dose as needed. Renal or hepatic impairment. Give thromboprophylaxis for combination therapy. Consider antiviral prophylaxis to prevent herpes zoster reactivation. Elderly (≥75yrs). Embry-fetal toxicity. Use

effective contraception during and for ≥30 days (females) or ≥90 days (males) after therapy completion. Pregnancy: avoid. Nursing mothers. Interactions: Increased risk of thrombosis with oral or hormonal contraceptives; consider alternatives during combination therapy. Increased fatal/serious toxicities in combination with melphalan + prednisone in newly diagnosed transplant-ineligible patients. Adverse reactions: Anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper RTI, hypokalemia, nausea, headache, peripheral edema; cardiac events, pulmonary HTN, acute kidney injury, infusion reactions, hemorrhage, TLS, hepatic toxicity/failure, TTP/HUS, PRES. How supplied: Single-use vial—1

LEUKERAN GlaxoSmithKline

℞

Alkylating agent. Chlorambucil 2mg; tabs. Indications: Palliative treatment of chronic lymphatic (lymphocytic) leukemia and malignant lymphomas (including lymphosarcoma, giant follicular lymphoma, and Hodgkin’s disease). Adults: See literature. 0.1–0.2mg/kg per day for 3–6 weeks. Reduce dose if leukocyte or platelet counts fall below normal values and discontinue if more severe depression occurs. Do not give full dose within 4 weeks of radio- or chemotherapy. Children: Not recommended. Warnings/Precautions: Compromised bone marrow function. History of seizure disorder or head trauma. Monitor blood weekly (during first 3–6 weeks, do WBC count 3–4 days after each weekly CBC). Discontinue if skin reactions occur. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: Avoid live vaccines. Myelosuppressives, radiotherapy potentiate antineoplastic effect. Caution with drugs that lower seizure threshold. Adverse reactions: Bone marrow suppression, seizures, fever, rash, hypersensitivity, urticaria, azoospermia, amenorrhea, sterility, hepato- and pulmonary toxicity, secondary malignancies, GI upset. How supplied: Tabs—50

MARQIBO Spectrum

℞

Vinca alkaloid. Vincristine sulfate liposome injection; after preparation, each vial contains 0.16mg/mL; for IV infusion. Indications: Philadelphia chromosome-negative (Ph–) acute lymphoblastic leukemia (ALL) in second or greater relapse or has progressed following ≥2 anti-leukemia therapies. Adults: 2.25mg/m2 IV over 1hr once every 7 days. Dose modifications for peripheral neuropathy: see full labeling. Children: Not established. Contraindications: Demyelinating conditions, including Charcot-Marie-Tooth syndrome. Intrathecal administration (death has occurred).

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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

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.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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

OPDIVO Bristol-Myers Squibb ℞

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

ONTAK Eisai

Adverse reactions: Fatigue, upper RTI, pyrexia, diarrhea, cough; immune-mediated reactions (may be fatal). How supplied: Single-use vial (4mL, 10mL)—1

leak syndrome (may be fatal), serious infusion reactions, visual impairment (monitor). Testing considerations: CD25 expression How supplied: Single-use vials (2mL)—6

℞

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

℞

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 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.

POMALYST Celgene

℞

Immunomodulator. Pomalidomide 1mg, 2mg, 3mg, 4mg; caps. Indications: In combination with dexamethasone for multiple myeloma, in patients who have received at least two prior therapies (including lenalidomide and a proteasome inhibitor), and have shown disease progression on or within 60 days of completion of the last therapy. Adults: Swallow whole; may be taken with water (with or without food). 4mg once daily on Days 1–21 of repeated 28-day cycles until disease progression; give with dexamethasone. Concomitant strong CYP1A2 inhibitors: consider alternatives, if necessary, reduce Pomalyst dose by 50%. Severe renal impairment requiring dialysis: initially 3mg daily; give dose after dialysis session on hemodialysis days. Hepatic impairment (mild or moderate): initially 3mg daily; (severe): 2mg daily. Dose modification for hematologic and other Grade 3/4 toxicities: see full labeling. Children: <18yrs: not established. Contraindications: Pregnancy (Cat.X): avoid during and for at least 4 weeks after completing therapy. Warnings/Precautions: Females of reproductive potential must commit either to abstain from heterosexual sex or to use two methods of reliable contraception, beginning 4 weeks prior to initiating, during therapy, dose interruptions and for 4 weeks after discontinuation. Obtain two negative pregnancy tests prior to initiating therapy: perform first test within 10–14 days, and second test within 24hrs prior to prescribing, and then weekly during first month, then monthly thereafter in women with regular menstrual cycles or every 2 weeks if irregular cycles. Males: must use latex or synthetic condom during therapy and up to 28 days after discontinuing, even after successful vasectomy; do not donate sperm. Patients must not donate blood during therapy and for 1 month after discontinuation. Venous and arterial thromboembolism; consider anticoagulation prophylaxis. Monitor for hematologic toxicities (esp. neutropenia); obtain CBCs weekly for first 8 weeks and monthly thereafter; may need dose interruption and/or modification. Hepatic or severe renal impairment on hemodialysis: adjust doses (see Adults). Monitor LFTs monthly; discontinue and evaluate if elevated liver enzymes occur; consider using lower dose when restarting. Risk of second primary malignancies. High tumor burden (monitor). Discontinue if angioedema, skin exfoliation, bullae, or other severe dermatologic reactions occur; do not restart. Nursing mothers: not recommended.

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 Epstein-Barr 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. Embryo-fetal 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. 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

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HEMATOLOGIC CANCER 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 single-agent 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. 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

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HEMATOLOGIC CANCER 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. 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, Stevens-Johnson 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.

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HEMATOLOGIC CANCER 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. 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.

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HEMATOLOGIC CANCER 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-to-severe neuritis with severe ENL: give concomitant corticosteroids (see full labeling). Consider dose reduction, delay, or discontinuation in those who develop NCI CTC Grade 3/4 adverse reactions. Children: <12yrs: not established. Contraindications: Pregnancy. Women who may become pregnant. Warnings/Precautions: Must register patient in STEPS program; patient must understand toxicity with fetal exposure. Counsel patient on need for contraception; female: use 2 forms of contraception 1 month before, during, and 1 month after therapy; male: use condom during and 1 month after therapy; obtain negative pregnancy test within 24 hours prior to starting treatment; repeat at least weekly for 1st month then every 4 weeks; get informed consent. Monitor for neuropathy monthly for first 3 months; discontinue if symptoms develop. Monitor for signs/symptoms of thromboembolic events, neutropenia, bradycardia, syncope, orthostatic hypotension, tumor lysis syndrome. Reevaluate if ANC <750/mm2; consider withholding if neutropenia persists. Monitor blood and platelet counts. Monitor for signs/symptoms of bleeding including petechiae, epistaxis, and GI bleed. Measure HIV viral load after 1st and 3rd months, and every 3 months thereafter. Discontinue if pregnancy or severe skin rash occurs. History of seizure. Avoid contact with non-intact capsule or powder content. Maximum 1 month per . Nursing mothers: not recommended. Interactions: Increased sedative effect with barbiturates, alcohol, chlorpromazine, reserpine. Caution with drugs associated with peripheral neuropathy. Avoid drugs (eg, rifampin, carbamazepine, St. John’s wort) that decrease effectiveness of hormonal contraceptives. Increased risk of thromboembolism with concomitant erythropoietic agents, or estrogencontaining therapies in those receiving thalidomide with dexamethasone. Adverse reactions: Fatigue, birth defects, somnolence, skin rash (eg, Stevens-Johnson

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER Syndrome, toxic epidermal necrolysis), headache, bradycardia, peripheral neuropathy, seizures, drowsiness, dizziness, orthostatic hypotension, leukopenia, anorexia, nausea, anxiety, asthenia, tremor, fever, weight loss, dry skin, neutropenia, increased HIV viral load, constipation, confusion, hypocalcemia, edema, dyspnea, thrombosis/embolism, thrombocytopenia. Note: Available only through STEPS program. Suspected fetal exposure must be reported to the FDA at (800) FDA-1088 and Celgene at (888) 423-5436. How supplied: Blister packs (50mg)—1, 28; (100mg, 150mg, 200mg)—28

TREANDA Teva

℞

Alkylating agent. Bendamustine HCl 25mg, 100mg; per vial; lyophilized pwd for IV infusion after reconstitution; preservative-free. Indications: Chronic lymphocytic leukemia (CLL). Indolent B-cell non-Hodgkin’s lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab or a rituximab–containing regimen. Adults: CLL: Give by IV infusion over 30mins. 100mg/m2 on Days 1 and 2 of a 28-day cycle, up to 6 cycles. Hematologic toxicity (≥Grade 3): reduce dose to 50mg/m2 on Days 1 and 2 of each cycle; if toxicity recurs, reduce dose to 25mg/m2 on Days 1 and 2. Non-hematologic toxicity (clinically significant ≥Grade 3): reduce dose to 50mg/m2 on Days 1 and 2 of each cycle. Subsequent cycles: may consider dose re-escalation. NHL: Give by IV infusion over 60mins. 120mg/m2 on Days 1 and 2 of a 21-day cycle, up to 8 cycles. Hematologic toxicity (Grade 4) or non-hematologic toxicity (≥Grade 3): reduce dose to 90mg/m2 on Days 1 and 2 of each cycle; if toxicity recurs, reduce dose to 60mg/m2 on Days 1 and 2. Delay treatment for Grade 4 hematologic toxicity or clinically significant ≥Grade 2 non-hematologic toxicity. Children: Not established. Warnings/Precautions: Myelosuppression; monitor CBCs including leukocytes, platelets, hemoglobin, neutrophils frequently; restart treatment based on ANC and platelet count recovery. Monitor for signs of infection or reactivation of infections (eg, hepatitis B, CMV, tuberculosis, herpes zoster); prophylaxis and treat prior to therapy if occur. Monitor for infusion or skin reactions, tumor lysis syndrome. Monitor LFTs prior to and during therapy. Renal impairment (mild or moderate): caution; (CrCl <40mL/min): not recommended. Hepatic impairment (mild): caution; (moderate or severe): not recommended. Avoid extravasation. Embryofetal toxicity. Pregnancy (Cat.D); avoid during and for 3 months after therapy cessation. Nursing mothers: not recommended. Interactions: May be potentiated CYP1A2 inhibitors (eg, fluvoxamine, ciprofloxacin) or antagonized by CYP1A2 inducers (eg, omeprazole, smoking); if needed, consider alternatives.

Adverse reactions: Lymphopenia, anemia, leukopenia, thrombocytopenia, neutropenia, pyrexia, nausea, vomiting, fatigue, diarrhea, constipation, anorexia, cough, headache, weight loss, dyspnea, stomatitis, increased bilirubin, increased AST/ALT; infection, infusion reactions (discontinue if severe), tumor lysis syndrome, skin reactions (if severe or progressive, withhold dose or discontinue), other malignancies (eg, myelodysplastic syndrome, acute myeloid leukemia, bronchial carcinoma). How supplied: Single-use vial—1

TREXALL Teva

℞

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

fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated. Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, non-absorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine) and nephrotoxic agents (eg, cisplatin). Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, GI upset, malaise, fatigue, chills, fever, dizziness, infection, myelosuppression, hepatotoxicity, renal toxicity, CNS toxicity, seizures (esp in children); interstitial pneumonitis, tumor lysis syndrome, skin reactions (may be fatal; eg, toxic epidermal necrolysis, Stevens-Johnson syndrome). How supplied: Tabs—30; soln (2mL, 4mL, 8mL, 10mL)—10 (single-use vials); pwd (1 gram)—1 (single-use vial)

TRISENOX Teva

℞

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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 moderately-to-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-to-severe hepatic impairment: reduce to 0.7mg/m2 in 1st cycle; may consider dose increase to 1mg/m2 or further decrease to 0.5mg/m2 in subsequent cycles based on tolerance. Children: Not established. Contraindications: Boron or mannitol sensitivity. Intrathecal administration. Warnings/Precautions: Hepatic impairment. Pre-existing severe neuropathy; treat only after careful risk-benefit assessment. Monitor for development or worsening of peripheral neuropathy; consider dose and/or schedule adjustment. Diabetes (closely monitor blood glucose). History of syncope. Avoid dehydration; give fluids and electrolytes. Heart disease (monitor for CHF). Interrupt therapy and evaluate if new or worsening cardiopulmonary symptoms develop. Monitor CBC frequently during therapy and platelets prior to each dose; adjust dose/schedule for thrombocytopenia (see full labeling). Monitor for toxicities. High tumor burden (monitor for tumor lysis syndrome). Pregnancy (Cat.D); avoid. Nursing mothers: not recommended. Interactions: 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

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 preexisting abnormalities prior to initiation. Risk of neutropenia; monitor CBCs during therapy; interrupt or reduce dose if severe. Severe renal impairment or on dialysis. Moderate or severe hepatic impairment: monitor closely. Embryofetal toxicity. Females of reproductive potential: should undergo pregnancy testing prior to initiation. Pregnancy; avoid. Use effective contraception during and for ≥1 month after final dose. Nursing mothers: not recommended. Interactions: See Contraindications. Concomitant strong CYP3A inhibitors after ramp-up phase (eg, ketoconazole, conivaptan, clarithromycin, indinavir, itraconazole, lopinavir, ritonavir, telaprevir, posaconazole, voriconazole); avoid use or reduce venetoclax steady daily dose by ≥75%. Avoid concomitant moderate CYP3A inhibitors (eg, erythromycin, ciprofloxacin, diltiazem, dronedarone, fluconazole, verapamil) or P-gp inhibitors (eg, amiodarone, azithromycin, captopril, carvedilol, cyclosporine, felodipine, quercetin, quinidine, ranolazine, rifampin, ticagrelor); consider alternatives; if inhibitor necessary, reduce venetoclax dose by ≥50% and monitor closely. Resume at prior venetoclax dose 2–3 days after discontinuing the inhibitor. Avoid concomitant strong CYP3A inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s Wort) or moderate CYP3A inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin); consider alternatives. Avoid live attenuated vaccines until B-cell recovery. Avoid grapefruit, Seville oranges,

and starfruit during treatment. Monitor INR closely with concomitant warfarin. Avoid P-gp substrates with narrow therapeutic index (eg, digoxin, everolimus, sirolimus); if necessary, take ≥6hrs before venetoclax. Adverse reactions: Neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, fatigue. How supplied: Starting Packs—1; Wallets 10mg—14; 50mg—7; Tabs 100mg—120

VESANOID Roche

℞

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

VIDAZA Celgene

℞

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

Indications: Myelodysplastic syndromes (refractory anemias, chronic myelomonocytic leukemia). Adults: Premedicate for nausea & vomiting. Rotate SC inj sites. Initially 75mg/m2 SC (doses >4mL divide equally into 2 syringes and inject into 2 separate sites, must administer within 1hr of reconstitution) or IV (infuse over 10–40mins, must complete within 1hr of reconstitution) daily for 7 days; repeat cycle every 4 weeks. May increase to 100mg/m2 after 2 cycles if no response and no toxicity. Treat for at least 4–6 cycles. Adjust subsequent doses based on nadir counts, hematologic response, and toxicities (eg, neutropenia, thrombocytopenia, decreased serum bicarbonate, BUN or SCr elevation); see full labeling. Children: Not established. Contraindications: Advanced malignant hepatic tumors. Warnings/Precautions: Myelosuppression. Monitor CBCs frequently for response and/or toxicity, at a minimum, prior to each dosing cycle. Renal or hepatic impairment. High tumor burden. Monitor serum bicarbonate, liver chemistries, and serum creatinine prior to initiation and with each cycle. Monitor for tumor lysis syndrome and treat as appropriate. Elderly. Embryo-fetal toxicity. Females and males of reproductive potential should use effective contraception. Pregnancy: avoid; verify status prior to initiation. Nursing mothers: not recommended. Adverse reactions: Nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, inj site erythema, constipation, neutropenia, ecchymosis, petechiae, rigors, weakness, hypokalemia; renal failure/tubular acidosis, hepatic coma. How supplied: Single-use vial—1

VUMON Bristol-Myers Squibb

℞

Topoisomerase inhibitor. Teniposide 10mg/mL; soln for IV infusion after dilution; contains benzyl alcohol, Cremophor EL (polyoxyethylated castor oil), dehydrated alcohol. Indications: Refractory childhood acute lymphoblastic leukemia. Adults and Children: See literature. Give as slow IV infusion (at least 30–60 minutes). Patients failing induction therapy with a cytarabine-containing regimen: 165mg/m2 + cytarabine twice weekly for 8 to 9 doses. Refractory to vincristine/prednisone-containing regimen: 250mg/m2 + vincristine weekly for 4 to 8 weeks + oral prednisone for 28 days. Warnings/Precautions: Severe myelosuppression. Monitor for hypersensitivity reactions following infusion; have epinephrine available. Risk of hypotension with rapid IV administration. Hepatic dysfunction. Monitor and obtain CBCs with differential, hemoglobin, platelets, renal and hepatic functions before, during, and after therapy. Down syndrome (use reduced dose). Monitor children with

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DRUG MONOGRAPHS

HEMATOLOGIC CANCER 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 cytarabinecontaining 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 thirdspace accumulations prior to administration. Embryo-fetal toxicity. Exclude pregnancy in females of reproductive potential; use effective contraception during therapy and for 6 months after final dose and for at least 3 months after final dose for men. Nursing mothers: not recommended. Interactions: Avoid live virus vaccines. Severe and fatal GI toxicity with concomitant NSAIDs. May be potentiated by penicillins (monitor) or probenecid (consider alternative). May potentiate theophylline. Increased bone marrow suppression with trimethoprim/sulfamethoxazole; monitor. Increased risk of soft tissue necrosis and osteonecrosis with radiation therapy. Caution with other hepatotoxic drugs (eg, azathioprine, retinoids, sulfasalazine). Adverse reactions: Ulcerative stomatitis, leukopenia, nausea, abdominal distress, elevated liver function tests, malaise, fatigue, chills, fever, dizziness, decreased resistance to infection; bone marrow suppression, infections, renal toxicity, GI toxicity, hepatotoxicity, pulmonary toxicity, hypersensitivity, dermatologic reactions, secondary malignancies, infertility. How supplied: Oral soln—120mL

ZEVALIN Spectrum

℞

Radionuclide (B-lymphocyte-restricted differentiation antigen [CD20] inhibitor). Ibritumomab tiuxetan 3.2mg/2mL; soln for IV inj; contains albumin; preservative-free. Indications: B-cell non-Hodgkin’s lymphoma (relapsed or refractory, low grade or follicular). Previously untreated follicular non-Hodgkin’s lymphoma in patients who achieve a partial or complete response to first-line chemotherapy. Adults: See literature. Prepare In-111 Zevalin and Y-90 Zevalin as directed. Initiate Zevalin therapy after recovery of platelets to ≥150,000/mm3 at least 6 weeks, but no more than 12 weeks, after the last dose of first-line chemotherapy. Administered in two steps. Step 1: Single infusion of rituximab followed by a fixed dose of 5mCi (1.6mg total antibody dose) of In-111 Zevalin given as a 10-minute IV push. Step 2 (7–9 days

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HEMATOLOGIC CANCER 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 nonHodgkin lymphoma (FL) in patients who have received at least 2 prior systemic therapies. Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least 2 prior systemic therapies. Limitations of use: not recommended for first-line treatment of CLL, FL, or SLL. Adults: Swallow whole. ≥18yrs: initially 150mg twice daily; continue until disease progression or unacceptable toxicity. Dose modifications: see full labeling. Children: <18yrs: not established. Contraindications: History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis. Warnings/Precautions: Risk of fatal/serious hepatotoxicity: monitor ALT/AST every 2 weeks for the first 3 months, every 4 weeks for the next 3 months, then every 1–3 months thereafter; if ALT/AST >3XULN, monitor weekly until resolved; if ALT/AST >5XULN, withhold and continue monitoring weekly until resolved; if ALT/AST >20XULN, discontinue permanently. Monitor for diarrhea or colitis; withhold if severe or hospitalization; discontinue if life-threatening. Risk of fatal/serious pneumonitis; monitor for pulmonary symptoms or a decline by >5% in oxygen saturation; if suspected, interrupt or discontinue as indicated. Risk of fatal/serious infections; monitor for signs/symptoms and interrupt if Grade ≥3. Risk of fatal/serious intestinal perforation; discontinue permanently if occurs. Monitor for severe cutaneous or serious allergic reactions; discontinue if occur. Monitor CBCs at least every 2 weeks for the first 6 months, and at least weekly if neutrophils <1.0Gi/L. Pregnancy (Cat.D); avoid. Use effective contraception during treatment and for at least 1 month after last dose. Nursing mothers: not recommended. Interactions: Avoid concomitant drugs that may cause hepatotoxicity or diarrhea. Avoid concomitant strong CYP3A inducers (eg, rifampin, phenytoin, St. John’s wort, carbamazepine) or CYP3A substrates (eg, oral midazolam). Concomitant strong CYP3A inhibitors (eg, ketoconazole); monitor for idelalisib toxicity. Adverse reactions: Diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, rash, neutropenia, ALT/AST elevations. How supplied: Tabs—60

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DRUG MONOGRAPHS

LUNG CANCER ABRAXANE Celgene

℞

Taxane antimicrotubule. Paclitaxel [bound to albumin (human)] 100mg/vial; pwd for IV infusion after reconstitution; solvent-free. Indications: First-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy. Adults: Do not treat if neutrophil count <1,500 cells/mm3 or platelets <100,000 cells/mm3. In combination with carboplatin: 100mg/m2 IV over 30 mins on Days 1, 8, and 15 of each 21-day cycle. Dose reductions for hematologic and neurologic adverse reactions, hepatic impairment: see full labeling. Avoid extravasation. Children: Not evaluated. Contraindications: Baseline neutrophil count <1,500 cells/mm3. Prior severe hypersensitivity reaction (do not rechallenge). Warnings/Precautions: Do not substitute for, or with, other paclitaxel products (due to formulation differences). Do frequent complete blood cell counts. Hepatic impairment (total bilirubin >5XULN or AST >10XULN): not recommended. Monitor for sensory neuropathy, sepsis, or pneumonitis. Renal dysfunction. Contains human albumin; remote risk of viral transmission. Use appropriate contraception (men and women). Pregnancy (Cat.D), nursing mothers: not recommended. Interactions: May potentiate or be potentiated by CYP2C8 and/or CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, efavirenz, nevirapine) and/or inhibitors (eg, ketoconazole, other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, nelfinavir). Adverse reactions: Bone marrow suppression (eg, neutropenia, anemia), infections, alopecia, sensory neuropathy (may require dose reduction or interruption), peripheral neuropathy, GI upset, mucositis, fatigue/asthenia, myalgia/arthralgia, abnormal ECG; alkaline phosphatase or AST elevation; dyspnea, edema, hypotension, rash (may be serious); rare: thrombotic events. How supplied: Single-use vial—1

ALECENSA Genentech

℞

Kinase inhibitor. Alectinib 150mg; caps. Indications: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

Adults: Swallow whole. Take with food. 600mg twice daily until disease progression or unacceptable toxicity. Dose modifications or dose reduction schedule: see full labeling. Children: Not established. Warnings/Precautions: Monitor liver function tests (eg, ALT, AST, total bilirubin) every 2 weeks for the first 2 months, then monthly and as clinically indicated; test more frequently if transaminase and bilirubin elevated; withhold, resume at reduced dose, or permanently discontinue based on severity. Evaluate if presence of worsening respiratory symptoms; withhold if ILD/pneumonitis diagnosed; permanently discontinue if no other cause identified. Monitor HR, BP regularly. If non-lifethreatening symptomatic bradycardia occurs, withhold until asymptomatic or HR ≥60bpm; permanently discontinue in case(s) of recurrence or life-threatening bradycardia if no contributing concomitant medication identified. Assess CPK every 2 weeks for the first month and as clinically indicated; withhold, resume, or reduce dose based on severity. Embryo-fetal toxicity. Pregnancy: avoid. Females of reproductive potential should use effective contraception during treatment and for 1 week after final dose; males should use effective contraception during treatment and for 3 months after final dose. Nursing mothers: not recommended (during and for 1 week after final dose). Interactions: Increased bradycardia with concomitant antihypertensives or other drugs known to cause bradycardia. Adverse reactions: Fatigue, constipation, edema, myalgia; hepatotoxicity, ILD/pneumonitis, bradycardia, CPK elevation. How supplied: Caps—240

ALIMTA Lilly

℞

Antifolate. Pemetrexed 100mg/vial, 500mg/vial; pwd for IV inj after reconstitution and dilution; preservative-free. Indications: Locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC): in combination with cisplatin as initial treatment, or as maintenance in patients whose disease has not progressed after 4 cycles of platinum-based 1st-line chemotherapy; or as a single agent after prior chemotherapy. Malignant pleural mesothelioma (MPM): in combination with cisplatin in patients whose disease is either unresectable or who are otherwise not candidates for curative surgery. Limitations of use: not for the treatment of squamous cell NSCLC.

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

ALUNBRIG Takeda

℞

Kinase inhibitor. Brigatinib 30mg, 90mg; tabs. Indications: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. Adults: Swallow whole. Initially 90mg once daily for first 7 days; if tolerated, increase to 180mg once daily until disease progression or unacceptable toxicity. Dose modifications or dose reduction levels: see full labeling. Children: Not established. Warnings/Precautions: Monitor for new or worsening respiratory symptoms esp. during 1st week of initiation; if occurs, withhold and evaluate for ILD/pneumonitis; resume at same

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LUNG CANCER dose for Grade 1 or reduced dose for Grade 2 severity; permanently discontinue for Grade 3/4 or recurrent Grade 1/2 ILD/pneumonitis. Monitor BP after 2 weeks and at least monthly thereafter; withhold for Grade 3 hypertension despite optimal antihypertensive therapy; resume at reduced dose upon improvement to Grade 1 severity; consider permanent discontinuation for Grade 4 or recurrent Grade 3 hypertension. Monitor HR and BP regularly; if symptomatic bradycardia occurs, withhold and evaluate any concomitant drugs that are known to cause bradycardia; resume at same or reduced dose after resolution; discontinue for life-threatening bradycardia if no contributing concomitant medication identified. Withhold and evaluate for new or worsening visual symptoms of Grade ≥2 severity; resume at reduced doses upon recovery to Grade 1 or baseline; permanently discontinue for Grade 4 visual disturbances. Monitor CPK, lipase, and amylase levels during treatment; withhold for Grade 3/4 elevation; resume at same or reduced dose upon recovery to Grade 1 or baseline. Assess fasting serum glucose prior to initiation and periodically thereafter; if not adequately controlled with optimal antihyperglycemics, withhold then consider dose reduction, or permanently discontinue based on severity. Embryo-fetal toxicity. Pregnancy: avoid. Females of reproductive potential should use effective non-hormonal contraception during treatment and for at least 4 months after final dose; males should use effective contraception during treatment and for at least 3 months after final dose. Nursing mothers: not recommended (during and for 1 week after final dose). Interactions: Avoid concomitant strong CYP3A inhibitors (eg, boceprevir, cobicistat, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan); if unavoidable, reduce Alunbrig dose by ~50%. Avoid grapefruit or grapefruit juice. Avoid concomitant strong CYP3A inducers (eg, rifampin, carbamazepine, phenytoin, St. John’s wort). May reduce efficacy of CYP3A substrates (eg, hormonal contraceptives). Caution with antihypertensives that cause bradycardia. Adverse reactions: Nausea, diarrhea, fatigue, cough, headache; ILD/pneumonitis, hypertension, bradycardia, visual disturbances, CPK elevation, pancreatic enzyme elevation, hyperglycemia, possible infertility in males. How supplied: Tabs 30mg—21, 180; 90mg—7, 30

AVASTIN Genentech

℞

Angiogenesis inhibitor. Bevacizumab 100mg, 400mg; per vial; soln for IV infusion after dilution; preservative-free. Indications: First-line treatment of unresectable, locally advanced, recurrent or metastatic non-

squamous, 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. 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 disease progression or not tolerated. Severe renal

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LUNG CANCER impairment (CrCl 15–29mL/min): 30mg once daily. Concomitant P-gp inhibitors: reduce afatinib daily dose by 10mg if not tolerated; resume previous dose after discontinuing the inhibitor. Concomitant P-gp inducers: increase afatinib daily dose by 10mg as tolerated; resume previous dose 2–3 days after discontinuing the inducer. Dose modification: see full labeling. Children: Not established. Warnings/Precautions: Permanently discontinue for life-threatening bullous, blistering, or exfoliative skin lesions, confirmed interstitial lung disease (ILD), severe druginduced hepatic impairment, persistent ulcerative keratitis, symptomatic left ventricular dysfunction, or severe/intolerable adverse reactions (at dose 20mg/day). Withhold for severe or prolonged diarrhea Grade ≥2 lasting for ≥2 consecutive days while taking antidiarrheal, prolonged cutaneous reaction Grade ≥2 (lasting >7 days) or intolerable, during evaluation of suspected ILD, renal dysfunction Grade ≥2, or worsening liver function. History of keratitis, ulcerative keratitis, or severe dry eye. Obtain LFTs periodically during treatment. Monitor closely in moderate-to-severe renal impairment or severe hepatic impairment; adjust dose if not tolerated. Embryo-fetal toxicity. Pregnancy (avoid). Females of reproductive potential should use effective contraception during therapy and for at least 2 weeks after final dose. Nursing mothers: not recommended (during therapy and for 2 weeks after final dose). Interactions: Potentiated by P-gp inhibitors (eg, ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, amiodarone). Antagonized by P-gp inducers (eg, rifampicin, carbamazepine, phenytoin, phenobarbital, St. John’s wort). Adverse reactions: Diarrhea, rash/dermatitis acneiform, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, pruritus; bullous/exfoliative skin disorders, ILD, hepatotoxicity, keratitis. How supplied: Tabs—30

HYCAMTIN GlaxoSmithKline

℞

Topoisomerase inhibitor. Topotecan (as HCl) 4mg/vial; pwd for IV infusion after reconstitution and dilution; contains mannitol; preservativefree. Indications: Small cell lung cancer sensitive disease after failure of 1st line chemotherapy. Adults: Verify dose using BSA. Usual max dose 4mg IV. Confirm baseline

neutrophils ≥1,500cells/mm3 and platelets ≥100,000cells/mm3 prior to 1st course of therapy. Give by IV infusion over 30 mins. 1.5mg/m2 daily for 5 consecutive days starting on Day 1 of a 21-day cycle. Dose adjustments, renal impairment: see full labeling. Children: Not established. ℞ Also: HYCAMTIN CAPSULES Topotecan (as HCl) 0.25mg, 1mg; caps. Indications: Relapsed small cell lung cancer with prior complete or partial response and at least 45 days from the end of 1st line chemotherapy. Adults: Confirm baseline neutrophils ≥1,500cells/mm3 and platelets ≥100,000cells/mm3 prior to 1st course of therapy. Swallow whole. 2.3mg/m2/day once daily for 5 consecutive days; repeat every 21 days. Dose adjustments, renal impairment: see full labeling. Children: Not established. Warnings/Precautions: Monitor peripheral blood cell counts during therapy; hold subsequent doses until neutrophils >1,000cells/mm3, platelets >100,000cells/mm3, and hemoglobin ≥9g/dL. History of interstitial lung disease, pulmonary fibrosis, lung cancer, thoracic exposure to radiation, use of pneumotoxic drugs and/or colony stimulating factors: increased risk of interstitial lung disease; monitor, discontinue if occurs. Moderate to severe renal impairment. Caps: severe diarrhea; may need to reduce dose. IV: avoid extravasation. Elderly. Use effective contraception during and for ≥1 month after last dose (in females), or during and for ≥3 months (in males with female partners). Pregnancy (Cat.D). Nursing mothers: not recommended. Interactions: IV: Myelosuppression potentiated with platinum agents. Neutropenia potentiated by G-CSF; administer ≥24hrs after last topotecan dose. Caps: Avoid concomitant P-glycoprotein inhibitors (eg, amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir, ritonavir, quercetin, quinidine, ranolazine, ticagrelor, verapamil) and BCRP inhibitors (eg, cyclosporine, eltrombopag). Adverse reactions: See full labeling. Neutropenia, leukopenia, thrombocytopenia, anemia, nausea, vomiting, diarrhea, anorexia, abdominal pain, stomatitis, headache, dyspnea, cough, pyrexia, alopecia, fatigue; infection, sepsis, interstitial lung disease, neutropenic colitis (may be fatal). How supplied: Single-use vials—1; Caps—10

IRESSA AstraZeneca

℞

Tyrosine kinase inhibitor. Gefitinib 250mg; tabs. Indications: First-line treatment of metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Limitations of use: not established in metastatic NSCLC with EGFR mutations other than exon 19 deletions or exon 21 substitution mutations. Adults: May disperse tabs in water; drink immediately or give via NG tube. Give 250mg once daily until disease progression or unacceptable toxicity occurs. Dose modifications for adverse reactions: see full labeling. Concomitant strong CYP3A4 inducers: increase to 500mg daily; resume at 250mg seven days after discontinuation of the CYP3A4 inducer. Children: Not established. Warnings/Precautions: Permanently discontinue if confirmed interstitial lung disease (ILD), severe hepatic impairment, GI perforation, or persistent ulcerative keratitis occurs. Withhold for up to 14 days if acute onset or worsening pulmonary symptoms, NCI CTCAE Grade ≥2 ALT and/or AST elevations, Grade ≥3 diarrhea or skin reactions, or severe or worsening ocular disorders (including keratitis) occurs. Interrupt or discontinue therapy if severe bullous and exfoliative skin disorders develop. Obtain periodic LFTs. Moderate and severe hepatic impairment; monitor. Use effective contraception during treatment and for at least 2 weeks after completion. Pregnancy, nursing mothers: not recommended. Interactions: Potentiated by strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole); monitor. Antagonized by strong CYP3A4 inducers (eg, rifampicin, phenytoin, tricyclics); see Adults. May be antagonized by drugs that increase gastric pH (eg, H2-blockers, antacids); take gefitinib 6 hours after or 6 hours before an H2-blocker or antacid. Avoid concomitant PPIs; if necessary, take gefitinib 12 hours after last dose or 12 hours before next PPI dose. May potentiate warfarin; monitor INR. Adverse reactions: Skin reactions, diarrhea, vomiting, decreased appetite, stomatitis; ILD, hepatotoxicity, GI perforation, ocular disorders. Testing considerations: EGFR mutation analysis. How supplied: Tabs—30

KEYTRUDA Merck

℞

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

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LUNG CANCER soln for IV infusion after dilution; both: preservative-free. Indications: First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥50%)] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. Treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinumcontaining chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda. First-line treatment of patients with metastatic nonsquamous NSCLC, in combination with pemetrexed and carboplatin. Adults: Give as IV infusion over 30mins. 200mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In 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

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DRUG MONOGRAPHS

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

OPDIVO Bristol-Myers Squibb

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol. Indications: Metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Adults: Give as IV infusion over 60mins. 240mg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: See full labeling. Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade

3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed 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, musculoskeletal pain, decreased appetite, cough, constipation; immune-mediated reactions (may be fatal). How supplied: Single-use vial (4mL, 10mL)—1

PORTRAZZA Lilly

℞

Human epidermal growth factor receptor (EGFR) inhibitor. Necitumumab 800mg/50mL; soln for IV infusion after dilution; preservative-free. Indications: In combination with gemcitabine and cisplatin, for first-line treatment of metastatic squamous non-small cell lung cancer. Limitations of use: not for treatment of non-squamous nonsmall cell lung cancer. Adults: Give by IV infusion over 60 mins prior to gemcitabine and cisplatin infusion. 800mg on Days 1 and 8 of each 3-week cycle; continue until disease progression or unacceptable toxicity. May premedicate with diphenhydramine HCl (or equivalent) if previously experienced a Grade 1/2

infusion-related reaction. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: Risk of cardiopulmonary arrest and/or sudden death, hypomagnesemia. History of coronary artery disease, CHF, or arrhythmias. Monitor serum electrolytes (eg, magnesium, potassium, calcium) prior to each infusion during therapy and for 8 weeks after last dose; withhold for Grade 3/4 electrolyte abnormalities and may resume once improved to Grade ≤2. Discontinue if serious or life-threatening venous/arterial thromboembolic events or infusion-related reactions occur. Discontinue if Grade 4 skin reactions or Grade 3 skin induration/fibrosis occurs. Limit sun exposure. Embryo-fetal toxicity. Pregnancy; avoid. Use effective contraception during treatment and for 3 months after last dose. Nursing mothers: not recommended (during therapy and for 3 months after last dose). Adverse reactions: Rash, dermatitis acneiform, vomiting, diarrhea, thromboembolic events, hypomagnesemia, hypocalcemia, hypokalemia; cardiopulmonary arrest, dermatologic toxicities, infusion reactions. How supplied: Single-use vial—1

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 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

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LUNG CANCER 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-tosevere 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

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

TAGRISSO AstraZeneca

TARCEVA Astellas and Genentech

℞

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

℞

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), 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

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DRUG MONOGRAPHS

LUNG CANCER skin conditions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis). Testing considerations: K-RAS mutation analysis, EGFR amplification analysis How supplied: Tabs—30

TECENTRIQ Genentech

℞

Programmed death-ligand 1 (PD-L1) blocking antibody. Atezolizumab 60mg/mL; soln for IV infusion after dilution; preservative-free. Indications: Metastatic non-small cell lung cancer (NSCLC) in patients with disease progression during or after platinum-containing chemotherapy. Adults: Give as IV infusion over 60mins. 1200mg every 3 weeks until disease progression or unacceptable toxicity. May give subsequent infusions over 30mins if first infusion tolerated. Children: Not established. Warnings/Precautions: Permanently discontinue if Grade 3/4 pneumonitis, AST or ALT >5×ULN or total bilirubin >3×ULN, Grade 4 diarrhea or colitis, Grade 4 hypophysitis, myasthenic syndrome/myasthenia gravis, Guillain-Barre or meningoencephalitis, Grade 3/4 ocular inflammatory toxicity, Grade 4 or recurrent pancreatitis, Grade 3/4 infusionrelated reactions, or Grade 4 rash. Withhold for Grade 2 pneumonitis, AST or ALT >3–5×ULN or total bilirubin >1.5–3×ULN, Grade 2/3 diarrhea or colitis, symptomatic hypophysitis, adrenal insufficiency, hypothyroidism, hyperthyroidism, Grade 3/4 hyperglycemia, Grade 2 ocular inflammatory toxicity, Grade 2/3 pancreatitis or Grade 3/4 increases in amylase or lipase levels (>2×ULN), Grade 3/4 infection, Grade 2 infusionrelated reactions, or Grade 3 rash; may be resumed when recover to Grade 0–1. Monitor for immune-related pneumonitis, hepatitis (obtain AST, ALT, bilirubin prior to and during treatment), diarrhea/colitis, endocrinopathies (hypophysitis, thyroid function, adrenal insufficiency, diabetes), meningitis or encephalitis, motor and sensory neuropathy, and acute pancreatitis; see full labeling for adverse reaction management details. Monitor for signs/symptoms of infection and treat with antibiotics for suspected or confirmed bacterial infections. Interrupt or slow the infusion rate in patients with mild or moderate infusion reactions. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity. Pregnancy. Use effective contraception during and for ≥5 months after final dose. Nursing mothers: not recommended (during and for ≥5 months after final dose).

Adverse reactions: Fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, constipation; immune-related reactions, lab abnormalities. How supplied: Single-dose vial (20mL)—1

TREXALL Teva

℞

Folic acid antagonist. Methotrexate sodium 5mg, 7.5mg, 10mg, 15mg; scored tabs. ℞ Also: Methotrexate injection Bedford Methotrexate 25mg/mL; soln for IV, IM, intraarterial, or intrathecal administration after dilution; preservative-free. ℞ Also: Methotrexate for injection Bedford Methotrexate 1g/vial; pwd for IV, IM, intra-arterial, or intrathecal administration after dilution; preservative-free. Indications: Lung cancer (squamous cell and small cell types). Adults: See literature. Children: Not established. Contraindications: Pregnancy (Cat. X). Nursing mothers. Warnings/Precautions: Be fully familiar with this drug’s toxicity before use. Discontinue if malignant lymphomas occur. Obtain baseline and monitor CBCs with differential, platelet counts, chest X-ray, and hepatic, renal and pulmonary function. During therapy monitor hematology monthly, renal and hepatic function every 1–2 months, more often if increasing dose or predisposed to toxicity (eg, dehydration). Discontinue immediately if blood counts drop significantly. Rule out pregnancy in women of childbearing potential; use effective contraception during therapy and for at least 1 ovulatory cycle afterwards for women and for at least 3 months afterwards for men. Interrupt therapy if vomiting, diarrhea, stomatitis, or pulmonary symptoms occur. Hepatic or renal impairment. Obesity. Diabetes. Peptic ulcer. Ulcerative colitis. Infection. Dehydration. Folate deficiency. Ascites, pleural effusions: evacuate fluid, monitor for toxicity and reduce dose or discontinue if needed. Elderly (use low doses and monitor closely). Debilitated. Interactions: Avoid live virus vaccines. Toxicity increased by NSAIDs, salicylates, phenytoin, sulfonylureas, sulfonamides, probenecid, folic acid antagonists. May be potentiated by penicillins (monitor), tetracyclines, chloramphenicol, non-absorbable broad spectrum antibiotics. May be antagonized by folic acid. May potentiate theophylline, mercaptopurine. Increased risk of soft tissue necrosis and osteonecrosis with radiotherapy.

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

XALKORI Pfizer

℞

Tyrosine kinase inhibitor. Crizotinib 200mg, 250mg; hard gel caps. Indications: Treatment of metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. Treatment of metastatic NSCLC that is ROS1-positive. Adults: Confirm ALK-positive NSCLC with an FDA-approved test before treating. Swallow whole. 250mg twice daily until disease progression or intolerance. Dose modification and/or dose reduction to 200mg twice daily may be required based on Grade 3 or 4 severity, then to 250mg once daily, or permanently discontinue if intolerable. Severe renal impairment (CrCl <30mL/min) not requiring dialysis: 250mg once daily. Dose reduction for hematologic and non-hematologic toxicities: see full labeling. Children: Not established. Warnings/Precautions: Monitor ALT, AST and total bilirubin every 2 weeks during first 2 months, then monthly, and more frequently for elevated transaminases; temporarily suspend, reduce dose, or permanently discontinue as clinically indicated. Monitor CBCs with differential monthly and more frequently if Grade 3 or 4 abnormalities, fever or infection occurs. Risk of severe pneumonitis: monitor for pulmonary symptoms; permanently discontinue if occurs. Congenital long QT syndrome; avoid. History of or predisposition for QTc prolongation (eg, CHF, bradyarrhythmias, electrolyte abnormalities, or those who are taking drugs known to prolong the QT interval): consider monitoring ECG, electrolytes periodically. Torsade de pointes, ventricular tachycardia, serious arrhythmia: permanently discontinue if QTc >500ms or ≥60ms change from baseline. Monitor HR and BP regularly; discontinue if life-threatening

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LUNG CANCER bradycardia occurs. Discontinue if onset of severe visual loss; perform eye evaluation. Hepatic impairment. Severe renal impairment. Embryo-fetal toxicity. Pregnancy; avoid. Use effective contraception during therapy and for at least 45 days (females) or 90 days (males) after final dose. Nursing mothers: not recommended (during therapy and for 45 days after final dose). Interactions: Avoid concomitant strong CYP3A inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole), grapefruit juice, or strong CYP3A inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John’s Wort). Avoid concomitant CYP3A substrates with narrow therapeutic indices (eg, alfentanil, cyclosporine, ergots, fentanyl, pimozide, quinidine, sirolimus, tacrolimus); if needed, reduce doses. Avoid concomitant agents known to cause bradycardia (eg, beta-blockers, non-dihydropyridine calcium channel blockers, clonidine, digoxin); adjust dose or discontinue. Caution with moderate CYP3A inhibitors. Dose reduction may be needed with coadministered drugs metabolized by CYP3A. Adverse reactions: Vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper RTI, dizziness, neuropathy, neutropenia; hepatotoxicity (may be fatal), pneumonitis (may be fatal), QT prolongation, bradycardia. How supplied: Caps—60

ZYKADIA Novartis

℞

Tyrosine kinase inhibitor. Ceritinib 150mg; hard gel caps. Indications: Treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. Adults: Take on an empty stomach (at least 1hr before or 2hrs after a meal). 750mg once daily until disease progression or unacceptable toxicity. Discontinue if 300mg once daily not tolerated. Dose modifications: see full labeling. If concomitant use of strong CYP3A4 inhibitors unavoidable: reduce ceritinib dose by 1/3. Children: Not established. Warnings/Precautions: Monitor for severe or persistent GI toxicity; if occurs, withhold until improved; resume at reduced dose. Monitor ALT/AST and total bilirubin once monthly, and more frequently if elevated transaminases develop; withhold then reduce dose, or permanently discontinue as clinically indicated. Congenital long QT syndrome; avoid. Patients with CHF, bradyarrhythmias, electrolyte abnormalities, or those who are taking drugs known to prolong the QTc interval; monitor ECG, electrolytes periodically. Permanently discontinue if QTc prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or serious arrhythmia develop. Monitor HR and BP regularly; fasting

serum glucose, lipase, amylase prior to initiation and periodically thereafter. Monitor for pulmonary symptoms as clinically indicated. Permanently discontinue if treatment-related interstitial lung disease (ILD)/pneumonitis, uncontrolled hyperglycemia, or life-threatening bradycardia occur. Moderate-to-severe hepatic impairment: not established. Embryo-fetal toxicity. Pregnancy. Use effective contraception during treatment and for 6 months (females) or 3 months (males) after completion. Nursing mothers: not recommended (during and for 2 weeks after completion). Interactions: See Adults. Potentiated by strong CYP3A4 inhibitors (eg, ritonavir, macrolides, ketoconazole, nefazodone), grapefruit juice; avoid. Avoid concomitant strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s Wort). Avoid concomitant CYP3A substrates (eg, alfentanil, cyclosporine, ergots, fentanyl, pimozide, quinidine, sirolimus, tacrolimus) or CYP2C9 substrates with narrow therapeutic indices (eg, phenytoin, warfarin); if unavoidable, reduce doses of these drugs. Avoid concomitant agents known to cause bradycardia (eg, 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.

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DRUG MONOGRAPHS

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

Indications: AIDS-related Kaposi’s sarcoma. Adults: Use appropriate preparation and route: see full labeling. Use SC route if platelets <50,000/mm3. 30 million IU/m2 IM or SC three times weekly; continue until rapid disease progression or maximal response achieved after 16 weeks; reduce dose by ½ or suspend therapy if severe adverse reactions occur; discontinue if persists. Children: Not recommended. Contraindications: Decompensated liver disease. Autoimmune hepatitis. Warnings/Precautions: May cause or exacerbate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders: monitor closely, discontinue if they worsen. Severe psychiatric disorders (esp. depression). Cardiovascular or pulmonary disease. Severe myelosuppression; discontinue if neutrophil count <0.5 X109/L or platelets 25X109/L. Permanently discontinue if severe (Grade 3) hepatic injury or decompensation (Child-Pugh score >6 [Class B and C]) develop. Thyroid abnormalities; discontinue if uncontrolled by medication. Diabetes. Coagulation disorders. Maintain adequate hydration. Monitor blood, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Psoriasis. Renal dysfunction. Transplant recipients. Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Caution with myelosuppressives, and drugs that can exacerbate depression. May potentiate theophylline (may double its levels). Adverse reactions: Flu-like symptoms (fever, headache, myalgia, fatigue); hepatic, hematologic, respiratory, skin, genitourinary system, CNS, cardiovascular, endocrine (esp. thyroid), GI, or visual disorders; colitis, hypertriglyceridemia, pancreatitis, infections, injection site reactions, dental and periodontal disorders; others (see full labeling). How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial—1; Soln (multidose vials): 18million, 25million IU/vial—1

INTRON A Merck

PANRETIN Eisai

DOXIL Janssen Biotech

℞

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

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

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

COTELLIC Genentech

℞

Kinase inhibitor. Cobimetinib 20mg; tabs. Indications: In combination with vemurafenib for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations. Adults: Confirm presence of BRAF V600E or V600K mutation prior to initiation. In combination with vemurafenib: 60mg once daily for first 21 days of each 28-day cycle until disease progression or unacceptable toxicity. Concomitant CYP3A inhibitors: see Interactions. Other dose modifications: see full labeling. Children: Not established. Warnings/Precautions: Review full labeling for vemurafenib prior to initiation. Monitor for new malignancies (cutaneous and non-cutaneous); perform skin evaluations prior to initiation, every 2 months during therapy, and for 6 months after discontinuation. Monitor for signs/symptoms of bleeding; withhold if Grade 3 hemorrhagic events occur; resume at lower dose if improved to Grade 0/1 within 4 weeks; discontinue if no improvement. Risk of cardiomyopathy; assess LVEF prior to initiation, after 1 month, and then every 3 months thereafter until discontinuation. Patients with baseline LVEF below institutional lower limit of normal or <50%: not established. Interrupt, reduce dose, or discontinue if severe skin reactions occur. Perform eye exams at regular intervals and for any visual disturbances. Manage serous retinopathy with treatment interruption, dose reduction, or discontinuation. Permanently discontinue if retinal vein occlusion occurs. Monitor liver tests prior to initiation, monthly during treatment, or more frequently as indicated; dose interruption, reduction, or discontinuation if Grade 3/4 abnormalities occur. Obtain baseline CPK and creatinine levels prior to initiation, periodically during treatment, and as clinically indicated for signs/symptoms of rhabdomyolysis. Avoid sun exposure. Severe renal impairment. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during therapy and for 2 weeks after final dose. Pregnancy. Nursing mothers: not recommended (during therapy and for 2 weeks after final dose). Interactions: Avoid concomitant strong or moderate CYP3A inhibitors (eg, itraconazole, erythromycin, ciprofloxacin). If short-term (≤14 days) use of moderate CYP3A inhibitors is unavoidable for patients taking cobimetinib 60mg, reduce to 20mg and resume at previous dose upon discontinuing the CYP3A inhibitor; for patients taking cobimetinib 20mg or 40mg, use alternative. Avoid concomitant strong or moderate CYP3A inducers (eg, carbamazepine, efavirenz, phenytoin, rifampin, St. John’s wort). Adverse reactions: Diarrhea, photosensitivity, nausea, pyrexia, vomiting, increased GGT,

CPK, ALT/AST and alkaline phosphatase, hypophosphatemia, lymphopenia, hyponatremia. How supplied: Tabs—63

EFUDEX Valeant

℞

Antimetabolite. Fluorouracil 2%, 5%; soln. ℞ Also: EFUDEX CREAM Fluorouracil 5%. Indications: Multiple actinic or solar keratoses. Superficial basal cell carcinoma when conventional therapy is impractical (5% only); see literature. Adults: Keratoses: Apply twice daily until erosion occurs (usually 2–4 wks). Basal cell carcinoma (5% only): Apply twice daily, usually for 3–6 weeks (obliteration may take 10–12 weeks). Children: Not recommended. Contraindications: Dihydropyrimidine dehydrogenase (DPD) deficiency. Pregnancy (Cat.X). Warnings/Precautions: Apply cautiously near eyes, nose, mouth. Avoid mucous membranes, occlusion, ulcerated/inflamed skin, exposure to UV light. Wash hands after application if fingers were used. Notify patients of expected skin reaction. Biopsy unresponsive lesions. Nursing mothers: not recommended. Adverse reactions: Pain or burning at application site, pruritus, irritation, hyperpigmentation. How supplied: Soln—10mL (w. drop dispenser); Crm—25g

ERIVEDGE Genentech

℞

Hedgehog pathway inhibitor. Vismodegib 150mg; caps. Indications: Treatment of adults with metastatic basal cell carcinoma, or locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Adults: Swallow whole. 150mg once daily, until disease progression or unacceptable toxicity. Children: Not established. Warnings/Precautions: Risk of embryo-fetal death and severe birth defects in pregnant women. Verify pregnancy status within 7 days prior to initiation of therapy. Females of reproductive potential should use effective contraception during therapy and for 24 months after final dose; male patients should use condoms (even after a vasectomy) during and for 3 months after final 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).

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DRUG MONOGRAPHS

SKIN CANCER Adverse reactions: Muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, vomiting, decreased appetite, constipation, arthralgias, ageusia; amenorrhea. Note: Report immediately exposure to Erivedge during pregnancy by contacting the Genentech Adverse Event Line at (888) 835-2555. How supplied: Caps—28

GLEEVEC Novartis

℞

Kinase inhibitor. Imatinib (as mesylate) 100mg, 400mg; scored tabs. Indications: Adults with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation as determined with an FDA-approved test or with c-Kit mutational status unknown. Adults with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP). Adults: Take with food and water. May disperse tab in water or apple juice and take promptly. ≥18yrs: ASM without D816V c-Kit mutation or status unknown (determine D816V c-Kit mutation status prior to initiation): 400mg once daily. ASM associated with eosinophilia: initially 100mg once daily; may increase to 400mg once daily if insufficient response. DFSP: 400mg twice daily. If severe non-hematologic reactions develop: interrupt dose; resume at a lower dose in hepatic dysfunction. Severe hepatic impairment: reduce dose by 25%. Renal or hematologic reactions: see full labeling. Avoid concomitant strong CYP3A4 inducers (eg, rifampin): if needed, increase imatinib dose by at least 50%. Children: Not recommended. Warnings/Precautions: Hepatic or renal impairment. Monitor weight and for fluid retention regularly; CBCs weekly for 1st month, bi-weekly for 2nd month, then periodically (eg, every 2–3 months); liver function at baseline then monthly or as needed; GI symptoms at baseline. Cardiovascular disease or risk factors; monitor. Immunosuppression and potential toxicities (liver, kidney, cardiac) from long-term use. Monitor for tumor lysis syndrome; correct clinically significant dehydration and treat high uric acid levels before initiating therapy. Monitor growth in children. Possible cardiogenic shock/LV dysfunction in conditions with high eosinophil levels (eg, HES/CEL, MDS/MPD, ASM); consider concomitant systemic steroid prophylaxis (1–2mg/kg) for 1 or 2 wks if abnormal ECG or serum troponin. Monitor TSH levels in thyroidectomy patients undergoing levothyroxine replacement. Embryo-fetal toxicity. Pregnancy (avoid); exclude status prior to initiation. Females

of reproductive potential should use highly effective contraception during treatment and for 14 days after cessation. Nursing mothers: not recommended (during and for 1 month after final dose). Interactions: Avoid grapefruit juice. Potentiated by CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, nefazodone, clarithromycin, telithromycin). Antagonized by strong CYP3A4 inducers (eg, dexamethasone, fosphenytoin, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, primidone, St. John’s wort, rifampin, rifabutin, rifampicin); consider alternatives. May potentiate drugs metabolized by CYP3A4 (eg, benzodiazepines, dihydropyridine calcium channel blockers, cyclosporine, ergots, alfentanil, fentanyl, pimozide, quinidine, certain statins, sirolimus, tacrolimus) or CYP2C9 (use heparin instead of warfarin). Caution with concomitant CYP2D6 substrates that have a narrow therapeutic window. Adverse reactions: Edema (may be severe), nausea, vomiting, musculoskeletal pain, diarrhea, muscle cramps, rash (may be severe; eg, erythema multiforme, 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

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

GENERIC NAME

℞

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

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

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DRUG MONOGRAPHS

SKIN CANCER INTRON A Merck

℞

Alpha interferon. Interferon alfa-2b, recombinant; 10 million, 18 million, or 50 million IU per vial; pwd; for inj after reconstitution/dilution; preservativefree; contains albumin. ℞ Also: INTRON A SOLN Interferon alfa-2b, recombinant; 10 million IU, 18 million IU, 25 million IU; per vial; for inj; contains m-cresol. Indications: Malignant melanoma. Adults: Induction: 20million IU/m2 IV over 20 mins, 5 consecutive days per week, for 4 weeks. Maintenance: 10 million IU/m2 SC 3 times per week for 48 weeks. See full labeling for appropriate preparation and route and for dose adjustments. Children: Not recommended. Contraindications: Decompensated liver disease. Autoimmune hepatitis. Warnings/Precautions: May cause or exacerbate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, or infectious disorders: monitor closely, discontinue if they worsen. Severe psychiatric disorders (esp. depression). Cardiovascular or pulmonary disease. Severe myelosuppression; discontinue if neutrophil count <0.5 X109/L or platelets 25X109/L. Permanently discontinue if severe (Grade 3) hepatic injury or decompensation (Child-Pugh score >6 [Class B and C]) develop. Thyroid abnormalities; discontinue if uncontrolled by medication. Diabetes. Coagulation disorders. Maintain adequate hydration. Monitor blood, thyroid, visual and liver function before and during therapy; EKG in cardiovascular disease and cancer patients. Psoriasis. Renal dysfunction. Transplant recipients. Elderly. Debilitated. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Caution with myelosuppressives, and drugs that can exacerbate depression. May potentiate theophylline (may double its levels). Adverse reactions: Flu-like symptoms (fever, headache, myalgia, fatigue); hepatic, hematologic, respiratory, skin, genitourinary system, CNS, cardiovascular, endocrine (esp. thyroid), GI, or visual disorders; colitis, hypertriglyceridemia, pancreatitis, infections, injection site reactions, dental and periodontal disorders; others (see full labeling). How supplied: Pwd (w. diluent): 10million, 18million, 50million IU/vial—1; Soln (multidose vials): 18million, 25million IU/vial—1

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

℞

Indications: Unresectable or metastatic melanoma. Adults: Give as IV infusion over 30mins. 200mg every 3 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions. Children: Not established. Warnings/Precautions: Monitor for pneumonitis; withhold dose if Grade 2 pneumonitis; permanently discontinue if Grade 3 or 4, or recurrent Grade 2 develops. Monitor for colitis; withhold dose if Grade 2 or 3 colitis; permanently discontinue if Grade 4 develops. Monitor for changes in liver function; withhold dose or discontinue based on severity of elevated liver enzymes. Monitor for changes in renal function; withhold dose if Grade 2 nephritis; permanently discontinue if Grade 3 or 4 develops. Monitor for hypophysitis; withhold dose if Grade 2 hypophysitis; withhold or discontinue if Grade 3 or 4 develops. Monitor for changes in thyroid function (at treatment initiation, during, and as clinically indicated) and signs/symptoms of thyroid disorders; withhold or discontinue if Grade 3 or 4 hyperthyroidism develops. Monitor for hyperglycemia and other diabetes symptoms; withhold if severe hyperglycemia until controlled. Withhold dose if Grade 4 hematological toxicity in cHL patients develops. 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 infusionrelated reactions; permanently discontinue if Grade 3 or 4 develops. Complications of allogeneic HSCT after Keytruda: monitor for hepatic VOD, Grade 3 or 4 acute GVHD, steroidrequiring febrile syndrome, and others. 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 FDA-approved 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 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

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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 embryofetal death or severe birth defects in pregnant women. Verify pregnancy status of females of reproductive potential prior to initiation. Advise females to use effective contraception during therapy and for at least 20 months after the last dose; male patients must use condoms and not to donate semen during therapy and for at least 8 months after last dose. Advise patients not to donate blood or blood products during therapy and for at least 20 months after last dose. Risk of musculoskeletal adverse reactions accompanied by serum creatine kinase (CK) elevations; temporarily interrupt or discontinue based on severity of reactions. Obtain baseline serum CK and creatinine (SCr) levels prior to initiation; periodically during treatment and as clinically indicated. Obtain serum CK and SCr levels at least weekly in those with musculoskeletal adverse reactions with concurrent serum CK elevation >2.5XULN until symptoms resolve. Pregnancy. Nursing mothers: not recommended during therapy and for 20 months after last dose. Interactions: Avoid concomitant strong CYP3A inhibitors (eg, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone) or moderate CYP3A inhibitors (eg, atazanavir, diltiazem, fluconazole); if moderate CYP3A inhibitor use necessary, administer for <14 days and monitor closely. Avoid concomitant strong or moderate CYP3A inducers (eg, carbamazepine, efavirenz, modafinil, phenobarbital, phenytoin, rifabutin, rifampin, St. John’s Wort). Adverse reactions: Muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, pruritus; anemia, hyperglycemia, increased SCr, CK, and LFTs. Note: To report exposure to Odomzo during pregnancy, call Novartis at (888) 669-6682. How supplied: Caps—30

OPDIVO Bristol-Myers Squibb

℞

Human programmed death receptor-1 (PD-1)blocking antibody. Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservativefree; contains mannitol. Indications: As a single agent for patients with BRAF V600 wild-type or BRAF V600 mutation (+) unresectable or metastatic melanoma. In combination with ipilimumab for unresectable or metastatic melanoma. Adults: Give as IV infusion over 60mins. 240mg every 2 weeks until disease progression or unacceptable toxicity. In combination with ipilimumab: 1mg/kg (followed by ipilimumab on the same day) every 3 weeks for 4 doses, then followed by 240mg every 2 weeks (as single agent) until disease progression or unacceptable toxicity. Dose modifications: see full labeling. Children: Not established. Warnings/Precautions: See full labeling. Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any lifethreatening (Grade 4) adverse reaction, Grade 3 or 4 pneumonitis, Grade 3/4 or recurrent colitis (with ipilimumab), Grade 4 or recurrent colitis (as single agent), AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash (or confirmed SJS or TEN), immune-mediated encephalitis, recurring Grade 3 adverse reactions, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, Grade 2 or 3 hypophysitis, Grade 2 adrenal insufficiency, Grade 3 hyperglycemia, Grade 3 rash (or suspected SJS or TEN), new onset moderateto-severe neurologic symptoms, other Grade 3 adverse reactions (1st occurrence); withhold dose, give corticosteroids, and resume when return to Grade 0 or 1. Interrupt or decrease infusion rate if mild or moderate infusion reactions occur; discontinue if severe or lifethreatening. Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Monitor for transplant-related complications (eg, hyperacute or Grade 3/4 acute GVHD,

steroid-requiring febrile syndrome, hepatic venoocclusive disease) and treat promptly. Moderate or severe hepatic impairment: not studied. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for ≥5 months after final dose. Pregnancy (esp. during 2nd & 3rd trimesters), nursing mothers: not recommended. Adverse reactions: Fatigue, 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.

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DRUG MONOGRAPHS

SKIN CANCER Obtain CBCs, differential and platelets, blood chemistries (electrolytes, renal and hepatic function tests), chest X-rays, serum creatinine (should be ≤1.5mg/dL before starting therapy), pulmonary function tests, arterial blood gases. Monitor for capillary leak syndrome, mental status changes, thyroid changes, diabetes onset. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Psychotropics may increase CNS toxicity. Increased toxicity with other nephrotoxic, hepatotoxic, myelotoxic, or cardiotoxic drugs. Hypersensitivity reactions with other antineoplastics. Myocardial injury and rhabdomyolysis risk increased with interferonalfa. Antagonized by glucocorticoids (avoid). β-blockers and other antihypertensives may potentiate hypotension. Delayed reactions to iodinated contrast media. May increase risk of allograft rejection. Adverse reactions: Hypotension, GI upset, oliguria, flu-like syndrome, respiratory disorders (eg, dyspnea), CNS effects (eg, confusion, somnolence), rash, metabolic and nutritional disorders (eg, bilirubinemia, increased creatinine), hyperglycemia, thyroid disorder, thrombocytopenia, anemia, impaired neutrophil function, capillary leak syndrome, cardiotoxicity, exacerbation of autoimmune and inflammatory disease, eosinophilia, possible antibody formation; others. How supplied: Single-use vials—1

SYLATRON Merck

℞

Alpha interferon. Peginterferon alfa-2b 296mcg, 444mcg, 888mcg; per vial; lyophilized pwd for SC inj after reconstitution. Indications: Adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy. Adults: Give by SC inj. Rotate inj sites. Premedicate with acetaminophen. ≥18yrs: 6mcg/kg/week for 8 doses, followed by 3mcg/kg/week for up to 5yrs. Renal impairment (moderate): initially 4.5mcg/kg/week for 8 doses, followed by 2.25mcg/kg/week for up to 5yrs; (severe or ESRD on dialysis): initially 3mcg/kg/week for 8 doses, followed by 1.5mcg/kg/week for up to 5yrs. Withhold dose if ANC <0.5x109/L, platelets <50x109/L, ECOG PS ≥2, or for non-hematologic toxicity ≥ Grade 3. Resume at reduced dose (see full labeling) when: ANC ≥0.5x109/L, platelets ≥50x109/L, ECOG PS 0–1, and non-hematologic toxicity has completely resolved or improved to Grade 1. Children: <18yrs: not established. Contraindications: Anaphylaxis to peginterferon alfa-2b or interferon alfa-2b. Autoimmune hepatitis. Hepatic decompensation (Child-Pugh score >6 [Class B and C]). Warnings/Precautions: Increased risk of serious depression, suicidal ideation, and

other neuropsychiatric disorders. Permanently discontinue for: persistent severe or worsening neuropsychiatric disorders (eg, depression, psychosis, encephalopathy); new onset ventricular arrhythmia or cardiovascular decompensation; new or worsening retinopathy; Grade 4 non-hematologic toxicity; severe (Grade 3) hepatic injury or hepatic decompensation; hypothyroidism, hyperthyroidism, or diabetes mellitus that cannot be effectively managed; or if unable to tolerate a dose of 1mcg/kg/week. Monitor for signs/symptoms of depression/psychosis every 3 weeks during first 8 weeks, then every 6 months, continue for at least 6 months after last dose. Perform eye exam in patients with retinopathy and those with vision changes during therapy. Monitor hepatic function with serum bilirubin, ALT/AST, alkaline phosphate, and LDH at 2 and 8 weeks, and 2 and 3 months following initiation, then every 6 months. Obtain TSH levels within 4 weeks prior to initiation, at 3 and 6 months following initiation, then every 6 months. Moderate-to-severe renal impairment (monitor). Pregnancy (Cat.C). Nursing mothers: not recommended. Interactions: Potentiates CYP1A2 (eg, caffeine) or CYP2D6 (eg, desipramine) substrates. Concomitant drugs with narrow therapeutic range metabolized by CYP1A2 or CYP2D6; monitor for increased toxicities. Adverse reactions: Fatigue, increased ALT/AST, pyrexia, headache, anorexia, myalgia, nausea, chills, inj site reactions; neuropsychiatric disorders. How supplied: Single-use vial—1 (w. diluent)

TAFINLAR 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-tosevere 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

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

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DRUG MONOGRAPHS

SKIN CANCER 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; until disease progression or unacceptable toxicity occurs. 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. How supplied: Tabs—112, 120

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ALPHABETICAL INDEX A Abiraterone Zytiga 52 Abraxane (inj) cancer, breast 14 cancer, pancreatic 22 non-small cell lung cancer 83 Actinic keratoses 92 Adcetris (inj) 60 Ado-trastuzumab Kadcyla 17 Afatinib Gilotrif 84 Afinitor cancer, breast 14 cancer, renal 43 progressive neuroendocrine tumors of pancreatic origin (pnet) 22 progressive non-functional neuroendocrine tumors (net) of gastrointestinal or lung origin 22 subependymal giant cell astrocytoma (sega) 12 Aldesleukin Proleukin (inj) 48, 95 Alecensa 83 Alectinib Alecensa 83 Alemtuzumab Campath (inj) 62 Alimta (inj) 83 Alitretinoin Panretin (ext) 91 Altretamine Hexalen 55 Alunbrig 83 Anaplastic astrocytoma 12 Anastrozole Arimidex 14 Arimidex 14 Aromasin 14 Arranon 60 Arsenic trioxide Trisenox (inj) 78 Arzerra (inj) 60 Asparaginase Erwinia chrysanthemi Erwinaze (inj) 65 Atezolizumab Tecentriq (inj) 50, 89 Avastin (inj) cancer, cervical 12, 27, 43, 55, 84 cancer, colorectal 12, 27, 43, 55, 84

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

cancer, ovarian cancer, renal glioblastoma non-small cell lung cancer Avelumab Bavencio (inj) Axitinib Inlyta Azacitidine Vidaza (inj)

12, 27, 55, 84 12, 27, 43, 55, 84 12, 27, 43, 55, 84 12, 27, 43, 55, 84 43, 92 46 80

B Basal cell carcinoma Bavencio (inj) cancer, bladder cancer, renal melanoma Beleodaq (inj) Belinostat Beleodaq (inj) Bendamustine Bendeka (inj) Treanda (inj) Bendeka (inj) Bevacizumab Avastin (inj) Bexarotene Targretin Targretin (ext) Bexxar Bicalutamide Casodex Blinatumomab Blincyto (inj) Blincyto (inj) Bone metastases Bortezomib Velcade (inj) Bosulif Bosutinib Bosulif Breast cancer Brentuximab vedotin Adcetris (inj) Brigatinib Alunbrig Busulfan Busulfex (inj) Myleran Busulfex (inj)

92, 95 43 43 92 60 60 61 78 61 12, 27, 43, 55, 84 76 76 61 44 62 62 2, 82 79 62 62 18, 20 60 83 62 71 62

C Cabazitaxel Jevtana (inj) Cabometyx Cabozantinib Cabometyx Cometriq Campath (inj) Cancer, bladder

46 44

44 23 62 43, 45–46, 50–51, 89 Cancer, breast 1, 14–21, 23, 28–29, 32, 45, 57, 59, 78, 89 Cancer, cervical 12, 27, 43, 55, 84–85 Cancer, colorectal 12, 16, 21, 23, 27–28, 30–32, 43, 55, 58, 84 Cancer, GI 16, 27, 29 Cancer, head and neck 1, 13, 20, 28, 57–59, 78, 89 Cancer, liver 30, 48 Cancer, lung 1, 20, 55, 57, 59, 71, 78, 83–89 Cancer, ovarian 12, 27, 55–57, 64, 84–85, 91 Cancer, pancreatic 16, 22–25, 28, 31, 49, 88 Cancer, prostate 15, 44–52 Cancer, renal 12, 27, 30, 43–44, 46–48, 50–51, 55, 84, 89, 95 Cancer, sarcoma 1–2 Cancer, stomach 16, 23, 28 Cancer, testicular 45 Cancer, thyroid 22–24, 30, 48 Capecitabine Xeloda 21, 32 Caprelsa 22 Carfilzomib Kyprolis (inj) 70 Casodex 44 Ceritinib Zykadia 90 Cerubidine (inj) 63 Cetuximab Erbitux (inj) 28, 58 Chlorambucil Leukeran 70 Chorioadenoma destruens 1, 20, 57, 59, 78, 89 Choriocarcinoma, gestational 1, 20, 57, 59, 78, 89 Clofarabine Clolar (inj) 63

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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.

Clolar (inj) Cobimetinib Cotellic Colorectal cancer Cometriq Cotellic Crizotinib Xalkori Cyramza (inj) cancer, gi cancer, lung Cytarabine DepoCyt (inj) Vyxeos (inj)*

63 92 28–29 23 92 89 27 84 64 81

D Dabrafenib Tafinlar Dacogen (inj) Daratumumab Darzalex (inj) Darzalex (inj) Dasatinib Sprycel Daunorubicin Cerubidine (inj) Vyxeos (inj)* Decitabine Dacogen (inj) Degarelix Firmagon (inj) Delatestryl Delestrogen (inj) Denileukin diftitox Ontak (inj) Denosumab Xgeva (inj) DepoCyt (inj) Dermatofibrosarcoma protuberans Dinutuximab Unituxin (inj) Doxil (inj) cancer, ovarian kaposi’s sarcoma multiple myeloma Doxorubicin, liposomal Doxil (inj) Durvalumab Imfinzi (inj)

87, 96 63 64 64 75 63 81 63 45 15 44 72 2 64 28, 66, 93 13 55, 64, 91 55, 64, 91 55, 64, 91 55, 64, 91 45

ALPHABETICAL INDEX

E Efudex (ext) 92 Eligard (inj) 44 Elotuzumab Empliciti (inj) 64 Eloxatin (inj) 27 Emcyt 44 Empliciti (inj) 64 Enzalutamide Xtandi 52 Erbitux (inj) cancer, colorectal 28, 58 cancer, head and neck 28, 58 Eribulin Halaven (inj) 1, 16 Erivedge 92 Erlotinib Tarceva 25, 88 Erwinaze (inj) 65 Erythema nodosum leprosum 77 Estrace cancer, breast 15, 45 cancer, prostate 15, 45 Estradiol Estrace 15, 45 Estradiol valerate Delestrogen (inj) 44 Estramustine Emcyt 44 Estrogens, conjugated Premarin 19, 48 Estrogens, esterified Menest 47 Everolimus Afinitor 12, 14, 22, 43 Evista 15 Evomela (inj) 65 Exemestane Aromasin 14

F Farydak Faslodex (inj) Femara Firmagon (inj) Fludara (inj) Fludarabine Fludara (inj) Fluorouracil Efudex (ext) Fluorouracil

65 15 15 45 66 66 92 16, 23, 28

Fluorouracil cancer, breast cancer, colorectal cancer, pancreatic cancer, stomach Flutamide Fulvestrant Faslodex (inj) Fusilev (inj)

16, 23, 28 16, 23, 28 16, 23, 28 16, 23, 28 45 15 28

G Gazyva (inj) 66 Gefitinib Iressa 85 GI stromal tumors 24, 28, 31, 49, 66, 93 Gilotrif 84 Gleevec dermatofibrosarcoma protuberans 28, 66, 93 gi stromal tumors 28, 66, 93 hypereosinophilic syndrome 28, 66, 93 leukemia, acute myeloid 28, 66, 93 leukemia, chronic eosinophilic 28, 66, 93 leukemia, chronic myelogenous 28, 66, 93 mastocytosis 28, 66, 93 myelodysplastic syndromes 28, 66, 93 Glioblastoma 12, 27, 43, 55, 84

H Halaven (inj) cancer, breast 16 cancer, sarcoma 1 Herceptin (inj) cancer, breast 16, 29 cancer, gi 16, 29 Hexalen 55 Histrelin Vantas 51 Hodgkin lymphoma 60, 69, 72 Hodgkin’s disease 71, 86 Hyaluronidase human Rituxan Hycela (inj)* 74 Hycamtin cancer, cervical 55, 85 cancer, lung 55, 85 cancer, ovarian 55, 85 Hydatidiform mole 1, 20, 57, 59, 78, 89 Hydrea cancer, head and neck 58 leukemia, chronic myeloid 67

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ALPHABETICAL INDEX Hydroxyurea Hydrea 58, 67 Hypercalcemia 82 Hypereosinophilic syndrome 28, 66, 93

I Ibrance Ibritumomab Zevalin (inj) Ibrutinib Imbruvica Iclusig Idamycin (inj) Idarubicin Idamycin (inj) Idelalisib Zydelig Ifex (inj) Ifosfamide Ifex (inj) Imatinib Gleevec Imbruvica Imfinzi (inj) Imlygic (inj) Inlyta Interferon alfa-2b Intron A (inj) Intron A (inj) kaposi’s sarcoma leukemia, hairy cell lymphoma, follicular melanoma Iodine I 131 Tositumomab Bexxar* Ipilimumab Yervoy (inj) Iressa Irinotecan Onivyde (inj) Istodax Ixabepilone Ixempra (inj) Ixazomib Ninlaro Ixempra (inj)

17 81 68 67 68 68 82 45 45 28, 66, 93 68 45 93 46 68, 91, 94 68, 91, 94 68, 91, 94 68, 91, 94 68, 91, 94 61 96 85 24 69 17 71 17

J Jakafi Jevtana (inj)

69 46

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

K Kadcyla 17 Kaposi’s sarcoma 55, 64, 68, 91, 94 Keytruda (inj) cancer, bladder 46 cancer, head and neck 58 cancer, renal 46 colorectal cancer 29 hodgkin lymphoma 69 melanoma 94 non-small cell lung cancer 85 Kisqali 18 Kyprolis (inj) 70

L Lanreotide Somatuline Depot (inj) 24 Lapatinib Tykerb 20 Lartruvo (inj) 1 Lenalidomide Revlimid 73 Lenvatinib Lenvima 23, 47 Lenvima cancer, renal 47 cancer, thyroid 23 Letrozole Femara 15 Leucovorin 30 Leukemia 70–71, 86 Leukemia, acute lymphoblastic 62–63, 65, 67, 70, 72–73, 75, 80–81 Leukemia, acute lymphocytic 63, 73 Leukemia, acute myeloid 28, 66, 68, 75, 81, 93 Leukemia, acute nonlymphocytic 63, 76 Leukemia, acute promyelocytic 78, 80 Leukemia, B-cell chronic lymphocytic 62, 66 Leukemia, chronic eosinophilic 28, 66, 93 Leukemia, chronic lymphocytic 60–61, 66, 68, 74, 78, 80, 82 Leukemia, chronic myelogenous 28, 62, 66, 71, 75–77, 93 Leukemia, chronic myeloid 67 Leukemia, hairy cell 68, 91, 94 Leukemia, T-cell acute lymphoblastic 60

Leukeran 70 Leuprolide Eligard (inj) 44 Lupron Depot 7.5mg (inj) 47 Levoleucovorin Fusilev (inj) 28 Lonsurf 30 Lupron Depot 7.5mg (inj) 47 Lymphoma, cutaneous T-cell 69, 72, 76, 79, 82 Lymphoma, follicular 68, 74, 82, 91, 94 Lymphoma, lymphocytic 74 Lymphoma, malignant 70 Lymphoma, mantle cell 68, 79 Lymphoma, marginal zone 68 Lymphoma, peripheral T-cell 60, 69 Lymphoma, small lymphocytic 68, 82 Lymphoma, T-cell lymphoblastic 60 Lymphomatous meningitis 64 Lymphosarcoma 71, 86 Lynparza 56

M Malignant pleural mesothelioma 83 Mantle cell lymphoma 73 Marqibo (inj) 70 Mastocytosis 28, 66, 75, 93 Mechlorethamine Mustargen (inj) 71, 86 Valchlor (ext) 79 Mekinist melanoma 94 non-small cell lung cancer 86 Melanoma 68, 91–97 Melanoma, metastatic 48, 95 Melphalan Evomela (inj) 65 Menest 47 Mercaptopurine Purinethol 73 Purixan 73 Methotrexate Trexall 1, 20, 57, 59, 78, 89 Xatmep 81 Methoxsalen Uvadex 79 Midostaurin Rydapt 75 Multiple myeloma 55, 64–65, 70–73, 77, 79, 82, 91

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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.

Mustargen (inj) cancer, lung hodgkin’s disease leukemia lymphosarcoma mycosis fungoides polycythemia vera Mycosis fungoides

71, 86 71, 86 71, 86 71, 86 71, 86 71, 86 1, 20, 57, 59, 71, 78, 86, 89

Mycosis fungoides-type cutaneous T-cell lymphoma Myelodysplastic syndromes Myleran

79 28, 63, 66, 80, 93 71

N Navelbine (inj) 86 Necitumumab Portrazza (inj) 87 Nelarabine Arranon 60 Neoplasms 44, 50 Neratinib Nerlynx 18 Nerlynx 18 Neuroblastoma 13 Neuroendocrine tumors 24, 31, 49 Nexavar cancer, liver 30, 48 cancer, renal 30, 48 cancer, thyroid 24, 30, 48 Nilotinib Tasigna 77 Ninlaro 71 Niraparib Zejula 57 Nivolumab Opdivo (inj) 48, 58, 72, 87, 95 Non-Hodgkin’s lymphoma 1, 20, 57, 59, 61, 74, 78, 81, 89 Non-small cell lung cancer 12, 25, 27, 43, 55, 83–90

O Obinutuzumab Gazyva (inj) Odomzo Ofatumumab Arzerra (inj) Olaparib Lynparza

66 95 60 56

Olaratumab Lartruvo (inj) Omacetaxine mepesuccinate Synribo (inj) Oncaspar (inj) Onivyde (inj) Ontak (inj) Opdivo (inj) cancer, head and neck cancer, lung cancer, renal hodgkin lymphoma melanoma Osimertinib Tagrisso Oxaliplatin Eloxatin (inj)

ALPHABETICAL INDEX 1 76 72 24 72 58 87 48 72 95 88 27

P Paclitaxel, protein-bound Abraxane (inj) 14, 22, 83 Palbociclib Ibrance 17 Panitumumab Vectibix (inj) 31 Panobinostat Farydak 65 Panretin (ext) 91 Pazopanib Votrient 1, 51 Pegaspargase Oncaspar (inj) 72 Peginterferon alfa-2b Sylatron (inj) 96 Pembrolizumab Keytruda (inj) 29, 46, 58, 69, 85, 94 Pemetrexed Alimta (inj) 83 Perjeta (inj) 18 Pertuzumab Perjeta (inj) 18 Polycythemia vera 69, 71, 86 Pomalidomide Pomalyst 72 Pomalyst 72 Ponatinib Iclusig 67 Portrazza (inj) 87 Premarin cancer, breast 19 cancer, prostate 48 Progressive neuroendocrine tumors of pancreatic origin (pNET) 22

Progressive non-functional neuroendocrine tumors (NET) of gastrointestinal or lung origin 22 Proleukin (inj) cancer, renal 48, 95 melanoma, metastatic 48, 95 Provenge (inj) 49 Purinethol 73 Purixan 73

R Radium Ra 223 dichloride Xofigo (inj) Raloxifene Evista Ramucirumab Cyramza (inj) Regorafenib Stivarga Revlimid Ribociclib Kisqali Rituxan (inj) Rituxan Hycela (inj) Rituximab Rituxan (inj) Rituxan Hycela (inj)* Romidepsin Istodax Rubraca Rucaparib Rubraca Ruxolitinib Jakafi Rydapt

52 15 27, 84 30 73 18 74 74 74 74 69 56 56 69 75

S Sarcoma, soft tissue Sipuleucel-T Provenge (inj) Skeletal-related events Soltamox Somatuline Depot (inj) Sonidegib Odomzo Sorafenib Nexavar Sprycel Stivarga Subependymal giant cell astrocytoma (SEGA)

1 49 2 19 24 95 24, 30, 48 75 30 12

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ALPHABETICAL INDEX Sunitinib Sutent 24, 31, 49 Superficial basal cell carcinoma 92 Sutent cancer, pancreatic 24, 31, 49 gi stromal tumors 24, 31, 49 neuroendocrine tumors 24, 31, 49 Sylatron (inj) 96 Synribo (inj) 76 Systemic anaplastic large cell lymphoma (sALCL) 60

T Tabloid Tafinlar melanoma non-small cell lung cancer Tagrisso Talimogene laherparepvec Imlygic (inj) Tamoxifen Soltamox Tamoxifen Tarceva cancer, pancreatic non-small cell lung cancer Targretin Targretin (ext) Tasigna Tecentriq (inj) cancer, bladder cancer, renal Temodar Temozolomide Temodar Temsirolimus Torisel (inj) Teniposide Vumon (inj) Tepadina (inj) breast cancer cancer, bladder cancer, breast cancer, ovarian Testosterone enanthate Delatestryl Thalidomide Thalomid Thalomid Thioguanine Tabloid Thiotepa Tepadina (inj)

76 96 87 88 93 19 20 25, 88 25, 88 76 76 77 50, 89 50, 89 12 12 50 80 20 50 20 56 15 77 77 76 20, 50, 56

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

Tipiracil Lonsurf* 30 Topotecan Hycamtin 55, 85 Torisel (inj) 50 Tositumomab Bexxar* 61 Trabectedin Yondelis (inj) 2 Trametinib Mekinist 86, 94 Trastuzumab Herceptin (inj) 16, 29 Treanda (inj) 78 Trelstar (inj) 50 Tretinoin Vesanoid 80 Trexall cancer, breast 1, 20, 57, 59, 78, 89 cancer, head and neck 1, 20, 57, 59, 78, 89 cancer, lung 1, 20, 57, 59, 78, 89 chorioadenoma destruens 1, 20, 57, 59, 78, 89 choriocarcinoma, gestational 1, 20, 57, 59, 78, 89 hydatidiform mole 1, 20, 57, 59, 78, 89 mycosis fungoides 1, 20, 57, 59, 78, 89 non-hodgkin’s lymphoma 1, 20, 57, 59, 78, 89 Trifluridine Lonsurf* 30 Triptorelin Trelstar (inj) 50 Trisenox (inj) 78 Tykerb 20

U Unituxin (inj) Uvadex

13 79

V Valchlor (ext) Valrubicin Valstar Valstar Vandetanib Caprelsa Vantas Vectibix (inj) Velcade (inj)

79 51 51 22 51 31 79

Vemurafenib Zelboraf Venclexta Venetoclax Venclexta Vesanoid Vidaza (inj) Vincristine sulfate liposome Marqibo (inj) Vinorelbine Navelbine (inj) Vismodegib Erivedge Vorinostat Zolinza Votrient cancer, renal cancer, sarcoma Vumon (inj) Vyxeos (inj)

97 80 80 80 80 70 86 92 82 51 1 80 81

X Xalkori Xatmep Xeloda cancer, breast cancer, colorectal Xgeva (inj) Xofigo (inj) Xtandi

89 81 21, 32 21, 32 2 52 52

Y Yervoy (inj) Yondelis (inj)

96 2

Z Zaltrap (inj) Zejula Zelboraf Zevalin (inj) Ziv-aflibercept Zaltrap (inj) Zoledronic acid Zometa Zolinza Zometa Zydelig Zykadia Zytiga

32 57 97 81 32 82 82 82 82 90 52

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