Oncology Nurse Advisor July/August 2014 by Haymarket Media

ONCOLOGY NURSE ADVISOR • JULY/AUGUST 2014

www.OncologyNurseAdvisor.com

July/August 2014

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

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FREE CONTINUING EDUCATION INSIDE! How the immune system is unleashed to fight cancer, PAGE 18

FEATURE

CRF: Exercise still trumps pharmaceutical interventions

COMMUNICATION CHALLENGES

Answering the unanswerable

THE ONA INTERVIEW

Integrating nursing care with the nutrition support team

THE TOTAL PATIENT

A novel way to encourage patients to eat more fruits and vegetables

ASK A PHARMACIST

VOLUME 5, NUMBER 4

Not all grapefruits have the same effect on drug metabolism

IMMUNOTHERAPY

Vaccines, antibodies, and cytokines: Prompting the body against cancer Anti CD-19 monoclonal antibody delivers a specific toxic drug to the malignant cell, causing it to leak or explode.

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EDITORIAL BOARD

Publisher Chad Holloway (201) 799-4878 chad.holloway@haymarketmedia.com

Ann J. Brady, MSN, RN-BC

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Jia Conway, DNP, FNP-BC, AOCNP, NP-C

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Nora Ray

Senior director of operations Audra Schlesinger Senior vice president, Haymarket Oncology Tammy Chernin, RPh CEO, Haymarket Media Inc Lee Maniscalco

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Subscriptions: www.OncologyNurseAdvisor.com/freesub Reprints: Wright’s Reprints (877) 652-5295 Permissions: www.copyright.com Oncology Nurse Advisor is the official publication of the National Coalition of Oncology Nurse Navigators. Oncology Nurse Advisor (ISSN 2154-350X), July/August 2014, Volume 5, Number 4. P ublished 6 times annually by Haymarket Media Inc, 114 West 26th Street, 4th Floor, New York, NY 10001. Oncology Nurse Advisor is available on a paid subscription basis at the following annual rates: USA $75, Canada $85, all other Foreign $110; Single copy price: USA $20; Foreign $30. To order, visit our Web site at www. OncologyNurseAdvisor.com or 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.

Huntington Cancer Center Pasadena, California

Cancer Care Associates of York York, Pennsylvania

Michele M. Farrington, BSN, RN, CPHON University of Iowa Hospitals and Clinics Iowa City, Iowa

Donald R. Fleming, MD Cancer Care Center, Davis Memorial Hospital Elkins, West Virginia

Arati Jairam-Thodla, MSN, CNP Northwestern Memorial Prentice Women’s Hospital Chicago, Illinois

Karen MacDonald, RN, BSN, CPON William Beaumont Hospital Royal Oak, Michigan

Marlene McGuire, RN, MA, ANP-C The Cancer Institute of New Jersey New Brunswick, New Jersey

Maribel Pereiras, PharmD, BCPS, BCOP Hackensack University Medical Center Hackensack, New Jersey

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

www.OncologyNurseAdvisor.com • JULY/AUGUST 2014 • ONCOLOGY NURSE ADVISOR 5

CONTENTS

July/August 2014

IN THE NEWS • Brain mets: Time for a new approach • Game changer for leukemia therapy • Navigator Notes: Using peer counselors to expand navigation services • Genetics training improves care and reduces unnecessary testing

CONTINUING EDUCATION How the immune system is unleashed to fight cancer

Kathy Boltz, PhD

42 24

FEATURES CRF relief: Exercise still brumps pharmaceutical interventions Bryant Furlow

STAT CONSULT Oxaliplatin (Eloxatin)

RADIATION & YOUR PATIENT A review of radiotherapy-induced hypopituitarism

Bryant Furlow

49 FIND US ON

COMMUNICATION CHALLENGES Answering the unanswerable Ann J. Brady, MSN, RN-BC

linkedin.com/company/oncology-nurse-advisor

plus.google.com/+Oncologynurseadvisor

@ONAcom

OncologyNurseAdvisor.com/app-download

facebook.com/OncologyNurseAdvisor

OncologyNurseAdvisor.com

6 ONCOLOGY NURSE ADVISOR • JULY/AUGUST 2014 • www.OncologyNurseAdvisor.com



www.OncologyNurseAdvisor.com

JOIN OUR COMMUNITY Submit a question to an oncology nurse advisor Have a question? Our panel of oncology clinicians is available to answer your questions. Submit questions to editor.ona@HaymarketMedia.com.

THE ONA INTERVIEW Integrating nursing care with the nutrition support team THE TOTAL PATIENT A novel way to get patients to eat their fruits and vegetables: Have them grow their own!

FROM CANCERCARE Bridging cancer care for the older adult patient Sarah Kelly, LSCW

ONA asks… Answer our poll question and compare your opinions with those of your colleagues on key nursing issues at OncologyNurseAdvisor.com Subscribe to ONA newsletters

Bette Weinstein Kaplan

Answer the ONA poll question

ASK A PHARMACIST Not all grapefruits have the same effect on drug metabolism

Stay current with daily news reports and special series from key oncology conferences on our Web site, sign up for our e-newsletters at OncologyNurseAdvisor.com/subscribe. Earn CE credits Each issue offers one new CE activity co-provided by the Nurse Practitioner Healthcare Foundation. Activities are active for 2 years.

Lisa A. Thompson, PharmD, BCOP •

ONCOLOGY NURSE ADVISOR FORUM • Is gallbladder cancer inherited? • Hepatocellular carcinoma with no cirrhosis • Diarrhea management in patients with rectal cancer • A career change to radiation oncology nursing • Optimal dosing for TMZ: 1 hour prior to RT vs bedtime

Socialize electronically

FEATURE ARTICLES • Specialized apps extend the reach of community resources

Keep up with the oncology field through our social media. We’re on Twitter and Facebook. Now, we’re on Pinterest, too. Follow us!

Bette Weinstein Kaplan

• Genomics vs genetics: How are they different? Kathy Boltz, PhD

ISSUES IN CANCER SURVIVORSHIP • The best cream for coffee may be the growing evidence of its cancer-preventive properties

ON THE

WEB

Bette Weinstein Kaplan

www.OncologyNurseAdvisor.com • JULY/AUGUST 2014 • ONCOLOGY NURSE ADVISOR 7

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

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

727-37345

DIGITAL

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

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

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

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

727-37345

DIGITAL

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

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

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

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

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

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

Chlorambucil (N=143)

All Grades

Grade 3/4

All Grades

Grade 3/4

121 (79)

52 (34)

96 (67)

25 (17)

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

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

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

1 (<1) 0 0

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

6 (4) 2 (1) 0 0

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

2 (1) 0 0 0

7 (5)

2 (1)

3 (2)

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

0 3 (2) 0

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

0 1 (<1) 0

11 (7)

5 (3)

11 (7)

3 (2)

2 (1)

6 (4)

1 (<1)

7 (5)

1 (<1)

12 (8) 8 (5)

4 (3) 0

7 (5) 2 (1)

3 (2) 0

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

Chlorambucil N=141

Laboratory Abnormality

All Grades n (%)

Grade 3/4 n (%)

All Grades n (%)

Grade 3/4 n (%)

Hemoglobin Decreased

134 (89)

20 (13)

115 (82)

12 (9)

Platelets Decreased

116 (77)

16 (11)

110 (78)

14 (10)

Leukocytes Decreased

92 (61)

42 (28)

26 (18)

4 (3)

Lymphocytes Decreased

102 (68)

70 (47)

27 (19)

6 (4)

Neutrophils Decreased

113 (75)

65 (43)

86 (61)

30 (21)

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

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

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

IN THE NEWS

Brain mets: Time for a new approach

way once they metastasize to the brain. This oversimplifica-

tion assumes that histologically diverse cancers respond the same way to chemotherapy and are equally sensitive (or insensitive)

scope of metastases, rather than just the number of metastases. • All cancers in the brain reflect the presence of micrometastases. Aggressively monitoring

for and treating individual brain metastases can improve disease control and patient survival. • Whole brain irradiation is unjustified because it causes disabling cognitive dysfunction if a patient lives long enough.

to radiation. It assumes that patients are at the same risk for subsequent brain cancer relapses, development of additional metastatic lesions, and have similar survival rates. This type of thinking overlooks important biological differences in brain metastases resulting from very different types of cancer, such as those originating in the lung, breast, or skin.

MRI scan revealing metastatic tumor in the brain

• The number of brain metastases is the best guide for disease management. Strict adherence

to the number of metastases can limit treatment options inappropriately. Physicians should look at the total tumor burden, including the size and

“We are in an era of personalized medicine, and we need to begin thinking that way. It is time for fresh thinking and new, critical anlyses.” 12 ONCOLOGY NURSE ADVISOR • JULY/AUGUST 2014 • www.OncologyNurseAdvisor.com

The risks and benefits of whole brain irradiation should be evaluated for each patient. New studies examining the cognitive impact of whole brain irradiation on thinking and learning are underway. • Most brain metastases cause obvious symptoms and therefore regular screening for brain metastases is unnecessary and does not affect survival. Advances in screening

allow detection of metastases earlier, before symptoms occur. This allows earlier treatment, which can affect quality of life and survival. Molecular and genetic subtyping will continue to reveal why brain metastases from specific primary tumors develop in some patients, but not in others. These answers should in turn influence how best to manage brain metastases in patients. “We are in an era of personalized medicine,” Kondziolka said, “and we need to begin thinking that way. It is time for fresh thinking and new, critical analyses.” ■

A BLUE-RIBBON TEAM of national experts on brain cancer said that professional pessimism and out-of-date myths rather than current science may compromise the care of patients with cancer that has metastasized to the brain. Assumptions underlying key clinical trials in the past are now out-of-date, and some physicians have lumped together brain metastases without regard to the primary site of the cancer. This has resulted in less-thanoptimal care for individual patients. Furthermore, insurers may question care that deviates from these entrenched misconceptions, the authors concluded. “It’s time to abandon this unjustifiable nihilism and think carefully about individualized care,” said lead author Douglas S. Kondziolka, MD, director of the gamma knife program in the department of neurosurgery at New York University, in New York, New York. The authors identified five leading misconceptions that may lead to poor care. • All tumor cell types act the same

Game changer for leukemia therapy CANCER CELLS decide whether to live or die after a short period of intense exposure to targeted therapy, opposing the current requirement for continuous treatment, according to a new study. The researchers, led by the South Australian Health and Medical Research Institute (SAHMRI) and the University of Adelaide’s Centre for Personalised Cancer Medicine in Adelaide, Australia, say this study presents a new treatment strategy that translates to a significant reduction in side effects for patients. The research team has been investigating the role of a common protein known as STAT5. They found that the activity of STAT5 appears to be a critical determinant of the decision for cancer cells to live or die. When they blocked STAT5 in conjunction with exposure to a regular anticancer treatment, the leukemia cells were more effectively targeted. They also found that timing was important, and that combining STAT5 inhibition with exposure to tyrosine kinase inhibitors for less than 1 hour was lethal to the progenitors of CML. This was in contrast to inhibiting JAK kinase, which did not cause cell death when it was combined with tyrosine kinase inhibitors. The authors concluded that combining tyrosine kinase inhibitors with inhibiting STAT5 is promising for the treatment of CML. ■

Navigator Notes: Using peer counselors to expand navigation services Navigation is not universally defined with consistency or by scope of work. In this column, we illustrate a collaborative model of patient support created to expand patient navigation contact throughout the cancer experience. The Breast Center at Sutter Pacific Medical Foundation in Santa Rosa, California, diagnoses approximately 140 cases of breast cancer per year. A nurse navigator and bilingual resource specialist work with patients at risk for or with newly diagnosed breast cancer at the diagnostic center. In an effort to expand patient support throughout the entire trajectory of care, we developed a philanthropically funded peer-counseling program. The director of navigation created the program, named WINGS, or Women Inspiring, Nurturing, Giving, and Supporting one another. ESTABLISHING PEERS

Peer support occurs when people provide knowledge, experience, emotional, social, or practical help to each other. It commonly refers to an initiative consisting of trained supporters and can take a number of forms, such as mentoring, listening, or counseling. Peer support is distinct from other forms of social support in that the source of support is a person who is similar in fundamental ways to the recipient of the support. The relationship between peers is one of equality. The peer counselor has “been there, done that” and can relate to others who are now experiencing similar life events. Peer counseling is unique in that patients talk with and receive understanding from someone who has had the same experiences. Literature reveals peer counselors can

decrease isolation and anxiety and increase the sense of normalcy and optimism for someone going through a difficult time. And, as stated by the helper therapy principle, providing peer support also benefits the well-being of the survivor-volunteers. THE WINGS PROGRAM

A detailed, programmatic plan was developed to address structure, finance, legalities, policies, and logistical components. A panel interviewed and selected potential volunteers who attended a 1-day training session. Two breast cancer survivors serve as coordinators of the program. They provide ongoing coaching and support for the volunteers. WINGS volunteers meet once a month with the peer counselor coordinators, a marriage and family therapist, the program director, and the coordinators to discuss patient issues. Breast Center patients with newly diagnosed breast cancer are given information about WINGS at their navigation visit for pathology results and resource visit. Those who wish to participate in the program complete enrollment forms. The coordinators then match new patients with an appropriate volunteer based on the diagnosis and anticipated treatment plan. The assigned volunteer contacts the patient and establishes the patient’s meeting preferences. Meeting locations are limited to a provider’s office, a public place, or phone support. The WINGS model serves to enhance and extend nurse navigation resources for patients. It is a cost effective, community-based prototype for improving the patient experience. ■

www.OncologyNurseAdvisor.com • JULY/AUGUST 2014 • ONCOLOGY NURSE ADVISOR 13

Take a bite out of G-CSF acquisition costs* GRANIX is another option in short-acting G-CSF therapy TM

» GRANIX demonstrated a 71% reduction in duration of severe neutropenia (DSN) vs placebo1 – GRANIX significantly reduced DSN when compared to placebo (1.1 days vs 3.8 days; p<0.001)1 – Efficacy was evaluated in a multinational, multicenter, randomized, controlled, Phase III study of chemotherapy-naïve patients with high-risk breast cancer receiving doxorubicin (60 mg/m2 IV bolus)/docetaxel (75 mg/m2)1 *Based on wholesale acquisition cost (WAC) of all short-acting G-CSF products as of November 11, 2013. WAC represents published catalogue or list prices and may not represent actual transactional prices. Please contact your supplier for actual prices.

» Safety was evaluated in 3 Phase III clinical trials1

Indication

Important Safety Information (continued)

» GRANIX (tbo-filgrastim) Injection is a leukocyte growth factor indicated for reduction

» Use in patients with sickle cell disease: Severe and sometimes fatal sickle cell crises can occur

in the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

in patients with sickle cell disease receiving hG-CSFs. Consider the potential risks and benefits prior to the administration of GRANIX in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis.

» Potential for tumor growth stimulatory effects on malignant cells: The granulocyte colony-

Important Safety Information » Splenic rupture: Splenic rupture, including fatal cases, can occur following the administration of human granulocyte colony-stimulating factors (hG-CSFs). Discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture in patients who report upper abdominal or shoulder pain after receiving GRANIX.

» Acute respiratory distress syndrome (ARDS): ARDS can occur in patients receiving hG-CSFs. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS.

» Allergic reactions: Serious allergic reactions, including anaphylaxis, can occur in patients receiving hG-CSFs. Reactions can occur on initial exposure. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim.

stimulating factor (G-CSF) receptor, through which GRANIX acts, has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded.

» Most common treatment-emergent adverse reaction: The most common treatment-emergent adverse reaction that occurred in patients treated with GRANIX at the recommended dose with an incidence of at least 1% or greater and two times more frequent than in the placebo group was bone pain. Please see brief summary of Full Prescribing Information on adjacent page. For more information, visit GRANIXhcp.com. Reference: 1. GRANIX TM (tbo-filgrastim) Injection Prescribing Information. North Wales, PA: Teva Pharmaceuticals; 2013.

Take a bite out of G-CSF acquisition costs* GRANIX is another option in short-acting G-CSF therapy TM

» Safety was evaluated in 3 Phase III clinical trials1

Indication

Important Safety Information (continued)

» GRANIX (tbo-filgrastim) Injection is a leukocyte growth factor indicated for reduction

» Use in patients with sickle cell disease: Severe and sometimes fatal sickle cell crises can occur

in the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

» Potential for tumor growth stimulatory effects on malignant cells: The granulocyte colony-

BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR GRANIX™ (tbo-filgrastim) Injection, for subcutaneous use SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE GRANIX is indicated to reduce the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Splenic Rupture Splenic rupture, including fatal cases, can occur following administration of human granulocyte colony-stimulating factors. In patients who report upper abdominal or shoulder pain after receiving GRANIX, discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture. 5.2 Acute Respiratory Distress Syndrome (ARDS) Acute respiratory distress syndrome (ARDS) can occur in patients receiving human granulocyte colony-stimulating factors. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS. 5.3 Allergic Reactions Serious allergic reactions including anaphylaxis can occur in patients receiving human granulocyte colony-stimulating factors. Reactions can occur on initial exposure. The administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine may reduce the severity of the reactions. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim. 5.4 Use in Patients with Sickle Cell Disease Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving human granulocyte colony-stimulating factors. Consider the potential risks and benefits prior to the administration of human granulocyte colony-stimulating factors in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis. 5.5 Potential for Tumor Growth Stimulatory Effects on Malignant Cells The granulocyte colony-stimulating factor (G-CSF) receptor through which GRANIX acts has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded. 6 ADVERSE REACTIONS The following potential serious adverse reactions are discussed in greater detail in other sections of the labeling: • Splenic Rupture [see Warnings and Precautions (5.1)] • Acute Respiratory Distress Syndrome [see Warnings and Precautions (5.2)] • Serious Allergic Reactions [see Warnings and Precautions (5.3)] • Use in Patients with Sickle Cell Disease [see Warnings and Precautions (5.4)] • Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions (5.5)] The most common treatment-emergent adverse reaction that occurred at an incidence of at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group was bone pain. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. GRANIX clinical trials safety data are based upon the results of three randomized clinical trials in patients receiving myeloablative chemotherapy for breast cancer (N=348), lung cancer (N=240) and non-Hodgkin’s lymphoma (N=92). In the breast cancer study, 99% of patients were female, the median age was 50 years, and 86% of patients were Caucasian. In the lung cancer study, 80% of patients were male, the median age was 58 years, and 95% of patients were Caucasian. In the non-Hodgkin’s lymphoma study, 52% of patients were male, the median age was 55 years, and 88% of patients were Caucasian. In all three studies a placebo (Cycle 1 of the breast cancer study only) or a non-US-approved filgrastim product were used as controls. Both GRANIX and the non-US-approved filgrastim product were administered at 5 mcg/kg subcutaneously once daily beginning one day after chemotherapy for at least five days and continued to a maximum of 14 days or until an ANC of ≥10,000 x 106/L after nadir was reached.

Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group. The overall incidence of bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-US-approved filgrastim product). Leukocytosis In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed in less than 1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies. 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of antibody development in patients receiving GRANIX has not been adequately determined. 7 DRUG INTERACTIONS No formal drug interaction studies between GRANIX and other drugs have been performed. Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution. Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies of GRANIX in pregnant women. In an embryofetal developmental study, treatment of pregnant rabbits with tbo-filgrastim resulted in adverse embryofetal findings, including increased spontaneous abortion and fetal malformations at a maternally toxic dose. GRANIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In the embryofetal developmental study, pregnant rabbits were administered subcutaneous doses of tbo-filgrastim during the period of organogenesis at 1, 10 and 100 mcg/kg/day. Increased abortions were evident in rabbits treated with tbo-filgrastim at 100 mcg/kg/day. This dose was maternally toxic as demonstrated by reduced body weight. Other embryofetal findings at this dose level consisted of post-implantation loss‚ decrease in mean live litter size and fetal weight, and fetal malformations such as malformed hindlimbs and cleft palate. The dose of 100 mcg/kg/day corresponds to a systemic exposure (AUC0-24) of approximately 50-90 times the exposures observed in patients treated with the clinical tbo-filgrastim dose of 5 mcg/kg/day. 8.3 Nursing Mothers It is not known whether tbo-filgrastim is secreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GRANIX is administered to a nursing woman. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. 8.4 Pediatric Use The safety and effectiveness of GRANIX in pediatric patients have not been established. 8.5 Geriatric Use Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111 patients were 65 years of age and older. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients. 8.6 Renal Impairment The safety and efficacy of GRANIX have not been studied in patients with moderate or severe renal impairment. No dose adjustment is recommended for patients with mild renal impairment. 8.7 Hepatic Impairment The safety and efficacy of GRANIX have not been studied in patients with hepatic impairment. 10 OVERDOSAGE No case of overdose has been reported. ©2013 Cephalon, Inc., a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved. GRANIX is a trademark of Teva Pharmaceutical Industries Ltd. Manufactured by: Distributed by: Sicor Biotech UAB Teva Pharmaceuticals USA, Inc. Vilnius, Lithuania North Wales, PA 19454 U.S. License No. 1803 Product of Israel GRX-40189 January 2014 This brief summary is based on TBO-003 GRANIX full Prescribing Information.

IN THE NEWS

FDA Update Belinostat (Beleodaq) was approved by the FDA for the treatment of peripheral T-cell lymphoma (PTCL), a rare and fast-growing type of nonHodgkin lymphoma. Belinostat works by stopping enzymes that contribute to T-cells becoming cancerous. It is indicated for patients whose disease returned after treatment (relapsed) or did not respond to previous treatment (refractory). Belinostat was evaluated in a clinical study involving 129 participants with relapsed or refractory PTCL. Results showed 25.8% of participants had their cancer disappear or shrink after treatment. The most common side effects reported were nausea, fatigue, fever, anemia, and vomiting. The drug was approved under the agency’s accelerated approval program. The FDA approved a new use for technetium 99m tilmanocept (Lymphoseek Injection), a radioactive diagnostic imaging agent used to help doctors determine the extent of metastasis of squamous cell carcinoma in the head and neck region. The agent is now approved for sentinel lymph node biopsy in patients with cancer of the head and neck. The new indication will allow for the option of more limited lymph node surgery in patients with sentinel nodes negative for cancer. The most common side effects identified in clinical trial were pain or irritation at the injection site. ■

Genetics training improves care and reduces unnecessary testing COUNSELING FROM a health care professional trained in genetics before genetic testing takes place may improve the quality of health care and help reduce unnecessary testing. “Pretest genetic counseling in which a health care provider takes a thorough family history and discusses the potential risks and benefits of genetic testing is the standard of care as recommended by the American Society of Clinical Oncology and National Society of Genetic Counselors,” said Tuya Pal, MD, a boardcertified geneticist at Moffitt Cancer Center, Tampa, Florida. Researchers surveyed 473 patients who underwent genetic testing for hereditary BRCA1 and BRCA2 gene mutations. Almost all study participants (97%) who saw a board-certified geneticist or genetic counselor recalled having a discussion before undergoing genetic testing. Only 59% of study participants who saw a health

ONA ASKS …

Almost all study participants who saw a boardcertified geneticist or genetic counselor recalled having a discussion before undergoing genetic testing.

care provider without training in genetics recalled having a discussion before genetic testing. “Health care providers with training in genetics are less likely to order expensive comprehensive genetic testing when less expensive testing may be appropriate,” said Deborah Cragun, PhD, postdoctoral fellow at Moffitt. Comprehensive testing included full BRCA1 and BRCA2 gene sequencing while less expensive testing looked at single-site or Ashkenazi Jewish founder mutation. “Our study found that health care providers with training in genetics ordered comprehensive testing for 9.5% of participants, compared to other health care providers who ordered comprehensive testing for 19.4% of participants. At the time of data collection, comprehensive genetic testing cost approximately $4,000, compared to $400 for the less expensive testing.” ■

YES

Oncology nurses spend a lot of time educating patients about the importance of screening, and we want to know if you practice what is preached. Are you up-todate with the cancer screenings appropriate for you? Go online to answer our poll question. We’ll publish the results and a new question in the next issue. …AND YOU ANSWERED In the last issue we asked how comfortable you are in discussing weight management with patients.

42% Comfortable 46% Somewhat comfortable 12% Not comfortable

www.OncologyNurseAdvisor.com • JULY/AUGUST 2014 • ONCOLOGY NURSE ADVISOR 17

CONTINUING EDUCATION Disclosure of Conflicts of Interest Medical Education Resources ensures balance, independence, objectivity, and scientific rigor in all our educational programs. In accordance with this policy, MER identifies conflicts of interest with its instructors, content managers, and other individuals who are in a position to control the content of an activity. Conflicts are resolved by MER to ensure that all scientific research referred to, reported, or used in a continuing education activity conforms to the generally accepted standards of experimental design, data collection, and analysis. MER is committed to providing its learners with high-quality activities that promote improvements or quality in health care and not the business interest of a commercial interest. The faculty reported the following financial relationships with commercial interests whose products or services may be mentioned in this activity: Name of faculty

Reported Financial Relationship

Kathy Boltz, PhD

No financial relationships to disclose

The content managers reported the following financial relationships with commercial interests whose products or services may be mentioned in this activity:. Name of Content Manager

Reported Financial Relationship

Joyce Pagán

No financial relationships to disclose

Planners and Manager from MER

No financial relationships to disclose

Disclaimer The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Medical Education Resources or Haymarket Medical. The authors have disclosed if there is any discussion of published and/or investigational uses of agents that are not indicated by the FDA in their presentations. The opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of Medical Education Resources or Haymarket Medical. Before prescribing any medicine, primary references and full prescribing information should be consulted. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. The information presented in this activity is not meant to serve as a guideline for patient management.

EDUCATIONAL OBJECTIVES After participating in this activity, clinicians should be better able to • Identify the components of the immune system • Describe the mechanism of action of various immunotherapies • List the names and indications of currently used immunologic agents.

STATEMENT OF NEED/PROGRAM OVERVIEW Oncology nurses are aware of the increasing number of immunotherapeutic agents under development, and they need to keep their knowledge of these emerging treatments up-to-date. In addition, research continues to provide more clear explanations of how the body’s natural defenses can be activated to prevent and cure cancer. This activity will review the components of the immune system, explain the mechanism of action of immunotherapies, and describe currently available immunotherapeutic agents. After refreshing their own understanding of immunotherapies, nurses can explain to patients how these treatments are used with greater confidence. FACULTY Kathy Boltz, PhD Phoenix, Arizona LEARNING GOAL/PURPOSE To better understand how cancer immunotherapies use the body’s natural defenses to identify and kill cancer cells. NURSING CREDIT Medical Education Resources is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. This CE activity provides 1 contact hour of continuing nursing education. Medical Education Resources is a provider of continuing nursing education by the California Board of Registered Nursing, Provider #CEP 12299, for 1 contact hour. METHOD OF PARTICIPATION There are no fees for participating in and receiving credit for this activity. During the period August 2014 through August 2015, participants must 1) read the learning objectives and faculty disclosures, 2) study the educational activity, 3) complete the posttest by selecting the best answer to each question on the posttest, 4) complete the evaluation form, and 5) continue to next section to claim credits and view your certificate. A statement of credit will be issued only upon receipt of a completed activity evaluation form and a completed posttest with a score of 70% or better. Statements of credit are available at the conclusion of the activity. MEDIA

Journal article and Web site (myCME.com; OncologyNurseAdvisor.com)

Co-provided by Medical Education Resources and Haymarket Media Inc.

18 ONCOLOGY NURSE ADVISOR • JULY/AUGUST 2014 • www.OncologyNurseAdvisor.com

TARGET AUDIENCE

PROGRAM INFORMATION

• This activity has been designed to meet the educational needs of registered nurses and nurse practitioners involved in the management of patients with cancer.

• Estimated time to complete this activity: 1 hour • Release date: August 2014 • Expiration date: August 2015

How the immune system is unleashed to fight cancer Cancer cells hide from the body’s natural defenses. This overview explains how immunotherapeutic strategies expose cancer cells to the immune system.

CD-19 antigens on the surface of a malignant B-cell mark the cell for destruction. A T-cell (left) delivers cytokines, which contribute to cell death.

KATHY BOLTZ, PhD

trategies that unleash the immune system to attack cancer cells are being developed at a rapid pace. Maintaining an up-to-date understanding of the immune system and an awareness of new immunotherapies and changing indications for existing ones is essential to providing effective cancer care. This article aims to increase oncology nurses’ knowledge of immunotherapies. Cancer immunotherapy involves using the body’s own immune system to fight cancer. Cancer cells avoid detection and elimination by the immune system, and so engaging the immune system against cancer is difficult. Foreign cells such as bacteria have proteins on their surface not normally found in the human body; however, cancer cells are more similar to normal cells and have fewer clear differences from normal cells. This makes it difficult for the immune system to recognize cancer cells as foreign. Immunotherapy treatments often seek to make cancerous cells more obvious to the immune system.

Continues on page 21

TO TAKE THE POST-TEST FOR THIS CE ACTIVITY

and apply for 1.0 contact hours, please go to myCME.com/CEAUG2014

www.OncologyNurseAdvisor.com • JULY/AUGUST 2014 • ONCOLOGY NURSE ADVISOR 19

CONTINUING EDUCATION | Cancer immunotherapy The immune system has two parts, known as the innate and adaptive immune systems. These systems differentiate between pathogens and self. They create an immune response against antigens, which are any substance that raises an immune response. The innate immune system is diverse. Its components include physical barriers such as skin and mucosal membranes; effector cells that include macrophages, natural killer (NK) cells, innate lymphoid cells, dendritic cells, mast cells, neutrophils, and eosinophils; pattern recognition mechanisms such as Toll-like receptors; and humoral mechanisms that include complement proteins and cytokines.1 Cytokines are a complex group of proteins that are produced when the immune system is activated.2 They allow immune cells to communicate and coordinate their attack on antigens. Cytokines include interleukins, interferons, and colony-stimulating factors, among others. The innate immune system works rapidly and is usually characterized by tissue inflammation. It uses repeated patterns to recognize pathogens and employs a variety of effector mechanisms to respond quickly. One of its roles is to initiate the adaptive immune system. The adaptive immune system consists of T and B cells. In contrast to the innate immune system, the adaptive system responds more slowly but is more specific. The adaptive immune system includes B cells, which produce thousands of highly targeted antibodies once activated; regulatory T cells, which provide checks on the activity of the immune system so it does not damage healthy cells; CD4+ helper T cells, which direct and support specialized cells such as B cells and CD8+ killer T cells; CD8+ killer T cells, which can each kill thousands of harmful cells; and antibodies, which seek and bind to antigen proteins. The innate immune system also creates memory of an antigen, which is important for cancer immunotherapy because it can decrease metastasis and limit the occurrence of a second malignancy.3 The innate immune system is linked to the adaptive immune system through dendritic cells.3 When the innate immune system is activated, the dendritic cells travel to nearby lymph nodes and present antigen to T cells, activating them. When the dendritic cell presents an antigen, the response to that antigen depends on the microenvironment where the dendritic cell found the antigen. Ultimately, T cells are responsible for cell-mediated immune responses, which are considered the most important mechanism used by the immune system to kill solid tumors.3 CANCER VACCINES Knowledge of how dendritic cells work has led to sipuleucel-T, which is based on ex vivo (cultured outside the body) activated dendritic cells. A patient’s monocytes, a precursor of dendritic cells, are incubated with a fusion protein that links the target antigen, Prostatic Acid Phosphatase, to a cytokine known as

granulocyte-macrophage colony-stimulating factor (GM-CSF). This fusion protein drives the monocytes to mature into dendritic cells. The target antigen causes the activated dendritic cells to produce an immune response against the prostate cancer. Sipuleucel-T was approved by the US Food and Drug Administration (FDA) to treat patients with metastatic prostate cancer. In a randomized, controlled trial, sipuleucel-T improved median survival by 4.1 months, compared with placebo.4 MONOCLONAL ANTIBODIES Monoclonal antibodies are now standard of care for a number of tumor types. Antibodies are proteins that bind to a specific antigen. Monoclonal antibodies are designed to recognize very specific antigens on certain types of tumor cells. Monoclonals circulate in the body until they find and attach to the antigen. Once attached, some monoclonal antibodies work by attracting other immune system cells that destroy the cells containing the antigen; others block tumor antigens or molecules that promote the survival of tumors.3,5 Commonly used monoclonal antibodies include trastuzumab (Herceptin), which targets HER2 and is FDA-approved for the treatment of breast cancer and metastatic gastric cancer; and rituximab, which targets CD20 and is FDA-approved for non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL). Trastuzumab’s target, the HER2 protein receptor, can be expressed in large amounts on the surface of some cancer cells, where it helps the cells to grow. When trastuzumab binds to the HER2 receptor, it inactivates the receptor. Antibodies

By blocking checkpoints, the cancer is less able to suppress the immune system, and the immune system can more effectively fight the cancer. such as trastuzumab and rituximab are known as naked monoclonal antibodies, meaning they do not have a drug or radioactive material attached to them. Most naked monoclonal antibodies work through antibody-dependent cell-mediated cytotoxicity (ADCC), in which natural killer cells recognize those cells coated with antibodies and kill them. Monoclonal antibodies can have a chemotherapy drug, toxic agent, or radioactive material attached to them. Ado-trastuzumab emtansine (TDM-1; Kadcyla) received FDA approval in 2013 for the treatment of metastatic HER2-positive breast cancer in patients who failed prior therapy with trastuzumab and a taxane.1 This antibody-drug conjugate adds the potent

20 ONCOLOGY NURSE ADVISOR • JULY/AUGUST 2014 • www.OncologyNurseAdvisor.com

microtubule-disrupting drug DM1 to trastuzumab—in other words, a targeted delivery of chemotherapy to cells that overexpress HER2.6 Also in 2013, brentuximab vedotin (anti-CD30MMAE [monomethyl auristatin E]; Adcetris) was approved by the FDA for the treatment of relapsed or refractory Hodgkin lymphoma or anaplastic large cell lymphoma.1 This drug uses the brentuximab antibody to target CD30, which has limited expression in healthy tissue but is expressed by Hodgkin lymphoma and anaplastic large cell lymphoma. Brentuximab vedotin delivers MMAE, a cytotoxic agent that causes cell death by apoptosis.7 An example of a monoclonal antibody with a radioactive particle attached is ibritumomab tiuxetan (Zevalin). Ibritumomab tiuxetan is an antibody against CD20 with yttrium-90 attached. It is FDA-approved for the treatment of refractory non-Hodgkin lymphoma.1 CD20 is expressed on the surface of lymphocytes, including the cancer cells of patients with non-Hodgkin lymphoma. The radiation enhances the killing effect of the antibody. NONSPECIFIC IMMUNOTHERAPIES AND ADJUVANTS Various immunotherapy strategies target cancer cells nonspecifically, stimulating the immune system in a more general way.8 These include immunomodulatory drugs such as thalidomide (Thalomid), lenalidomide (Revlimid), pomalidomide (Pomalyst), and imiquimod (Aldara, Zyclara, generics). Another immunotherapy strategy is the live attenuated virus Bacille CalmetteGuerin; this virus is used in the treatment of the bladder. All immune reactions involve cytokines, and several nonspecific cancer immunotherapy strategies use cytokines.9 Cytokines interact in complex ways to provide homeostasis and immune control through positive and negative feedback mechanisms. Interleukin-2 is a type of cytokine that leads to the growth of T lymphocytes. It was FDA-approved for the treatment of advanced renal cell carcinoma in 1992 and for metastatic melanoma in 1998; but its toxicity limits its use to patients with excellent organ function.2 It had an objective response rate of 16% in 270 melanoma patients, and the 6% of patients who achieved complete response had a durable response. Its toxicities include fever, chills, myalgias, diarrhea, nausea, anemia, thrombocytopenia, hepatic dysfunction, myocarditis, confusion, and a predisposition to infection; but these effects are dose-dependent, largely predictable, and reversible. Interleukin-2 can only be used at well-established treatment centers with clinicians experienced in administering interleukin-2 therapy. At high doses, interleukin-2 is given in the inpatient setting. Another type of cytokine is interferons, which were discovered in the 1950s.2 Analyses of high-dose interferon-alfa use in melanoma cases found a consistent benefit for high-risk patients with melanoma, as it improved relapse-free survival by 13% to 18% and overall survival by 10% to 11%. Notably,

interferon is difficult to tolerate, and its toxicity limits its use and often leads to treatment discontinuation. Predominant side effects include myelotoxicity, elevation of liver enzymes, nausea, vomiting, flulike symptoms, and neuropsychiatric symptoms. Interferon-alfa is only recommended for patients with a risk of relapse greater than 30%. It is FDA-approved for hairy cell leukemia, chronic myelogenous leukemia, follicular non-Hodgkin lymphoma, cutaneous T-cell lymphoma, kidney cancer, melanoma, and Kaposi sarcoma. Granulocyte-macrophage colony-stimulating factor (GM-CFS) is another cytokine that stimulates the immune system. GM-CSF boosts white blood cells after chemotherapy, and is FDA-approved to help increase the number and function of white blood cells after bone marrow transplantation.10 GM-CFS is indicated for cases of bone marrow transplantation failure or engraftment delay, before and after peripheral blood stem cell transplantation, and following induction chemotherapy in older patients with acute myelogenous leukemia. Patients taking GM-CSF have commonly experienced fever, liver-associated events, skin-associated events, infection, nausea, metabolic disturbances, and diarrhea. TARGETING IMMUNE SYSTEM CHECKPOINTS Much recent excitement in oncology has been generated by cancer immunotherapy approaches that target immune system checkpoints. When a T cell interacts with an antigen-presenting cell, the downstream T cell responses are affected by both costimulatory and coinhibitory signals. Coinhibitory signals include cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death receptor-1 (PD-1), along with programmed death receptor ligand-1 and -2 (PD-L1 and PD-L2). Strategies targeting these inhibitory signals are potentially very powerful because cancer exploits these checkpoints to grow unchecked. Blocking these checkpoints unblocks the immune system, and current results indicate that it is producing durable responses. An important challenge with these treatments is that the unchecked immune system results in immune-related adverse events (irAEs). By blocking the checkpoints, the cancer is less able to suppress the immune system, and then the immune system can more effectively fight the cancer. Treatments targeting these immune checkpoints are being investigated for solid tumors, melanoma, renal cell cancer, non-small cell lung cancer, hepatocellular carcinoma, prostate cancer, glioma, glioblastoma multiforme, pancreatic cancer, triple-negative breast cancer, gastric cancer, urothelial cancer, head and neck cancers, and colorectal cancer.11 The first FDA-approved treatment that blocks immune checkpoints was ipilimumab (Yervoy). Ipilimumab is a monoclonal antibody to CTLA-4 indicated for the treatment of metastatic melanoma, based on a phase III trial in which ipilimumab increased median overall survival by 3.6 months, to 10.0 months

www.OncologyNurseAdvisor.com • JULY/AUGUST 2014 • ONCOLOGY NURSE ADVISOR 21

CONTINUING EDUCATION | Cancer immunotherapy TABLE 1. Immunological reagents against cancer Immunotherapy

Mechanism/target

Indications

Brentuximab vedotin (Adcetris)

Targets CD30 with the cytotoxic agent MMAE

Anaplastic large cell lymphoma, Relapsed or refractory Hodgkin lymphoma

Trastuzumab emtansine (Kadcyla)

HER2 receptor

HER2+ metastatic breast cancer

Antibody-drug conjugates

Antibody-radioparticle conjugate Ibritumomab tiuxetan (Zevalin)

Targets CD20 with yttrium-90 attached

Refractory non-Hodgkin lymphoma

Culture dendritic cells to target the antigen prostatic acid phosphatase

Metastatic prostate cancer

Granulocyte-macrophage colony-stimulating factor (Leukine)

Stimulates immune system

• Before and after peripheral blood stem cell transplantation • Bone marrow transplantation failure or engraftment delay • Following induction chemotherapy in older patients with acute myelogenous leukemia

Interferon-alfa

• Activates JAK-STAT pathway • Modulates function of natural killer cells and T cells • Activates distribution of cellular subsets • Induces pro-apoptosis genes

Chronic myelogenous leukemia, Cutaneous T-cell lymphoma, Follicular non-Hodgkin lymphoma, Hairy cell leukemia, Kaposi sarcoma, Kidney cancer, Melanoma

Interleukin-2

Increased T lymphocytes

Advanced renal cell carcinoma, Metastatic melanoma

Augment natural killer cell cytotoxicity Increase interleukin-2 secretions

Newly diagnosed multiple myeloma

Bevacizumab (Avastin)

Vascular endothelial growth factor

Breast cancer, Colorectal cancer, Non-small cell lung cancer

Cetuximab (Erbitux)

Epidermal growth factor receptor

Colorectal cancer, Head and neck cancer

Ipilimumab (Yervoy)

Blockades CTLA-4 for immune checkpoint blockade

Metastatic melanoma

Rituximab (Rituxan)

CD20 B-cell surface antigen

Chronic lymphocytic leukemia, Non-Hodgkin lymphoma

Trastuzumab (Herceptin)

HER2 receptor

HER2+ breast cancer, HER2+ metastatic gastric cancer

Cancer vaccine Sipuleucel-T (Provenge) Cytokines

Immunomodulatory drug Thalidomide (Thalomid) Monoclonal antibodies

instead of the 6.4 months for patients who did not receive the agent.12 Of interest with CTLA-4 blockades, complete tumor regression for a prolonged duration occurred in most of the few patients who achieved complete tumor regression.13 However, 10% to 15% of patients treated with ipilimumab in the first phase III trial experienced severe or life-threatening toxicity. The irAEs most commonly experienced were diarrhea, enterocolitis, hepatitis, dermatitis, and endocrinopathies. These typically occurred several weeks into the course of treatment. Also, patients who experienced refractory or severe irAEs required immunosuppressants, increasing their risk for opportunistic infections. Combining ipilimumab with GM-CSF resulted in improved overall survival in a recent phase II study with 245 patients with metastatic melanoma. The median overall survival was 17.5 months with the combination versus 12.7 months with

ipilimumab alone.14 The 1-year survival rates were 68.9% with the combination and 52.9% with ipilimumab alone. These results suggest synergy between the two treatments. The combination resulted in fewer grade 3-5 adverse events in the combination arm (45% of patients) than in the ipilimumab alone arm (58% of patients). Recent reports have described combining ipilimumab with nivolumab, an antibody against the immune checkpoint PD-1. A small phase III trial of this combination in 53 patients with advanced melanoma resulted in a 2-year survival rate of 75%.15 More than half (62%) of the patients experienced grade 3 or 4 adverse events, with the most common ones being elevated levels of lipase, aspartate aminotransferase, and alanine aminotransferase.15,16 These rates of adverse events were higher than the rates with either treatment alone. Notably, the majority of the patients had durable responses.

22 ONCOLOGY NURSE ADVISOR • JULY/AUGUST 2014 • www.OncologyNurseAdvisor.com

Monoclonal antibodies targeting PD-L1 are also in development.13 These, as with the other checkpoint inhibitors, are being tested against a variety of tumors, including non-small cell lung cancer, melanoma, colorectal cancer, renal cell carcinoma, ovarian cancer, pancreatic cancer, and breast cancer. New approaches are being developed to measure response to checkpoint blockades because response measures that are appropriate for chemotherapeutic treatments, such as new lesions indicate progressive disease, are not appropriate for checkpoint blockades.13 Checkpoint blockades are immunomodulatory antibodies that can cause an apparent worsening of the disease before the disease ultimately stabilizes or tumors regress. Responses can take a long time to become apparent; for example, the average time to achieve a complete response to ipilimumab in one long-term study was 30 months.17 In addition, prolonged periods of stable disease can occur in patients who do not meet the criteria for an objective response. Efforts are ongoing to develop alternative response criteria, known as immune-related response criteria.18

2. Buchbinder EI, McDermott DF. Interferon, interleukin-2, and other cytokines.

ADOPTIVE CELLULAR THERAPY

12. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in

Hematol Oncol Clin North Am. 2014;28(3):571-583. 3. Harris TJ, Drake CG. Primer on tumor immunology and cancer immunotherapy. J Immunother Cancer. 2013;1:12. 4. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411-422. 5. Finn OJ. Cancer immunology. N Engl J Med. 2008;358(25):2704-2715. 6. About Kadcyla. Genentech. http://www.kadcyla.com/hcp/drug-information/ her2-targeted-adc-structure. Accessed July 16, 2014. 7. Adcetris is a CD30 directed therapy. SeattleGenetics. http://adcetris.com/hcp/ mechanism-of-action.php. Accessed July 16, 2014. 8. American Cancer Society. Cancer Immunotherapy. http://www.cancer.org/acs/ groups/cid/documents/webcontent/003013-pdf.pdf. Accessed July 16, 2014. 9. Lippitz BE. Cytokine patterns in patients with cancer: a systematic review. Lancet Oncol. 2013;14(6):e218-e228. 10. Leukine sargramostim. Sanofi-Aventis. http://www.leukine.com/patientinterstitial. Accessed July 16, 2014. 11. Perez-Gracia JL, Labiano S, Rodriguez-Ruiz ME, et al. Orchestrating immune check-point blockade for cancer immunotherapy in combinations. Curr Opin Immunol. 2014;27:89-97.

Another area of active research is the use of adoptive T cell therapy.3 T cells are stimulated outside the body and then, once activated, reinfused into patients. T cells used for this type of therapy can include tumor infiltrating lymphocytes (TILs), which are engineered to express a cancer-specific T cell receptor, and T cells engineered to express a chimeric antigen receptor (CAR). The CAR has both the extracellular portion of an antibody and the T cell receptor signaling machinery. Notably, TILs require high-dose interleukin-2, which comes with significant toxicity. The CAR approach also has potential toxicity, but offers promise, such as for chronic lymphoid leukemia, where the engineered cells stayed at high levels in the blood and bone marrow for 6 months and remission was ongoing at 10 months.19

patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-723. 13. Kyi C, Postow MA. Checkpoint blocking antibodies in cancer immunotherapy. FEBS Lett. 2014;588(2):368-376. 14. Hodi FS, Lee SJ, McDermott DF, et al. Multicenter, randomized phase II trial of GM-CSF (GM) plus ipilimumab (Ipi) versus Ipi alone in metastatic melanoma: E1608. In: 2013 ASCO Annual Meeting; May 31-June 4, 2013; Chicago, IL; Abstract CRA9007. 15. Sznol M, Kluger H, Callahan MK, et al. Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). In: 2014 ASCO Annual Meeting; May 30-June 3, 2014; Chicago, IL. Abstract LBA9003. 16. Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122-133.

THE FUTURE IN IMMUNOTHERAPY

17. Prieto PA, Yang JC, Sherry RM, et al. CTLA-4 blockade with ipilimumab: long-

Cancer immunotherapies such as the monoclonal antibodies rituximab and trastuzumab are now familiar in the clinic. New and emerging treatments that harness the immune system to fight cancer offer options where previous choices were poor until recently, particularly for melanoma. These therapies are being tested in many types of cancer, and they offer hope for durable responses. ■ Kathy Boltz is a medical writer based in Phoenix, Arizona. REFERENCES 1. Raval RR, Sharabi AB, Walker AJ, et al. Tumor immunology and cancer immunotherapy: summary of the 2013 SITC primer. J Immunother Cancer. 2014;2:14.

term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res. 2012;18(7):2039-2047. 18. Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412-7420. 19. Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365(8):725-733.

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www.OncologyNurseAdvisor.com • JULY/AUGUST 2014 • ONCOLOGY NURSE ADVISOR 23

FEATURE | Cancer-related fatigue

CRF relief: Exercise still trumps pharmaceutical interventions Recent studies show the evidence continues to support exercise and holistic measures as the most effective intervention for cancer-related fatigue. BRYANT FURLOW

he pathophysiologic roots of cancerrelated fatigue (CRF) remain poorly understood, but CRF is a pervasive problem, affecting the vast majority of patients with cancer and frequently persisting for months or even years after treatment. CRF is debilitating and can profoundly impact a patient’s quality of life; its severity correlates with depression and prognosis. Yet patients do not always raise concerns about their fatigue with clinicians. Although the evidence base for managing CRF is relatively small, physical exercise and dexamethasone appear to be helpful interventions. Communication with patients about CRF symptoms and treatment options might improve detection and assessment. Cancer-related fatigue is defined as persistent tiredness, weakness, or exhaustion that interferes with a patient’s ability to function physically, emotionally, cognitively, or socially.1,2 Patients report that CRF is both physically debilitating and socially isolating—more so even than pain or nausea.3 “CRF is associated with decreased survival and interferes with employment, enjoyment of life, relationships, and motivation to battle the cancer,” notes Tami Borneman, RN, MSN, CNS, FPCN, of the City of Hope Cancer Center, in Duarte, California.4 Onset of cancer-related fatigue can precede treatment, but clearly becomes more acute in many patients undergoing traditional anticancer therapies; symptoms persist for months or years

24 ONCOLOGY NURSE ADVISOR • JULY/AUGUST 2014 • www.OncologyNurseAdvisor.com

in a third of cancer survivors, studies suggest.1,5 A recent study found that 45% of patients undergoing active anticancer treatment report moderate to severe CRF.5 CRF is also being reported by patients receiving targeted therapies such as sunitinib (Sutent, generic).6 With improving survival times for cancer patients, CRF among patients undergoing treatment and survivors seems unlikely to wane—and might well become even more common in the near future. Despite its impact, however, patients do not always volunteer that they are experiencing CRF, and clinicians do not always ask. For example, documenting fatigue in the patient’s medical record is uncommon.4 As a result, CRF is believed to be underdetected and undertreated.1,4 CRF is typically measured via patient self-report using a scale of 0 to 10 (0 representing no fatigue, and 10 representing severe fatigue), although several formal instruments have been developed and validated (eg, the Brief Fatigue Inventory [BFI] and the Functional Assessment of Cancer Therapy Instrument-Fatigue [FACIT-F] scale).4,7 The National Comprehensive Cancer Network (NCCN) recommends all patients with cancer be assessed for CFR at diagnosis and at each chemotherapy appointment.2 PATHOPHYSIOLOGY Contributing factors include comorbidities, radiation therapy, chemo- and targeted anticancer therapies, surgery, and polypharmacy.4 The underlying pathophysiologic underpinnings of CRF are poorly understood, although various lines of evidence implicate central nervous system neuroendocrine-immune inflammatory processes, including proinflammatory cytokines, and suggest that peripheral (muscular) fatigue does not play as important a role.1,8-11 Cytokine antagonists were recently proposed as a potential pharmacotherapy for CRF.10 Genotype and gene expression research underway includes work on the role of proinflammatory cytokine gene variants in CRF associated with breast cancer.1,10,12 If early findings are confirmed in larger studies, genotyping might allow meaningful stratification of patients by risk for CRF, and identify targets for drug development.10 Meanwhile, however, even though evidence-based guidelines for CRF interventions have been promulgated, there are not yet simple, sure-bet answers to the question of how best to manage CRF.2,3,13-15 More studies have recruited cancer survivors than currently treated cancer patients, and more advanced/palliative treatment patients have been studied, than patients with early stage cancers.

Patient education is important, including communication about the potential fatigue-worsening effects of opiates for pain control and the importance of hydration, nutrition, energy-conservation, and physical activity in maintaining better alertness and energy levels.4 In general, patients with

Patients with mild CRF should be encouraged to engage in physical activity and try other nonpharmaceutical options. mild CRF should be encouraged to engage in physical activity and try other nonpharmaceutical interventions, whereas patients with moderate or severe CRF may require pharmacotherapeutic interventions.4 PHYSICAL ACTIVITY Some evidence shows modest improvements in CRF associated with physical activity regimens, and physical exercise is the only intervention “supported by a body of evidence of sufficient rigor to … be considered for carefully screened patients with cancer experiencing fatigue.”15 The authors of a 2012 meta-analysis of data from 34 randomized controlled clinical studies concluded that physical exercise offers “significant but small” reductions in CRF among patients with breast cancer.16 Adding resistance exercise to aerobic exercise appears to yield larger benefits in patients’ physical and functional quality-of-life scores.16 Recent studies also suggest CRF symptom improvements associated with deep-water aquatic exercise regimens (eg, deep-water running, three times a week) among breast cancer survivors.17,18 Early research has also yielded preliminary support for cognitive-behavioral therapy (CBT), CBT with hypnosis, massage, relaxation training, education and information provision, yoga, and acupuncture.16,19-21 Omega-3 polyunsaturated fatty acid supplements also may decrease inf lammation and fatigue among cancer survivors, leading to calls for additional study of omega-3 PUFA supplements and CRF among breast cancer survivors.22 PHARMACOTHERAPIES In addition to nonpharmaceutical interventions, several investigational pharmacotherapies have been proposed for

www.OncologyNurseAdvisor.com • JULY/AUGUST 2014 • ONCOLOGY NURSE ADVISOR 25

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FEATURE | Cancer-related fatigue CRF. Unfortunately, few of these enjoy clear evidence of benefits. A recent meta-analysis of erythropoietin-stimulating agents, for example, found no overall evidence of improved CRF symptoms.13 As described below, the promise of psychostimulants as an effective treatment for cancer-related fatigue has yet to receive definitive support in recent clinical studies. A 2013 double-blind, randomized, placebo-controlled clinical trial of 84 patients with advanced cancers reported that the anti-inf lammatory corticosteroid dexamethasone offered improved CRF and quality of life compared with placebo.14 The study used the FACIT-F scale, and measured outcomes at days 8 and 15 after initiation of dexamethasone or placebo administration, but not at later points in time.14 “Our data suggest that dexamethasone acts rapidly in relieving CRF,” the authors reported, adding that the effect might reflect the effect of dexamethasone on proinflammatory cytokines rather than mood-related neurotransmitters.14 Methylphenidate is a psychostimulant used to treat attention deficit disorder (ADD).3 Methylphenidate, which increases brain levels of the neurotransmitter dopamine, has been used off-label in the treatment of depression and fatigue.3 Preliminary study suggested it might also alleviate CRF, particularly among patients who are administered opiates for pain management.23 However, given concerns about potential side effects and addictiveness, compelling clinical trial outcomes would be necessary to justify the widespread or routine use of methylphenidate to prevent or treat CRF.1 Disappointingly, recent studies provide little such support for methylphenidate’s widespread use. A 2013 randomized, placebo-controlled clinical trial concluded that neither methylphenidate nor nursing telephone support interventions (either alone or in combination) improve CRF compared with placebo.23 The finding appears to be consistent with the randomized controlled clinical trial evidence as a whole. The authors of a recently published meta-analysis of data from five other randomized controlled clinical trials of methylphenidate for CRF treatment concluded that further confirmation is needed before firm recommendations on their usage and safety can be promulgated.3 Although the meta-analysis suggested that the efficacy of methylphenidate might improve with prolonged treatment durations (P = 0.03), the available clinical trial data provided limited evidence overall that methylphenidate is effective against CRF.3 Modafinil, another psychostimulant, has been studied as a potential pharmacotherapy for docetaxel chemotherapyassociated severe CRF. However, a newly reported phase 3 randomized double-blind, placebo-controlled clinical study of 83 patients, found no statistically significant difference in CRF

The challenge is to identify CRF and quantify its severity, but many patients may not report experiencing the effect. between patients receiving 200 mg/day modafinil and those assigned to receive placebo.24 There is therefore, to date, no evidence that modafinil is an effective intervention against CRF. IN SUMMARY Cancer-related fatigue is a common side effect, and almost half of patients undergoing treatment for cancer will experience moderate to severe CRF. The challenge is to identify CRF and quantify its severity, but many patients may not report experiencing the effect. Furthermore, despite the availability of validated formal tools for measuring CRF, it is typically measured via subjective patient self-report. Evidence on effective management is limited. Physical exercise and nonpharmaceutical interventions are helpful for patients with mild to moderate CRF. For more severe cases, dexamethasone was shown to be more effective than placebo. However, no studies to date support the use of methylphenidate and modafinil, both psychostimulants, as effective agents for managing CRF. ■ Bryant Furlow is a medical journalist based in Albuquerque, New Mexico. REFERENCES 1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Cancerrelated fatigue. Version 1.2014. www.nccn.org/professionals/physician_gls/ pdf/fatigue.pdf. Accessed July 15, 2014. 2. Minton O, Berger A, Barsevick A, et al. Cancer-related fatigue and its impact on functioning. Cancer. 2013;119(suppl 11):2124-2130. doi:10.1002/cncr.28058. 3. Gong S, Sheng P, Jin H, et al. Effects of methylphenidate in patients with cancer-related fatigue: a systematic review and meta-analysis. PLoS One. 2014;9(1):e84391. doi:10.1371/journal.pone.0084391. 4. Borneman T. Assessment and management of cancer-related fatigue. J Hosp Palliat Nurs. 2013;15(2):77-86. doi:10.1097/NJH.0b013e318286dc19. 5. Wang XS, Zhao F, Fisch MJ, et al. Prevalence and characteristics of moderate to severe fatigue: a multicenter study in cancer patients and survivors. Cancer. 2014;120(3):425-432. 6. Cella D, Davis MP, Négrier S, et al. Characterizing fatigue associated with sunitinib and its impact on health-related quality of life in patients with metastatic renal cell carcinoma [published online ahead of print March 13, 2014]. Cancer. 2014;120(12):1871-1880. References continue on page 32

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FEATURE | Cancer-related fatigue 7. Alexander S, Minton O, Stone PC. Evaluation of screening instruments for

17. Cuesta-Vargas AI, Buchan J, Arroyo-Morales M. A multimodal physiother-

cancer-related fatigue syndrome in breast cancer survivors. J Clin Oncol.

apy programme plus deep water running for improving cancer-related

2009;27(8):1197-1201.

fatigue and quality of life in breast cancer survivors. Eur J Cancer Care

8. Bower JE. Cancer-related fatigue: links with inflammation in cancer patients and survivors. Brain Behav Immun. 2007;21(7):863-871. doi:10.1016/j. bbi.2007.03.013.

(Engl). 2014;23(1):15-21. doi:10.1111/ecc.12114. 18. Cantarero-Villanueva I, Fernández-Lao C, Cuesta-Vargas AI, et al. The effectiveness of a deep water aquatic exercise program in cancer-related

9. Dantzer R, Heijnen CJ, Kavelaars A, et al. The neuroimmune basis of fatigue. Trends Neurosci. 2014;37(1):39-46. doi:10.1016/j.tins.2013.10.003. 10. Bower JE, Lamkin DM. Inflammation and cancer-related fatigue: mecha-

fatigue in breast cancer survivors: a randomized controlled trial. Arch Phys Med Rehabil. 2013;94(2):221-230. doi:10.1016/j.apmr.2012.09.008. 19. Molassiotis A, Bardy J, Finnegan-John J, et al. Acupuncture for cancer-

nisms, contributing factors, and treatment implications. Brain Behav Immun.

related fatigue in patients with breast cancer: a pragmatic random-

2013;30(suppl):S48-S57. doi:10.1016/j.bbi.2012.06.011.

ized controlled trial. J Clin Oncol. 2012;30(36):4470-4476. doi:10.1200/

11. Kisiel-Sajewicz K, Siemionow V, Seyidova-Khoshknabi D, et al. Myoelectrical manifestation of fatigue less prominent in patients with cancer related fatigue. PLoS One. 2013;8(12):e83636. 12. Bower JE, Ganz PA, Irwin MR, et al. Cytokine genetic variations and fatigue among patients with breast cancer. J Clin Oncol. 2013;31(13):1656-1661. doi:10.1200/JCO.2012.46.2143. 13. Bohlius J, Tonia T, Nüesch E, et al. Effects of erythropoiesis-stimulating agents on fatigue- and anemia-related symptoms in cancer patients: systematic review and meta-analysis of published and unpublished data [published online ahead of print April 17, 2014]. Br J Cancer. 2014;111(1):33-45. 14. Yennurajalingam S, Frisbee-Hume S, Palmer JL, et al. Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized placebo-controlled trial in patients with advanced cancer. J Clin Oncol. 2013;31(25):3076-3082. doi:10.1200/JCO.2012.44.4661. 15. Mitchell SA, Beck SL, Hood LE, et al. Putting evidence into practice: evidencebased interventions for fatigue during and following cancer and its treatment. Clin J Oncol Nurs. 2007;11(1):99-113. doi:10.118/07.CJON.99-113. 16. Fong DY, Ho JW, Hui BP, et al. Physical activity for cancer survivors: meta-

JCO.2012.41.6222. 20. Montgomery GH, David D, Kangas M, et al. Randomized controlled trial of a cognitive-behavioral therapy plus hypnosis intervention to control fatigue in patients undergoing radiotherapy for breast cancer. J Clin Oncol. 2014;32(6):557-563. doi:10.1200/JCO.2013.49.3437. 21. Kiecolt-Glaser JK, Bennett JM, Andridge R, et al. Yoga’s impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial. J Clin Oncol. 2014;32(10):1040-1049. doi:10.1200/ JCO.2013.51.8860. 22. Alfano CM, Imayama I, Neuhouser ML, et al. Fatigue, inflammation, and ω-3 and ω-6 fatty acid intake among breast cancer survivors. J Clin Oncol. 2012;30(12):1280-1287. doi:10.1200/JCO.2011.36.4109. 23. Bruera E, Yennurajalingam S, Palmer JL, et al. Methylphenidate and/or a nursing telephone intervention for fatigue in patients with advanced cancer: a randomized, placebo-controlled, phase II trial. J Clin Oncol. 2013;31(19):2421-2427. doi:10.1200/JCO.2012.45.3696. 24. Hovey E, de Souza P, Marx G, et al; MOTIF Investigators. Phase III, randomized, double-blind, placebo-controlled study of modafinil for fatigue in

analysis of randomised controlled trials. BMJ. 2012;344:e70. http://www.bmj.

patients treated with docetaxel-based chemotherapy. Support Cancer

com/content/344/bmj.e70. Accessed July 15, 2014.

Care. 2014;22(5):1233-1242. doi:10.1007/s00520-013-2076-0.

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Mechanism of action

• Cycle-phase nonspecific • Binds to DNA forming cross-links, which inhibits DNA replication and transcription • Synergistic antiproliferative activity of oxaliplatin and fluorouracil exhibited in vitro and in vivo Dosage and Administration

• IV administration in combination with 5-fluorouracil (5-FU)/leucovorin every 2 weeks ——Day 1 ■■ 85 mg/m2 + leucovorin (200 mg/m 2) over 120 minutes; followed by 5-FU (400 mg/m2 IV bolus over 2-4 minutes, followed by 600 mg/m2 as a 22-hour continuous infusion) ——Day 2 ■■ Leucovorin (200 mg/m2) over 120 minutes; followed by 5-FU (400 mg/m2 IV bolus over 2-4 minutes, followed by 600 mg/m2 as a 22-hour continuous infusion) • If there are persistent grade 2 neurosensory events that do not resolve ——Adjuvant setting: Reduce oxaliplatin dose to 75 mg/m2 ——Advanced colorectal cancer: Reduce oxaliplatin dose to 65 mg/m2 • After recovery from grade 3/4 GI toxicities (despite prophylactic treatment) or grade 4 neutropenia or grade 3/4 thrombocytopenia. Delay next dose until neutrophils ≥1.5 x 106/L and platelets ≥75 x 109/L ——Adjuvant setting: Reduce oxaliplatin dose to 75 mg/m2

——Advanced colorectal cancer: Reduce oxaliplatin dose to 65 mg/m2 • Patients with severe renal impairment (creatinine clearance <30 mL/min) ——Initial recommended dose is 65 mg/m 2 • Discontinue if grade 3 neurosensory events persist • Never prepare a final dilution with a sodium chloride solution or other chloride-containing solutions • Should only be given in dextrose-containing solutions, incompatible with normal saline • Care should be taken to avoid extravasation of the drug Special Populations

• Pregnant women ——Pregnancy category D ——Oxaliplatin may cause fetal harm when administered to a pregnant woman. • Nursing mothers ——Absolute contraindication ——Decision should be made to discontinue nursing or discontinue the drug • Pediatric patients ——Efficacy not established for patients younger than 18 years • Geriatric patients ——No significant effect of age on the clearance of ultrafilterable platinum has been observed Black Box Warning

• Anaphylactic reactions have been reported

40 ONCOLOGY NURSE ADVISOR • JULY/AUGUST 2014 • www.OncologyNurseAdvisor.com

——May occur within minutes of administration ——Epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms of anaphylaxis Warnings/Precautions

• Oxaliplatin should not be administered to patients with a history of known allergy to oxaliplatin or other platinum compounds • Acute or persistent peripheral neuropathy consistently associated with oxaliplatin treatment ——Acute neuropathy is reversible and symptoms may be exacerbated by cold Adverse Effects

• Most frequent: Abdominal pain with cramps; anemia; anorexia; arthralgia; back pain; chest pain; chills; constipation; cough; dehydration; diarrhea; dizziness; dyspepsia; dyspnea; edema; fatigue; fever; headache disorder; injection site sequelae; insomnia; nausea; neuropathy; neutropenic disorder; palmar-plantar erythrodysesthesia; paresthesia; rhinitis; stomatitis; thrombocytopenic disorder; thromboembolic disorder; upper respiratory infection; vomiting • Less frequent: Allergic reactions; alopecia; anxiety; depression; dysgeusia; dysuria; epistaxis; eye tearing; flatulence; flushing; gastroesophageal reflux; hiccups; hyperglycemia; hyperhidrosis; hypoalbuminemia; hypocalcemia; hypokalemia; hyponatremia; peripheral edema; pharyngitis; pulmonary fibrosis; skin rash • Rare: Acute pancreatitis; anaphylaxis; angioedema; dysarthria; GI obstruction; granulocytopenic disorder; hearing loss; hemolytic uremic syndrome; hypersensitivity drug reactions; hyporeflexia; hypotension; ileus; increased urinary frequency; leukopenia; Lhermitte sign; metabolic acidosis; muscle weakness; optic neuritis; reduced visual acuity; renal disease; severe diarrhea; twitching; vision loss; visual field defect Drug Interactions

• Anticoagulants ——Prolongation of prothrombin time (PT) and international normalized ratio (INR) sometimes associated with hemorrhage reported in patients treated with oxaliplatin/fluorouracil/leucovorin concomitantly with oral anticoagulant therapy • Antibiotic: nalidixic acid • Immunotherapy: live vaccines, immunosuppressives, immunomodulators, and natalizumab (Tysabri)

What to tell your patient

• Oxaliplatin is given as an infusion through a vein (intravenously or IV). • Most people do not experience all of the side effects listed. • Onset and duration of side effects are often predictable. • Side effects are almost always reversible and will go away after treatment. There are many ways to help minimize or prevent side effects. Call your nurse or doctor for medical advice about side effects. • Common side effects: Diarrhea; fatigue; high blood pressure; low blood counts; mouth sores; nausea and possible occasional vomiting; peripheral neuropathy, or tingling, numbness or pain of the hands or feet that is often set off by cold; poor appetite • Peripheral neuropathy is often dose related; therefore, your nurse or doctor will monitor this symptom with you and adjust your dose accordingly. • Less common side effects: Constipation; coughing; fever; generalized pain; headache; temporary abnormal liver function test results • Contact your health care provider immediately, day or night, if you should experience fever of 100.5ºF (38ºC) or higher, or chills (possible signs of infection), or any of the following ——Black or tarry stools, or blood in your stools or urine; diarrhea; extreme fatigue; inability to eat or drink for 24 hours or have signs of dehydration; mouth sores/ skin rash; nausea; severe abdominal pain; vomiting • Before starting this treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.). • Do not receive any kind of immunization or vaccination without your doctor’s approval while taking this medication. • Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. • This drug is classified as pregnancy category D, which means it may be hazardous to the fetus. • For both men and women: Do not conceive a child (get pregnant) while on this medication. Barrier methods of contraception, such as condoms, are recommended. ——You should discuss with your doctor when you may safely become pregnant after therapy. • Do not nurse while on this medication. ■ Originally published in May/June 2011; updated by Joyce Pagán.

www.OncologyNurseAdvisor.com • JULY/AUGUST 2014 • ONCOLOGY NURSE ADVISOR 41

©THINKSTOCK

RADIATION & YOUR PATIENT

A review of radiotherapyinduced hypopituitarism Bryant Furlow Radiotherapy is integral to the treatment of pediatric and adult brain, endocrine, and nasopharyngeal tumors, but can induce late endocrine system effects such as hypopituitarism, with potentially profound implications for survivors’ growth, sleep cycle, sexual functioning, osteoporosis risk, and quality of life. Nurses play key roles in assessing and educating patients, and devising and communicating long-term posttreatment patient care and surveillance plans. This column reviews the risks, detection, and management of radiotherapy-induced hypopituitarism.

ith new anticancer treatments, such as checkpointblockade immunotherapies, novel patterns of late neuroendocrine system dysfunctions, known as

endocrinopathies, are emerging among patients with cancer.1 Longstanding patterns of radiation-induced hypopituitarism (RIH) and other endocrinopathies among survivors who have undergone radiotherapy for brain and nasopharyngeal (head-and-neck) tumors might also change with better dose-targeting modalities like intensitymodulated radiotherapy (IMRT) and radiosurgery, which spare healthy tissues.2-7 However, even with IMRT, endocrine organs will still sometimes be exposed to radiation fields. “IMRT for tumors away from the H-P axis is not expected to result in pituitary dysfunction, as the H-P axis will be spared from irradiation,” explains Ken H. Darzy, MD, FRCP, MBChB, of Queen Elizabeth II Hospital in Welwyn Garden City, Hertfordshire, United Kingdom. “However, with nearby tumors it may not be possible to spare the H-P axis completely and a degree of pituitary dysfunction may be expected.” RIH will also continue to be a risk faced by patients treated for pediatric and adult endocrine system neoplasms, such as pituitary adenomas, or prophylactic whole-body or wholebrain irradiation.3,8-10 One recent study found that gamma knife stereotactic radiosurgery for pituitary adenomas yielded superior radiation sparing of hypothalamus tissue compared with IMRT and Linac-based 3D-conformal radiotherapy (CRT), with resulting lower rates of early RIH; 12.5% of patients who underwent radiosurgery experienced one or more hormone deficits after irradiation, compared with 72% of patients who underwent CRT and 50% of patients who received IMRT.7 (A previous study found a long-term new hypopituitarism rate of 30% among patients

42 ONCOLOGY NURSE ADVISOR • JULY/AUGUST 2014 • www.OncologyNurseAdvisor.com

undergoing stereotactic radiosurgery for pituitary adenomas, after a followup period of up to 150 months.11) Sparing hypothalamus tissue from irradiation was once thought to reduce RIH risk but that no longer appears to be the case.3 Nevertheless, the irradiation of neuroendocrine organs is commonly not considered in radiotherapy planning, and nasopharyngeal cancer treatment guidelines do not specify hypopituitarism as a long-term adverse event following radiotherapy.2 Oncology nurses should be familiar with RIH. Nurses are often responsible for creating late effects treatment summaries, and care and surveillance plans, and communicating risks and plans to patients and pediatric patients’ caregivers or guardians.12 Because of the occurrence of secondary cancers among adult survivors of childhood cancers, oncology nurses are likely to encounter patients in oncology settings who have RIH stemming from treatment during childhood or adolescence. With longer

RIH effects are more pronounced among people treated as children and adolescents than during adulthood. survival times among patients treated for cancer, and a consequently increasing prevalence of patients with late endocrinopathies, nurses and cancer center managers have identified a need to improve nurses’ expertise in endocrine late effects of cancer treatment.13

Hormones affected by RIH include growth hormone, gonadotropin, ACTH, prolactin, and TSH. RIH is irreversible and progressive, causing impaired production of key hormones and resulting in growth disruption, circadian and sleep disturbances, sexual side effects, elevated risk of osteoporosis and obesity, and reduced quality of life.3 Onset can occur soon after radiotherapy ends or years later. The pituitary gland secretes several hormones, which interact in sometimes complex ways with other endocrine glands, such as the adrenal and thyroid glands, and the ovaries and testicles. RIH-associated pituitary hormone deficiencies can cause downstream target organ deficiencies in the secretion of cortisol, thyroxine, estrogen, and testosterone, with numerous resulting signs and symptoms (See Signs, symptoms, and associations of hypopituitarism). Generally, RIH effects are more pronounced among people treated as children and adolescents than during adulthood; for example, RIH-associated growth hormone deficits can impair a child’s eventual adult height or stature. Up to 41% of all survivors of childhood cancers, and nearly all children who received radiation doses greater than 30 Gy, experience endocrinopathies, of which RIH-associated growth hormone deficiency is the most common form.2 The risk of RIH appears to climb during the decade following irradiation of endocrine organs, making long-term

surveillance important in timely diagnosis and clinical intervention.2,3 Overall, a recent meta-analysis of data from 18 studies concluded that RIH occurs to some degree in 66% of adult patients whose hypothalamus or pituitary glands were included in cranial radiotherapy fields for nonpituitary (brain or nasopharyngeal) tumors; growth hormone deficiency prevalence was 45%.4 “The onset and severity of radiationinduced hypopituitarism primarily depends on the total radiation dose, the fraction size, and the time allowed between fractions for tissue repair (ie, duration of the radiation schedule),” notes Darzy.9 Larger radiation dose fractions “inflict more damage on the H-P axis than do schedules administered over a long duration” with smaller fraction doses. Generally, radiation doses less than 40 Gy are associated with isolated RIH-associated deficiencies in growth hormone or gonadotropin (the second most common manifestation of RIH).3 Intensive radiotherapy doses exceeding 50 to 60 Gy can cause deficiencies in multiple other hormones as well, including adrenocorticotropic hormone (ACTH), in up to 60% of patients at 10 years postradiation.3,9 ACTH deficiencies can trigger hypoadrenalism and cortisol deficiency, which can cause fatigue, muscle weakness, nausea, dizziness, weight loss, and hypoglycemia.12 In prepubertal children, and particularly girls, even radiation doses less than 25 Gy can increase the risk of precocious puberty.2 Prolactin and TSH hormone levels can be assessed using blood tests, as indicated by signs and symptoms of RIH, and treated with dopamine agonists such as cabergoline and L-thyroxine replacement therapy, respectively.2 Gonadotropin dysfunction is inferred by low serum

Signs, symptoms, and associations of hypopituitarism The healthy anterior pituitary gland secretes several hormones: • Growth hormone (GH) • Adrenocorticotropic hormone (ACTH) • Thyrotropin (TSH) • Luteinizing hormone (LH) • Follicle-stimulating hormone (FSH) • Prolactin • Gonadotropin Depending on which of these are affected by radiotherapy-induced pituitary dysfunction, symptoms can vary. Onset of symptoms can be gradual. Symptoms are nonspecific and may be subclinical, and go undiagnosed for several years. Symptoms include: • Fatigue • Weight changes (weight loss or increased fat mass and reduced lean body mass) • Decreased appetite • Decreased sex drive and sexual function • Infertility • Changes in menstrual cycles or lactation in breastfeeding women • Hot flashes • Hair loss • Sensitivity to cold • Difficulty staying warm • Sleep disturbances • Cardiovascular disease • Impaired skeletal growth (height or stature) during childhood and adolescence SOURCES Darzy KH. Radiation-induced hypopituitarism. Curr Opin Endocrinol Diabetes Obes. 2013;20(4):342-353; Hypopituitarism: symptoms. Mayo Clinic Web site. http:// www.mayoclinic.org/diseases-conditions/hypopituitarism/ basics/symptoms/con-20019292. Accessed July 17, 2014.

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RADIATION & YOUR PATIENT testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in males, and low FSH, LH, and estradiol in women on menstrual cycle day 2, or simply low FSH and LH among postmenopausal women.2 In children, growth hormone-releasing hormone analog therapy can correct gonadotropin deficiencies.2 SURVEILLANCE AND FOLLOW-UP

The hormones affected by RIH include growth hormone, and less frequently, gonadotropin, ACTH, prolactin, and thyroid-stimulating hormone

A normal ITT result 10 years after radiation exposure usually eliminates the need for further annual testing. (TSH).2 Because the risk and severity of radiation-induced endocrinopathies increase over time after radiotherapy, posttreatment plans should include long-term monitoring for hypopituitarism for children and adolescents, to ensure timely detection and intervention with hormone replacement therapies.3,9 For adult cancer survivors, testing is undertaken only if signs and symptoms of endocrinopathy emerge. The Insulin Tolerance Test (ITT) is considered a gold standard for identifying RIH growth hormone deficiency.3 “A failed response to the ITT in cranially-irradiated patients is accepted as diagnostic of GH deficiency without the need to resort to further tests,” he notes.9 (Arginine-stimulating testing [AST] is not as sensitive for detecting RIH as ITT.9) Typically, growth

hormone therapy is deemed indicated if peak growth hormone response to ITT is 7 μg/L or less for a child, or 3 μg/L or less for an adult.9 A child’s rate of growth in stature is also a sensitive measure of growth hormone status, Darzy notes. “In the absence of other etiologies for growth retardation, the presence of significant growth deviation over a 1-year period (ie, growth velocity below the 25th percentile) … is highly suggestive of clinical growth hormone deficiency.”9 Because growth hormone replacement therapy may not be safe for 1 to 3 years after cancer treatment (the peakrisk period for recurrence, during which time it could facilitate growth of uneradicated tumors), testing usually should not begin within the first year after treatment.9 Thereafter, if growth rate is appropriate for a patient’s pubertal status, Darzy advises that subsequent growth be closely monitored and growth hormone response to ITT be tested annually.9 A normal ITT result 10 years after radiation exposure “usually eliminates the need for further annual testing,” Darzy reports.9 ■

4. Appelman-Dijkstra NM, Kokshoorn NE, Dekkers

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

10. Erridge SC, Conkey DS, Stockton D, et al.

OM, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(8):2330-2340. doi:10.1210/ jc.2011-0306. 5. Bernát L, Hrušák D. Hypothyroidism after radiotherapy of head and neck cancer. J Craniomaxillofac Surg. 2014;42(4):356-361. doi:10.1016/j.jcms.2013.09.009. 6. Lin Z, Wang X, Xie W, et al. Evaluation of clinical hypothyroidism risk due to irradiation of thyroid and pituitary glands in radiotherapy of nasopharyngeal cancer patients. J Med Imaging Radiat Oncol. 2013;57(6):713-718. doi:10.1111/1754-9485.12074. 7. Elson A, Bovi J, Kuar K, et al. Effect of treatment modality on the hypothalamic-pituitary function of patients treated with radiation therapy for pituitary adenomas: hypothalamic dose and endocrine outcomes. Front Oncol. 2014;4:73. doi:10.3389/fonc.2014.00073. 8. Gapstur R, Gross CR, Ness K. Factors associated with sleep-wake disturbances in child and adult survivors of pediatric brain tumors: a review. Oncol Nurs Forum. 2009;36(6):723-731. doi:10.1188/09.ONF.723-731. 9. Darzy KH. Radiation-induced hypopituitarism after cancer therapy: who, how and when to test. Nature Clin Pract Endocrinol Metabol. 2009;5(2):88-99. doi:10.1038/ncpendmet1051. Radiotherapy for pituitary adenomas: longterm efficacy and toxicity. Radiother Oncol.

REFERENCES 1. Furlow B. Autoimmune endocrinopathies:

2009;93(3):597-601. 11. Xu Z, Lee Vance M, Schlesinger D, Sheehan

clinician and patient awareness, com-

JP. Hypopituitarism after stereotactic

munication are key. CancerTherapy Advisor.

radiosurgery for pituitary adenomas.

http://www.cancertherapyadvisor.com/

Neurosurgery. 2013;72(4):630-637. doi:10.1227/

autoimmune-endocrinopathies-clinicianand-patient-awareness-communication-are-

NEU.0b013e3182846e44. 12. Schultz PN. Hypopituitarism in patients with a

key/article/345709/. Published May 6, 2014.

history of irradiation to the head and neck area:

Accessed July 17, 2014.

diagnoses and implications for nursing. Oncol

2. Sathyapalan T, Dixit S. Radiotherapy-induced hypopituitarism: a review. Expert Rev Anticancer Ther. 2012;12(5):669-683. doi:10.1586/era.12.27. 3. Darzy KH. Radiation-induced hypopituitarism.

Nurs Forum. 1989;16(6):823-826. 13. Warnock C, Siddall J, Freeman J, Greenfield D. Emerging nursing roles for late effects care for children and young adults with cancer. Eur J

Curr Opin Endocrinol Diabetes Obes. 2013;20(4):

Oncol Nurs. 2013;17(2):242-249. doi:10.1016/

342-353. doi:10.1097/MED.0b013e3283631820.

j.ejon.2012.07.009.

44 ONCOLOGY NURSE ADVISOR • JULY/AUGUST 2014 • www.OncologyNurseAdvisor.com

COMMUNICATION CHALLENGES

Answering the unanswerable

Ann J. Brady, MSN, RN-BC

On one hand, “What do I do?” was a question about her difficulty breathing. But “What do I do?” was also an existential question.

hat do you do when a patient asks you a question you don’t know how to answer? What strategies do you employ when faced with an uncomfortable reality with a patient?

CASE “What do I do?” Janet reached her hand out to me. She had walked to the bathroom with minor assistance, but when she got back into bed, she was overwhelmed by shortness of breath. The pulse oximeter pinged repeatedly and the pink light flashed in time to it: ping, flash 82%; ping, flash 83%; ping, flash 86%. I silenced the alarm and sat down in the bedside chair. In truth, the same words were going through my head. I had a long-standing relationship with Janet. Her metastatic breast cancer was diagnosed when she was in her early 30s, and she had been fighting it for more than 10 years. Her

oncologist controlled her cancer with chemo and radiation while she refused to let cancer control her life. Janet embodied the word fighter as she trudged through treatment after treatment. She outlived all of the prognostications and now had widespread metastatic disease: bone mets, lung mets, brain mets. I looked down at her as she tried to rest against the pillow. One hand wrapped around the oxygen mask, which she pressed to her face. She was cushnoid from steroids, one eye drooped from brain lesions, and she was bald and no longer wrapped her head in stylish scarves and hats. It came down to this: there was nothing left to do. Up until then her cancer fight was directed toward the next treatment; she embraced them all and somehow had thrived. But her marathon was about to end, and she struggled to accept that there was nothing left to do. “What do I do?” She repeated, searching my eyes as if I had an answer. I knew there were different levels to her question. On one hand, “What do I do?” was a question about her difficulty breathing. But “What do I do?” was also an existential question. The first question was easier so I started there. I gently rubbed her hand. I lowered my voice, slowed the pace of my words, “Breathe Janet, breathe. Let the oxygen go to work.” Then, “Easy breaths. You’re okay.” Her breathing eased and she relaxed. The silenced pulse ox flashed 93%. I stayed for a few more minutes without saying anything more. She was too exhausted for talk but smiled and closed her eyes. I walked out to the nurse’s station. Hailey, her nurse, asked how Janet was doing. I told her what she had asked. “I didn’t know what to say,” I said. Continues on page 46

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COMMUNICATION CHALLENGES

To answer both levels of the question, all I needed to do was stay where I was until she caught up to me.

“Oh,” Hailey said, “You have trouble figuring out what to say, too?” Her surprise surprised me. I told her, “There are plenty of times I don’t know what to say.” I’d known Janet for many years. I’d been a nurse for more years than Hailey; to her that meant I would know what to say. I shrugged. I wished it were that simple. “That makes me feel better,” said Hailey. We laughed then, a nervous agreement in our discomfort. What was interesting was that both of us thought there was a response to Janet’s question. In some ways, the question was rhetorical. There was no response—that was what made it unanswerable. I had offered her comfort, a warm hand, a willingness to stay in spite of the uneasiness of the moment. I walked away from the nurse’s station wondering if I had done enough. I had supported Janet over the years, working with her through treatments and symptom control. I watched her fight her disease long after I would have given up. Other caregivers believed Janet was unrealistic or in denial. But whenever Janet started a new treatment, she always said she knew it was about buying more time. She could clearly articulate the pros and cons and understood her prognosis yet still believed in fighting. Even so she was surprised when the end drew near. DISCUSSION I listened to a TED talk recently given by Sebastian Junger.1 He had been embedded with a company of soldiers in Afghanistan.

JOIN THE CONVERSATION • How would you have answered Janet’s question? • What strategies do you employ when faced with an uncomfortable reality with a patient?

ON THE

WEB

Go to OncologyNurseAdvisor.com/challenges_ question to share how you would have answered Janet’s question and your strategies for handling an uncomfortable reality with a patient.

As part of his presentation, he talked about one of the many times he was shot at. The bullet hit the wall close to his head, and he felt the splinters of wood on his face before he heard the sound of the shot. He explained that a bullet moves faster than the speed of sound, so the sound arrives after the impact. The sequencing meant there was no time to flinch. By the time he realized he’d been shot at, it was past the time to duck. As I thought about Janet, I remembered that TED talk. She lived like Junger and the soldiers he was embedded with. What happened to her body happened before her brain could process it, like a bullet she didn’t hear coming. She had ended up where she knew she would, yet the end came upon her suddenly. The communication challenge with Janet started when I met her. From the beginning, she made it clear that she intended to fight and would not give up. “I may not be able to beat this but no one is going to keep me from trying.” I never pushed her into what sounded like a more realistic approach. Had any of our conversations been misleading? Should I have been surprised by her surprise? The uncomfortable situation made me second-guess myself. Maybe I communicated more by sitting and holding her hand than I ever would have if I tried to pretend we weren’t at the place we were. I wish there had been something else to do. I wish there were another treatment, a trial, or some alternative. But there wasn’t. “What do I do?” To answer both levels of that question, all I needed to do was stay where I was until she caught up to me. And I communicated that by holding her hand and letting her know I was there. That was what I did. ■ Ann Brady is the symptom management care coordinator at the Cancer Center, Huntington Hospital, Pasadena, California. REFERENCE 1. Junger S. Why veterans miss war. TED Ideas worth spreading* Web site. https://www.ted.com/talks/ sebastian_junger_why_veterans_miss_war. Posted May 2014. Accessed June 30, 2014.

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THE ONA INTERVIEW

Integrating nursing care with the nutrition support team

Nurses can perform a nutrition screen to determine risk for nutritional deficiencies and follow up with a referral to a dietitian.

aintaining nutritional status in patients undergoing cancer treatment is one of the more challenging aspects of oncology nursing. The side effects of cancer and treatment such as fatigue, nausea and vomiting, and altered taste, to name a few, can make meeting daily nutritional requirements difficult for patients. Some patients may require parenteral or enteral nutrition support to ensure they receive adequate nutrients in the course of their cancer journey. Oncology Nurse Advisor (ONA) talked to Noreen Luszcz, RD, MBA, CNSC, nutrition program director for Walgreens Infusion Services, about how oncology nurses can work with the infusion services clinicians to ensure patients undergoing cancer treatment are receiving adequate nutrition. Every nutrition patient cared for by Walgreens Infusion Services receives their care from a home nutrition support team, which includes registered dietitians and specially trained infusion nurses and pharmacists. These teams work with a patient’s physicians and nurses to provide nutrition therapy in the patient’s home. ONA: Weight and eating habits are sensitive topics for many people. What would be an optimal approach for nurses to use when talking to patients about their weight or eating habits? LUSZCZ: This topic can be difficult for oncol-

ogy patients as they may struggle with weight loss, food aversions, loss of appetite, and the inability to meet daily nutritional needs. Some

questions nurses can ask to tailor the discussion are: What is your day-to-day routine like? Do you eat regular meals? What have you had to eat and drink today? How about snacks? Are you able to eat throughout the day? Nurses should consider weight and eating habits as part of their overall health assessment of the patient. Best practices for discussing nutritional needs include • Emphasize the importance of nutrition • Provide suggestions for improving nutrition intake • Connect the patient with a registered dietitian for further advice ONA: How are deficits that indicate a need for nutrition therapy identified? LUSZCZ: Caloric deficits are identified by

overall weight loss. Weight loss includes the breakdown of both fat and muscle tissue. The percent of weight loss over time can be categorized on a range from significant to severe and is a key indicator for the need for calories, protein, and vitamins/minerals via oral, enteral, and parenteral routes. Other physical signs that may be attributed to nutrient deficiencies can be observed during the nurse examination such as dry, scaly skin (vitamin A or essential fatty acid deficiency); spoon-shaped nails (iron deficiency); distorted taste (zinc deficiency), and vertical cracks in the lips (B-vitamin deficiency). Nurses can perform a nutrition screen to determine risk for nutritional deficiencies and follow up with a referral to a dietitian for a comprehensive nutrition assessment, if indicated. Oncology patients

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THE ONA INTERVIEW

The patient should keep a daily food diary for the nurse and dietitian to review, and the nurse should pay careful attention to the patient's physical appearance.

who cannot eat, will not eat, or cannot eat enough over an extended period of time, in conjunction with significant weight loss, may be candidates for nutritional support. ONA: How does obesity impact nutritional assessment? LUSZCZ: People with cancer, at any size, are

at risk of malnourishment. A comprehensive assessment by a dietitian is best to determine nutritional needs. For example, the patient may not be consuming enough protein; therefore, even obese patients should undergo a comprehensive assessment by a dietitian. ONA: How should a nurse prepare the patient with cancer for managing home nutrition therapy? LUSZCZ: An oncology nurse can typically

advise patients on what to expect during their home nutrition support therapy and answer questions the patient may have; but after that, the nurse can call in the home infusion experts to handle most of the details. Home infusion nurses who are part of the patient’s home nutrition support team can conduct many activities that prepare and train the patient for home nutrition support. ONA: What patient concerns and frequently asked questions should nurses be prepared to answer when discussing home nutrition support for patients with cancer? LUSZCZ: The following are examples of

frequently asked nutrition support questions. • What type of side effects may I encounter with enteral or parenteral nutrition? • How long will I need to be on nutrition support? • Who can I call if I have questions, especially at odd hours? • When should I call my physician? If the patient’s oncology nurse does not have the answers to these questions, the patient can be referred to the home nutrition support team members for help, advice, and education about their home nutrition support therapy process.

ONA: For how long would a patient continue home nutrition support therapy? LUSZCZ: The duration of home nutrition

support therapy can vary depending on the patient’s overall condition, disease state, degree of malnutrition, comorbidities etc. A person may be on short-term nutrition support (up to 6 months) or long-term nutrition support (6 months to lifelong) if they are unable to maintain their nutritional needs by oral route alone. ONA: What are the indicators that a patient no longer needs to continue home nutrition support therapy? LUSZCZ: If a patient reaches a goal weight,

has a healthy BMI, is able to tolerate oral intake, and laboratory test results are in order and energy restored, the patient is probably a good candidate to be weaned off nutrition support. During the weaning process, which can take 1 to 3 weeks, the patient will be monitored for weight changes, increases in oral intake, tolerance of oral intake, and the patient’s overall condition is assessed. ONA: How is the patient’s return to eating solid food managed when home nutrition support therapy is no longer needed? LUSZCZ: Patients may be eating limited

amounts of oral food and drinking fluids while receiving nutrition support. During the transition off nutrition support, the patient gradually increases oral intake while decreasing the nutrition support formula. A registered dietitian should be involved to guide the process and assess the patient’s progress. The weaning process can take only a few days if treatment is not severe, if there are no side effects, and the patient is able to tolerate solid foods. However, a slower pace is better, so patients should be encouraged not to rush the weaning process. The patient should keep a daily food diary for the nurse and/or dietitian to review, and the nurse should pay careful attention to the patient’s physical appearance. To read the ONA Interview with Noreen Luszcz in its entirety, go to www.OncologyNurseAdvisor. com/ONAinterview-Luszcz. ■

48 ONCOLOGY NURSE ADVISOR • JULY/AUGUST 2014 • www.OncologyNurseAdvisor.com

THE TOTAL PATIENT

A novel way to get patients to eat their fruits and vegetables: Have them grow their own! Bette Weinstein Kaplan

here are times when a handson approach can provide the best results. For example, we know that a diet rich in fruits and vegetables is beneficial in preventing and fighting cancer. Similarly, the health benefits of exercise are indisputable. However, getting survivors and patients with cancer to take advantage of these well-known facts can often prove to be difficult. For Wendy Demark-Wahnefried, PhD, RD, the answer was simple: use the hands-on approach to encourage patients and survivors to start their own vegetable gardens and provide help for them along the way.

HARVEST FOR HEALTH Demark-Wahnefried and her group call their program Harvest for Health.1 The associate director for cancer prevention and control in the Comprehensive Cancer Center at the University of Alabama at Birmingham (UAB), Demark-Wahnefried is also a professor in the University of Alabama at Birmingham Department of Nutrition Sciences and a registered dietitian. The Harvest for Health program has several goals. Based on prior studies, the developers of Harvest for Health hypothesized that a gardening intervention would improve a patient’s physical activity, quality of life, and physical functioning. The group also

theorized that the process of growing fruits and vegetables would increase the patient’s consumption of these foods. Prior studies documented that community-based gardening programs can lead to the participants having increased physical activity and functioning, a healthier diet, and improvements in psychosocial well-being and health-related quality of life.2,3

After 1 year, 40% of patients increased fruit and vegetable consumption by at least one serving a day. Fresh air, exercise, and the joy of growing what you eat—how could that not make someone feel better? In order to evaluate just how much better, the Harvest for Health team designed a pilot study of a 1-year gardening intervention in 2011. The study was a community-based partnership between UAB and the Alabama Cooperative Extension System. There were eight adults (mean age 56 years) and four children (mean age 10 years) enrolled, with an even distribution of males and

females. Their cancers were breast, prostate, or any childhood cancer. Although the children were still being treated, the adults had undergone treatment 2 years earlier. All had permission from their oncologists to take part in the project. The primary caregivers of the children also participated.1 MASTER GARDENERS For this study, the research team recruited Master Gardeners from the Master Gardener Program. This nationwide program is offered by the National Institute of Food and Agriculture, and is available through each state’s Cooperative Extension System. The program recruits and trains volunteers to educate the public about landscaping and gardening. In order to be certified as a Master Gardener, an applicant volunteers for at least 60 hours of instruction and community service, often with an annual follow-up. DemarkWahnefried’s group easily recruited Master Gardeners from nearby localities to work with the patients in 12 one-on-one teams. Each patient and Master Gardener worked together to plan, plant, maintain, and harvest three gardens at the homes of the patients. A MAJOR SUCCESS The research team completed physical and psychological assessments of the Continues on page 51

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FROM

Bridging cancer care for the older adult patient Sarah Kelly, LSCW

An important aspect of care is to work with older adults to assess strengths and provide feedback regarding self-care.

lder adults are the fastestgrowing population segment in the United States, with their numbers expected to double by 2030. It is projected that this growth will result in a 45% increase in the number of people diagnosed with cancer. In order to provide the best outcomes for this population, we must acknowledge and address the unique challenges older adult patients and caregivers face in the cancer experience. A cancer diagnosis at any age can bring on feelings of anxiety, uncertainty, and depression. These feelings may be compounded in adults already grappling with psychological and social issues related to aging and becoming more dependent on others. In addition to these concerns, older adults facing cancer may also be managing comorbid health issues and age-related cognitive challenges.

oss is another factor. This can refer to the loss of independence and loss of health, physical and psychosocial. In addition, patients and caregivers may be coping with stress related to physical aspects of diagnosis and treatment, lack of support, spiritual concerns, lack of resources, and financial concerns. Many older patients and caregivers struggle to adjust to these changes, which affect identity and meaning. As oncology health professionals, we are in the unique position to provide care and support. The Institute of Medicine’s comprehensive 2013 report, Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis, addresses the rapidly changing landscape

of cancer care and provides recommendations to meet the needs of the older adult-patient population.1 The report highlights what many oncology health professionals experience as we work with older adults to navigate their care.

he older adult patient has a rich history and a wealth of knowledge and experience, as well as numerous strengths that can assist them in coping with a cancer diagnosis. As oncology health professionals, we must communicate respect, acceptance, and selfdetermination. An important aspect of care is to work with older adults to assess strengths and provide feedback regarding self-care. Through assessment, the older adult patient’s skill areas, learning style, and individual needs can be evaluated. The patient’s knowledge and skill set can be a huge strength in helping them as they navigate diagnosis and treatment. Today, older adults find themselves in an increasingly complex consumer-centric medical system, where they are expected to take an active role in managing their care and may be ill-equipped to do so. Many caregivers are also older adults and are navigating not only their loved one’s care, but also their own age-related health issues. Establishing an environment that is patient-centered and supportive is integral in laying the groundwork for effective care. An open, direct conversation with the older adult patient about patient-centered care and how health care has evolved is vital. Access to medical information through technology has expanded, providing patients with myriad resources that, while helpful, may be

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confusing.2 Overwhelmed, they may refrain from asking key questions about their care or feel unsure about where to access important (and accurate) health information. It is important to encourage and assist older adult patients to become self-advocates in this capacity. Clear communication, health literacy, and plain language can greatly improve adherence to treatment and health outcomes. Plain language is communication that patients can understand the first time they read or hear it. Key elements of plain language include organizing information so that the most important points come first, breaking complex information into understandable chunks, using simple language, and defining technical terms.3 Assessing the patient

The Total Patient Continued from page 49

participants at baseline, 6 months, and 1 year. After 1 year, 60% of the participants increased their physical activity by more than 30 minutes per week, while 40% increased their fruit and vegetable consumption by at least one serving a day. On study completion the participants exhibited more strength, especially in their hands. They also showed better mobility and were able to get up and down more easily. The feedback from patients and Master Gardeners alike was extremely positive. Many of the cancer survivors said that gardening encouraged them to eat a healthier diet, especially more vegetables. They all planned to continue gardening, and one participant enrolled in the Master Gardener program so that she could help other cancer survivors, as she was helped. The Master Gardeners who

and utilizing effective communication tools can make a huge difference in care.

n essential part of healthy aging is fostering independence. Aging brings many changes that can include loss of independence due to physical, cognitive, and social changes. These changes can also be brought on by a cancer diagnosis. Oncology health professionals can play a vital role by working with patients’ and caregivers’ strengths, providing them with clear health information and encouraging them to participate in their care. ■

REFERENCES 1. Levit LA, Balogh EP, Nass SJ, Ganz PA, eds. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis. Washington DC: The National Academies Press; 2013. http://www. iom.edu/Reports/2013/Delivering-High-QualityCancer-Care-Charting-a-New-Course-for-aSystem-in-Crisis.aspx. Accessed July 9, 2014. 2. Centers for Disease Control and Prevention. Improving Health Literacy of Older Adults. Atlanta, GA: US Department of Health and Human Services; 2009. http://www.cdc.gov/health literacy/pdf/olderadults.pdf. Accessed July 9, 2014. 3. American Psychological Association. What Practitioners Should Know About Working With Older Adults. Washington DC: American Psychological Association; 1998. http://www.

Sarah Kelly is coordinator for Older Adult Services at CancerCare.

worked on the study were extremely enthusiastic. The study is ongoing, and has expanded to other counties in Alabama that surround Birmingham. Harvest for Health now receives support from the National Cancer Institute. The University of Alabama at Birmingham provides garden tools and seedlings, and will prepare a 4x8-foot raised bed in the yard of a participant’s home or provide large gardening containers on wheels for a porch or patio. Master Gardeners now visit with the survivors monthly for 1 year, offering advice and answering the questions that new gardeners have. According to one Master Gardener: “It was both educational for me and challenging to share the experiences of another individual with a totally different background and life. It was refreshing to see how something as simple as regular communication and support could make a radical difference in attitude and approach to life.”1

apa.org/pi/aging/resources/guides/ practitioners.pdf. Accessed July 9, 2014.

The authors hope that Harvest for Health will become a national program, and conclude: “A mentored gardening intervention among cancer survivors represents a novel and holistic strategy to improve physical function, fruit and vegetable consumption, and physical activity in cancer survivors.”1 ■ Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey. REFERENCES 1. Blair CK, Madan-Swain A, Locher JL, et al. Harvest for health gardening intervention feasibility study in cancer survivors. Acta Oncol. 2013;52(6):1110-1118. 2. Brown VM, Allen AC, Dwozan M, et al. Indoor gardening older adults: effects on socialization, activities of daily living, and loneliness. J Gerontol Nurs. 2004;30(10):34-42. 3. Tse MM. Therapeutic effects of an indoor gardening programme for older people living in nursing homes. J Clin Nurs. 2010;19(7-8):949-958.

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ASK A PHARMACIST

Not all grapefruits have the same effect on drug metabolism We hear a lot about the effect of grapefruit on many medications because the furanocoumarins in grapefruits block the enzyme that breaks down the medication in the body, so one serving of grapefruit can make it seem like a person is taking multiple doses of the drug. Does this mean that eating grapefruit can allow you to take lower doses of the drug?

Grapefruit products (and some other citrus products) contain chemicals called furanocoumarins that inhibit activity of cytochrome (CYP) 3A4, an enzyme responsible for the breakdown of many medications (Can citrus juices interfere with drug metabolism? [Ask A Pharmacist]. Oncol Nurs

Advis. 2011;2[4]:48; Consuming regular orange juice during drug therapy. [Ask A Pharmacist]. Oncol Nurs Advis. 2013;4[2]:51). Inhibiting CYP3A4 can increase the levels of drugs that are metabolized by CYP3A4. However, different medications are metabolized by CYP3A4 to a different extent. A drug that is metabolized extensively by CYP3A4 will have a substantial increase in serum concentrations, whereas a drug that is only a minor metabolite of CYP3A4 will have a much smaller, if any, increase in serum concentration. It is also important to note that not all grapefruit products contain the same type or amount of furanocoumarins. There are multiple furanocoumarins present in various strains of grapefruit; each of these inhibit CYP3A4 to a different degree. Furanocoumarin content varies based on the specific strain of grapefruit, storage conditions, growing conditions, and the timing of harvest, and may also be altered by processing techniques used to prepare grapefruit products.1 Because of the lack of standardization in furanocoumarin content, administering a drug with grapefruit juice would not result in consistent serum concentrations. This may increase the patient’s risk of toxicity or reduce effectiveness (for example, if a patient consumes grapefruit products that contain fewer active furanocoumarins they would not achieve the target concentrations). This principle is also true for many other drug-food interactions in oncology,

such as with the tyrosine kinase inhibitor lapatinib (Tykerb). Serum concentrations of lapatinib are increased when it is taken with a high-fat meal. Unfortunately, these increases are not consistent. A study evaluating this interaction found that taking lapatinib with a high-fat meal increased lapatinib exposure anywhere from 1.7fold to up to 23.55-fold.2 Because there were substantial variations in drug exposure, even when patients were given the same meal, lapatinib should not be taken with food due to the risk of increased toxicity or reduced efficacy. Consistent serum concentrations are important with chemotherapy medications, as many of these have a narrow window between lack of efficacy (concentrations too low) and elevated toxicity (concentrations too high). Attempting to administer a lower dose due to these drug-food interactions may likely result in a patient having too much or too little drug exposure. Thus, it is important to follow a medication’s food recommendations and to advise patients taking these drugs about any potential drug-food or drug-drug interactions. ■ REFERENCES 1. Hanley MJ, Cancalon P, Widmer WW, Greenblatt DJ. The effect of grapefruit juice on drug disposition. Expert Opin Drug Metab Toxicol. 2011;7(3):267-286. 2. Koch KM, Reddy NJ, Cohen RB, et al. Effects of food on the relative bioavailability of lapatinib in cancer patients. J Clin Oncol. 2009;27(8):1191-1196.

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

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