ONA September/October 2016 by Haymarket Media

ONCOLOGY NURSE ADVISOR • SEPTEMBER/OCTOBER 2016

September/October 2016

www.OncologyNurseAdvisor.com A F O R U M F O R P H YS I C I A N A S S I S TA N T S

FEATURE

SIDE-EFFECT MANAGEMENT Virtual and Vital: Social Media Communities and Cancer

FEATURE

Using CBT Principles in Daily Patient Interactions

COMMUNICATION CHALLENGES

Identifying and Managing Postmastectomy Pain Syndrome in Survivors PMPS is a neuropathic sequela of surgery and radiation therapy that affects up to 50% of women with breast cancer

When You’re Too Nice

ISSUES IN CANCER SURVIVORSHIP

Dietary Omega-3 Intake After CRC Diagnosis and Survival

THE TOTAL PATIENT

Misperceptions Continue to Stigmatize Palliative Care

FROM CANCERCARE

Dating Challenges Throughout the Cancer Journey

VOLUME 7, NUMBER 5

ASK A PHARMACIST Adverse Events Related to Checkpoint Inhibitors

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PUBLISHING STAFF Editor Joyce Pagán editor.ona@haymarketmedia.com Senior digital content editor Rick Maffei Oncology writer Jason Hoffman, PharmD, RPh Contributing writer Bette Weinstein Kaplan Group art director, Haymarket Medical Jennifer Dvoretz

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Oncology Nurse Advisor (ISSN 2154-350X), September/October 2016, Volume 7, Number 5. P ublished 6 times annually by Haymarket Media Inc, 275 7th Avenue, 10th Floor, New York, NY 10001. Oncology Nurse Advisor is available for single copy purchases at the following rates. Price per copy: USA $20; Foreign $30. To order call (800) 558-1703. For advertising sales, call (646) 638-6000 (M-F, 9am-5pm, ET). Postmaster: Send changes of address to Oncology Nurse Advisor, P.O. Box 316, Congers, NY 10920. 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.

EDITORIAL BOARD Ann J. Brady, MSN, RN-BC Huntington Cancer Center Pasadena, California Jiajoyce R. Conway, DNP, CRNP, AOCNP Cancer Care Associates of York York, Pennsylvania Marianne Davies, DNP, ACNP, AOCNP Smilow Cancer Center @ Yale New Haven New Haven, Connecticut Frank dela Rama, RN, MS, AOCNS Palo Alto Medical Foundation Palo Alto, California Donald R. Fleming, MD Cancer Care Center, Davis Memorial Hospital Elkins, West Virginia Susanne Menon, NP, OCN Center for Gynecologic Oncology Massachusetts General Hospital Cancer Center Boston, Massachusetts Leah A. Scaramuzzo, MSN, RN-BC, AOCN Billings Clinic, Inpatient Cancer Care Billings, Montana Lisa A. Thompson, PharmD, BCOP Kaiser Permanente Colorado Rosemarie A. Tucci, RN, MSN, AOCN Lankenau Hospital Wynnewood, Pennsylvania

4 ONCOLOGY NURSE ADVISOR • SEPTEMBER/OCTOBER 2016 • www.OncologyNurseAdvisor.com

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CONTENTS 7

IN THE NEWS • SES Factors Impact Myeloma Survival • Novel Train-the-Trainer Program Improves Communication for Nurses • Genomic Sequencing Data May Widen Racial and Ethnic Health Disparities • Frailty Index May Predict Outcomes in Older Patients … and more

NAVIGATOR NOTES Novel CRC Screening Option Opens Door to New Conversations

September/October 2016

Nada Mlinarevich, MPH, RN, CCRC

FEATURES Using CBT Principles in Daily Patient Interactions Maria Chi, LCSW-R

Virtual and Vital: Social Media Communities and Cancer Megan Garlapow, PhD

Kinase Inhibitors: Managing Side Eﬀects in GI Cancers Debra Hughes

47 FIND US ON

STAT CONSULT • Regorafenib (Stivarga) • Ruxolitinib ( Jakafi)

Continues on page 6

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STAT CONSULT

CONTENTS 37

Crizotinib (Xalkori) Crizotinib is a kinase inhibitor indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) in patients whose tumors are ALK-positive and metastatic NSCLC in patients whose tumors are ROS1-positive.

September/October 2016

RADIATION & YOUR PATIENT Identifying and Managing PMPS After Breast Cancer Treatment Bryant Furlow

COMMUNICATION CHALLENGES When You’re Too Nice Ann J. Brady, MSN, RN-BC

ISSUES IN CANCER SURVIVORSHIP Increasing Dietary Omega-3 Intake After Colorectal Cancer Diagnosis Improves Survival

Helicobacter Pylori and Cancer Risk This fact sheet explores the links that H pylori may have with gastric and other cancer types.

PUBLISHERS’ ALLIANCE: DOVE PRESS

THE TOTAL PATIENT Patients’ and Caregivers’ Misperceptions Continue to Stigmatize Palliative Care Bette Weinstein Kaplan

OncoTargets and Therapy

45 FROM CANCERCARE Dating Challenges Throughout the Cancer Journey Angelique Caba, LCSW-R

FACT SHEETS Calcium and Cancer Prevention This fact examines the sources of dietary calcium and possible links to cancer prevention.

Quality of Life and Cosmetic Result of Single-Port Access Endoscopic Thyroidectomy via Axillary Approach in Patients With Papillary Thyroid Carcinoma This research reviews the effects of singleport access transaxillary totally endoscopic thyroidectomy on outcomes following surgery, including quality of life and cosmetic result, in patients with papillary thyroid carcinoma.

Bette Weinstein Kaplan

VIDEO Liver Cancer, Hepatocellular Carcinoma, and Hepatoma Robert G. Gish, MD, talks about liver cancer, hepatocellular carcinoma, and hepatoma.

ASK A PHARMACIST Managing Adverse Events Related to Checkpoint Inhibitors Lisa A. Thompson, PharmD, BCOP

PUBLISHERS’ ALLIANCE: AME PUBLISHING CO Outcomes in Patients With Brain Metastasis From Esophageal Carcinoma This research examines factors associated with survival in patients with brain metastasis from esophageal cancer Journal of Gastrointestinal Oncology

ON THE

WEB

6 ONCOLOGY NURSE ADVISOR • SEPTEMBER/OCTOBER 2016 • www.OncologyNurseAdvisor.com

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IN THE NEWS SES Factors Impact Myeloma Survival Sociodemographic factors, not race or ethnicity, impact survival of younger patients with multiple myeloma. Despite recent advances in the treatment of patients with multiple myeloma, improvements in survival have been found predominantly among young and white patients. Therefore, researchers sought to evaluate how sociodemographic factors and race/ethnicity impact survival in younger patients with multiple myeloma. For the study, investigators analyzed overall survival data from 10,161 patients who were younger than 65 years at diagnosis between 2007 and 2012 and included in the Surveillance, Epidemiology, and End Results (SEER-18) program. Sociodemographic factors assessed were marital status, insurance status, median household income, and educational achievement in the county of residence. Results showed that inclusion in the SEER registry, age, male sex, marital status (other than married), insurance status (uninsured or Medicaid), and county-level income (lowest 2 quartiles) were associated with an increased risk of death; however, race/ethnicity did not correlate with survival. The 4-year estimated overall survival rate was 71.1%, 63.2%, 53.4%, and 46.5% (P <.001), respectively, for patients with 0, 1, 2, or 3 adverse sociodemographic factors. Researchers also found that Hispanic and nonHispanic black patients had more adverse sociodemographic factors and worse overall survival compared with non-Hispanic white patients. “This finding strongly suggests that there is a huge disparity in outcomes that could potentially be overcome by improving access and affordability of treatments,” said Luciano Costa, MD, PhD, of the University of Alabama at Birmingham. “With the recent emphasis on comparative effectiveness in oncology, it also becomes crucial that all variables affecting outcomes — including sociodemographic factors — are accounted for when comparisons between different therapeutic approaches and health care systems are made.”

MASCC Updates Guidelines for CINV Prevention in Children The Multinational Association of Supportive Care in Cancer (MASCC) and the European Society for Medical Oncology (ESMO) have updated their 2009 consensus recommendations for the prevention of acute chemotherapyinduced nausea and vomiting (CINV) in pediatric patients with cancer. Key recommendations of the 2016 guidelines include: • For children receiving high or moderately emetogenic chemotherapy, prophylaxis for acute CINV should include a 5-HT3 antagonist (eg, granisetron, ondansetron, palonosetron) with or without dexamethasone and/or aprepitant.

• For children receiving low emeotgenic chemotherapy, a 5-HT3 antagonist alone is recommended. • Children receiving chemotherapy of minimal emetogenicity should not receive CINV prophylaxis. Of note, young children who are unable to swallow oral solid dosage forms or children whose weight does not allow appropriate dosing with the oral solid dosage forms available may be unable to receive aprepitant. Fosaprepitant, the intravenous formulation of aprepitant, cannot be routinely recommended currently due to a lack of pediatric experience with this agent. These recommendations were based on an original literature review of 25 randomized studies, including 8 published since 2009, that evaluated CINV prophylaxis in children younger than 18 years. Despite new data, significant research

Read more at http://bit.ly/2cjMepe.

Frailty Index May Predict Outcomes in Older Patients A deficit-accumulation frailty index constructed from a comprehensive geriatric assessment may predict outcomes in older patients with cancer. Because frailty has been suggested as a domain for clinicians to consider when treating older patients with Greater toxicities in prefrail/frail patients cancer, researchers sought to evaluate a frailty index from a mostly selfadministered comprehensive geriatric assessment. Five hundred patients age 65 years and older underwent the geriatric assessment prior to the receipt of chemotherapy. Investigators constructed the 51-item frailty index, and then examined cutoff values for patients in the robust/ nonfrail (cutoff value, 0.0 to less than 0.2), prefrail (cutoff value, 0.2 to less than 0.35), and frail (cutoff value, 0.35 or greater) groups. Of those evaluated, 50% were considered were nonfrail, 39% were prefrail, and 11% were frail. Researchers found that older age (80 years or older), lower education, living alone, and higher stage of disease were associated with prefrail/frail status. Results showed that prefrail/frail patients were more likely to experience grade 3 or worse toxicities but not to require dose interruption or reduction. They also had a higher likelihood of drug discontinuation and hospitalization. Read more at http://bit.ly/2deFniT.

Nurses Are Key to Referrals to Inpatient Integrative Medicine Services In a review of referrals to integrative medicine services at Abbott Northwestern Hospital in Minneapolis, Minnesota, researchers found that most doctors are supportive or neutral about referring patients to the integrative medicine (IM)

services offered. This National Institute of Health (NIH)funded study found that levels of engagement ranged from ordering the services for all patients, with allowance for patients to opt out, to relying on nurses and mid-level practitioners to suggest which patients should be offered these services. Use of integrative medicine along with conventional medicine is becoming more common in the United States. In the outpatient setting, patients access these services as independent consumers. In the inpatient setting, however, access to such services is largely clinician controlled and little is known about the interaction between referral processes, clinician attitude, and patient use. Therefore, researchers conducted this study to better understand the flow of referrals for integrative medicine for hospitalized patients. A referral is defined as an order placed in the patient’s electronic health record (EHR). The researchers reviewed referrals for integrative therapies of all inpatients 18 years and older between July 2012 and December 2014 at Abbott Northwestern Hospital, a 630-bed tertiary care hospital with a well-established integrative medicine program. In addition, they interviewed 15 physicians, 15 nurses, and 7 administrators to assess their perspectives on referring patients for these services. The greatest number of referrals was made for patients hospitalized for 3 days or less (5801 of 50,782 patients). Although a larger proportion of patients with hospital stays of 10 days or longer was referred for IM services, the absolute number of these patients was smaller (2942 of 7466 patients). Interview responses followed 3 general themes: criteria used to make referrals, factors influencing the referral process, and concerns and challenges related to having an IM program in the hospital. The most significant findings of this study were that, when IM services are available, physicians and nurses will refer patients to them; referrals are driven largely by length of stay and severity of patient symptoms; and IM referrals are often generated by nurses, whose decisions get a great deal of support from physicians. Read more at http://bit.ly/2cpLnUc.

For full news stories visit OncologyNurseAdvisor.com

(both P <.0001). The study further revealed that patient sex and disease-specific risk factors at baseline did not significantly improve the prognosis of fatigue at any of the 3 assessment points.

16 ONCOLOGY NURSE ADVISOR • SEPTEMBER/OCTOBER 2016 • www.OncologyNurseAdvisor.com

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NAVIGATOR NOTES

s a growing number of Americans face cancer diagnoses, the role of oncology nurses in helping them navigate the journey ahead becomes increasingly important. The nursepatient relationship has the power to impact patients’ quality of life and even clinical outcomes. Although much of the conversation with patients will likely revolve around treatment and follow-up, nurses also have a unique opportunity to create meaningful dialogue about prevention, including talking to patients about cancer screening. The challenge is that while we know how crucial screening is to early detection, treatment success, and long-term outcomes, patient adherence to screenings is notoriously low. Colorectal cancer (CRC) is a great example of the importance of screening. The second deadliest form of cancer in the United States — second only to lung cancer — colorectal cancer is expected to kill more than 49,000 people this year.1 The good news is that because of the slow progression of polyps from benign to malignant, the 5-year survival rate when diagnosis is made at an early stage is greater than 90%.2 Even better, if polyps are identified and removed in the precancerous phase, colorectal cancer can be prevented.3 Unfortunately, more than 23 million Americans in the recommended group (50 years and older; earlier for some groups and those with a family history) avoid screening.4 As a result, many cases are not diagnosed until the late stages, when the 5-year survival rate is a mere 12%.2

Novel CRC Screening Option Opens Door to New Conversations Nada Mlinarevich, MPH, RN, CCRC

Colon cancer cells seen on scanning electron micrograph

SCREENING OPTIONS The reasons for the low rate of colorectal cancer screening adherence (less than 60% nationally) vary widely and include everything from fear to

embarrassment to inconvenience. Historically, patients also have had limited options when choosing the right screening method for their lifestyle. Colonoscopy is considered by many to be the primary strategy for a visual inspection of the entire colon for signs of cancer and precancer and allows for the removal of potentially problematic tissue or polyps. Although the procedure is highly effective, some patients are unwilling or unable to undergo colonoscopy because it is invasive, requires dietary and medication restrictions, and includes extensive bowel preparation and often sedation. Still, for those who avoid colonoscopy, there are options. In June 2016, the United States Preventive Services Task Force (USPSTF) updated their colorectal cancer screening recommendations. They list various screening methods, and explain to consumers that “the best CRC screening test is the one that you and your doctor decide is right for you.”5 Additional tests, such as the fecal occult blood test (FOBT) and fecal immunochemical test (FIT), were developed to help meet the need for noninvasive screening options. Both tests are designed to detect occult blood in the stool. However, because there are unrelated conditions that can cause blood in the stool, and not all polyps or lesions bleed, these tests on their own may not be reliable for the detection of cancer or precancer. In addition, the fecal occult blood test has many potential causes for false positive results and a low level of

[The FDA] explains to consumers that “the best CRC screening test is the one that you and your doctor decide is right for you.” www.OncologyNurseAdvisor.com • SEPTEMBER/OCTOBER 2016 • ONCOLOGY NURSE ADVISOR 17

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NAVIGATOR NOTES

sensitivity, while the fecal immunochemical test delivers only a moderate level of sensitivity. A NEW OPTION Now, another colorectal cancer screening option is available to patients, giving nurses a timely reason to engage with patients about the importance of following through with preventive screening. In August 2014, the FDA approved Cologuard ®, the f irst noninvasive multitarget stool DNA (mt-sDNA) screening test for colorectal cancer. The concept is straightforward. Every day, normal cells, along with abnormal cells from cancer or precancers, are shed from the colon wall and picked up by the stool as it passes through the colon. Cologuard uses mt-sDNA technology to detect altered DNA and blood associated with colorectal cancer and precancer. The blood detection is similar to FIT and FOBT. FDA approval was based on the results of a 10,000-patient, multicenter study.6 The pivotal study compared the performance of mt-sDNA test to a leading fecal immunochemical test using colonoscopy as the reference method. The results showed that the mt-sDNA test detected 92% of cancers and 42% of advanced adenomas with 87% specificity. The process of completing the mtsDNA test is simple. First, a health care provider orders the test, and a collection kit is sent to the patient’s home. The patient collects a stool sample at his/ her convenience — no medication, dietary restrictions, bowel preparation, sedation, time off from work, or transportation required. Once the collection is complete, the patient ships the kit in a prepaid UPS mailer directly to the lab for processing.

Test results are sent to the prescribing provider approximately 2 weeks from the time patients submitted their stool sample. Those patients with positive scores are referred for diagnostic colonoscopy. Patients with negative results should continue to participate in a screening program at an interval and with a method appropriate for the individual patient based on their conversation with the prescribing clinician. In addition, screening adherence rates increase when follow-up is conducted.7 Exact Sciences Laboratories, which

More than half of CRC deaths could be avoided with regular screening. performs the Cologuard test, hosts a patient navigation system that conducts phone follow-up to remind patients who receive an mt-sDNA collection kit to complete and send the test back for analysis while also supporting health care providers in their efforts to get patients screened. The screening test is intended for use with patients age 50 years and older at average risk who are typical candidates (asymptomatic) for colorectcal cancer screening. People should not use this test if they have diarrhea or blood in their urine or stool; a history of colorectal cancer, adenomas, or other related cancers; a positive result from another colorectal cancer screening method within the last 6 months; have a condition associated with high risk for colorectal cancer, such as inflammatory bowel disease (IBD); or have

a relevant familial (hereditary) cancer syndrome such as HNPCC (hereditary nonpolyposis colorectal cancer) or Lynch syndrome. The screening test was not evaluated in high-risk patients. The programmatic performance of Cologuard (ie, benefits and risks with repeated testing over an established period of time) has not been studied. Performance has not been evaluated in adults who have been previously tested with Cologuard. Noninferiority or superiority of Cologuard programmatic sensitivity as compared to other recommended screening methods for colorectal cancer and advanced adenomas has not been established. Clearly, colorectal cancer is a public health concern that requires immediate attention given the nature of the disease and the significant advancements in screening options. Research tells us that more than half of colorectal cancerrelated deaths could be avoided with regular screening, so the onus is on all of us to drive adherence and save lives.8 The availability of new testing options offers nurses a timely reason to connect with patients, understand their lifestyle, fears, family history, work, transportation, and socio-economic challenges in order to help them find the test that best fits their needs. The bottom line is that the right test is the one that gets done, and there is no better time than now to educate and encourage patients to take a more proactive role in their health — this is one area (of many) where nurses can have a significant and lasting impact. ■ Nada Mlinarevich is director of medical affairs at Exact Sciences Corporation, Madison, Wisconsin. Go to the online version of this article at http:// bit.ly/2cWXY1X to read the references.

18 ONCOLOGY NURSE ADVISOR • SEPTEMBER/OCTOBER 2016 • www.OncologyNurseAdvisor.com

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FEATURE | Cognitive-behavioral Therapy

Using CBT Principles in Daily Patient Interactions Cognitive-behavioral therapy techniques help patients turn their negative thoughts into positive attitudes, as well as find purpose in their life. MARIA CHI, LCSW-R

his was my first meeting with Harry, and as soon as he lowered himself into my chair with a heavy sigh, I knew it would be a difficult counseling session. “There’s no point,” he said. “I might as well die right now.” After spending some time to establish that he was not suicidal but rather voicing his distress prompted by a recent cancer diagnosis, I asked Harry to tell me when there was a point. What were his reasons for being alive now? After thinking for a while, he told me that he looked forward to talking to his brother every day, and he cherished the rescue dog that had been part of his family for the last 3 years. Over several more conversations, Harry identified many more reasons for living, however long or short his life might be. Harry’s initial comments represent one of the most common types of distorted thoughts — focusing solely on the negative — that people tend to have when facing difficult problems.1 These thoughts are distortions not in the sense that they reflect false problems, but in the way that they highlight certain parts of a situation to the exclusion of all others. When Harry said that there was absolutely no reason to live his life every day because he was just going to die anyway, he was using a mental filter that only took the negative into account. When he was able to identify some reasons for living, things that gave him purpose, he showed that he could see more than one truth about his situation. Harry’s negative mental filter represents just one type of cognitive error that we all tend

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to use at certain times. Other common types of cognitive distortions include: • Black-and-white thinking Seeing things in extremes (“I’m either going to be cured or I’m going to die.”) • Overgeneralization Viewing one negative event as indicative of your entire life or character (“My husband spends so much time taking care of me. I’m such a weak and needy person.”) • Discounting the positive Discarding positive experiences despite the evidence (“My test results show that the treatment is working, but I think the cancer will probably return.”) • Mind-reading Assuming others’ thoughts and intentions (“My friend hasn’t called me to see how I’m doing because she doesn’t care about me.”) • “Should” statements Directing yourself or others with unrealistic “shoulds” (“I should not burden my friends and family or ask for help, no matter what.”) • Personalizing Believing that you are the sole cause of an external event (“If I wasn’t so stressed out, I would not have gotten cancer. It’s all my fault.”)2 USING CBT TECHNIQUES Cognitive behavioral therapy (CBT) is a way to challenge the above distortions and replace them with more adaptive thoughts that reflect a more complete picture of the situation.1 In turn, people learn to cope more effectively with their cancer. From 2009 to 2013, the National Cancer Institute funded multiple CBT training sessions for clinicians engaged in supportive counseling with cancer survivors. The prevalence of these training sessions indicates the growing recognition of cognitive behavioral therapy as an evidence-supported technique for a variety of people who seek psychosocial help. For people with cancer, cognitive behavioral therapy offers a way to cope with the stressors related to having a life-threatening illness. Health care professionals can use CBT techniques on a regular basis. To start, ask your patient to write down typically distressing thoughts as they occur. When does the patient tend to have these thoughts? Are the thoughts triggered by certain events? How does the patient feel when having these thoughts? How does the patient’s body feel? What does the patient usually do to cope with these thoughts and feelings? Does it work? Exploring this process is the key to changing what does not work. Although feelings seem automatic and uncontrollable, they are caused by our thoughts and beliefs about the things that happen to us. Once we identify those thoughts and whether they are helpful or not, we can choose new thoughts that are

based in reality but cause less distress. Thinking something different helps us do something different.2 For example, if your patient thinks “I absolutely cannot tolerate getting chemotherapy” every time he or she goes for a treatment, the patient will likely feel anxious, fearful, or angry in the room. The patient may have clenched fists and become irritable, or avoid getting treatment. By helping your patient answer the following questions, the patient might gain a new perspective: • What is the evidence for your thought or belief? “I get very upset whenever I enter the treatment room. My stomach is in knots when I see the chemo chair.” • What is the evidence contrary to your belief? “Even though I feel anxious, I usually show up for treatment. My stomach eventually relaxes and I can sit down.” • What would your friend think about your belief? “He would tell me that I can handle more than I think, that I’ve dealt with worse things in the past.” • What is a more helpful way to look at this? “Getting chemo is an unpleasant experience, but it’s not the end of the world. I have been dealing with it, and with support, I can continue to do so.” While helping your patients to challenge their negative thoughts and replace them with more constructive beliefs, you must first acknowledge their distress. Moving too quickly to new thoughts can be invalidating. Acknowledge what is true about your patients’ negative beliefs, but then point out that few things in life are true in all instances all the time. How is it helping your patient to hold onto those distorted thoughts, to dwell exclusively on the negative parts? Looking at all sides of a situation leads to a better quality of life. Harry knew he had a serious illness and initially felt hopeless. His belief that there was “no point” prevented him from living. Once he started paying attention to more than one truth about his situation — that he was still alive today and that he still had reasons to live — he rediscovered his life. And he chose to make the most out of it. ■ Maria Chi is social work internship program director at CancerCare. REFERENCE 1. Cagle JG, Loscalzo M. Using cognitive and behavioral approaches throughout the cancer experience. In: Christ G, Messner C, Behar L, eds: Handbook of Oncology Social Work: Psychosocial Care for People With Cancer. New York, NY: Oxford University Press; 2015:345-350. 2. Sage N, Sowden M, Chorlton E, Edeleanu A. CBT for Chronic Illness and Palliative Care: A Workbook and Toolkit. West Sussex, England: Wiley; 2008.

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FEATURE | Social Media

Virtual and Vital: Social Media Communities and Cancer Social media has become a mainstay of day-to-day life. For patients with cancer, it can be a lifeline to unprecedented support that is unique to their needs. MEGAN GARLAPOW, PhD

atients with just about any disease can participate in social media to both provide and receive emotional support and to gain new information about the disease and its treatment. A 2015 study in the Journal of the American Pharmacists Association ( JAPhA) reviewed results from 35 studies worldwide and noted, “Social media platforms have the potential to help patients and practitioners overcome multiple barriers in the delivery of health care.”1 Social media for patients with cancer can involve their surrounding community of family members, caregivers, friends, nurses, and doctors, or it can be tailored only to patients. Increasingly, social media platforms serve as important outlets of credible health communication. “There are a plethora of social platforms available to cancer patients and their families. But not all are created equally or intended to serve the same purpose,” Stacey Tinianov, patient and community engagement and advocacy consultant in San Francisco, California, said in an interview with Oncology Nurse Advisor. She explained that sites such as CaringBridge and WhatFriendsDo allow patients with cancer to update their friends and family on their care and to ask for and organize support, while social platforms such as PatientsLikeMe, Smart Patients, and MyBCTeam are made for patients to interact with other patients for peer-to-peer support and knowledge exchange. “Twitter and public Facebook groups provide more expansive social platforms with a global

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reach and often a mixed audience that includes patients, caregivers, providers, and researchers,” Tinianov said. Patients can therefore choose 1 or many social media platforms in which to participate, with “new social sites seeming to crop up daily,” Tinianov added. Wisdo is an online community assisting people as they move through the challenges of serious illnesses by providing wisdom from people who have already faced those challenges. Although Wisdo does not focus exclusively on cancer, it does include support communities for people with breast or prostate cancer and will soon expand into more than 15 different types of cancer. “Wisdo helps people take on life’s greatest challenges by equipping them with wisdom from those who’ve been there,” Boaz Gaon, CEO and director of communities at Wisdo .com in Mountain View, California, said in an interview with Oncology Nurse Advisor. “Our community members identify the major ‘steps’ that were part of their own journey through a certain life chal-

That connections are made virtually does not diminish their value or importance. lenge or opportunity, and then they add specific insights (tips, reflections, etc) to help others know what to expect and never feel lonely,” he said. A major benefit of social media is that it is accessible from anywhere and at any time, allowing patients, family members, and health care providers to bypass the energy, emotions, and time spent seeking support in person. “Connecting with others who understand your fears, questions, anxieties, side effects, etc, is one of the most valuable elements of social media platforms,” Tinianov said. “And if you’re anxious about an upcoming scan and unable to sleep at 3 AM, you will likely find company and comfort online.” Tinianov also noted that for patients who feel uncomfortable sharing in a face-to-face forum, social media platforms can help them find the support they need. But the fact that connections are made virtually does not diminish their value or importance. “When connections made via social media are powerful, people inevitably extend their relationships offline, either through email, phone calls, or face-to-face interaction,” she said.

In addition to overcoming fear and loneliness, these outlets can augment clinical advice by providing insights and suggestions to patients with cancer that they might not receive otherwise. “When we asked breast cancer survivors and their family members to identify the major steps that make up the breast cancer experience, they suggested steps like ‘Cutting your hair before chemotherapy, ‘Informing your employer about your diagnosis,’ and ‘Going back to work after treatment,” Gaon explained. “This wisdom is usually found and shared online more than in official pamphlets and clinical textbooks.” NURSES, NURSE NAVIGATORS, AND SOCIAL MEDIA PLATFORMS

Some social media platforms can benefit the cancer community beyond patients. Nurses and nurse navigators can use the outlets to improve their comprehension of their patients. “Whether [nurses and nurse navigators] join the conversation or just listen in to the dialogue, a better understanding of the concerns, fears, goals, challenges, and successes of cancer patients and their families helps to provide additional whole-person context,” Tinianov said. Not only can nurses and nurse navigators learn about their patients through participation in social media platforms, but they can also provide important insights to these communities. “Nurses are wisdom personified,” Gaon said. “They know that there is more to being a patient than just going through the clinical steps of an illness. Nurses provide practical, emotional, and physical support when you need it the most. They are the backbone of health care.” OBSTACLES AND OPPORTUNITIES Many social media platforms face the challenge of helping patients overcome the intense loneliness that can accompany diagnosis, treatment, and recovery. And the cancer community’s social media platforms seem to provide ample advice in this area. “So many people have gone through so many cancers and still, for the average cancer patient, cancer is such a lonely experience,” Gaon said. “Instead of walking on a path that has been created by others, many patients feel lost, unequipped, and lacking visibility of the road ahead.” In addition to these obstacles, patients participating in social media platforms may be at an increased risk for a privacy breach. Continues on page 24

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FEATURE | Social Media The JAPhA article noted that, “one of the major gaps that exists is a lack of investigation into the actual risks with using social media compared with other technologies. Are patients with social media profi les more likely to experience a breach of privacy than patients who stay away from these sites but use electronic mail for communication with a health professional?” And the abundance of social media platforms can act as an additional barrier. “When searching on Google, a patient is presented with an endless list of links. And when searching on social networks, one is presented with an ocean of ‘feed,’” Gaon noted. “But patients and their families often like to see the slightly bigger picture: a glimpse of the road ahead based on the experiences of others.” But by outlining a possible path and organizing those steps, patients with cancer just beginning the journey will “have torchlights where others had only darkness,” Gaon said.

THE FUTURE FOR SOCIAL MEDIA PLATFORMS The future of social media seems positive for patients with cancer, their friends and families, and their nurses. The potential for these platforms to overcome loneliness and isolation while providing credible health care communication poise them to become integral to the cancer care community. “In 10 years, [Wisdo hopes] to be perceived as a company and movement that has improved human lives by creating a world in which people in need always know what to expect and never ever feel lonely,” Gaon said. “We think it’s a worthy mission — one worth dedicating our lives to.” ■ Megan Garlapow is medical writer based in Phoenix, Arizona. REFERENCE 1. Mattingly TJ 2nd. Innovative patient care practices using social media. J Am Pharm Assoc. 2015;55(3):288-293.

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FEATURE | Gastrointestinal cancer

Kinase Inhibitors: Managing Side Eﬀects in GI Cancers A review of adverse effects and recommended management for 3 kinase inhibitors indicated for the treatment of gastrointestinal cancers. DEBRA HUGHES

3-dimensional CT reconstruction scan of the stomach with a massive GIST (yellow)

he first kinase inhibitor, imatinib mesylate (Gleevec), was approved in 2001 for the treatment of gastrointestinal stromal tumor (GIST).1 Sunitinib maleate (Sutent) is approved for GIST after disease progression or intolerance to imatinib2; and second-generation regorafenib (Stivarga) is approved for locally advanced, unresectable, or metastatic GIST previously treated with imatinib and sunitinib as well as metastatic colorectal cancer.3 Oral agents represent a convenience for patients. Yet, because each agent has a different dosage and recommended route of administration ( Table 1), managing treatment can be complex. To be able to counsel patients on what to watch for and when to report signs or symptoms that might require dose interruptions or modifications of imatinib, sunitinib, or regorafenib, a heightened awareness of adverse reactions and warnings and precautions cannot be underestimated. This article summarizes the adverse-effect management information included in the prescribing information for each of the 3 kinase inhibitors. All place women at risk for embryofetal toxicity; therefore, women of childbearing potential should use highly effective contraception to avoid becoming pregnant while on these medications and avoid breastfeeding. Both females of childbearing potential and males with female partners of childbearing potential taking regorafenib should continue to use effective contraception for 2 months after the final dose.1-3

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TABLE 1. Kinase Inhibitors for GIST and Metastatic Colorectal Cancer: Indication, Recommended Dose, and Administration1-3 Generic (Trade Name)

Indication

Recommended Dose

Administration

Imatinib mesylate (Gleevec)

Kit (CD117) positive unresectable and/or metastatic malignant GIST

Metastatic and/or unresectable GIST: 400 mg orally, once daily

Take with a meal and a large glass of water

Adjuvant treatment following resection of Kit (CD117) positive GIST

Adjuvant treatment, GIST: 400 mg orally, once daily

Can be dissolved in water or apple juice for patients having difficulty swallowing

Mild to moderate hepatic impairment: 400 mg orally, once daily Severe hepatic impairment: 300 mg/day

Regorafenib (Stivarga)

Metastatic CRC previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy

Daily dosing of 800 mg and above should be accomplished using the 400 mg tablet to reduce exposure to iron

160 mg orally, once daily for the first 21 days of each 28-day cycle

With a low-fat meal

50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off

With or without food

Locally advanced, unresectable, or metastatic GIST previously treated with imatinib mesylate and sunitinib malate Sunitinib (Sutent)

GIST after disease progression on or intolerance to imatinib mesylate

Dose interruptions and/or dose adjustments of 12.5 mg recommended based on individual safety and tolerability Key: CRC, Colorectal cancer; GIST, Gastrointestinal stromal tumor.

For all 3 agents, the most important side effect is the potential to cause serious liver problems that can sometimes lead to death. Patients should inform their oncology nurse if they experience itching 2; signs of jaundice, including dark urine1-3; or if they have nausea or vomiting or pain or discomfort in the right upper stomach area.2,3 ADVERSE EFFECTS AND MANAGEMENT Hepatotoxicity that may result in death or require liver

transplant is a concerning risk with these agents; therefore, monitoring liver function (transaminases, bulirubin, and alkaline phosphatase) prior to initiating treatment (baseline) and at specified intervals, or as clinically indicated, throughout treatment is recommended. Liver failure manifests as jaundice, elevated transaminases, and/or hyperbilirubinemia in conjunction with encephalopathy, coagulopathy, and/or renal failure. Recommended monitoring schedule for patients receiving imatinib is at baseline, then monthly or as clinically

indicated. Withold imatinib as follows: elevated bilirubin is greater than 3 times the institutional upper limit of normal (IULN), withhold until less than 1.5 times the IULN; liver transaminases greater than 5 times the IULN, withhold until less than 2.5 times the IULN. When treatment can be resumed, dose reductions are 400 mg to 300 mg, 600 mg to 400 mg, or 800 mg to 600 mg in adult patients; 340 mg/ m2/day to 260 mg/m 2/day in children.1 Liver dysfunction was most often characterized by a hepatocellular pattern of injury that occurred within the first 2 months of treatment in patients receiving regorafenib. Due to this incidence, recommended monitoring schedule is at baseline then at least every 2 weeks during the first 2 months of treatment, and monthly beyond the first 2 months, or as clinically indicated. Liver function should be monitored weekly in patients with elevated tests results until improved to less than 3 times the ULN or baseline.3 Continues on page 28

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FEATURE | Gastrointestinal cancer Regorafenib should be temporarily held, then depending on the severity and persistence of hepatotoxicity, reduce the dose or permanently discontinue. For grade 3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation, reduce dose to 120 mg but only resume if the potential benefit outweighs the risk of hepatotoxicity. If grade 3 AST/ALT elevation occurs at this dose, reduce dose further to 80 mg after recovery. Permanently discontinue treatment if AST or ALT is more than 20 times the ULN, if AST or ALT is more than 3 times the ULN with concurrent bilirubin more than 2 times the ULN, or if AST or ALT recurs at more than 5 times ULN despite dose reduction to 120 mg. Resume treatment only if the potential benefit outweighs the risks after any grade 4 adverse reaction.3 In patients receiving sunitinib, obtain liver function test results at baseline, during each treatment cycle, and as clinically indicated. Interrupt treatment for grade 3 or grade 4 drug-related hepatic adverse events, and discontinue treatment if hepatic adverse events are not resolved. If severe changes in liver function are seen or the patient develops other signs or symptoms of liver failure, do not restart sunitinib. Safety of this drug has not been established for patients with ALT or AST greater than 2.5 times the ULN, or greater than 5.0 times the ULN if due to liver metastases.2 Cardiovascular events such as heart failure and left ventricular dysfunction (LVF); current cardiac disease, risk factors for cardiac failure, or a history of renal failure are adverse effects to assess for in patients treated with these kinase inhibitors. In the setting of imatinib for GIST, watch for signs and symptoms consistent with cardiac or renal failure and initate appropriate treatment. Most cases of congestive heart failure and left ventricular dysfunction were reported in patients with comorbidities known to be risk factors for cardiovascular events, such as advanced age or previous medical history of cardiac disease. Clinicians should watch for signs and symptoms consistent with cardiac or renal failure and treat accordingly.1 Withhold regorafenib in patients with GI cancers if new or acute cardiac ischemia or infarction develops. Treatment can be resumed after resolution of symptoms, if the potential benefits outweigh the risks of future cardiac ischemia.3 In patients receiving sunitinib presenting with clinical manifestations of congestive heart failure, discontinuation of treatment is recommended. Patients who experience declines in left ventricular ejection fraction (LVEF) may need treatment with an antihypertensive or diuretic.2 Because clinical trials excluded patients who presented with cardiac events within 12 months prior to administration of sunitinib, whether patients with concomitant cardiovascular

conditions are at higher risk of developing drug-related LVEF is not known. Clinicians are advised to perform baseline and periodic evaluations of LVEF during treatment, including a baseline evaluation of ejection fraction in patients without cardiac risk factors.2 Additional cardiovascular-related cautions include patients with a history of QT interval prolongation, those taking antiarrhythmics, or those with preexisting cardiac disease, bradycardia, or electrolyte disturbances. Monitoring patients receiving sunitinib with on-treatment electrocardiography and laboratory measures of electrolytes should be considered.2 Hypertension incidence is increased in patients receiving regorafenib, with onset during the first cycle in most of those who develop the condition. Regorafenib should not be initiated in patients whose blood pressure is not adequately controlled. Blood pressure should be monitored weekly for the first 6 weeks then every cycle, or more frequently as indicated. The drug may need to be withheld temporarily or permanently if severe or uncontrolled hypertension develops.3 Hypertension in patients receiving sunitinib should be controlled with standard antihypertensive therapies. A temporary interruption in therapy is recommended if severe hypertension develops; treatment can resume when hypertension is controlled.2 Hemorrhage was reported in clinical trials of these kinase inhibitors, including grade 3/4 hemorrhage with imitanib in patients with newly diagnosed chronic myelogenous leukemia (CML) and unresectable or metastatic GIST. However, in a randomized trial comparing imatinib and nilotinib in newly diagnosed Ph+ CML, GI hemorrhage occurred but was not grade 3/4.1 Regorafenib should be permanently discontinued in patients who develop severe or life-threatening hemorrhage. INR levels should be monitored more frequently in patients receiving warfarin.3 Nosebleeds were the most common form of hemorrhage reported in patients taking sunitinib; less common bleeding events including rectal, gingival, upper gastrointestinal, genital, and wound bleeding. Tumor-related hemorrhage may occur suddenly, with treatment-emergency grade 3 and 4 hemorrhage observed as early as cycle 1 and as late as cycle 6 in patients with GIST. Clinical assessment of tumor-related hemorrhage should include serial complete blood counts and physical examinations.2 OTHER SIGNIFICANT WARNINGS Imatinib Patients receiving imatinib should be weighed

regularly, with careful investigation of any unexpected rapid weight gain.1 Higher dose and age older than 65 years increase

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the probability of edema. Severe fluid retention should be managed with drug interruption and diuretics. Patients should be advised to use caution regarding driving or operating machinery, as dizziness, blurred vision, and somnolence have been reported. Other reported adverse events include gastrointestinal perforation; bullous dermatologic reactions such as erythema multiforme and Stevens-Johnson syndrome; and growth retardation in children and preadolescents.1 Regorafenib Adverse reactions involving the skin and subcutaneous tissues occur more often in patients treated with regorafenib, including hand-foot skin reaction (HFSR), grade 3 rash, serious adverse reactions of erythema multiforme, and Stevens-Johnson syndrome.3 Incidence of all grades of HFSR was higher in Asian patients. Recommended management is dose reduction or permanently discontinue therapy on the basis of severity and persistence of dermatologic toxicity.

Hemorrhage was reported in clinical trials of these kinase inhibitors for CML and GIST. Although rare, reversible posterior leukoencephalopathy (RPLS), which occurred in 1 of 1200 patients receiving regorafenib in clinical trials, should be suspected in patients presenting with seizures, severe headache, visual disturbances, confusion, or altered mental function. Discontinue treatment for any patient who develops RPLS. Treatment should be discontinued if the patient develops gastrointestinal perforation or fistula, also rare (0.6% of 1200 patients across all clinical trials). Formal studies of the effect of regorafenib on wound healing have not been conducted; however, vascular endothelial growth factor receptors (VEGFR) can impair wound healing. Therefore, discontinuing treatment at least 2 weeks prior to scheduled surgery is recommended. Resume treatment on the basis of clinical judgment of adequate wound healing; discontinue treatment in patients with wound dehiscence.3 Sunitinib Tumor lysis syndrome (TLS) has been reported, primarily occurring in patients with GIST or renal cell carcinoma.2 Patients at risk for TLS were those with a high tumor burden prior to treatment. Management includes monitoring and treatment as clinically indicated. Some patients receiving sunitinib as monotherapy or in combination with bevacizumab experienced thrombotic microangiopathy (TMA). Sunitinib should be discontinued in patients who develop TMA. Discontinuing the drug has led to reversal of the effects of TMA.

Obtain baseline and periodic urinalysis during treatment to assess for developing or worsening proteinuria, with follow-up measurement of 24-hour urine protein as clinically indicated. If 24-hour urine protein is 3 g or higher, interrupt sunitinib treatment and reduce the dose. Repeat episodes or nephritic syndrome warrants discontinuing treatment with sunitinib. Assess patients for erythema multiforme, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Discontinue treatment if the patient presents with signs or symptoms of these dermatologic toxicities, such as progressive skin rash often with blisters or mucosal lesions. Treatment should not be resumed if SJS or TEN is suspected and if the patient develops necrotizing fasciitis. Obtaining baseline laboratory measurement of thyroid function is recommended, with close monitoring for signs and symptoms of thyroid dysfunction. Patients with suspected thyroid dysfunction, such as hypothyroidism, hyperthyroidism, or thyroiditis, should undergo laboratory tests for monitoring thyroid function; treat as needed per standard medical practice. Sunitinib is associated with hypoglycemia in patients with GIST or renal cell carcinoma, and this effect may be worse in patients with diabetes. Regular blood glucose measurements should be performed during treatment and after discontinuing the drug. Patients with diabetes may need dose modifications of their antidiabetes medications. Preventive dentistry to reduce the risk of osteonecrosis of the jaw should be considered prior to initiating treatment. Invasive dental procedures should be avoided, particularly if the patient is receiving intravenous bisphosphate therapy. Sunitinib may impair wound healing; therefore, treatment should be temporarily interrupted in patients undergoing major surgical procedures. Because clinical experience in regard to resuming treatment is limited, the decision to do so should be on the basis of clinical judgment of recovery from surgery. Clinicians are also advised to monitor for adrenal insufficiency in patients undergoing major surgery, as well as those experiencing stress such as trauma or severe infection.2 ■ Debra Hughes is a medical writer based in Lusby, Maryland. REFERENCES 1. Gleevec [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2015. 2. Sutent [package insert]. New York, NY: Pfizer, Inc; 2015. 3. Stivarga [package insert] .Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; 2016.

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Write for ONA! Oncology Nurse Advisor offers clinical updates and evidence-based guidance to the oncology nurse community and includes regular coverage of topics such as the safe handling and administration of chemotherapy drugs, side effect management, new developments in specific cancers, palliative care, communication with patients and family, and cancer survivorship. We welcome contributions from readers in the following categories: Oncology Nurse Advisor Forum: Answers to clinical questions and advice for clinical problems. Readers may submit questions and requests for advice that are 50 to 100 words long. The author should include full name and degrees, name of institution or practice, and city and state. Feature article: Oncology Nurse Advisor welcomes feature articles on the administration and handling of chemotherapy drugs; side-effect management; communication with patients, families, and colleagues; whatâ&#x20AC;&#x2122;s new in the treatment of specific cancers or cancer-related conditions; survivorship issues; patient navigation; and other topics of interest to oncology nurses. Manuscripts should be 1200 to 2000 words long and should include a brief reference list. Reflections: These are brief, reflective essays on a topic related to oncology practice or narratives recounting a meaningful experience with a patient. Manuscripts should be 800 to 1200 words long. Case Study: This department focuses on clinical cases of interest to oncology nurses. Manuscripts should be written in the standard case-followed-by-discussion format and should be 1500 to 2000 words long. A brief reference list may accompany the discussion section. Please include a list of 3 to 5 take-home points (teaching points) for the reader. The PDF template in our Author Guidelines is an easy, step-by-step guide for writing up your Case Study. Ask a Pharmacist: In this department, our oncology pharmacist answers readersâ&#x20AC;&#x2122; drug-related questions. Questions should be 50 to 100 words. The author should include full name and degrees, name of institution or practice, and city and state. See our author guidelines, available at www.OncologyNurseAdvisor.com, for more details.

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STAT CONSULT

Regorafenib (Stivarga) Drug Type

• Kinase inhibitor

Indications

• Treatment of patients with ——Metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-based, oxaliplatin-based, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy ——Locally advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate Mechanism of Action

• Regorafenib is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment • In in vivo models, regorafenib demonstrated antiangiogenic activity and inhibition of tumor growth as well as antimetastatic activity Dosage and Administration

• Dosage: 160 mg • Administer orally once daily with food (low-fat breakfast) for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity • Regorafenib should be taken at the same time each day Dosage Adjustments

• Interrupt regorafenib for the following ——Grade 2 hand-foot skin reaction (HFSR) that is

recurrent or does not improve within 7 days despite dose reduction ■■ Interrupt therapy for a minimum of 7 days for grade 3 HFSR ——Symptomatic grade 2 hypertension ——Any grade 3 or 4 adverse reaction • Reduce dose of regorafenib to 120 mg ——The first occurrence of grade 2 HFSR of any duration ——After recovery of any grade 3 or 4 adverse reaction ——Grade 3 AST/ALT elevation ■■ Only resume if potential benefit outweighs risk of hepatotoxicity • Reduce dose to 80 mg ——Reoccurrence of grade 2 HSFR at 120-mg dose ——After recovery of any grade 3 or 4 adverse reaction at 120 mg (except hepatotoxicity) • Discontinue regorafenib permanently for the following ——Failure to tolerate 80-mg dose ——Any occurrence of AST or ALT >20 × ULN ——Any occurrence of AST or ALT >3 × ULN with concurrent bilirubin >2 × ULN ——Re-occurrence of AST or ALT >5 × ULN despite dose reduction to 120 mg ——Any grade 4 adverse reaction ■■ Only resume if potential benefit outweighs risks Specific Populations

• Pregnancy ——Based on animal studies and its mechanism of action, regorafenib can cause fetal harm when administered to a pregnant woman. Continued on page 32

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STAT CONSULT ——Advise pregnant women of the potential hazard to fetus • Nursing mothers ——Because of potential for serious adverse reactions in breastfed infants from regorafenib, women should not breastfeed during treatment and for 2 weeks after final dose • Pediatric ——Not established • Geriatric ——No overall differences in safety and effectiveness were observed between older and younger patients • Renal impairment ——No dose adjustment is recommended for patients with mild renal impairment. ——Limited PK data available from patients with moderate impairment (CrCl 30-59 mL/min). ——Regorafenib has not been studied in patients with severe impairment or end-stage renal disease. • Hepatic impairment ——No dose adjustment recommended in patients with mild or moderate hepatic impairment. ——Regorafenib not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C), since it has not been studied in this population. Boxed Warnings

• Severe and sometimes fatal hepatotoxicity has occurred in clinical trials ——Monitor hepatic function prior to and during treatment ——Interrupt and then reduce or discontinue regorafenib for hepatotoxicity as manifested by elevated liver function tests or hepatocellular necrosis, depending upon severity and persistence Contraindications

• None Warnings and Precautions

• Cardiac ischemia and infarction ——Withhold regorafenib for new or acute cardiac ischemia/infarction and resume only after resolution of cute ischemic events • Dermatologic toxicity ——Interrupt and then reduce or discontinue regorafenib depending on severity and persistence of dermatologic toxicity • Embryo-fetal toxicity ——Regorafenib can cause fetal harm

——Females of reproductive potential and males with partners of reproductive potential should be advised to use effective contraception during therapy and for 2 months after last dose • Gastrointestinal perforation or fistula ——Discontinue regorafenib • Hemorrhage ——Permanently discontinue regorafenib for severe or life-threatening hemorrhage • Hepatotoxicity ——Monitor liver function tests and dose reduce or discontinue based on severity and duration • Hypertension ——Temporarily or permanently discontinue regorafenib for severe or uncontrolled hypertension • Reversible posterior leukoencephalopathy syndrome (RPLS) ——Discontinue regorafenib • Wound healing complications ——Withhold regorafenib before surgery ——Discontinue in patients with wound dehiscence Adverse Effects

• Most common adverse reactions (≥20%) ——Asthenia/fatigue ——Decreased appetite/food intake ——Decreased weight ——Diarrhea ——Dysphonia ——Fever ——GI and abdominal pain ——Hand-foot skin reaction ——Hypertension ——Infection ——Pain ——Rash ——Mucositis ——Nausea Drug Interactions

• Concomitant use of regorafenib with strong CYP3A4 inducers ——Concomitant use decreases exposure of regorafenib ——Avoid concomitant use of regorafenib with strong CYP3A4 inducers ■■ Rifampin, phenytoin, carbamazepine, phenobarbital, and St John’s wort • Concomitant use of regorafenib with strong CYP3A4 inhibitors

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——Concomitant use increases exposure of regorafenib ——Avoid concomitant use of regorafenib with strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, and voriconazole) What to Tell Your Patient

• Regorafenib is a prescription medicine used to treat people with ——Colon or rectal cancer that has spread to other parts of the body and for which the patients have received previous treatment with certain chemotherapy medicines ——A rare stomach, bowel, or esophagus cancer called GIST (gastrointestinal stromal tumors) that cannot be treated with surgery or that has spread to other parts of the body and for which the patients have received previous treatment with certain medicines • Ask your patient about all his or her medical conditions, including ——Liver or bleeding problems ——High blood pressure ——Heart problems or chest pain ——Plans for any surgical procedures or recent surgery • Ask your patient about all medicines he or she is taking, including any vitamins and herbal supplements • Pregnancy ——Regorafenib can cause fetal harm if taken by a pregnant woman ■■ There is no available data on humans; however, regorafenib caused fetal death and birth defects in rats and rabbits at doses lower than the recommended doses for humans ——Females of reproductive potential are advised to use effective contraception during treatment and for 2 months after last dose. ——Males with female partners of reproductive potential are advised to use effective contraception during treatment and for 2 months after last dose. ——There is no data on the effect on human fertility; however, results from animal studies indicate regorafenib can impair fertility in males and females. • Nursing mothers ——There is no data on if regorafenib is excreted in human milk, its effects on breastfed infants, or on milk production. ——Because of the potential for serious adverse reactions in breastfed infants, do not breastfeed during treatment and for 2 months after the last dose • Take regorafenib exactly as your physician tells you

• You will usually take regorafenib 1 time a day for 21 days, then stop for 7 days ——Repeat this cycle for as long as your physician tells you to do so • Swallow regorafenib tablets whole with water after a low-fat meal • Take regorafenib at the same time each day with a lowfat meal that contains less than 600 calories and less than 30% fat • Do not take 2 doses on the same day to make up for a missed dose • Avoid drinking grapefruit juice and taking St. John’s wort during treatment • Regorafenib can cause serious side effects, including ——Bowel perforation (a tear in your stomach or intestinal wall) ——Decreased blood flow to the heart and heart attack ——Hand-foot skin reaction (a skin problem) ——High blood pressure ——Liver problems ——Posterior leukoencephalopathy ——Severe bleeding (hemorrhage) ——Wound healing problems • Your clinician may change your dose, temporarily stop, or permanently stop treatment with regorafenib if you have certain side effects • These are the most common side effects of regorafenib. (These are not all the possible side effects of this medication.) ——Abdominal pain ——Diarrhea ——Fever ——Infection ——Loss of appetite ——Mucositis ——Nausea ——Pain in other parts of your body ——Tiredness, weakness, fatigue ——Voice change or hoarseness ——Weight loss • Tell your nurse or doctor about any side effect that bothers you or that does not go away • Store regorafenib at room temperature: 68°F to 77°F (20°C to 25°C) • Keep regorafenib in the bottle that it comes in; do not put tablets in a daily or weekly pill box • Keep the dessicant in the bottle to help keep tablets dry Prepared by Jason Hoffman, PharmD, RPh.

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STAT CONSULT

Ruxolitinib (Jakafi) Drug Type

• Kinase inhibitor

Indications

• Treatment of patients with ——Polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea ——Intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post essential thrombocythemia myelofibrosis Mechanism of Action

• Ruxolitinib, a kinase inhibitor, inhibits Janus associated kinases (JAKs) JAK1 and JAK2, which mediate signaling of various cytokines and growth factors that are important for hematopoiesis and immune function • JAK signaling involves recruitment of signal transducers and activators of transcription (STATs) to cytokine receptors, activation and subsequent localization of STATs to the nucleus leading to modulation of gene expression • Myelofibrosis and polycythemia vera are myeloproliferative neoplasms known to be associated with dysregulated JAK1 and JAK2 signaling Dosage and Administration

• Myelofibrosis ——Starting dose is based on patient’s baseline platelet count ■■ Greater than 200×109/L : 20 mg ■■ 100×109/L to 200×109/L: 15 mg ■■ 50×109/L to less than 100×109/L: 5 mg • Polycythemia vera ——Starting dose: 10 mg • Administer orally twice daily with or without food • For patients unable to ingest tablets, administer through a nasogastric tube (8 French or greater) as follows

——Suspend 1 tablet in approximately 40 mL of water with stirring for approximately 10 minutes ——Within 6 hours after the tablet has dispersed, suspension can be administered through a nasogastric tube using an appropriate syringe ——Tube should be rinsed with approximately 75 mL of water • When discontinuing therapy for reasons other than thrombocytopenia, gradual tapering of dose may be considered, for example by 5 mg twice daily each week • A complete blood count (CBC) and platelet count must be performed before initiating therapy, every 2 to 4 weeks until doses are stabilized, and then as clinically indicated Dosage Adjustments

• Myelofibrosis ——Interrupt treatment for platelet counts less than 50×109/L or absolute neutrophil count (ANC) less than 0.5×109/L for patients starting treatment with a platelet count of 100×109/L or greater ■■ After recovery of platelet counts greater than 50×109/L and ANC greater than 0.75×109/L, dosing may be restarted ——Dose reductions should be considered if platelet counts decrease ——If response is insufficient and platelet and neutrophil counts are adequate, doses may be increased in 5-mg increments twice daily to a maximum of 25 mg twice daily for patients starting treatment with a platelet count of 100×109/L or greater ■■ Doses should not be increased during the first 4 weeks of therapy and not more frequently than every 2 weeks

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——Interrupt treatment for platelet counts less than 25×109/L or ANC less than 0.5×109/L for patients starting treatment with a platelet count of 50×109/L to less than 100×109/L ■■ After recovery of platelet counts greater than 35×109/L and ANC greater than 0.75×109/L, dosing may be restarted ——If response is insufficient and platelet and neutrophil counts are adequate, doses may be increased in 5-mg increments twice daily to a maximum of 10 mg twice daily for patients starting treatment with a platelet count of 50×109/L to less than 100×109/L ■■ Doses should not be increased during the first 4 weeks of therapy and not more frequently than every 2 weeks ——Interrupt treatment for bleeding requiring intervention regardless of current platelet count ——Once the bleeding event has resolved, consider resuming treatment at the prior dose if the underlying cause of bleeding has been controlled ——If the bleeding event has resolved but the underlying cause persists, consider resuming treatment at a lower dose • Polycythemia vera ——Dose reductions should be considered for hemoglobin and platelet count decreases ——Interrupt treatment for hemoglobin less than 8 g/dL, platelet counts less than 50×109/L, or ANC less than 1.0×109/L ■■ After recovery of hematologic parameter(s) to acceptable levels, dosing may be restarted ——After restarting ruxolitinib following treatment interruption, doses may be titrated, but maximum total daily dose should not exceed 5 mg less than dose that caused dose interruption ■■ Exception: dose interruption following phlebotomyassociated anemia ——If response is insufficient and platelet, hemoglobin, and neutrophil counts are adequate, doses may be increased in 5-mg increments twice daily to a maximum of 25 mg twice daily Specific Populations

• Pregnancy ——Ruxolitinib should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus ——Advise pregnant women of the potential hazard to fetus • Nursing mothers

——Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of drug to mother • Pediatric ——Not established • Geriatric ——No overall differences in safety and effectiveness were observed between older and younger patients • Renal impairment ——Dose adjustment is recommended for patients with moderate or severe renal impairment, or if patient is receiving dialysis • Hepatic impairment ——Dose of ruxolitinib should be reduced in patients with mild, moderate, or severe hepatic impairment Boxed Warnings

• None Contraindications

• None Warnings and Precautions

• Lipid elevations ——Assess lipid levels 8 to 12 weeks from initiation of therapy and treat as needed • Risk of infection ——Assess patients for signs and symptoms of infection and initiate appropriate treatment promptly ——Serious infections should have resolved before starting ruxolitinib therapy • Risk of non-melanoma skin cancer ——Perform periodic skin examinations • Symptom exacerbation ——Interruption or discontinuation of ruxolitinib may cause symptom exacerbation ——Manage with supportive care and consider resuming ruxolitinib treatment • Thrombocytopenia, anemia, and neutropenia ——Manage by dose reduction, or interruption, or transfusion Adverse effects

• Most common nonhematologic adverse reactions (>10%) ——Bruising

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STAT CONSULT ——Dizziness ——Headache • Most common hematologic adverse reactions (>20%) ——Anemia ——Thrombocytopenia Drug Interactions

• Concomitant use of ruxolitinib with strong CYP3A4 inhibitors or fluconazole ——Modify dose of ruxolitinib when given concomitantly with strong CYP3A4 inhibitors (eg, boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and fluconazole doses of 200 mg or less • Myelofibrosis ——For patients with a platelet count of 100×109/L or greater ■■ Modify dose to 10 mg twice daily ——For patients with a platelet count of 50×109/L to less than 100×109/L ■■ Modify dose to 5 mg twice daily • Polycythemia vera ——For patients on a stable dose of 10 mg twice daily or greater, decrease dose by 50% ——For patients on 5 mg twice daily, reduce to 5 mg once daily ——For patients on 5 mg once daily, avoid strong CYP3A4 inhibitor or f luconazole, or interrupt ruxolitinib treatment What to Tell Your Patient

• Ruxolitinib is a prescription medicine used to treat people with ——Certain types of myelofibrosis ——Polycythemia vera who have already taken hydroxyurea and it did not work well enough or they could not tolerate it • Before administering ruxolitinib, ask your patient to list all his or her medical conditions, including if he or she has/had ——An infection ——Tuberculosis or has been in close contact with someone who has tuberculosis ——Hepatitis B or liver problems ——Kidney problems or are on dialysis ——Skin cancer in the past • Are you pregnant or plan to become pregnant?

——No adequate, well-controlled studies of ruxolitinib use in pregnant women ——In embryofetal toxicity studies, late resorptions and reduced fetal weights at maternally toxic doses occurred ——You need to discuss with your doctor if the potential benefits of taking ruloxitinib justifies the potential risk to your fetus • Are you breastfeeding or plan to breastfeed? ——Whether ruxolitinib is excreted in human milk is not known ——Because many drugs are excreted in human milk, you must talk to your doctor about whether to discontinue nursing or discontinue taking ruloxitinib, taking into account the importance of this drug to you • Ask about all medicines, especially medications for fungal infections, bacterial infections, HIV/AIDS • Take ruxolitinib exactly as you are told • Do not change your dose or stop taking ruxolitinib without first talking to your physician • You can take ruxolitinib with or without food • Ruxolitinib can be given through a nasogastric tube, if you are unable to swallow pills • Do not drink grapefruit juice while taking ruxolitinib • If you take too much ruxolitinib, call the clinic or your doctor or go to the nearest hospital emergency room right away ——Take the ruxolitinib bottle with you • If you miss a dose, take your next dose at your regular time ——Do not take 2 doses at the same time • You will need regular blood tests during your treatment ——Your physician may change your dose or stop your treatment based on the blood test results • Ruxolitinib can cause serious side effects, including ——Cholesterol increases ——Infection ——Low blood cell counts ——Skin cancers • The most common side effects include ——Bruising ——Dizziness ——Headache ——Low platelet count ——Low red blood cell count • Tell your nurse or doctor if you have any side effect that bothers you or that does not go away • Store ruxoltinib at room temperature 68°F to 77°F (20°C to 25°C) Prepared by Jason Hoffman, PharmD, RPh.

36 ONCOLOGY NURSE ADVISOR • SEPTEMBER/OCTOBER 2016 • www.OncologyNurseAdvisor.com

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Identifying and Managing PMPS After Breast Cancer Treatment Bryant Furlow Breast cancer surgery and adjuvant radiotherapy can damage nerves and cause postmastectomy pain syndrome (PMPS), with important implications for patients’ quality of life and survivorship care. Oncology nurses play a crucial role in spotting patients at high risk for PMPS, educating them about symptoms, and monitoring (and documenting the need for monitoring) for PMPS during recovery and survivorship.

ostmastectomy pain syndrome is a chronic, potentially progressive, and debilitating neuropathic sequela of breast cancer treatment

that persists beyond 3 months.1,2 Affecting up to half of women who undergo breast cancer surgery, postmastectomy pain syndrome typically involves aching, tingling, itching, electric shock-like, or burning pain in the chest wall or underarm (armpit or upper arm).1-3 Some patients have only one such symptom, but others experience combinations of these painful sensations; one woman described the intense throbbing and itching she felt as “poison ivy lit by a blowtorch.”4 Shoulder movement sometimes causes acute exacerbations of symptoms. PMPS symptoms can persist for many years, and pain intensity can vary over time. Postmastectomy pain syndrome can have profound impacts on cancer survivors’ quality of life, social and sexual functioning, and ability to work. Sleep disturbance and anxiety are common among women with PMPS and may affect pain severity.1,3,5 Yet PMPS is not always discussed with patients before they undergo surgery and adjuvant radiotherapy.4 Despite its name, postmastectomy pain syndrome also has been reported by women who underwent breast-conserving surgery (BCS), and the adverse effect is no more common following mastectomy than BCS.3 Perhaps surprisingly, postsurgical complications such as lymphedema or cellulitis do not appear to predict postmastectomy pain syndrome, despite shared risk factors such as axillary lymphadenectomy.6 With declining rates of full axillary lymphadenectomy, PMPS incidence may be declining.1 RISK FACTORS Postmastectomy pain syndrome is believed to arise from tissue and nerve damage associated with resection. Resection of tissue in the breast’s upper outer quadrant or axillary lymph

nodes appears to increase the risk of symptoms.1,3,7 Women undergoing breast cancer surgery routinely receive adjuvant regional radiotherapy to kill residual tumor cells and micrometastases. Several studies have found that adjuvant radiotherapy following mastectomy or BCS is associated with a higher risk for PMPS than surgery without radiotherapy. 3,8,9 A 2009 study of PMPS found that the odds ratio for adjuvant radiotherapy was 1.5 (95% CI, 1.08-2.07; P =.03), meaning that women who underwent adjuvant radiotherapy faced a 50% higher risk for PMPS compared with women who underwent breast cancer surgery without radiotherapy.3 Other risk factors have also been identified. Chief among these is patient age (eg, younger than 35 years at diagnosis).7,10 Younger women are more likely to experience PMPS, but whether this is related to different psychosocial stressors and anxiety or age-related nerve tissue responses to surgery and radiotherapy is not clear.1,3 Some studies suggest that presurgical breast pain and acute pain immediately following breast surgery might increase the risk for PMPS.3 A prior history of headache is also predictive of PMPS.7 Frequent headache has been linked to central sensitization — hypersensitivity that, over time, leaves a person prone to chronic pain.7 Frequent headache is a risk factor for other regional pain syndromes, in addition to PMPS.7 The neurologic processes involved in PMPS are poorly understood and likely involve aberrations in the peripheral nervous system that, over time, contribute to central nervous system problems.11 ASSESSMENT AND EDUCATION Patients’ subjective and reported pain experiences appear to correlate with

RADIATION & YOUR PATIENT

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RADIATION & YOUR PATIENT objective electroneurophysiologic measures of nerve impulse transmission near sites of pain, according to a recent pilot study.11 If confirmed in larger studies, this may provide a rationale for diagnostic nerve testing in assessing PMPS. Current clinical examinations for suspected PMPS include manually assessing for sensory changes and muscular weakness, as well as reduced range-ofmotion in the shoulder and arm. Patients undergoing breast cancer surgery and adjuvant radiotherapy should be advised to tell their health care providers if they have persisting chest, armpit, or upper-arm pain 3 months after treatment, or if they expe-

Patients should be reassured that PMPS is not a sign of disease recurrence. rience changes in how they can use their arms (such as arm weakness, or worsened pain associated with shoulder movement).1,10 Nurses should note risk factors (patient age, procedure, preoperative headache, postoperative acute pain) and the need to monitor for signs of PMPS throughout recovery and in survivorship planning.10 During posttreatment recovery, patients should be asked about pain and discomfort in the chest and upper arm, and whether some activities make that pain or discomfort worse.10 Importantly, patients should be reassured that PMPS is not a sign of tumor recurrence but rather a late effect of treatment.10

studies have not established whether optimal management of PMPS is different for patients who have undergone adjuvant radiotherapy than for those who have not.10 Proposed treatment strategies range from topical lidocaine for mild symptoms to antidepressants and opioid and nonopioid pain medications, even nerve-block injections with steroids or anesthetics, for severe cases. Lidocaine 5% topical ointment is often recommended to women with PMPS, and preliminary clinical research suggests that perioperative lidocaine infusion, and possibly also piritramide, might be preventive, reducing the risk of subsequent development of PMPS.8,9 Other treatment options include lifestyle changes and physical therapy. Lifestyle accommodations include using a cane or walker and physical activity regimens involve walks and stretching exercises. Recent, preliminary research suggests that autologous fat grafting at surgical scar sites might reduce PMPSassociated pain in women who have undergone BCS plus radiotherapy.12 ■

4. Pfaff LG. When pain persists after breast cancer surgery. New York Times. June 8, 2015. http://well.blogs.nytimes.com/2015/06/08/ pain-after-breast-cancer-surgery-pmps/. Accessed August 22, 2016. 5. Belfer I, Schreiber KL, Shaffer JR, et al. Persistent postmastectomy pain in breast cancer survivors: analysis of clinical, demographic, and psychosocial factors. J Pain. 2013;14(10):1185-1195. 6. Schreiber KL, Martel MO, Schnol H, et al. Persistent pain in postmastectomy patients: comparison of psychophysical, medical, surgical, and psychosocial characteristics between patients with and without pain. Pain. 2013;154(5):660-668. 7. Courceiro TC, Valença MM, Raposo MC, Orange FA, Amorim MM. Prevalence of postmastectomy pain syndrome and associated risk factors: a cross-sectional cohort study. Pain Manag Nurs. 2014;15(4):731-737. 8. Steyaert A, Forget P, Dubois V, Lavand’homme P, De Kock M. Does the perioperative analgesic/anesthetic regimen influence the prevalence of long-term chronic pain after mastectomy? J Clin Anesth. 2016 Apr 6. doi: 10.1016/j.jclinane.2015.07.010. [Epub ahead of print] 9. Terkawi AS, Sharma S, Durieux ME, Thammishetti S, Brenin D, Tioririne M.

Bryant Furlow is a medical journalist based in Albuquerque, New Mexico.

Perioperative lidocaine infusion reduces the incidence of post-mastectomy chronic pain: a double-blind, placebo-controlled random-

REFERENCES 1. Post-mastectomy pain syndrome. American Cancer Society website. http://www.cancer. org/treatment/treatmentsandsideeffects/ physicalsideeffects/pain/post-mastectomy-

ized trial. Pain Physician. 2015;18(2):E139-E146. 10. Bokhari F, Sawatzky JA. Chronic neuropathic pain in women after breast cancer treatment. Pain Manag Nurs. 2009;10(4):197-205. 11. Hojan K, Wojtysiak M, Huber J, Molińska-

pain-syndrome. Last revised February 12,

Glura M, Wiertel-Krawczuk A, Milecki P.

2016. Accessed August 22, 2016.

Clinical and neurophysiological evaluation

2. Alves Nogueira Fabro E, Bergmann A, do

of persistent sensory disturbances in breast

Amaral E Silva B, et al. Post-mastectomy

cancer women after mastectomy with

pain syndrome: incidence and risks. Breast.

or without radiotherapy. Eur J Oncol Nurs.

2012;21(3):321-325. 3. Gärtner R, Jensen MB, Nielsen J, Ewertz

2016;23:8-14. doi: 10.1016/j.ejon.2016.03.007. 12. Maione L, Vinci V, Caviggioli F, et al.

M, Kroman N, Kehlet H. Prevalence of and

Autologous fat graft in postmastectomy

TREATMENT OPTIONS

factors associated with persistent pain

pain syndrome following breast conservative

The evidence base for PMPS treatment interventions remains sparse, and

following breast cancer surgery. JAMA.

surgery and radiotherapy. Aesthetic Plast Surg.

2009;302(18):1985-1992.

2014;38(3):528-532.

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COMMUNICATION CHALLENGES

When You’re Too Nice

Ann J. Brady, MSN, RN-BC

Our implied agreement was that our conversations would focus on her physical symptoms. So, why was she asking me this?

ow do you respond to a patient who tells you not to discuss their prognosis? Do you ever go back to a patient to revise a previous interaction, ask for a conversational “do over”?

CASE Cynthia held her hand up in a way that made me think of the popular gesture “Talk to the hand.” She had stage IV lung cancer and was undergoing radiation therapy for metastases to her pelvis. She had made it clear to all of her caregivers that she did not want anyone to “beat me over the head with a prognosis when it won’t change anything.” Those of us involved in her care abided by her request, and instead focused on the things she would let us help her with. Her bone metastases were painful and required nearly daily adjustments to her med regimen. Managing her pain was challenged by her reluctance to take too much pain medication. My strategy focused on her Functional Pain

Goal, since it was a rationale that made sense to her. Each day I asked the same question about her pain, “Better, worse, or the same?” and continued from there. As I gained her trust, she began to take effective doses of pain medication. Yet, she maintained her stance of not discussing her prognosis. One day, after a difficult night with increased pain and little sleep, rather than answering my question she abruptly asked one of her own: “Am I dying?” This question can stop any of us in our tracks, but was especially so with Cynthia. Our implied agreement was that our conversations would focus on her physical symptoms. So, why was she asking me this? I’d like to say I seized the moment. I responded brilliantly and that prompted an open discussion about how she was doing. But her question caught me unawares, and instead I fumbled my way through. “You’ve told me you didn’t want any discussion about prognosis.” She nodded agreement. “I don’t.” Okay, I thought, we are back at baseline. As a way of obliquely answering her question, I reviewed her treatment and the objective and subjective assessment of her current condition. Again she nodded in what I thought was agreement. Until she asked another question, and I found myself flummoxed again: “Do you think I only have a few weeks to live?” Her question had a certain urgency to it, so I answered quickly. “No, no. That isn’t what I am saying,” which was true. Her cancer was advanced, but she was stable. There was an awkward pause before we returned to the conversation about her pain. I went back to encouraging her to take the effective dose of medications for her pain. She smiled, accepting the information without returning to her difficult

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COMMUNICATION CHALLENGES

Now, when faced with a question that comes out of nowhere, I start by clarifying what I have communicated in words, and actions.

question. I waved as she and her husband left, feeling like I had just had the least therapeutic conversation with a patient ever. Ever. I went through the rest of my busy work day, but it was one of those interactions I could not get out of my mind. I told the story to a couple of people, and we laughed nervously. It is never easy to answer the am-I-dying question, even harder if you’ve been instructed by the patient not to go there. Overnight I continued to mull over the exchange and decided to take a second run at it. The next day Cynthia’s pain was better and she was looking and feeling a bit more upbeat. I said to her, “I want to go back to your question from yesterday because I didn’t do a very good job of answering. Are you okay with that?” She shrugged, nonplussed. She may have moved past the impetus for asking the question, but I thought revisiting it was important so I pushed on. “I’m wondering if something happened to make you ask me that question because it surprised me after all the times you said you didn’t want any predictions.” Cynthia and her husband both smiled. I imagined they had discussed the awkwardness of the conversation. She said, “It’s just that you have been so attentive. Every day I come in and we discuss my pain. Plus, my son has been calling me more often. I thought maybe you weren’t telling me something.” In all of my perseverating over what I had or hadn’t said to her, and how I thought I had not handled her question very well, I had not stopped to ask where the question came from.

JOIN THE CONVERSATION • How do you respond to a patient who tells you not to discuss their prognosis? • Do you ever go back to a patient to revise a previous interaction, ask for a conversational “do over”?

ON THE

WEB

Go to http://bit.ly/2cZS9kt to discuss with your colleagues how you handle avoiding a discussion on a topic a patient is not prepared to handle or how you were caught off-guard by a question on a topic the patient does not want to talk about.

DISCUSSION Dr. Patricia Benner, a well-known and respected nursing theorist, introduced the concept that expert nurses develop skills and understanding of patient care over time.1 She identified nursing practice as a continuum, from novice to expert.1 In this column, I often use real experiences from my practice to highlight the kinds of communication challenges we face as nurses. In spite of my experience handling difficult conversations, my supposed expert status, I am a novice with each patient. Truly, we all are. What was my takeaway? I had no idea that my attentiveness, my being too nice had triggered anxiety about the subtext of my interaction. When I asked her if I could return to the original question, I expected her to tell me her doctor had said something new, or she read something on the Internet. Instead, she interpreted my attentiveness as having another meaning. It would be impossible to predict how each conversation or each action may be interpreted. But this experience reminded me to ask not just about my instructions or about symptoms, but about more hidden concerns. “Is there anything else you are wondering about?” Maybe then Cynthia would have initiated a conversation before she had worked up her anxiety. There are many nuances to communication challenges. Even being too nice may be misinterpreted and perceived as a negative. Next time, I can inquire more openly. With Cynthia, my focus was specific: her pain was the highest order of care, but inadvertently my attention to it triggered an alternate explanation to her. Now, when I am faced with a question that comes out of nowhere, I start by clarifying what I have communicated in words, and actions. ■ Ann Brady is the symptom management care coordinator at the Cancer Center, Huntington Hospital, Pasadena, California. REFERENCE 1. Benner P. From novice to expert. Am J Nurs. 1982; 82(3):402-407. doi: 10.2307/3462928.

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ISSUES IN CANCER SURVIVORSHIP

Increasing Dietary Omega-3 Intake After Colorectal Cancer Diagnosis Improves Survival Bette Weinstein Kaplan

olorectal cancer is the second most prevalent form of cancer and the third leading cause of death by cancer in the United States. The disease was diagnosed in more than 1.2 million people, and in 2015, approximately 49,700 deaths were attributed to it. However, because of advances in diagnosis and treatment, almost 65% of patients with colorectal cancer live more than 5 years, and more than 58.3% live more than 10 years.1 Although many studies point to lifestyle and dietary practices that affect the risk for colorectal cancer, none address survival. For many people living with colorectal cancer, this represents a significant void. They would want to know: If lifestyle and dietary factors can affect their risk of developing colorectal cancer, what, if any, lifestyle or dietary changes can influence survival for those who already have the disease? NEW BENEFITS OF OMEGA-3 PUFAS

Recently published research demonstrated that the marine omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA), inhibit blood supply to colorectal cancer cells, thus suppressing tumor growth and angiogenesis. In addition, some reports suggest that taking omega-3 PUFA supplements can increase the antitumor activity of

some chemotherapy agents used to treat colorectal cancer. Omega-3 PUFAs also decrease the cachexia caused by cancer; patients taking PUFA supplements eat better and experience less anorexia and weight loss. A team of researchers at Massachusetts General Hospital, Harvard, MIT, and Dana-Farber Cancer Institute studied the association between consumption of marine omega-3 PUFAs and survival for patients with colorectal cancer. The researchers reviewed 2 prospective cohorts: the Nurses’ Health Study (NHS), which compiled data on 121,700 female nurses ages 30 to 55 years in 1976, and the Health Professionals Follow Up Study (HPFS), which collected data on 51,529 male health professionals ages 40 to 75 years in 1986. The goal was to evaluate whether increasing consumption of marine omega-3 PUFAs improved survival for patients with colorectal cancer after diagnosis. Thus, from the health and dietary data on 173,229 health professionals, the investigators focused on 1659 patients who developed colorectal cancer.1 THE DATA Participants completed detailed questionnaires on their lifestyles and medical histories at enrollment and at 2-year intervals thereafter. Information included smoking habits, regular use of aspirin or nonsteroidal inflammatory

drugs, and type and frequency of exercise. Participants also provided food histories at 4-year intervals. The Food Frequency Questionnaires categorized consumption from never or less than once a month to 6 or more times a day. Data on consumption of marine omega-3 PUFAs (EPA, DHA, and DPA) from foods and fish oil supplements were also collected.

An increase of at least 0.15 g daily reduced risk of dying by 70%. Every time participants completed the biannual questionnaire, they were asked if they had received a diagnosis of colorectal cancer in the prior 2 years. If the response was “yes,” the researchers asked for permission to obtain the patients’ medical records and pathology reports. If a participant had died from colorectal cancer, the research team asked the next-of-kin for permission to review the patient’s medical records and pathology reports. There were 561 deaths due to colorectal cancer, 153 due to cardiovascular disease, and 113 due to other cancers.1 Continued on page 44

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THE TOTAL PATIENT

Patients’ and Caregivers’ Misperceptions Continue to Stigmatize Palliative Care Bette Weinstein Kaplan

lthough palliative care is a recognized therapeutic intervention that can improve patients’ quality of life, the lines between palliative care and hospice can be blurred in the eyes of patients and family. Current recommendations are that palliative care is most effective when initiated early in the course of treatment. However, even though hospice comes at a later stage of illness, both modalities are subject to confusion and stigma resulting from patients’ misconceptions. Early palliative care improves the life expectancy, mental outlook, and psychological and physical health of patients with cancer. And yet, through a series of interviews designed to assess patient and caregiver perceptions of palliative care, a group of physicians in Canada found that palliative care was often associated with loss of hope, end-of-life care, even death.1 For this 4-month randomized, controlled trial, conducted at Princess Margaret Cancer Centre in Toronto, Canada, researchers enrolled 48 patients, randomized to an intervention group (n = 26) or a control group (n = 22). To qualify for the study, patients had to have a diagnosis of advanced cancer and an estimated survival expectancy of 6 to 24 months. Researchers also enrolled 23 caregivers, randomizing them to the 2 groups (14 to the

intervention group, 9 to the control group). Patients ranged in age from 57 years to 65 years. Involved cancer sites were lung, gastrointestinal, genitourinary, breast, and gynecologic. The intervention group received standard oncology care plus an early referral for palliative care, which included a consultation and at least a monthly follow-up at an outpatient oncology

The [study] authors do not believe a new name is going to change the stigma. palliative care clinic for the duration of the study. The control group received standard oncology care only; however, they received palliative care if they requested it. Twenty-two patients in the intervention group and 20 in the control group underwent chemotherapy. IT MEANS PROGNOSIS IS POOR The researchers interviewed patients and caregivers about their perceptions of palliative care. Participants from both groups described palliative care as being synonymous with end-of-life care. One study participant associated palliative care directly with death: “It

means death to me. It does. The end.” Comments from other participants expressed the same dim outlook regarding prognosis when palliative care is initiated. “The nurse looking after him took him on another floor. That’s where the palliative are. People are here to die, or they’ll never get out of here or something like that.” “Well, when you think palliative care, you think the person’s on death row.”1 No hope Palliative care was interpreted as a passive modality; the care you get when nothing further can be done. The patient is dying and there is no hope left. “Because when it comes to palliative, they’re always sad that they didn’t help, that all is over.” “The stage of palliative care, hope is kind of more or less gone.”1 For the bedridden Patients described palliative care as care provided when a patient is bedridden and so incapacitated that self-care is impossible. “I guess palliative care is when you’re pretty much at that stage where you can’t take care of yourself anymore.” “When you think palliative care, you think bedridden, unable to look after yourself on any level.”1 Comfort care Most of the patients and caregivers did understand that palliative care was really comfort care; however, they still had misperceptions regarding prognosis. “I thought, what the heck is that? Then I realized they’re just

42 ONCOLOGY NURSE ADVISOR • SEPTEMBER/OCTOBER 2016 • www.OncologyNurseAdvisor.com

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THE TOTAL PATIENT trying to keep you comfortable until you die. Can’t ask for any more.” “Our impression, or my impression at least, of palliative care was sort of keep them doped, keep them comfortable, make them as comfortable as you can before he goes.”1 For many patients and caregivers, their only prior familiarity with palliative care was if they had had relatives or friends who received end-of-life care, and for whom they said palliative care was the last resort. Some participants said they tried not to think about palliative care, because the thought was negative and frightening. Others admitted they had no idea of what it actually was. A BETTER UNDERSTANDING At the end of the study period, patients’ opinions changed for the better. Participants in the intervention group were more receptive to palliative care after having received it. One patient in the intervention group said, “I certainly

Survivorship Continued from page 41

HIGHER INTAKE, LOWER RISK An association was seen between higher intake of marine omega-3 PUFAs after colorectal cancer diagnosis and a lower risk of cancer-specific death. The investigators found that participants who increased their consumption of marine PUFAs after diagnosis had the lowest risk of dying from colorectal cancer. A moderate reduction in all-cause mortality was also seen in this group regardless of whether their marine omega-3 intake was in the form of oily fish or fish oil supplements.1 In addition, participants who boosted their marine PUFA consumption

don’t now see it as I’m in the final box or the chamber.”1 “I see that it now comes on in an earlier stage of my treatment. … Earlier stage, rather than palliative care as in when they’re no longer treating you. So this is palliative care while they’re still treating you,” is how one participant explained it.1 Patients and caregivers in both groups shared thoughts on how they make palliative care seem more appealing. “Well, I think just in my own head, just to make me feel more comfortable, I referred to her as my ‘medication specialist,’ as opposed to my ‘palliative care doctor’ vs my ‘oncologist,’ right? ... [To others] I say that I’m seeing my ‘medication specialist.’ “Sometimes if they ask a little more, then I will say that she is actually in the palliative care department, but they branch out a little bit, and they deal with people like me. … Why? Because if I told people I was seeing a palliative care doctor, they would think

I was going to die in a few weeks or months.”1 Some participants in the intervention group proposed calling palliative care supportive care.1 The authors do not believe a new name is going to change the stigma associated with this care. “A name change may be considered, but would achieve nothing without a fundamental shift in the manner in which palliative care is practiced and portrayed,” concluded the study authors.1 They call for better educating the public, patients, and health care providers to correct the misconceptions surrounding palliative care. ■

tended to exercise more but drank alcohol more; however, they were less likely to smoke. These participants also took vitamin D, multivitamins, and enriched their diets with fiber. Other noteworthy factors in participants in whom the association between increased marine omega-3 intake and reduced risk of death was the clearest included these patients were not on aspirin therapy, they had a body mass index (BMI) of less than 25 kg/m 2, and they were taller. An increase in marine omega-3 intake of at least 0.15 g daily after colorectal cancer diagnosis produced a 70% reduction in risk of dying from colorectal cancer. Conversely, reducing daily marine omega-3 intake was associated with

a 10% increase in risk of dying from colorectal cancer. These results prompted the research team to recommend patients with colorectal cancer increase their intake of marine omega-3 PUFAs. The researchers also call for additional studies to validate their findings.1 ■

Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey. REFERENCE 1. Zimmermann C, Swami N, Krzyzanowska M, et al. Perceptions of palliative care among patients with advanced cancer and their caregivers. CMAJ. 2016;188(10):E217-E227. doi: 10.1503/cmaj.151171.

Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey. REFERENCE 1. Song M, Zhang X, Meyerhardt JA, et al. Marine ω-3 polyunsaturated fatty acid intake and survival after colorectal cancer diagnosis. Gut. 2016 Jul 19. doi: 10.1136/gutjnl-2016-311990. [Epub ahead of print]

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FROM

ating may be the furthest thing from the minds of people coping with a cancer diagnosis. But for many, it is the challenges of dating that are at the forefront. Along with these challenges are a seemingly endless trail of thoughts and questions: When will I feel ready to start dating again? How will it affect my sex life? Why would anyone want to date a cancer patient? How do I tell the person I am with that I have cancer? What should I tell them? The list is never-ending and the complexity of feelings that arise can be overwhelming. But no matter where a person is in their cancer journey, whether they have a new diagnosis, are in active treatment, or are posttreatment survivors, to have fears and concerns about dating and sexual intimacy is normal. Empowering these patients to build upon their strengths so as not to let these fears adversely affect their current relationships or prevent them from pursuing future relationships can play a huge role in the healing process. Regardless of where a person is in their cancer journey, adjusting to the emotional and physical changes that accompany a diagnosis can be challenging. As a professional oncology social worker at CancerCare, I have found that there is no right or wrong when addressing the challenges of dating, but there are ways to provide support along the way. Slow and Steady Dating is never easy, especially when cancer is the unwelcomed third wheel. Encourage

Dating Challenges Throughout the Cancer Journey Angelique Caba, LCSW-R

patients to pace themselves. Their relationships may not be exactly as they were before cancer came into the picture, but then again neither are they. The same can be said for those not in relationships and looking to begin dating. Nevertheless, encourage them to start off small, such as an informal

group activity or social event. These are opportunities to socialize and relax with friends in a way that can make meeting new groups of people feel less daunting. Doing so can help build confidence and self-esteem. Be Informed There are many emotional and physical changes that can accompany a diagnosis. Fatigue, pain, decreased libido, and emotional sensitivity are just a few of the struggles patients may identify. Maintain an open dialogue with patients and help to encourage them to communicate with their health care team as a way of staying informed of the unique challenges and struggles cancer can have on dating. No one gets through cancer without some fear or anxiety. It can be helpful for patients to discuss these fears with those around them rather than trying to shoulder the load on their own. Although this may be a source of embarrassment for some patients, remind them that you are here to help. Breaking through the silence and helping patients give a voice to the thoughts and questions that undoubtedly race through their minds can help them feel a sense of empowerment. Patients may also benefit from talking to a specialist to help address any complex issues surrounding their sexual health. Disclosure The decision to disclose one’s cancer diagnosis is very personal, as are the questions of when to do so and how. While there may never be the perfect time to disclose, the best time to do so is when the patient feels ready. Before deciding, patients may want to consider how they would like

There is no right or wrong when addressing the challenges of dating, but there are ways to provide support along the way. www.OncologyNurseAdvisor.com • SEPTEMBER/OCTOBER 2016 • ONCOLOGY NURSE ADVISOR 45

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the conversation to go. Some patients may benefit from preparing — writing down what they would like to say or even practicing with a friend can help relieve some of their anxiety. Before sharing, encourage patients to consider what would make them feel most comfortable. Being open and honest goes a long way. Doing so can help build trust and is the foundation of a lasting relationship. Intimacy and Sexuality Talking about intimacy or sexuality in a relationship, though at times uncomfortable, is very important. Remind patients that intimacy is not just about sex. It is also touching, affection, and closeness with someone, not just physically but emotionally as well. The effects of cancer and treatments can also negatively impact a patient’s body image and may lead some to feel self-conscious. Help patients address these insecurities

head-on by maintaining open communication and encouraging them to do the same. It can also be extremely helpful for patients to speak with a professional oncology social worker, such as the ones at CancerCare who provide free services to help patients and their loved ones navigate the challenges that arise along with a cancer diagnosis. Reassure patients that, no matter what the diagnosis or treatment, there are many ways to be intimate and feel pleasure. Despite that aspects of sexuality may be different, intimacy and pleasure are possible. Whether in a new or long-standing relationship, encourage patients to be open to these differences. Get Support Remind patients that having a strong network of support is crucial. Although friends and family can be a good source of support, they are only the beginning. Encourage

patients to seek professional support as well. CancerCare provides free counseling with licensed oncology social workers who can help connect patients to other resources in their community. Individual counseling allows patients the opportunity to address all the complexities and challenges that dating poses following a cancer diagnosis. Attending a support group that offers them the opportunity to share their experiences with others in a similar situation can offer validation that they are not alone. Some patients may have different reactions, views, and experiences with dating after a cancer diagnosis, but communication and understanding are important starting points in ensuring patients receive the support they need. ■ Angelique Caba is director of social work administration at CancerCare.

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ASK A PHARMACIST

Managing Adverse Events Related to Checkpoint Inhibitors The new checkpoint inhibitor drugs are being used to treat more and more cancers, and have different side effects than other chemotherapy drugs. How should the side effects of these drugs be managed? —Name withheld on request

Numerous checkpoint inhibitors have been approved in the last several years, including the CTLA-4 antibody ipilimumab (Yervoy) and agents targeted against the programmed cell death receptor 1 (PD-1) and its ligand (PDL1) such as pembrolizumab (Keytruda), nivolumab (Opdivo), and atezolizumab (Tecentriq). These drugs work in different ways to block inhibition of the immune system, thus increasing immune effects against multiple malignancies

including melanoma, non-small cell lung cancer (NSCLC), and others. Due to their unique mechanism of action, these medications are associated with immune-mediated adverse events resulting from the activation of the immune system. These adverse events vary, and may include rash, diarrhea or colitis, hepatotoxicity, neurotoxicity, endocrinopathies (such as hypophysitis or hypothyroidism), and immune-mediated toxicity to other organ systems. These adverse events can be severe and may even result in death; thus proper identification and management is critical. Immune-related adverse events (IRAEs) are graded in a manner consistent with the criteria used for other toxicities: grade 1 represents mild symptoms; grade 2, moderate symptoms; grade 3, symptoms are considered severe; and grade 4, symptoms are life-threatening. In general, patients experiencing mild, grade 1 IRAEs can be managed supportively (eg, topical corticosteroids for a mild rash or loperamide for a patient with 1 to 2 episodes of diarrhea per day).1,2 If patients experience grade 2 IRAEs, treatment with the immune checkpoint inhibitor should be held. Patients should receive supportive care, and may also require treatment with systemic corticosteroids. Once toxicity has resolved to grade 1 or better and the patient is on a low dose of corticosteroids (eg, less than 7.5 mg prednisone equivalent per day), treatment may be resumed.

Patients experiencing grade 3 or 4 IRAEs should have the causative agent permanently discontinued. The patient should receive supportive care and high doses of corticosteroids (typically 1 to 2 mg/kg prednisone equivalent per day).1 If the patient’s symptoms improve to grade 1 or better with corticosteroids, the corticosteroid can be gradually tapered (over at least 1 month). If the patient’s symptoms do not improve within a few days of receiving high doses of corticosteroids, alternate therapies such as infliximab (Remicade) may need to be considered.1,2 Appropriate patient selection for these therapies is critical to reduce the likelihood of severe immune-related adverse events. Patients with a history of clinically significant autoimmune illness (such as inflammatory bowel disease) were excluded from clinical studies of these medications and may not be appropriate candidates for these treatments. Early detection of adverse events, such as those included in the ipilimumab (Yervoy) REMS program, are also crucial. ■ REFERENCES 1. Weber JS, Kähler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol. 2012;30(21):2691-2697. 2. Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol. 2016;13(8):473-486.

Lisa A. Thompson, PharmD, BCOP Clinical Pharmacy Specialist in Oncology Kaiser Permanente, Colorado

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