JUNE 2012, VOl 5, NO 5

JUNE 2012

www.TheOncologyNurse.com

VOL 5, NO 5

OVARIAN CANCER

CANCER CENTER PROFILE

Screening for Ovarian Cancer

University of Arizona Cancer Center Passing on the Passion of Oncology Nursing

By D. “Jeff” Nordquist, RN, MS, CS, FNP, Nurse Practitioner Karin Goodman, RN, CNP, Adult Nurse Practitioner Mayo Clinic, Rochester, Minnesota

O

varian cancer is said to “whisper,” because the symptoms are seldom obvious. The most frequent symptoms seen in women diagnosed with ovarian cancer are abdominal bloating, pelvic or abdominal pain, difficulty eating/feeling full fast, or urinary symptoms.

These are often passed off as nothing other than symptoms of getting older,

Deanna Sigl, RN, BSN, MSN-Ed, OCN, an oncology nurse at the University of Arizona Cancer Center, Orange Grove Campus, confers with a patient.

Photo courtesy the University of Arizona Cancer Center.

he University of Arizona Cancer Center, located in Tucson, was founded in 1976 as a division of the University of Arizona’s College of Medicine. In 1990, the University of Arizona Cancer Center was designated as a Comprehensive Cancer Center by the National Cancer Institute (NCI). As such, the center is not only focused on patient care, but also conducts translational and clinical research into the development and delivery of therapies to reduce the morbidity and morphology of cancer. It is only 1 of 2 comprehensive cancer centers in the 5-state region of Arizona, Colorado, Nevada, New Mexico, and Utah.

With the mission of preventing and curing cancer, the University of Arizona Cancer Center carries out its research across several programs,

T

Continued on page 31

gaining weight, or related to menopause.

However, this whispering disease is the most lethal of all the breast and gynecologic cancers and accounts for more deaths than any other cancer of the female reproductive system.1 The American Cancer Society estimates that about 22,280 women will be Continued on page 16

PERSONALIZED MEDICINE IN ONCOLOGY

Personalizing Lung Cancer Care: A Nursing Perspective

By Tara L. Rich, MSN, RN, CNP Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio

I

n catching up with breast cancer and several hematologic malignancies, non–small cell lung cancer (NSCLC) has made recent advances in targeting genomic mutations that will provide us with the ability to offer more targeted treatment options. Researchers at Massachusetts General Hospital Cancer

Center have developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes.1 In this study, the SNaPshot assay identified 51% of tumors as having at least 1 mutation, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%), and translocations Continued on page 30

NEWS BRIEFS

Mastectomy Risk Twice as High With Brachytherapy

By Alice Goodman

B

rachytherapy after lumpectomy is associated with greater morbidity and need for mastectomy compared with whole-breast radiation, according to a large retrospective study of Medicare claims for older women with early invasive breast cancer (JAMA. 2012;307:1827-1837). Five years after treatment, the rate of mastectomy was twice as high in women

INSIDE Faces at the ONs 37th aNNual cONgress . . . . . . . . . . . .

A View From the Floor

treated with brachytherapy versus whole-breast radiation. Both short- and long-term complications were significantly greater in women treated with brachytherapy in this review. The rate of 5-year overall survival was the same in both groups (ie, brachytherapy and whole-breast radiation): 87%.

Brachytherapy is becoming increas-

cOmplimeNtary ce

..........

14 20

Considerations in Lymphoma—Ask the Experts: Mantle Cell Lymphoma the patieNt’s VOice

.........

28

Let the Truth Be Told About Pain!

Continued on page 8 ©2012 Green Hill Healthcare Communications, LLC

geNetic cOuNseliNg

.......

Lobular Breast Cancer and “Abdominal Cancer” cONFereNce News: ascO 2012 aNNual meetiNg . . . . . . .

Abstracts of Interest NutritiON with KareN

Amazing Asparagus

.....

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40 42

The median age of patients treated in the VISTAยง trial was 71 years (range: 48-91).

NOW APPROVED FOR SUBCUTANEOUS ADMINISTRATION*

Survival never gets old VELCADE® (bortezomib) delivered >13-month overall survival advantage in combination with MP† vs MP alone for previously untreated multiple myeloma (median 56.4 vs 43.1 months‡; 60.1-month median follow-up§)

VELCADE (bortezomib) Indication and Important Safety Information INDICATION

▼

CONTRAINDICATIONS

▼

ADVERSE REACTIONS WARNINGS, PRECAUTIONS AND DRUG INTERACTIONS ▼

▼

▼ ▼ ▼

▼ ▼

Living Proof

Brief Summary INDICATIONS: VELCADE® (bortezomib) for Injection is indicated for the treatment of patients with multiple myeloma.

VELCADE is indicated for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy.

CONTRAINDICATIONS: VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol.

VELCADE is contraindicated for intrathecal administration.

WARNINGS AND PRECAUTIONS: VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. Complete blood counts (CBC) should be monitored frequently during treatment with VELCADE. Peripheral Neuropathy: VELCADE treatment causes a peripheral neuropathy that is predominantly sensory. However, cases of severe sensory and motor peripheral neuropathy have been reported.

Patients with pre-existing symptoms (numbness, pain or a burning feeling in the feet or hands) and/or signs of peripheral neuropathy may experience worsening peripheral neuropathy (including ≥ Grade 3) during treatment with VELCADE. Patients should be monitored for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain or weakness. In the Phase 3 relapsed multiple myeloma trial comparing VELCADE subcutaneous vs. intravenous the incidence of Grade ≥ 2 peripheral neuropathy events was 24% for subcutaneous and 41% for intravenous. Grade ≥ 3 peripheral neuropathy occurred in 6% of patients in the subcutaneous treatment group, compared with 16% in the intravenous treatment group. Starting VELCADE subcutaneously may be considered for patients with pre-existing or at high risk of peripheral neuropathy.

Patients experiencing new or worsening peripheral neuropathy during VELCADE therapy may benefit from a decrease in the dose and/or a less dose-intense schedule. In the single agent phase 3 relapsed multiple myeloma study of VELCADE vs. Dexamethasone following dose adjustments, improvement in or resolution of peripheral neuropathy was reported in 51% of patients with ≥ Grade 2 peripheral neuropathy in the relapsed multiple myeloma study. Improvement in or resolution of peripheral neuropathy was reported in 73% of patients who discontinued due to Grade 2 neuropathy or who had ≥ Grade 3 peripheral neuropathy in the phase 2 multiple myeloma studies. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma.

Hypotension: The incidence of hypotension (postural, orthostatic, and hypotension NOS) was 13%. These events are observed throughout therapy. Caution should be used when treating patients with a history of syncope, patients receiving medications known to be associated with hypotension, and patients who are dehydrated. Management of orthostatic/postural hypotension may include adjustment of antihypertensive medications, hydration, and administration of mineralocorticoids and/or sympathomimetics.

Cardiac Disorders: Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have been reported, including reports in patients with no risk factors for decreased left ventricular ejection fraction. Patients with risk factors for, or existing heart disease should be closely monitored. In the relapsed multiple myeloma study of VELCADE vs. dexamethasone, the incidence of any treatment-emergent cardiac disorder was 15% and 13% in the VELCADE and dexamethasone groups, respectively. The incidence of heart failure events (acute pulmonary edema, cardiac failure, congestive cardiac failure, cardiogenic shock, pulmonary edema) was similar in the VELCADE and dexamethasone groups, 5% and 4%, respectively. There have been isolated cases of QT-interval prolongation in clinical studies; causality has not been established.

Pulmonary Disorders: There have been reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome (ARDS) in patients receiving VELCADE. Some of these events have been fatal. In a clinical trial, the first two patients given high-dose cytarabine (2 g/m2 per day) by continuous infusion with daunorubicin and VELCADE for relapsed acute myelogenous leukemia died of ARDS early in the course of therapy. There have been reports of pulmonary hypertension associated with VELCADE administration in the absence of left heart failure or significant pulmonary disease. In the event of new or worsening cardiopulmonary symptoms, a prompt comprehensive diagnostic evaluation should be conducted.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): There have been reports of RPLS in patients receiving VELCADE. RPLS is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. Brain imaging, preferably MRI (Magnetic Resonance Imaging), is used to confirm the diagnosis. In patients developing RPLS, discontinue VELCADE. The safety of reinitiating VELCADE therapy in patients previously experiencing RPLS is not known.

Gastrointestinal Adverse Events: VELCADE treatment can cause nausea, diarrhea, constipation, and vomiting sometimes requiring use of antiemetic and antidiarrheal medications. Ileus can occur. Fluid and electrolyte replacement should be administered to prevent dehydration.

Thrombocytopenia/Neutropenia: VELCADE is associated with thrombocytopenia and neutropenia that follow a cyclical pattern with nadirs occurring following the last dose of each cycle and typically recovering prior to initiation of the subsequent cycle. The cyclical pattern of platelet and neutrophil decreases and recovery remained consistent over the 8 cycles of twice weekly dosing, and there was no evidence of cumulative thrombocytopenia or neutropenia.

The mean platelet count nadir measured was approximately 40% of baseline. The severity of thrombocytopenia was related to pretreatment platelet count. In the relapsed multiple myeloma study of VELCADE vs. dexamethasone, the incidence of significant bleeding events (≥Grade 3) was similar on both the VELCADE (4%) and dexamethasone (5%) arms. Platelet counts should be monitored prior to each dose of VELCADE. Patients experiencing thrombocytopenia may require change in the dose and schedule of VELCADE. There have been reports of gastrointestinal and intracerebral hemorrhage in association with VELCADE. Transfusions may be considered. The incidence of febrile neutropenia was <1%.

Tumor Lysis Syndrome: Because VELCADE is a cytotoxic agent and can rapidly kill malignant cells, the complications of tumor lysis syndrome may occur. Patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.

Hepatic Events: Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Other reported hepatic events include increases in liver enzymes, hyperbilirubinemia, and hepatitis. Such changes may be reversible upon discontinuation of VELCADE. There is limited re-challenge information in these patients.

Hepatic Impairment: Bortezomib is metabolized by liver enzymes. Bortezomib exposure is increased in patients with moderate or severe hepatic impairment; these patients should be treated with VELCADE at reduced starting doses and closely monitored for toxicities.

Use in Pregnancy: Pregnancy Category D. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE. Bortezomib administered to rabbits during organogenesis at a dose approximately 0.5 times the clinical dose of 1.3 mg/m2 based on body surface area caused post-implantation loss and a decreased number of live fetuses.

ADVERSE EVENT DATA: Safety data from phase 2 and 3 studies of single-agent VELCADE (bortezomib) 1.3 mg/m2/dose administered intravenously twice weekly for 2 weeks followed by a 10-day rest period in 1163 patients with previously treated multiple myeloma (N=1008, not including the phase 3, VELCADE plus DOXIL® [doxorubicin HCI liposome injection] study) and previously treated mantle cell lymphoma (N=155) were integrated and tabulated. In these studies, the safety profile of VELCADE was similar in patients with multiple myeloma and mantle cell lymphoma.

In the integrated analysis, the most commonly reported adverse events were asthenic conditions (including fatigue, malaise, and weakness); (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheral neuropathy NEC (including peripheral sensory neuropathy and peripheral neuropathy aggravated); (39%), thrombocytopenia and appetite decreased (including anorexia); (each 36%), pyrexia (34%), vomiting (33%), anemia (29%), edema (23%), headache, paresthesia and dysesthesia (each 22%), dyspnea (21%), cough and insomnia (each 20%), rash (18%), arthralgia (17%), neutropenia and dizziness (excluding vertigo); (each 17%), pain in limb and abdominal pain (each 15%), bone pain (14%), back pain and hypotension (each 13%), herpes zoster, nasopharyngitis, upper respiratory tract infection, myalgia and pneumonia (each 12%), muscle cramps (11%), and dehydration and anxiety (each 10%).

Twenty percent (20%) of patients experienced at least 1 episode of ≥Grade 4 toxicity, most commonly thrombocytopenia (5%) and neutropenia (3%). A total of 50% of patients experienced serious adverse events (SAEs) during the studies. The most commonly reported SAEs included pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia (each 3%).

In the phase 3 VELCADE + melphalan and prednisone study in previously untreated multiple myeloma, the safety profile of VELCADE administered intravenously in combination with melphalan/prednisone is consistent with the known safety profiles of both VELCADE and melphalan/prednisone. The most commonly reported adverse events in this study (VELCADE+melphalan/prednisone vs melphalan/prednisone) were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%), nausea (48% vs 28%), peripheral neuropathy (47% vs 5%), diarrhea (46% vs 17%), anemia (43% vs 55%), constipation (37% vs 16%), neuralgia (36% vs 1%), leukopenia (33% vs 30%), vomiting (33% vs 16%), pyrexia (29% vs 19%), fatigue (29% vs 26%), lymphopenia (24% vs 17%), anorexia (23% vs 10%), asthenia (21% vs 18%), cough (21% vs 13%), insomnia (20% vs 13%), edema peripheral (20% vs 10%), rash (19% vs 7%), back pain (17% vs 18%), pneumonia (16% vs 11%), dizziness (16% vs 11%), dyspnea (15% vs 13%), headache (14% vs 10%), pain in extremity (14% vs 9%), abdominal pain (14% vs 7%), paresthesia (13% vs 4%), herpes zoster (13% vs 4%), bronchitis (13% vs 8%), hypokalemia (13% vs 7%), hypertension (13% vs 7%), abdominal pain upper (12% vs 9%), hypotension (12% vs 3%), dyspepsia (11% vs 7%), nasopharyngitis (11% vs 8%), bone pain (11% vs 10%), arthralgia (11% vs 15%) and pruritus (10% vs 5%).

In the phase 3 VELCADE subcutaneous vs. intravenous study in relapsed multiple myeloma, safety data were similar between the two treatment groups. The most commonly reported adverse events in this study were peripheral neuropathy NEC (38% vs 53%), anemia (36% vs 35%), thrombocytopenia (35% vs 36%), neutropenia (29% vs 27%), diarrhea (24% vs 36%), neuralgia (24% vs 23%), leukopenia (20% vs 22%), pyrexia (19% vs 16%), nausea (18% vs 19%), asthenia (16% vs 19%), weight decreased (15% vs 3%), constipation (14% vs 15%), back pain (14% vs 11%), fatigue (12% vs 20%), vomiting (12% vs 16%), insomnia (12% vs 11%), herpes zoster (11% vs 9%), decreased appetite (10% vs 9%), hypertension (10% vs 4%), dyspnea (7% vs 12%), pain in extremities (5% vs 11%), abdominal pain and headache (each 3% vs 11%), abdominal pain upper (2% vs 11%). The incidence of serious adverse events was similar for the subcutaneous treatment group (36%) and the intravenous treatment group (35%). The most commonly reported SAEs were pneumonia (6%) and pyrexia (3%) in the subcutaneous treatment group and pneumonia (7%), diarrhea (4%), peripheral sensory neuropathy (3%) and renal failure (3%) in the intravenous treatment group.

DRUG INTERACTIONS: Bortezomib is a substrate of cytochrome P450 enzyme 3A4, 2C19 and 1A2. Co-administration of ketoconazole, a strong CYP3A4 inhibitor, increased the exposure of bortezomib by 35% in 12 patients. Therefore, patients should be closely monitored when given bortezomib in combination with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir). Co-administration of omeprazole, a strong inhibitor of CYP2C19, had no effect on the exposure of bortezomib in 17 patients. Co-administration of rifampin, a strong CYP3A4 inducer, is expected to decrease the exposure of bortezomib by at least 45%. Because the drug interaction study (n=6) was not designed to exert the maximum effect of rifampin on bortezomib PK, decreases greater than 45% may occur. Efficacy may be reduced when VELCADE is used in combination with strong CYP3A4 inducers; therefore, concomitant use of strong CYP3A4 inducers is not recommended in patients receiving VELCADE. St. John’s Wort (Hypericum perforatum) may decrease bortezomib exposure unpredictably and should be avoided. Co-administration of dexamethasone, a weak CYP3A4 inducer, had no effect on the exposure of bortezomib in 7 patients. Co-administration of melphalan-prednisone increased the exposure of bortezomib by 17% in 21 patients.

However, this increase is unlikely to be clinically relevant.

USE IN SPECIFIC POPULATIONS: Nursing Mothers: It is not known whether bortezomib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from VELCADE, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: The safety and effectiveness of VELCADE in children has not been established.

Geriatric Use: No overall differences in safety or effectiveness were observed between patients ≥age 65 and younger patients receiving VELCADE; but greater sensitivity of some older individuals cannot be ruled out.

Patients with Renal Impairment: The pharmacokinetics of VELCADE are not influenced by the degree of renal impairment. Therefore, dosing adjustments of VELCADE are not necessary for patients with renal insufficiency. Since dialysis may reduce VELCADE concentrations, VELCADE should be administered after the dialysis procedure. For information concerning dosing of melphalan in patients with renal impairment, see manufacturer’s prescribing information.

Patients with Hepatic Impairment: The exposure of bortezomib is increased in patients with moderate and severe hepatic impairment. Starting dose should be reduced in those patients.

Patients with Diabetes: During clinical trials, hypoglycemia and hyperglycemia were reported in diabetic patients receiving oral hypoglycemics. Patients on oral antidiabetic agents receiving VELCADE treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetic medication.

Please see full Prescribing Information for VELCADE at VELCADEHCP.com.

VELCADE, MILLENNIUM and are registered trademarks of Millennium Pharmaceuticals, Inc. Other trademarks are property of their respective owners.

Millennium Pharmaceuticals, Inc., Cambridge, MA 02139 Copyright © 2012, Millennium Pharmaceuticals, Inc. All rights reserved.

Printed in USA

V-12-0151

4/12

3:01 PM

Editorial Board EDITOR-IN-CHIEF

Cassandra J. Hammond, RN,

Dolores “Jeff” Nordquist, RN, MS,

Rita Wickham,

MSN, CRNP

CS, FNP

Avid Education Partners, LLC Sharpsburg, MD

Mayo Clinic Rochester, MN

Northern Michigan University Independent Oncology & Palliative Care Consultant Marquette, MI

Elizabeth Bilotti,

Shannon Hazen,

RN, MSN, APRN, BC, OCN

RN, BSN, OCN

Melinda Oberleitner, RN,

Karla Wilson, RN, MSN, FNP-C, CPON

DNS, APRN, CNS

City of Hope National Medical Center Duarte, CA

Beth Faiman, PhD(c), MSN, APRNBC, AOCN Cleveland Clinic Taussig Cancer Institute Cleveland, OH

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Catherine Bishop, DNP, NP, AOCNP

Novant Health Presbyterian Cancer Center Charlotte, NC

Patricia Irouer Hughes, RN, MSN,

College of Nursing and Allied Health Professions University of Louisiana Lafayette, LA

Jayshree Shah, NP

Piedmont Healthcare Rex, GA

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Deena Damsky Dell, MSN, RN-BC,

Taline Khoukaz,

Gary Shelton,

NP, MSN, ACNP-C

AOCN, LNC

University of Southern California Norris Cancer Center & Hospital Los Angeles, CA

MSN, NP, ANP-BC, AOCNP

Sibley Memorial Hospital Johns Hopkins Medicine Washington, DC

Fox Chase Cancer Center Philadelphia, PA

BSN, OCN

PhD, RN, AOCN

Pharmacy John F. Aforismo, BSc Pharm, RPh, FASCP RJ Health Systems International, LLC Wethersfield, CT

Nutrition Karen Connelly, RD, CSO

NYU Clinical Cancer Center New York, NY

Somerset Medical Center Somerville, NJ

Wendy DiSalvo,

Sandra E. Kurtin,

Lori Stover, RN,

DNP, APRN, AOCN

RN, MS, AOCN, ANP-C

BSN

Patient Advocate Peg Ford

Western Pennsylvania Cancer Institute Pittsburgh, PA

Ovarian Cancer Advocacy Alliance Coronado, CA

Joseph D. Tariman, PhD,

Social Work Carolyn Messner,

APRN, BC

DSW, MSW, LCSW-R, BCD

Genentech New London, NH

Denice Economou, RN, MN, CNS, AOCN

Arizona Cancer Center Tucson, AZ

Ann McNeill, MSN, RN, NP-C, OCN

City of Hope National Medical Center Duarte, CA

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Northwestern University Myeloma Program Chicago, IL

Constance Engelking, RN,

Kena C. Miller, RN, MSN, FNP

Jacqueline Marie Toia, RN, MS, DNP

MS, CNS, OCN

Roswell Park Cancer Institute Buffalo, NY

Northwestern University Myeloma Program Chicago, IL

The CHE Consulting Group, Inc. Mt. Kisco, NY

CancerCare New York, NY

Managed Care and Pharmaceutical Management Burt Zweigenhaft, BS BioPharma Partners LLC New York, NY

Amy Ford, RN,

Patricia Molinelli,

BSN, OCN

MS, RN, APN-C, AOCNS

Quintiles Dallas, TX

Pamela Hallquist Viale, RN, MS, CS, ANP, AOCN

Isabell Castellano, RN

Somerset Medical Center Somerville, NJ

Saratoga, CA

Bristol-Myers Squibb Children’s Hospital Robert Wood Johnson University Hospital New Brunswick, NJ

Sharon S. Gentry,

Ellen A. Neylon,

Connie Visovsky,

Jeanne Westphal, RN

RN, MSN, AOCN

MSN, FNP, CCRP, OCN

RN, PhD, APRN

Meeker County Memorial Hospital Litchfield, MN

Derrick L. Davis Forsyth Regional Cancer Center Winston-Salem, NC

www.TheOncologynurse.com

Columbia University Medical Center Center for Lymphoid Malignancies New York, NY

University of South Florida College of Nursing Tampa, FL

JunE 2012 I VOL 5, nO 5

5

From the Editor

I

t’s been a busy time in the world of oncology. The Oncology Nursing Society (ONS) held its 37th Annual Congress in May while the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO) took place this month. The Oncology NurseAPN/PA (TON) was at both events. Our coverage of the news from the ONS and ASCO meetBeth Faiman, PhD(c), MSN, APRN-BC, AOCN ings starts with this issue and will Editor-in-Chief continue over the next several issues.

Be sure to check out our “view from the floor” to see what was going on at the ONS congress in New Orleans—maybe you’ll see yourself or recognize some of your colleagues in our photos. We talked to several nurse presenters at ONS and have articles about how 2 new programs can help nurses prepare their patients for bone marrow transplant (a DVD) or chemotherapy (an online program).

PUBLISHING STAFF Senior Vice President, Sales & Marketing Philip Pawelko phil@greenhillhc.com Publisher John W. Hennessy john@greenhillhc.com Director, Client Services Joe Chanley joe@greenhillhc.com Editorial Director Kristin Siyahian kristin@greenhillhc.com Managing Editor Kristen Olafson kristen@greenhillhc.com Quality Control Director Barbara Marino Production Manager Stephanie Laudien Business Manager Blanche Marchitto blanche@greenhillhc.com Executive Administrator Jackie Luma

With all the major news coming from the ASCO meeting in Chicago, we present our summary of abstracts of interest to TON readers. These studies are important to oncology nurses as they update us on the status of some of the latest research and give us a perspective that is not specific to nurses.

In addition to the news from the ONS and ASCO meetings, this issue addresses a variety of topics—everything from importance of screening for the “whispering disease” of ovarian cancer to a nursing perspective on personalized medicine in lung cancer care.

We continue to hear from MMA, a patient undergoing treatment for cancer. She gives us a very valuable perspective on how we as professionals interact with patients on the topic of pain. How individuals perceive pain is subjective, but we all know that many of the procedures our patients undergo are painful. MMA tells us how one nurse helped her by telling “the truth about pain.” The topic of pain is the subject of our new reader poll (see page 28). Please go to www.TheOncologyNurse.com to participate in the poll and tell us how you discuss pain with your patients. l

Circulation Department circulation@greenhillhc.com

Noteworthy Numbers

Editorial Contact: Telephone: 732.656.7935 Fax: 732.656.7938

GH Green Hill Healthcare Communications

, LLC ™

™

Your Innovative Partners in Medical Media

241 Forsgate Drive, Suite 205C Monroe Twp, NJ 08831 The Oncology Nurse-APN/PA®, ISSN 1944-9798 (print); ISSN 1944-9801 (online) is published 11 times a year by Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831.

Telephone: 732.656.7935. Fax: 732.656.7938. Copyright ©2012 by Green Hill Healthcare Communications, LLC. All rights reserved. The Oncology Nurse-APN/PA® logo is a registered trademark of Green Hill Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America.

EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, The Oncology Nurse-APN/PA®, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. E-mail: kristin@greenhillhc. com. YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $105.00; institutions, $135.00; single issues, $17.00. Orders will be billed at individual rate until proof of status is confirmed. Prices are subject to change without notice. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed to REPRINT PERMISSIONS DEPARTMENT, Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. The ideas and opinions expressed in The Oncology Nurse-APN/PA® do not necessarily reflect those of the Editorial Board, the Editorial Director, or the Publisher. Publication of an advertisement or other product mention in The Oncology Nurse-APN/PA® should not be construed as an endorsement of the product or the manufacturer’s claims.

Readers are encouraged to contact the manufacturer with questions about the features or limitations of the products mentioned. Neither the Editorial Board nor the Publisher assumes any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other healthcare professional, relying on independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Every effort has been made to check generic and trade names, and to verify dosages. The ultimate responsibility, however, lies with the prescribing physician.

Please convey any errors to the Editorial Director.

BPA Worldwide membership applied for April 2011.

6

JunE 2012 I VOL 5, nO 5

Although an uncommon cancer, sarcoma, which can arise in various connective tissues and therefore has many subtypes, is a frightening disease for both the young and old. For example, some types of bone cancer occur primarily in children, while others affect mostly adults. As we recognize Sarcoma Awareness Week this month, let’s delve into some statistics surrounding this multifaceted cancer.

Primary bone cancer is rare and accounts for less than 0.2% of all cancers.

In 2012, an estimated 2890 people will be diagnosed with new cases of primary bone cancer.

Approximately 1410 deaths will occur in 2012 from this disease.

Different types of bone cancer are more likely to occur in certain populations: • Ewing sarcoma family of tumors (ESFTs) appears most often in children and adolescents under 19 years of age – These tumors are more prevalent in boys than in girls – In North America each year, about 225 children and teens are diagnosed with Ewing tumors

– Most of the patients are white, either nonHispanic or Hispanic; this disease is very rare among African Americans; it also seldom occurs in other racial groups • Osteosarcoma generally occurs between ages 10 and 19 years; however, people over age 40 who have other conditions, such as Paget disease, are at increased risk of developing this cancer – About 800 new cases of osteosarcoma are diagnosed each year in the United States, with 400 of these developing in children and teens – About 10% of all osteosarcomas occur in people older than age 60 years

• The risk for chondro sarcoma increases with advancing age – Patients aged 40 and older make up 70% of chondrosarcoma cases – The average age at diagnosis is 51 years; most cases are diagnosed at an early stage and are low grade For all cases of bone cancer combined (in both adults and children), the 5-year relative survival is about 70%.

Furthermore, with modern surgical techniques, 9 out of 10 people who have bone cancer in an arm or leg may not need amputation.

Sources www.cancer.gov/cancertopics/types/bone; http://www.cancer.org/Cancer/BoneCance r/DetailedGuide/bone-cancer-what-iscancer; http://www.cancer.net/patient/ Cancer+Types/Sarcoma?sectionTitle=Aft er%20Treatment.

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News Briefs Mastectomy Risk Twice as High With Brachytherapy Continued from cover ingly more common in the United States. An estimated 10% of women with invasive breast cancer are now receiving brachytherapy as an alternative to whole-breast irradiation following lumpectomy. The appeal of brachytherapy versus whole-breast radiation is its delivery of radiation to a smaller field as well as its shorter course of treatment. Whole-breast radiation typically involves daily treatments for 7 weeks.

The lead author was Grace L. Smith, MD, University of Texas MD Anderson Cancer Center in Houston.

The study included 92,735 women aged 67 years or older with invasive breast cancer diagnosed between 2003 and 2007 and followed through 2008.

Following lumpectomy, 85,783 women (92.5%) were treated with whole-breast radiation and 6952 (7.5%) underwent brachytherapy. A year later, brachytherapy led to infection of the skin or soft tissue in 16.20% of patients versus 10.33% of those treated with wholebreast radiation; furthermore, the rate of noninfectious complications was significantly greater in the brachytherapy group: 16.25% versus 9.0%.

efficacy of brachytherapy versus wholebreast radiation, but results will not be available for several years.

“These results represent, to our knowl-

edge, the first comprehensive, population-based study to directly compare the clinical outcomes associated with use of breast brachytherapy versus standard

whole-breast radiation in older patients.

Additional study is required to confirm the validity and generalizability of these findings,” wrote the authors. l

TREANDA® (bendamustine HCI) for Injection is his chemo.

This is his therapy.

Five years after treatment, the rate of mastectomy was twice as high in women treated with brachytherapy versus whole-breast radiation.

At 5 years, the rates of other complications were also higher in the brachytherapy group compared with the whole-breast radiation group: breast pain, 14.55% versus 11.92%; fat necrosis, 8.26% versus 4.05%; and rib fracture, 4.53% versus 3.62%, respectively.

Limitations of the study include its retrospective nature, being based on Medicare claims data, and not taking into consideration improvements in technology since 2007 in delivering brachytherapy. Only a randomized controlled trial can definitively compare the 2 radiation techniques. An ongoing phase 3 randomized controlled trial sponsored by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the Radiation Therapy Oncology Group (RTOG) is currently comparing the safety and

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News Briefs

Lower Radiation Dose Effective for Thyroid Cancer

L

ower radioiodine doses given with recombinant human thyrotropin (thyrotropin alfa) was as effective as high-dose radioiodine, and the low-

dose treatment was associated with fewer side effects. Use of thyrotropin alfa along with low-dose radiation allows patients to avoid fatigue, lethar-

gy, and weight gain associated with thyroid hormone withdrawal. These results suggest that thyroid cancer treatment can be transformed into a safer, shorter

session, according to researchers.

The radioiodine dose used in the HiLo trial was one-third of the currently used Continued on page 10

Single-agent TREANDA tripled median PFS* 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.

PROGRESSION-FREE SURVIVAL (PFS): CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) Survival distribution function

TREANDA (n=153)

1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1

Chlorambucil (n=148)

18 months median PFS

6 months median PFS

P<.0001 HR†=0.27 (95% CI‡: 0.17, 0.43)

0

5

10

15

20

25

30

35

40

45

Months *TREANDA (95% CI: 11.7, 23.5) vs chlorambucil (95% CI: 5.6, 8.6). † HR=hazard ratio. ‡ CI=confidence interval.

• TREANDA was compared with chlorambucil in a randomized, open-label, phase 3 trial in treatment-naïve patients with Binet stage B or C (Rai stages I-IV) CLL who required treatment (N=301) • TREANDA is administered with a convenient dosing schedule – The recommended dose for TREANDA is 100 mg/m2 administered intravenously over 30 minutes on Days 1 and 2 of a 28-day treatment cycle, up to 6 cycles – In the phase 3 trial, patients received chlorambucil at a dose of 0.8 mg/kg orally on Days 1 and 15 (n=148) of a 28-day treatment cycle, up to 6 cycles • In the pivotal phase 3 trial, the most common non-hematologic adverse reactions (frequency ≥15%) were pyrexia (24%), nausea (20%), and vomiting (16%) (n=153). The most common hematologic abnormalities (frequency ≥15%) were anemia (89%), thrombocytopenia (77%), neutropenia (75%), lymphopenia (68%), and leukopenia (61%) (n=150) Important Safety Information • Serious adverse reactions, including myelosuppression, infections, infusion reactions and anaphylaxis, tumor lysis syndrome, skin reactions including SJS/TEN, other malignancies, and extravasation, have been associated with TREANDA. Some reactions, such as myelosuppression, infections, and SJS/TEN (when TREANDA was administered concomitantly with allopurinol and other medications known to cause SJS/TEN), have been fatal. Patients should be monitored closely for these reactions and treated promptly if any occur • Adverse reactions may require interventions such as decreasing the dose of TREANDA, or withholding or delaying treatment • TREANDA is contraindicated in patients with a known hypersensitivity to bendamustine or mannitol. Women should be advised to avoid becoming pregnant while using TREANDA

Discover the elements of efficacy and safety LEARN MORE AT WWW.TREANDA.COM Please see accompanying brief summary of full Prescribing Information.

©2012 Cephalon, Inc., a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd.

All rights reserved. TRE-2460 March 2012

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JunE 2012 I VOL 5, nO 5

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News Briefs Lower Radiation Dose Effective for Thyroid Cancer Continued from page 9 level, setting a new standard of care, they said. â&#x20AC;&#x153;We are delighted that this study of thyroid cancer care will change international approaches to treating the disease more safely, by reducing the chance of another cancer developing later in life and other side effects.

Patients will have a better quality of life, they will be treated more quickly, which will keep the disruption to their lives at a minimum, as well as saving NHS money,â&#x20AC;? stated lead author Ujjal Mallick, MD, Freeman Hospital in Newcastle, United Kingdom.

Study results were published in the May 2 issue of the New England Journal of Medicine. HiLo was a randomized, noninferiority trial comparing low-dose and high-dose radioiodine, each in combination with either thyrotropin alfa or thyroid hormone withdrawal

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.

Brief Summary of Prescribing Information for Chronic Lymphocytic Leukemia 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.

CONTRAINDICATIONS: TREANDA is contraindicated in patients with a known hypersensitivity (eg, anaphylactic and anaphylactoid reactions) to bendamustine or mannitol. [See Warnings and Precautions] WARNINGS AND PRECAUTIONS: Myelosuppression. Patients treated with TREANDA are likely to experience myelosuppression. In the two NHL studies, 98% of patients had Grade 3-4 myelosuppression. Three patients (2%) died from myelosuppression-related 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 closely.

In the clinical trials, blood counts were monitored every week initially. Hematologic nadirs were observed predominantly in the third week of therapy. Hematologic nadirs may require dose delays if recovery to the recommended values have 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 â&#x2030;Ľ 1 x 109/L and the platelet count should be â&#x2030;Ľ 75 x 109/L. [See Dosage and Administration]. Infections. Infection, including pneumonia and sepsis, has been reported in patients in clinical trials and in post-marketing reports. Infection has been associated with hospitalization, septic shock and death. Patients with myelosuppression following treatment with TREANDA are more susceptible to infections.

Patients with myelosuppression following TREANDA treatment should be advised to contact a physician if they have symptoms or signs of infection. Infusion Reactions and Anaphylaxis. 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. Patients should be asked about symptoms suggestive of infusion reactions after their first cycle of therapy. Patients who experienced Grade 3 or worse allergic-type reactions were not typically rechallenged. Measures to prevent severe reactions, including antihistamines, antipyretics and corticosteroids should be considered in subsequent cycles in patients who have previously experienced Grade 1 or 2 infusion reactions. Discontinuation should be considered in patients with Grade 3 or 4 infusion reactions. Tumor Lysis Syndrome. Tumor lysis syndrome associated with TREANDA treatment has been reported in patients in clinical trials and in post-marketing 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 maintaining adequate volume status, 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. Skin Reactions. A number of skin reactions have been reported in clinical trials and post-marketing safety reports. These events have included rash, toxic skin reactions and bullous exanthema.

Some events occurred when TREANDA was given in combination with other anticancer agents, so the precise relationship to TREANDA is uncertain. 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. Therefore, patients with skin reactions should be monitored closely. If skin reactions are severe or progressive, TREANDA should be withheld or discontinued. 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. There are postmarketing reports of bendamustine extravasations resulting in hospitalizations from erythema, marked swelling, and pain. Precautions should be taken to avoid extravasations, including monitoring of the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of TREANDA. Use in Pregnancy. 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.

ADVERSE REACTIONS: 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. 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; Infections; Infusion Reactions and Anaphylaxis; Tumor Lysis Syndrome; Skin Reactions; Other Malignancies. Clinical Trials Experience in CLL. The data described below reflect exposure to TREANDA in 153 patients. TREANDA was studied in an active-controlled trial.

The population was 45-77 years of age, 63% male, 100% white, and had treatment naĂŻve CLL. 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. In the randomized CLL clinical study, 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 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 randomized CLL clinical study and 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 â&#x2030;Ľ 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 Chlorambucil (N=153) (N=143) System organ class Preferred term All Grades Grade 3/4 All Grades Grade 3/4 Total number of patients with at least 1 adverse reaction 121 (79) 52 (34) 96 (67) 25 (17) Gastrointestinal disorders Nausea 31 (20) 1 (<1) 21 (15) 1 (<1) Vomiting 24 (16) 1 (<1) 9 (6) 0 Diarrhea 14 (9) 2 (1) 5 (3) General disorders and administration site conditions Pyrexia 36 (24) 6 (4) 8 (6) 2 (1) Fatigue 14 (9) 2 (1) 8 (6) 0 Asthenia 13 (8) 0 6 (4) 0 Chills 9 (6) 0 1 (<1) 0 Immune system disorders Hypersensitivity 7 (5) 2 (1) 3 (2) 0 Infections and infestations Nasopharyngitis 10 (7) 0 12 (8) 0 Infection 9 (6) 3 (2) 1 (<1) 1 (<1) Herpes simplex 5 (3) 0 7 (5) 0 Investigations Weight decreased 11 (7) 0 5 (3) 0 Metabolism and nutrition disorders Hyperuricemia 11 (7) 3 (2) 2 (1) 0 Respiratory, thoracic and mediastinal disorders Cough 6 (4) 1 (<1) 7 (5) 1 (<1) Skin and subcutaneous tissue disorders Rash 12 (8) 4 (3) 7 (5) 3 (2) Pruritus 8 (5) 0 2 (1) 0

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JunE 2012 I VOL 5, nO 5

Table 2: Incidence of Hematology Laboratory Abnormalities in Patients Who Received TREANDA or Chlorambucil in the Randomized CLL Clinical Study Chlorambucil TREANDA (N=141) (N=150) Grade 3/4 All Grades Grade 3/4 All Grades Laboratory Abnormality n (%) n (%) n (%) 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) In the randomized CLL clinical study, 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 significant deterioration does not occur. Post-Marketing 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. 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] OVERDOSAGE: The intravenous LD 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. DOSAGE AND ADMINISTRATION: 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 â&#x2030;ĽÂ Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to â&#x2030;¤Â Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) â&#x2030;ĽÂ 1 x 109/L, platelets â&#x2030;ĽÂ 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] 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. Reconstitution/Preparation for Intravenous Administration. t Aseptically SFDPOTUJUVUF FBDI 53&"/%" WJBM BT GPMMPXT t NH 53&"/%" WJBM "EE N- PG POMZ Sterile Water for Injection, USP t NH 53&"/%" WJBM "EE N- PG POMZ 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 VTFE t "TFQUJDBMMZ XJUIESBX UIF WPMVNF OFFEFE GPS UIF SFRVJSFE EPTF CBTFE PO NH N- DPODFOUSBUJPO BOE 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 0.2â&#x20AC;&#x201C;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 BENJYUVSF TIPVME CF B DMFBS BOE DPMPSMFTT UP TMJHIUMZ ZFMMPX TPMVUJPO t 6TF 4UFSJMF 8BUFS GPS *OKFDUJPO 641 GPS reconstitution and then either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride *OKFDUJPO 641 GPS EJMVUJPO BT PVUMJOFE BCPWF /P PUIFS EJMVFOUT IBWF CFFO TIPXO UP CF DPNQBUJCMF t 1BSFOUFSBM 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. 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.

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.

HOW SUPPLIED/STORAGE AND HANDLING: 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. Procedures for the proper handling and disposal of anticancer drugs should be considered. Several guidelines on the subject have been published. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate. 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 singleuse vial and NDC 63459-391-20 TREANDA (bendamustine hydrochloride) for Injection, 100 mg in 20 mL amber single-use vial. 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.

before ablation. Of 438 randomized patients with stage T1-3 nonmetastatic thyroid cancer, 421 were evaluable.

Successful thyroid ablation was achieved in 85% of the low-dose radioiodine group versus 88.9% in the high-dose radioiodine group and 87.1% in the group undergoing thyroid hormone withdrawal. These percentages were within the 95% confidence intervals for noninferiority. Results were similar for low-dose radioiodine plus thyrotropin alfa (84.3%) versus high-dose radioiodine plus thyroid hormone withdrawal (87.6%) or high-dose radioiodine plus thyrotropin alfa (90.2%).

These results suggest that thyroid cancer treatment can be transformed into a

50

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TRE-2500 (Label Code: 00016287.06) This brief summary is based on TRE-006 TREANDA full Prescribing Information.

April 2012

safer, shorter session, according to researchers.

About 3 times as many patients randomized to high-dose radioiodine were hospitalized for at least 3 days versus those in the low-dose group: 36.3% versus 13%, respectively. More adverse events were observed with high-dose radioiodine as well: 33% versus 21% in the low-dose group (P = .007); adverse events were 23% in the thyrotropin alfa group versus 30% in the group undergoing thyroid hormone withdrawal.

Current treatment is surgical removal of the thyroid gland followed by radioactive iodine taken in a capsule to destroy any remaining thyroid tissue that could presumably harbor cancer cells. This high-dose treatment requires at least 2 days of isolation in hospital for the radiation to dissipate.

High-dose radioiodine is associated with late-occurring side effects that affect quality of life. The low-dose treatment can be done on an outpatient basis and has fewer side effects.

The rationale for the study was that newer surgical techniques are more successful in ablating thyroid tissue and therefore lower radioiodine doses could be adequate.

The trial also showed that patients can continue taking thyroid hormone tablets if they are given thyroid-stimulating hormone (ie, thyrotropin alfa) before they take low-dose radioactive iodine. l â&#x20AC;&#x201D;AG

1:54 PM

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News Briefs

Age and Comorbidity Affect Treatment Access for Lung Cancer

Y

ounger patients were more likely than older patients to get guideline-recommended treatment for non–small cell lung cancer (NSCLC); conversely, the older the patient, the less likely treatment was provided, according to a large study of veterans that was reported in the May 1 edition of the Journal of Clinical Oncology.

Advancing age was the strongest negative predictor of receiving guidelinerecommended treatment, regardless of cancer stage and comorbidity.

“Individualized decisions that go beyond age and include comorbidity are needed to better target NSCLC treatments to older patients who may reasonably benefit,” wrote lead author Sunny Wang, MD, San Francisco Veterans Affairs Medical Center, California. “It is clear that we fixate on age in deciding whether to pursue cancer treatments, including lung cancer treatments.

Instead, we should be looking at our patients’ overall state of health,” she stated in a news release from the University of California San Francisco (UCSF).

Previous studies show that older patients in good health can benefit

such sick patients to toxic treatments.

The study included 20,501 patients aged 65 years and older treated at the San Francisco VA Medical Center and UCSF from 2003 to 2008. Patients were stratified by age (65 to 74 years; 75 to 84

Rates of treatment decreased more with advancing age than with worsening comorbidity for all stages.

from treatment for NSCLC, while those with comorbidities may not be able to tolerate chemotherapy and radiation. Also, significant comorbidity can lower life expectancy, raising doubt as to the wisdom of subjecting

years; and 85 years or older), Charlson comorbidity index score (0, 1 to 3, and 4 or above), and cancer stage (I to II, IIIA to IIIB, and IIIB with malignant effusion to IV).

Guideline-recommended treatment

was given to 51% of patients with local, 35% with regional, and 27% with metastatic disease. Rates of treatment decreased more with advancing age than with worsening comorbidity for all stages. Older patients with no comorbidity (who could presumably benefit from treatment) had lower rates of treatment than younger patients with severe comorbidity. For example, the rate of surgery was significantly different in favor of younger patients: 50% of patients aged 75 to 84 years with local disease had surgery compared with 57% of those aged 65 to 74 years with severe comorbidity (P <.001).

“The message from our study is don’t base cancer treatment strictly on age.

Don’t write off an otherwise healthy 75year-old, and don’t automatically decide to treat a really ill 65-year-old without carefully assessing the risks and benefits for that patient,” Wang said in the UCSF news release.

She and her colleagues are currently conducting a follow-up study to compare survival in patients included in the study. l —AG

Human Papilloma Virus–Positive Oropharyngeal Cancers Respond to Radiation Alone

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HPV Image Source: Laboratory of Tumor Virus Biology

A

ccording to a presentation at the recent European Society for Radiotherapy and Oncology (ESTRO) meeting in Barcelona, Spain, oropharyngeal cancers in patients who are positive for the human papilloma virus (HPV) and who never smoked or were light smokers may be treated effectively with radiotherapy alone, potentially sparing these selected patients from additional chemotherapy and its toxicity.

In a retrospective analysis of 181 patients on the Danish Head and Neck Cancer Group database treated between 1992 and 2005 for advanced oropharyngeal cancer, HPV-positive patients had significantly improved local control, disease-specific survival, and overall survival at 5 years compared with HPV-negative patients.

Analysis of smoking history showed that HPV-positive patients with a smoking history of less than 10 packyears (1 pack-year equals 20 cigarettes per day for 1 year) had improved outcomes compared with HPV-negative patients and those with a smoking history of more than 10 pack-years.

“This study is part of an ongoing debate about how to treat patients according to known prognostic factors, in this case, tumor HPV status and smoking history,” stated Pernille Lassen, a radiation oncology resident

When smoking history was accounted for, favorable outcomes were observed in HPV-positive light smokers or nonsmokers.

at Aarhus University Hospital, Aarhus, Denmark. “These findings confirm the highly significant independent influence of HPV status on tumor control and survival in advanced oropharyngeal cancer that is

treated with radiotherapy alone, without chemotherapy. Our results suggest that use of radiotherapy alone may be a safe treatment strategy in patients who are light or nonsmokers, while sparing them the side effects associated with

chemotherapy. However, it is still too early to select patients for a specific treatment based on these factors; we still need more data,” she stated, according to a press release from ESTRO. All patients in the study received accelerated radiotherapy consisting of 6 fractions over 5 days along with nimorazole, a radiation sensitizer. No chemotherapy was used. Of the 181 patients, 103 (57%) were HPV positive. Tumor control was achieved in 81% of HPV-positive patients versus 48% of patients who were HPV negative. Five-year disease-specific survival was 90% versus 56%, respectively, and 5-year overall survival was 77% versus 38%, respectively.

When smoking history was accounted for, favorable outcomes were observed in HPV-positive light smokers or nonsmokers. For HPV-positive light smokers or nonsmokers versus HPVpositive heavy smokers, 5-year outcomes were as follows: tumor control at primary site, 91% versus 77%; diseasespecific survival, 96% versus 81%; and overall survival, 90% versus 63%, respectively.

Seventy-six of the 78 HPV-negative patients were heavy smokers, and their outcome was significantly worse than HPV-positive patients, with a 5-year disease-specific survival of 50% to 52%. l —AG

JunE 2012 I VOL 5, nO 5

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News Briefs

Olaparib Maintenance Therapy Potentially Useful for Aggressive Ovarian Cancer

O

laparib maintenance therapy extended progression-free survival (PFS) in women with an aggressive form of platinum-sensitive ovarian cancer with a previous response to platinum-based chemotherapy.

Women receiving olaparib lived a mean of 4 months longer and also had a longer time to disease progression than those who had no maintenance therapy. These were the conclusions of a phase 2 study published in the New England Journal of Medicine on April 12, 2012.

“Maintenance treatment with olaparib was associated with significant improvement in PFS in patients with platinumsensitive, relapsed, high-grade serous ovarian cancer. At this interim analysis, this did not translate into an overall survival benefit,” wrote the authors. They noted that 21% of patients in the main-

tenance arm were still on olaparib, indicating prolonged disease control in some patients. They also emphasized a need to identify biomarkers that could be used to

diagnosed ovarian cancer will respond to platinum-based chemotherapy, but most will relapse with only short-lived responses to subsequent lines of therapy.

Maintenance therapy after response to first-line platinum-based therapy is an ongoing area of investigation to determine if response can be prolonged. select patients most likely to respond to treatment with a poly ADP ribose polymerase (PARP) inhibitor, such as olaparib, so that this therapy could be targeted to the appropriate population.

About 80% of patients with newly

Maintenance therapy after response to first-line platinum-based therapy is an ongoing area of investigation to determine if response can be prolonged.

In the phase 2 trial, 265 patients were randomized to double-blind treat-

ment with olaparib 400 mg BID or placebo. Median PFS was 8.4 months in the olaparib group versus 4.8 months with placebo, representing a 65% reduced risk of progression that was statistically significant (P <.001). The benefit of maintenance therapy was observed across all subgroups studied.

Time to progression was also significantly longer in the group receiving olaparib: median 8.3 months versus 3.7 months for placebo, again a highly significant 65% reduction in risk of progression (P <.001).

The interim analysis reported in the New England Journal of Medicine found no significant difference between groups in overall survival: median 29.7 months for olaparib and 29.9 months for placebo.

The most commonly reported adverse events for olaparib versus placebo were nausea, 68% versus 35%; fatigue, 49% versus 38%; vomiting, 32% versus 14%; and anemia, 17% versus 5%, respectively. Most adverse events were grade 1 or 2. l —AG

Health Behaviors Worse Among Cancer Survivors Than Patients With No History of Cancer

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large, population-based study found that a significant proportion of female cancer survivors had poor health behaviors compared with women who have not had cancer (Rausch SM, et al. Am J Clin Oncol.

2012;35:22-31).

Several differences in engaging in health behaviors emerged among primary cancer types, with more cervical cancer survivors reporting being current smokers and regular alcohol users compared with other cancer types. Ovarian and uterine cancer survivors reported being obese more often than other cancer types, and the largest weight gain was observed among cervical cancer survivors. By contrast, leukemia survivors reported engaging in regular mammography more often, had a higher percentage of “never” smokers, and a higher percentage of normal-weight individuals compared with individuals with other primary cancers.

Even though more than half of all cancer deaths in the United States can

be attributed to health behaviors such as smoking (30%), poor dietary choices and obesity (25%-30%), and physical inactivity, very little is known about these behaviors in cancer survivors, wrote the authors of this study. “There is considerable need for additional studies to document the prevalence of cancerrelated risk factors in a diverse sample of cancer survivors,” they added.

The study included almost 20,000 women aged 35 years and older with no prior breast cancer who presented for screening mammography. Participants were given a self-assessment questionnaire about their health behaviors and previous cancer history.

The questionnaire was completed by 18,510 women—15,797 with no cancer history and 2713 cancer survivors.

Health behaviors assessed included smoking, alcohol consumption, physical activity, weight, use of complementary and alternative medicine (CAM), mammography screening, and overall selfrating of health during the past year.

Mean age was 58 years, mean body mass index (BMI) was 26 kg/m2, and 74% had education beyond high school.

Compared with women who did not have cancer, cancer survivors were about 5 years older on average, had a similar BMI, and 4% more had education beyond high school.

Cancer survivors were less likely than women with no cancer history to report that they had “excellent” health: 13.6% versus 21.5%, respectively; that they engaged in moderate or strenuous exercise: 56.5% versus 63.3%, respectively; and that they used CAM: 57.4% versus 60.2%, respectively. Cancer survivors were more likely to be current smokers (6.3% vs 5.5%) and to rate their overall health as “poor” (15.9% vs 9.1%, respectively), and to gain more weight over time.

Cancer survivors reported more regular participation in mammography screening than women with no cancer: 91.1% versus 86.3%, respectively; the difference was more marked in patients

younger than age 40: 80.2% versus 74.3%, respectively.

Cancer survivors were more likely to have had a smoking history; 59% versus 63.7%, respectively, reported being “never” smokers; 34.6% versus 30%, respectively, reported being “former” smokers; and 6.3% versus 5.9% said they were current smokers. The smoking rates were similar between cancer survivors and those without cancer for women older than age 65, whereas cancer survivors aged 30 to 49 years were more likely to be current smokers than women of the same age group who were not cancer survivors: 13% versus 8.5%, respectively.

The authors state that presenting for screening mammography is “a teachable moment” when healthcare providers can educate cancer survivors and discuss risky behaviors. Studies such as this one suggest that there is much room for improvement in areas such as smoking, alcohol consumption, exercise, and weight gain. l —AG

Visit our user-friendly Web site www.TheOncologyNurse.com In addition to Web-only exclusives, news coverage, journal articles, contests, and polling questions, you’ll have the opportunity to earn Continuing Education credits at NO CHARGE by participating in a number of activities offered!

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News Briefs

Acute Lymphoblastic Leukemia: RemissionInduction Failure Can Be Treated

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ailure of remission-induction therapy in pediatric acute lymphoblastic leukemia (ALL), although rare, can lead to highly adverse outcomes, but outcomes differ according to type of ALL: B-cell or T-cell, as well as other characteristics (Schrapps M, et al. N Engl J Med. 2012;366:1371-1381).

The study showed that patients with childhood ALL who fail on induction therapy are highly heterogeneous. Tcell leukemia appears to be associated with improved outcomes if treated with allogeneic stem-cell transplant, while precursor B-cell leukemia with no adverse features appears to be better treated with chemotherapy.

According to the authors, “These findings have considerable implications, since transplantation is generally considered to be standard of care for such patients.”

The study was based on 1041 children and adolescents (aged 0-18 years) with newly diagnosed ALL who experienced failure after 4 to 6 weeks of remission-induction therapy; these children were culled from 44,017 patients with childhood ALL treated by 14 cooperative study groups between 1985 and 2000.

Patients with induction failure tended to have high-risk features that included older age, high leukocyte count, T-cell

leukemia phenotype, the Philadelphia chromosome, and 11q23 rearrangement.

With a median follow-up of 8.3 years, the 10-year survival rate was 32%.

Characteristics associated with a particularly poor outcome included age of 10 years or more, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy. Improved outcomes in precursor B-cell ALL were associated with high hyperdiploidy (a modal chromosome number >50) and age of 1 to 5 years; these patients composed about 25% of the sample.

Improved outcomes in T-cell ALL

were seen with allogeneic stem-cell transplant from matched, related donors. Children younger than 6 years with precursor B-cell ALL and no adverse genetic features had a 10-year survival rate of 72% when treated with chemotherapy only. l —AG

Did You Know?

ASCO has issued a provisional clinical opinion to offer palliative care to all patients with metastatic cancer.

—J Clin Oncol. 2012;30:880-887.

Oral Supplement in Malnourished Cancer Patients Does Not Improve Survival

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ral nutritional interventions do increase nutritional intake and result in weight gain in some malnourished patients with cancer as well as improve some aspects of quality of life (QOL), but do not seem to increase survival, according to a systematic review and meta-analysis of the literature (Baldwin C, et al. J Natl Cancer Inst. 2012;104:371-385).

Lead author Christine Baldwin, PhD, RD, School of Medicine, King’s College, London, United Kingdom, said that current international guidelines recommend oral interventions in this group of patients, assuming they are able to swallow, but this recommendation is not based on level A evidence from well-designed randomized trials. Since several studies have attempted to evaluate the effect of oral interventions in cancer patients but have reached variable conclusions, she and her colleagues wanted to revisit the question by reviewing the literature.

The systematic review and metaanalysis included 13 studies with a total of 1414 adult cancer patients with cancer of all sites and stages who were either malnourished or at risk of malnutrition and compared oral nutritional interventions versus usual care.

The patient population, quality, and design of these studies were quite heterogeneous, which is a limitation of the review, Baldwin said.

Seven of the studies included assessment of QOL, 5 of them using the EORTC cancer-specific questionnaire. There was a great deal of vari-

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ability in the findings, but after adjusting for heterogeneity, oral nutritional interventions were associated with statistically significant improvement in “emotional functioning,” “global QOL,” and “dyspnea” and “loss of appetite” symptom scales. Changes in other QOL scales did not reach statistical significance. No effect on mortal-

ity was observed in patients who received oral nutritional intervention.

“The findings suggest that oral nutritional interventions have no effect on survival and that the effect on body weight and energy intake is inconsistent, but that statistically significant improvements in some aspects of QOL may be achieved,” wrote

Baldwin. She pointed out that several of the studies included in the review were of poor quality, emphasizing the need for more in-depth research to characterize the benefits of oral nutritional support in cancer patients and to strengthen the evidence base for nutritional management in this group of patients. l —AG

O utstanding O pportunity Outstanding Opportunity ffor or

O ONCOLOGY NCOLOGY NP NP

IIMMEDIATE MMEDIATE O OPPORTUNITY PPORTUNITY for an experienced Oncology NP at Marshall Hematology and Oncology, an independent, nonprofit community healthcare provider located in the heart of the Sierra Foothills between Sacramento and South Lake Tahoe.

R RESPONSIBILITIES ESPONSIBILITIES F FOR OR ONCOLOGY ONCOLOGY N NP P IINCLUDE: NCLUDE: Work collaboratively with oncologist to provide direct patient care to outpatient population and oversee chemotherapy administration.

Management experience required to facilitate staff ff,, physician, infusion center, clinic operations and oversight. Requires current CA RN license, BLS certification, Masters of Science degree in nursing with 12-24 months of specialized classroom and ex xperimental learning as a nurse practitioner, minimum 2 years related clinical experience. Oncology certification strongly preferred. Certification by the American Nurse Credentialing Center to be obtained within 12 months of employment and must apply for, be awarded, and maintain privileges as an Allied Health Professional in accordance with the bylaws, rules & regulations of the medical staff of Marshall Medical Center.

Marshall Medical Center includes Marshall Hospital, several outpatient facilities, a group of primary and specialty care physicians and many community health and education programs. Marshall has over 190 affiliated physicians and a team of over 1200 employees providing quality healthcare ser vices to more than 150,000 residents of El Dorado County.

FOR MORE MORE IN INFORMATION FORMATION PLEASE PL EASE CONTACT: CONT TACT: Sharee Vance, Physician Relations Specialist 530.672.7002 or svance@marshallmedical.orrg Marshall Medical Center 1100 Marshall Way, Placerville, CA

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JunE 2012 I VOL 5, nO 5

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Faces at the ONS 37th Annual Congress

A View From the Floor The Oncology Nursing Society 37th Annual Congress was held in New Orleans, Louisiana, on May 3-6, 2012.

The Oncology Nurse-APN/PA (TON) was thereâ&#x20AC;Ś

Nursing colleagues from MedStar Franklin Square Medical Center in Baltimore, Maryland, gather outside a podium session.

Argelis McIntire, RN, MSN, a nursing instructor from Cheyenne, Wyoming, reviews a best practice poster.

Christine Bookbinder and Neely Giannano, from Boston, Massachusetts, take a break from the action during congress.

Nichole Williams, Harley Isaacs, and Paige Wildmann, all from Maryland, stop by the TON booth to sign up to receive the publication. Enjoy your reading!

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JunE 2012 I VOL 5, nO 5

Our own editor-in-chief, Beth Faiman, PhD(c), MSN, APRN-BC, AOCN, makes a presentation during a multiple myeloma educational program.

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Faces at the ONS 37th Annual Congress

A group of oncology nurse colleagues from Scripps Mercy in San Diego, California, gather in the exhibit hall.

Congratulations to Heather Pruim, RN, BSN, OCN, CBCN, of Olympia Fields, Illinois, the winner of our iPad giveaway.

Kristine Deano Abueg, RN, MSN, OCN, CBCN, from Roseville, California, reviews a poster about best practices for oral adherence to chemotherapy.

German Rodriguez, RN, MSN, from New York, New York, studies a poster.

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JunE 2012 I VOL 5, nO 5

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Ovarian Cancer Screening for Ovarian Cancer Continued from cover diagnosed with ovarian cancer in 2012, and 15,500 women will die of ovarian cancer.1 Approximately 75% of women will survive 1 year after diagnosis and treatment. The 5-year survival rate is 46%, an increase of less than 10% since 1974, when the survival rate was 37%.

Those diagnosed at an early stage (stage I) have a 5-year survival rate of 94%; however, only about 15% of all ovarian cancers are diagnosed at this early stage.

One in 71 women will have a diagnosis of ovarian cancer in her lifetime, representing about 3% of all cancers that occur in women. It is the ninth most frequent type of cancer diagnosed in American women (Table 1). Ovarian cancer is more common in women over 50 to 60 years of age (depending on the source), and uncommon in women younger than 40 years.

Table 1 The Most Common Cancers Among American Women Type 1. Breast 2. Lung and bronchus 3. Colon and rectum 4. Uterine 5. Thyroid 6. Non-Hodgkin lymphoma 7. Melanoma of the skin 8. Kidney and renal pelvis 9. Ovarian

Estimated New Cases 2012

Estimated Death Rate 2012

226,870 109,690 70,040 47,130 43,210 31,970 32,000 24,520 22,280

39,510 72,590 25,220 8010 1000 8620 3120 4920 15,500

Source: American Cancer Society. Cancer Facts & Figures 2012. Atlanta, GA: American Cancer Society; 2012.

Genetic Risk Factors greater the chance for a mutation to The most significant risk occur in the epithelial cells. Under this factor for ovarian cancer is causative theory, early menstruation, having an inherited muta- late menopause, and nulliparity would Types of Ovarian Cancer tion in 1 or both of 2 genes increase a women’s risk of ovarian canEpithelial ovarian cancer is called breast cancer gene 1 cer, while late menstruation, early the most frequently diag(BRCA1) and breast cancer menopause, pregnancy and breast-feednosed type of ovarian cancer, gene 2 (BRCA2). These ing, and use of oral contraceptive medaccounting for approximategenes were originally identi- ication would be protective. ly 90% of ovarian cancers.2 fied in families with multiple Pituitary gonadotropin hormones The epithelium is the cover- D. “Jeff” Nordquist, cases of breast cancer, which are also thought to affect the risk of RN, MS, CS, FNP ing of the ovary. As the is how they got their name; ovarian cancer. This theory submits tumor grows on the surface they are responsible for that during ovulation there is a surge of the ovary and becomes larger, it can about 10% of ovarian cancers.3 of hormones produced by the pituitary The second genetic link that increas- gland, which in turn increase the stimshed cells like seeds directly into the abdominal cavity, a process called seed- es the risk of developing ovarian cancer ulation of estrogen.3 This increase in ing. The shed cells can implant or seed involves an inherited syndrome called estrogen can affect the epithelial cells themselves into other tissue and organs hereditary nonpolyposis colorectal can- of the ovary, causing them to develop in the abdominal and pelvic cavities cer (HNPCC). Individuals in HNPCC into inclusion cysts that may transfamilies are at increased risk for cancers form into cancerous tumors.3 and form new tumors in these sites.

Germ cell ovarian tumors grow in the egg-producing cells of the ovary.

These tumors are uncommon, seen approximately 5% of the time, and Epithelial ovarian cancer is the most frequently often benign. Germ cell tumors occur diagnosed type of ovarian cancer, accounting for most often in girls, teenagers, and young women. If the germ cell tumor is approximately 90% of ovarian cancers. cancerous, a high percentage of patients can be cured with surgery and chemotherapy.

Sex cord tumors form in the connective or stromal tissue cells of the of the uterus, colon, ovary, stomach, Decreasing of Risk of Ovarian Cancer ovaries. Sex cord tumors generally and small intestine.

Protective Factors occur in women younger than 40 years Several factors are seen to protect a but can occur in older women. These Age as a Risk Factor tumors are generally slower growing The risk of ovarian cancer increases woman against ovarian cancer. The risk with age, with a median age at diagnosis of ovarian cancer is decreased at a rate of and do not spread rapidly.

12% for every pregnancy. of 63 years.1 Risk Factors of Ovarian Cancer Also, if the last birth is Although the causes of epithelial ovari- Hormonal and between the ages of 30 and 35 years, a woman’s risk of an cancer are still being uncovered, Reproductive Risk Factors ovarian cancer can be researchers have identified a number of One of the leading causation reduced by as much as factors that increase a woman’s odds of theories of ovarian cancer is 58% compared with a developing epithelial ovarian cancer. that of incessant ovulation.3 woman who has never Much less is known about risk factors for When the ovum leaves the been pregnant.3 ovary during the ovulatory germ cell and stromal tumors.

Women who have Risk factors for epithelial ovarian can- cycle, there is an increased risk breast-fed their babies for cer can be divided into 3 categories: of wounding to the epithelial Karin Goodman, 18 months or more have a genetic factors, age, and hormonal/ layer of the ovary. The more RN, CNP reduced risk of ovarian ovulatory cycles that occur, the reproductive factors.

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cancer due to the suppression of ovulation, resulting in a decrease in the gonadotropin levels.

Tubal ligations may alter growth factors and hormonal levels, thereby decreasing the risk of epithelial ovarian cancers, as well as preventing carcinogens and inflammatory factors from reaching the ovary from the uterus.

Likewise, a hysterectomy decreases the risk of ovarian cancer, with the added benefit of making it easier to examine the ovaries during the pelvic examination.

Progesterone plays a role in the risk of ovarian cancer. When a woman experiences a higher level of progesterone, either through pregnancy or the use of oral contraceptive pills, it is thought to cause a change in the cell cycle and induce apoptosis of the cells of the epithelium of the ovary. The protection offered by the increase in progesterone is thought to last long after the progesterone levels return to normal.3 Available Screening Tests for Ovarian Cancer A number of screening tests have been evaluated, and the 2 that have remained and are consistently referenced in the literature are the CA125 blood test and the use of transvaginal ultrasound (TVU).

CA125 tests for a protein produced by the cancerous epithelial cells of the ovaries. Approximately 90% of women with epithelial ovarian cancer have an elevation of this marker. Unfortunately, in the majority of these women the cancer is at an advanced stage when diagnosed. Studies have also shown that CA125 is not a reliable marker for ovarian cancer, as it can be elevated in 2% to 3% of the postmenopausal population who do not have ovarian cancer. Many factors can cause a rise in CA125, including inflammation of the peritoneum, pelvic infection, or another cancer.4 TVU has proven to be the most promising imaging test to screen for ovarian cancer. There is some indication that the combination of the CA125 blood test and the TVU may have increased sensitivity.4 Organizational Recommended Screening Guidelines for Ovarian Cancer A number of guidelines for ovarian cancer screening have been published.

There is agreement among these bodies that there is insufficient evidence to indicate that routine screening of the general public will result in fewer deaths from ovarian cancer. There are, however, indications for scheduled screening for those at an increased risk of developing ovarian cancer. Table 2 provides a summary of the most recent guidelines.5-11 Continued on page 18

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CML therapies have improved the lives of patients.

But a gap in treatment persists.

While current tyrosine kinase inhibitors (TKIs) are considered effective therapies for chronic myeloid leukemia (CML) patients, challenges remain. Clinical trials have shown treatment failures often occur for reasons not related to drug efficacy. A significant portion of patients discontinue treatment due to drug-related adverse events.1,2

Scan the QR code to learn more about why patients discontinue CML therapies, or visit CMLResponseProject.com.

Use your mobile device and tag reader app to scan the barcode.

References: 1. Shah NP, Cortes JE, Schiffer CA, et al. Five-year follow-up of patients with imatinib-resistant or -intolerant chronic-phase chronic myeloid leukemia (CML-CP) receiving dasatinib. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2011; Chicago, IL. 2. Le Coutre PD, Giles FJ, Pinilla-Ibarz J, et al. Nilotinib in imatinib-resistant or -intolerant patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): 48-month follow-up results of a phase 2 study. Poster presented at: 53rd ASH Annual Meeting and Exposition; December 10-13, 2011; San Diego, CA. Š2012 ARIAD Pharmaceuticals, Inc. All rights reserved.

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Ovarian Cancer Screening for Ovarian Cancer Continued from page 16 National Comprehensive Cancer Network (NCCN) Recommendations The NCCN defines women at high risk for developing ovarian cancer as those who have a family history of ovarian cancer, a BRCA mutation, or a personal history of breast cancer. It recommends that these women begin screening between the ages of 30 and 35 or 5 to 10 years before the age when a family member was diagnosed with ovarian cancer.

Screening should be done every 6 months utilizing a combination of CA125 and TVU. The NCCN also recommends that high-risk women consider a prophylactic salpingo-oophorectomy at the completion of childbearing.5 National Cancer Institute Recommendations The National Cancer Institute has made the following statement of benefit: There is inadequate evidence to determine whether routine screening for ovarian cancer with the serum marker CA125, TVU, or pelvic examinations would result in a decrease in mortality from ovarian cancer.6 US Department of Health & Human Services Recommendations The US Department of Health & Human Services guidelines are evidence-based, using the American College of Radiology and the Scottish Intercollegiate Guidelines Network guidelines.7 The US Department of Health & Human Services is in agreement with the NCCN that there is insufficient evidence to recommend routine screening for ovarian cancer for the general population and that a prophylactic oophorectomy should be considered when childbearing is no longer desired. For women at high risk for developing ovarian cancer, preventive counseling should be started in their early 20s by a gynecologic oncologist or geneticist. The benefits of oral contraceptive use and genetic testing should be addressed and considered.

US Preventive Services Task Force Recommendations The US Preventive Services Task Force recommendations found that while screening for ovarian cancer using TVU and CA125 would be beneficial for women determined to be at high risk for ovarian cancer, the risks outweigh the benefits for those who have no signs or symptoms.8 Memorial Sloan-Kettering Cancer Center Recommendations Memorial Sloan-Kettering Cancer Center has posted detailed recommen-

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Table 2 Organizational Ovarian Cancer Screening Recommendations5-11 High Risk National Comprehensive Cancer Network5

Increased Risk

Screening every 6 months with TVU and CA125 at 30-35 years of age; or 5-10 years before age at diagnosis of ovarian cancer in family members

National Cancer Institute6 Inadequate evidence

General Population Does not recommend routine screening

Inadequate evidence

Inadequate evidence

US Department of Health Preventive counseling in & Human Services7 early 20s by gynecologic oncologist or geneticist; discuss salpingo-oophorectomy following completion of childbearing

Insufficient evidence to recommend routine screening

US Preventive Services Task Force8

Does not recommend routine screening

Screening with TVU and CA125 may be helpful

Memorial Sloan-Kettering TVU and CA125 testing Genetic counseling may be Annual gynecologic/pelvic Cancer Center9 starting at 30-40 years of age; of value examination consider salpingo-oophorectomy following completion of childbearing American College of Obstetricians and Gynecologists10,11

TVU and CA125 every 6 months, beginning at 30-35 years of age, or 5-10 years before the earliest age at diagnosis of ovarian cancer in relative

Does not recommend routine screening

Abbreviation: TVU, transvaginal ultrasound.

dations for ovarian cancer screening. It divided high-risk women into 2 groups: (1) those with a 3 to 6 times increased risk, and (2) those with a known genetic mutation, and provided recommendations for each group.9

history suggestive of a hereditary cancer syndrome. 11 Screening should begin between the ages of 30 and 35 years and take place every 6 months.

If the woman has a relative with ovarian cancer, screening should begin 5

Two screening trials show benefits in terms of diagnosing ovarian cancer at an earlier stage.

However, survival benefits of an earlier diagnosis are yet to be seen.

American College of Obstetricians and Gynecologists (ACOG) Recommendations ACOG does not recommend routine screening for ovarian cancer in women who are at low risk of developing ovarian cancer.10 However, in women who are at high risk for developing ovarian cancer, screening is recommended utilizing CA125 and TVU. 10 Women at high risk are defined as those who are of Ashkenazi Jewish descent, have a BRCA1 or BRCA2 mutation, or have a family

to 10 years before the age of diagnosis of that family member.11 New Research Recommendations Two screening trials show benefits in terms of diagnosing ovarian cancer at an earlier stage. However, survival benefits of an earlier diagnosis are yet to be seen.

PLCO Screening Recommendations A large screening trial called the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial took place across the United States between

November 1993 and July 2001. It randomized 78,216 women, aged 55 to 74 years, to undergo usual care or annual screening. The screening arm included TVU at the time of the initial examination, followed by annual TVU for a length determined by the study. The screening arm also specified yearly CA125 drawn for 4 years. The usual care group underwent a routine pelvic examination with palpation of the ovaries.

Buys and colleagues recently published the long-term results of the trial.12 In the intervention group, 212 ovarian cancers were diagnosed, with 118 deaths as a result of ovarian cancer. In the usual care group, 176 ovarian cancers were diagnosed, with 100 deaths.

There was no statistically significant difference in overall survival between the groups. There was very little difference in the stage of ovarian cancer being diagnosed between the groups. In the screening arm, 69% of the cancers were diagnosed at a late stage versus 78% in the usual care group.12 The authors concluded that screening did not impact survival.

University of Kentucky Ovarian Cancer Screening Trial The University of Kentucky Ovarian Cancer Screening Trial resulted in an

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Ovarian Cancer algorithm used to determine the screening and frequency of tests based on outcome after 37,293 women were screened between January 1987 and June 2011.13 Using the algorithm, 47 invasive epithelial ovarian cancers and 15 borderline tumors (also referred to as tumors of low malignant potential) were detected.

Of the 47 patients diagnosed with invasive cancer, 70% had early-stage disease (stage I or II), and 30% had advanced-stage (stage III). In contrast, of the 2560 unscreened women who were diagnosed and entered into the Kentucky Tumor Registry during this time, 27% had stage I/II disease, and 46% had stage III disease. The screening group also had advanced-stage cancer diagnosed at stage IIIA and IIIB more consistently than the control group, which tended to have a higher incidence of stage IIIC ovarian cancer.13 The authors concluded that using an algorithm to determine screening can result in ovarian cancers being detected at an earlier stage, which will hopefully lead to an overall survival benefit.

2. Hartmann LC, Loprinzi C. Mayo Clinic Guide to Women’s Cancers. Rochester, MN: Mayo Clinic Health Information; 2005.

3. Vo C, Carney M. Ovarian cancer hormonal and environmental risk effect. Obstet Gynecol Clin North Am. 2007;34:687-700.

4. Clarke-Pearson DL. Screening for ovarian cancer. N Engl J Med. 2009;361:170-177.

5. National Cancer Care Network. Genetic screening for ovarian cancer. www.nccn.org. Accessed December 4, 2011.

6. National Cancer Institute. Ovarian cancer screening. www.cancer.gov. Accessed November 7, 2011.

7. United States Department of Health & Human

Services. Screening for ovarian cancer. www.guideline. gov/syntheses/synthesis.aspx?id=16420&search=ovari an+cancer+screening. Accessed November 18, 2011.

8. U.S. Preventive Task Force. Screening for ovarian cancer. www.uspreventiveservicestaskforce.org/uspstf/usps ovar.htm. Accessed February 20, 2012.

9. Memorial Sloan-Kettering Cancer Center. Ovarian cancer screening guidelines. www.mskcc.org. Accessed November 7, 2011.

10. American College of Obstetricians and Gynecologists Committee on Gynecologic Practice. Committee Opinion No. 477: the role of the obstetrician-gynecologist in the early detection of epithelial ovarian cancer.

Obstet Gynecol. 2011;117:742-746.

Individualizing Treatment for DCIS of the Breast: New Molecular Approaches LOG ON TODAY TO PARTICIPATE

www.coexm.com/ace09 TARGET AUDIENCE

It has yet to be determined if detecting ovarian cancer at an earlier stage will lead to a statistically significant increase in overall survival.

This initiative will target medical oncologists, hematologists, breast surgeons, radiation oncologists, oncology nurses, advanced practice nurses, nurse practitioners, physician assistants, oncology pharmacists, managed care professionals, and others with clinical research and management interest in treatment of ductal carcinoma in situ (DCIS) and early-stage breast cancer.

STATEMENT OF NEED Ability to detect DCIS has dramatically improved in recent decades, and the current incidence of DCIS is several-fold higher than in the 1970s and 1980s, largely due to increased use of mammography screening.1,2 However, attempts to identify subsets of DCIS women who may be spared radiotherapy and perhaps treated with surgery alone have heretofore been unsuccessful. This inability to predict which patients will develop recurrent DCIS or invasive disease has complicated DCIS management. Many clinicians and other healthcare professionals dealing with patients diagnosed with DCIS are unaware or incompletely knowledgeable about the most recent results from a clinical trial examining the ability of the 12-gene assay, using a prespecified DCIS algorithm, to predict recurrence risk, and the implications these findings may have for management of their patients with DCIS. 1. Kerlikowske K. Epidemiology of ductal carcinoma in situ. J Natl Cancer Inst Monogr. 2010;2010:139-141.

2. Virnig BA, Tuttle TM, Shamliyan T, Kane RL. Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst. 2010;102:170-178.

Conclusion The ability to effectively screen for ovarian cancer remains elusive. The sensitivity and specificity of our current screening methods, either CA125 or TVU, remain too low to achieve meaningful benefit for early diagnosis or reduction in mortality. Recent research studies utilizing CA125 and TVU together as a multimodal screening program, taking into account other risk factors such as age, parity, and family history, may lead to an algorithm that will result in more cancers being detected at an early stage. It has yet to be determined if detecting ovarian cancer at an earlier stage will lead to a statistically significant increase in overall survival. l References

11. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 103.

Hereditary breast and ovarian cancer syndrome. Obstet Gynecol. 2009;113:957-966.

12. Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305:2295-2303.

13. van Nagell JR Jr, Miller RW, DeSimone CP, et al.

Long-term survival of women with epithelial ovarian cancer detected by ultrasonographic screening. Obstet Gynecol. 2011;118:1212-1221.

EDUCATIONAL OBJECTIVES After completion of this activity, participants will be better able to: • Identify approaches currently available or in development to predict recurrence risk in DCIS patients • Explain how the 12-gene expression assay for DCIS was developed and how it compares with the 21-gene assay for early invasive breast cancer • Describe the design and findings of the ECOG 5194 validation study • Apply the 12-gene assay for DCIS into clinical decision-making • Explain relevant information about the 12-gene DCIS assay and DCIS score to patients

Release Date: May 8, 2012 Expiration Date: May 7, 2013

FACULTY Chair: Lawrence J. Solin, MD, FACR, FASTRO Chairman Department of Radiation Oncology Albert Einstein Medical Center Philadelphia, PA

E. Shelley Hwang, MD, MPH Professor and Chief, Breast Surgery Duke University Medical Center Durham, NC

Kathy D. Miller, MD Associate Professor Department of Medicine IU School of Medicine Indianapolis, IN This activity is supported by an educational grant from Genomic Health, Inc.

ACCREDITATION Physicians: Creative Educational Concepts, Inc. (CEC) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. CEC designates this enduring educational activity for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Nurses: CEC is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s (ANCC) Commission on Accreditation. CEC provides this activity for 1.0 contact hour. Learners are advised that accredited status does not imply endorsement by the provider or ANCC of any commercial products displayed in conjunction with an activity.

Case Managers: This activity has been approved for 1.0 clock hour through 12/31/12 by the Commission for Case Manager Certification. Case Managers number 790005057.

1. American Cancer Society. Ovarian cancer. www.can cer.org. Accessed January 11, 2012.

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JunE 2012 I VOL 5, nO 5

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CONTINUING EDUCATION JUNE 2012 • VOLUME 4 • NUMBER 1

4th Annual

CONSIDERATIONS

Lymphoma

™

IN

ASK THE EXPERTS: Mantle Cell Lymphoma LETTER PUBLISHING STAFF President & CEO Brian F. Tyburski

Chief Operating Officer Pam Rattananont Ferris

Director, Medical & Scientific Services Linda M. Ritter, PhD linda@coexm.com

Editorial Director Susan Berry susan@coexm.com

Associate Director Elizabeth S. Cohen liz@coexm.com

Copyeditor Dana Delibovi

FROM THE

EDITOR-IN-CHIEF

According to recent estimates from the American Cancer Society, approximately 70,130 individuals will be diagnosed with non-Hodgkin lymphoma (NHL) in 2012 and about 18,940 deaths will be attributed to the disease. There has been significant progress in the treatment of these hematologic malignancies, including the development and approval of new, highly effective therapies. However, more progress is needed and numerous questions remain unanswered regarding the application and interpretation of recent clinical advances.

The goal of our 4th annual “Considerations in Lymphoma” newsletter series is to provide clinicians with the latest evidence-based strategies for managing NHL in the era of novel agents. To address the needs of key members of the interdisciplinary team, frequently asked questions have been posed to physicians, midlevel providers, and pharmacists from leading cancer centers specializing in the treatment of lymphoma. In this first issue, experts from Fox Chase Cancer Center discuss the effective management of mantle cell lymphoma. It is our hope that the insight, knowledge, and experience offered by these professionals will facilitate the optimal care of your patients with NHL.

Sincerely, Stephanie A. Gregory, MD The Elodia Kehm Chair of Hematology Professor of Medicine Director, Lymphoma Program Rush University Medical Center/Rush University Chicago, IL

Director, Production and Manufacturing Alaina Pede

Director, Creative and Design Robyn Jacobs

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FACULTY Mitchell R. Smith, MD, PhD Director, Lymphoma Service Fox Chase Cancer Center Philadelphia, PA

Barbara Rogers CRNP, MN, AOCN, ANP-BC Adult Hematology-Oncology Nurse Practitioner Fox Chase Cancer Center Philadelphia, PA

Dwight Kloth, PharmD, FCCP, BCOP Director of Pharmacy Fox Chase Cancer Center Philadelphia, PA

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Executive Administrator Jackie Luma

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Supported by educational grants from Millennium: The Takeda Oncology Company and Spectrum Pharmaceuticals

This activity is jointly sponsored by Medical Learning Institute, Inc., and Center of Excellence Media, LLC.

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CONSIDERATIONS IN LYMPHOMA Sponsor This activity is jointly sponsored by Medical Learning Institute, Inc., and Center of Excellence Media, LLC.

Learning Institute, Inc. and the Center of Excellence Media, LLC. The Medical Learning Institute, Inc. is accredited by the ACCME to provide continuing medical education for physicians.

Target Audience The activity was developed for physicians, nurses, and pharmacists involved in the treatment of patients with mantle cell lymphoma.

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Provider approved by the California Board of Registered Nursing, Provider Number 15106, for 1.25 contact hours.

Educational Objectives Upon completion of this activity, the participant will be able to: • Analyze results of recent clinical trials investigating the incorporation of newer agents into mantle cell lymphoma (MCL) treatment • Discuss the safety and efficacy of adding radioimmunotherapy to chemotherapy regimens for patients with MCL • Summarize common toxicities associated with treatments for MCL, and identify current approaches to reduce or ameliorate these effects Commercial Support Acknowledgment This activity is supported by educational grants from Millennium: The Takeda Oncology Company and Spectrum Pharmaceuticals.

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Barbara Rogers CRNP, MN, AOCN, ANP-BC, is on the advisory board for Celgene and Teva, and on the speakers bureau for Allos, Millennium: The Takeda Oncology Company, Spectrum Pharmaceuticals and Teva. *Dwight Kloth, PharmD, FCCP, BCOP, is the director of the pharmacy advisory board for Amgen, Celgene, Eisai, Hospira, and Prostrakan. *Content will include non-FDA-approved uses.

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Current and Emerging Treatment Strategies in Mantle Cell Lymphoma Mitchell R. Smith, MD, PhD Director, Lymphoma Service Fox Chase Cancer Center, Philadelphia, PA

ple, a minority of patients (about 5%-10%) have indolent disease.2-4 Therefore, it is important to factor in cell proliferation and other disease characteristics, in addition to age and performance status, to ensure that patients are not “overtreated.” MCL is essentially an incurable disease, and we do not want to subject individuals to severe drug-related toxicities that may shorten survival.

Introduction Mantle cell lymphoma (MCL) is an uncommon, clinically heterogeneous subtype of B-cell lymphoma. Although survival rates for patients

Which regimens can be used when an intensive approach to frontline treatment is necessary?

have improved over the past decade, the disease remains incurable.

An individualized approach to treatment is essential, taking into account age, performance status, and whether a patient needs more or less aggressive therapy. In this article, Mitchell R. Smith, MD, PhD, answers questions related to the treatment of newly diagnosed and relapsed/refractory MCL and provides insights on recent developments that may lead to improved clinical outcomes.

Which factors need to be considered when choosing frontline therapy for patients with MCL?

Age, performance status, pace of disease, and goals of therapy are all important factors to consider when deciding on an approach to initial treatment.

Older patients and individuals with compromised health status cannot tolerate some of the more intensive regimens used to treat MCL, such as those containing high-dose chemotherapy. Younger, more fit individuals can often endure these regimens1; however, this approach may not always be required. For exam-

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To date, the best published outcomes data have been observed with a regimen of rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-HyperCVAD) alternating with rituximab plus high-dose methotrexate and cytarabine (R-MA).5,6 Investigators from MD Anderson Cancer Center recently published 10-year follow-up data on the safety and efficacy of this regimen, which they studied in an MCL population with no upper age limit. Survival was good, but toxicity was significant, especially in older patients.5,6 The Gruppo Italiano Studio Linfomi (GISL) reported that R-HyperCVAD/ R-MA was effective in patients 70 years, but only 22 of 60 patients could actually complete the 8 planned cycles.7 The Southwest Oncology Group (SWOG) also conducted a study that reached more or less the same conclusion: R-HyperCVAD/R-MA was difficult to complete, but the regimen provided reasonable results for those who could tolerate it.8 At our institution, we often use R-HyperCVAD/R-MA in patients who are 60 years of age or younger, and we ensure that patients near the cutoff age have good performance status before we decide to use this regimen.

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Figure. Response rates with VcR-CVAD plus rituximab maintenancea in MCL: interim results (n=76).18

96%

100

75%

Patients (%)

80 60 40

21% 20

results suggest applicability in select older patients. These regimens appear to be feasible therapeutic options, but longer follow-up is necessary.

An emerging trend is to combine ASCT with shorter courses of R-HyperCVAD/R-MA. The upcoming US Intergroup S1106 trial will treat patients 65 years old with 2 rather than 4 cycles of R-HyperCVAD/R-MA, followed by consolidation therapy and ASCT.13 This strategy will allow patients to receive intensive cytoreduction before transplantation. In my opinion, ASCT is easier for patients to endure than the 4 additional rounds of RHyperCVAD/R-MA used in the traditional protocol. S1106 also has a comparative arm of less-intensive induction with bendamustine plus rituximab (BR), followed by ASCT. Hopefully, results from this trial will offer insight on how intensive cytoreduction really needs to be prior to transplantation.

0

Overall Response

Complete Response

Partial Response

a

Given to patients achieving stable disease, partial response, or complete response to VcR-CVAD. MCL indicates mantle cell lymphoma; VcR-CVAD: bortezomib, rituximab, cyclophosphamide, vincristine, doxorubicin, and dexamethasone.

Table. R-CHOP (4 cycles) Followed by RIT Consolidation With 90 Y-Ibritumomab Tiuxetan in MCL: Efficacy Results at 5-Year Follow-up (n=57)19 Endpoint PFS ➢ PFS in patients 65 years ➢ PFS in patients >65 years Overall response rate ➢ CR/CRu ➢ PR Number of patients in whom response improved after RIT Estimated median OS ➢ 5-year OS in patients 65 years ➢ 5-year OS in patients >65 years

Result 31 months 32 months 25 monthsa 82% 56% 26% 23/44 76 month

No significant difference between age groups.

Significant difference between age groups (P=.023).

CR/Cru indicates complete response/complete response unspecified; MCL, mantle cell lymphoma; OS, overall survival; PFS, progression-free survival; PR, partial response; RCHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; RIT, radioimmunotherapy. b

For patients aged 60 to 70 years who are diagnosed with aggressive disease, we often use rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP),9 followed by consolidation with myeloablative chemotherapy and autologous stem cell transplantation (ASCT). A randomized trial by the European MCL Network (MCL net) showed that, in MCL patients treated with CHOP or R-CHOP, myeloablative radiochemotherapy plus ASCT prolonged progression-free survival (PFS) compared with interferon maintenance.10 The MCL net also studied a variation in treatment: alternating courses of R-CHOP plus rituximab, dexamethasone, cytarabine, and cisplatin (RDHAP), followed by high-dose cytarabine-based myeloablation and ASCT.11 This regimen had acceptable toxicity compared with a regimen of R-CHOP followed by cyclophosphamide-based myeloablation and ASCT. Similarly, the Nordic Lymphoma Group reported favorable outcomes with dose-intensified R-CHOP alternating with R-A, followed by ASCT.12 Although neither of these trials included patients older than 65 years, the favorable toxicity

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R-CHOP remains a common choice for patients who cannot tolerate aggressive treatment. Responses to this regimen are good, but not durable, in MCL.14 As a result, researchers are searching for alternative therapies. In a phase 3 trial by the German Study Group Indolent Lymphomas (StiL), Rummel and colleagues showed that BR was more effective (with better tolerability) than R-CHOP in a population of lymphoma patients that included individuals with MCL.15 This study has been the genesis of many ongoing trials of regimens based on BR. For example, the US Intergroup E1411 trial, which is set to open in the next few months, will evaluate a regimen of BR with or without bortezomib as frontline therapy.16 Kahl and colleagues studied a modified R-HyperCVAD regimen, which omitted the alternating cycle of R-MA but included rituximab maintenance.17 The results were intriguing, so the approach was extended to the ECOG E1405 trial, which also added bortezomib.18 This study of VcRCVAD plus rituximab maintenance is now accrued and closed; interim results showed a high complete response (CR) rate (Figure), but we need longer follow-up to see whether this translates into better PFS and OS.

76 months 66 monthsb

a

22

Which regimens can be used when a less-intensive approach to frontline treatment is necessary?

Hopefully, results from this trial will offer insight on how intensive cytoreduction really needs to be prior to transplantation.

Our group conducted a separate ECOG trial (E1499), which evaluated RCHOP for 4 cycles (instead of the traditional 6 cycles), followed by a dose of radioimmunotherapy (RIT) with 90Y-ibritumomab tiuxetan.19 This is a brief regimen, applicable to the vast majority of MCL patients, which results in relatively good outcomes (Table). We are using R-CHOP followed by RIT more frequently, keeping in mind that we do not have the breadth of data on this regimen for MCL that we do for follicular lymphoma via the phase 3 First-Line Indolent Trial.20 It appears that BR, modified R-HyperCVAD (with or without bortezomib) followed by rituximab maintenance, and R-CHOP followed by RIT are all reasonable choices for patients who require less-intensive regimens.

Two of these options include consolidation of response, which I think is an important consideration in MCL. In the studies of modified R-HyperCVAD, rituximab maintenance appeared to be helpful.17,18 We have learned more from an MCL net trial conducted in elderly patients, which compared R-CHOP versus rituximab, fludarabine, and cyclophosphamide (R-FC), after which patients were ran-

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CONSIDERATIONS IN LYMPHOMA

domized a second time to rituximab maintenance versus interferon.21 Patients receiving R-CHOP followed by rituximab maintenance had an excellent outcome, much better than we usually see in MCL—4-year OS was 87%, although this was limited to R-CHOP responders. Results were not as good with R-CHOP followed by interferon maintenance or R-FC followed by either type of maintenance. Moreover, R-FC followed by rituximab maintenance produced the highest infection rate (50%) of any induction/maintenance combination in the trial. One of the lessons of this study is that R-FC is probably not a good regimen for initial treatment of elderly patients with MCL. Another lesson is that, when R-CHOP or a similar regimen is used for initial therapy, rituximab maintenance is clearly beneficial.

Ongoing trials continue to refine the role of maintenance therapy in MCL. For instance, the E1411 trial discussed earlier will also compare rituximab maintenance with lenalidomide-rituximab maintenance.16 What investigational agents and regimens are showing promise in the treatment of MCL?

We are excited about drugs that target the B cell receptor signaling pathway, including the Bruton’s tyrosine kinase inhibitor ibrutinib (PCI-32765).

Wang and colleagues recently presented data showing a high response rate with single-agent ibrutinib in the relapsed/refractory setting for MCL.22 The phosphatidylinositol 3-kinase (PI3K) inhibitor GS-1101 (formerly known as CAL-101) is also demonstrating good activity.23 Both ibrutinib and GS1101 are well-tolerated oral agents.22,23 BCL2 pathway inhibitors, such as obatoclax, navitoclax, and oblimersen, may also have a role in MCL.24 The mammalian target of rapamycin (mTOR) inhibitors, notably temsirolimus and everolimus, have clinical activity in MCL.25,26 Investigators are beginning to assess whether dual PI3K/mTOR inhibition may be effective in the treatment of the disease.27 Combining mTOR inhibition with something that targets B-cell receptor signaling allows us to hit 2 pathways. In principle, the cell will be less likely to have, or to develop, resistance to such a combination. There is also growing interest in the use of histone deacetylase inhibitors in combination with other agents for the treatment of MCL.28 A number of studies are combining investigational agents with chemotherapy or approved novel agents. One example is a trial of obatoclax plus bortezomib for the treatment of relapsed and refractory MCL.29 Trials like these reflect a useful strategy: combining a B-cell signaling agent and a pro-apoptotic agent, which may signal cells not to divide and at the same time to undergo cell death.

Bortezomib is the only targeted agent approved by the US Food and Drug Administration for the treatment of relapsed MCL. Two groups recently evaluated bortezomib plus BR in trials of previously treated patients with lymphoma, including MCL.30,31 The results were interesting, and the combination was tolerable. While it may be advantageous to add these drugs together to treat patients with relapsed/refractory disease, it is not clear whether we should give bendamustine and bortezomib together or sequentially in this setting. Rituximab plus lenalidomide also has a role in the treatment of relapsed/refractory MCL. Given the clinical activity and tolerability of this combination,32 it is also being explored as maintenance therapy.

Clearly, we have entered a very productive period of research in the treatment of the disease. Novel targeted agents and new combination regimens have the potential to prolong survival and improve clinical outcomes for patients diagnosed with MCL.◆ References 1. Ghielmini M, Zucca E. How I treat mantle cell lymphoma. Blood. 2009;114:1469-1476.

2. Ondrejka SL, Lai R, Smith SD, Hsi ED. Indolent mantle cell leukemia: a clinicopathological

variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis. Haematologica. 2011;96:1121-1127.

3. Vizcarra E, Martínez-Climent JA, Benet I, et al. Identification of two subgroups of mantle cell leukemia with distinct and biological features. Hematol J. 2001;2:234-241.

4. Fernàndez V, Salamero O, Espinet B, et al. Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Res. 2010;70:1408-1418.

5. Romaguera JE, Fayad L, Rodriquez MA, et al. High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus Hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol. 2005;23:7013-7023.

6. Romaguera JE, Fayad LE, Feng L, et al. Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma. Br J Haematol. 2010;150:200-208.

7. Merli F, Luminari S, Ilariucci F, et al. Rituximab plus HyperCVAD alternating with high dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma, a multicentre trial from Gruppo Italiano Studio Linfomi. Br J Haematol. 2012;156:346-353.

8. Epner EM, Unger J, Miller T, et al. A multi center trial of hyperCVAD+Rituxan in patients with newly diagnosed mantle cell lymphoma. Blood (ASH Annual Meeting Abstracts). 2007;110: Abstract 387.

9. Lenz G, Dreyling M, Hoster E, et al. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol. 2005;23:184-1992.

10. Dreyling M, Lenz G, Hoster E, et al. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progressionfree survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005;105:2677-2684.

11. Hermine O, Hoster E, Walewski J, et al. Alternating courses of 3x CHOP and 3x DHAP plus rituximab followed by a high dose ARA-C containing myeloablative regimen and autologous stem cell transplantation (ASCT) is superior to 6 courses CHOP plus rituximab followed by myeloablative radiochemotherapy and ASCT in mantle cell lymphoma: results of the MCL younger trial of the European Mantle Cell Lymphoma Network (MCL net). Blood (ASH Annual Meeting Abstracts). 2010;116:Abstract 110.

12. Geisler CH, Kolstad A, Laurell A, et al. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo–purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008;112: 2687-2693.

13. Bernstein S; Southwest Oncology Group (SWOG). Phase II randomized study of induction therapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, dexamethasone, methotrexate, cytarabine, and leucovorin calcium versus rituximab and bendamustine hydrochloride followed by consolidation therapy and autologous stem cell transplantation in older patients with previously untreated mantle cell lymphoma (S1106). http://cancer.gov/clinicaltrials/search/view?cdrid=707601&version=healthprofessional. Accessed May 7, 2012.

14. Howard OM, Gribben JG, Neuberg DS, et al. Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: molecular complete responses are not predictive of progression-free survival. J Clin Oncol. 2002;20:1288-1294.

15. Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab is superior in respect of progression free survival and CR rate when compared to CHOP plus rituximab as firstline treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: final results of a randomized phase III study of the StiL (Study Group Indolent Lymphomas, Germany).

Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 405.

16. Smith MR; Eastern Cooperative Oncology Group (ECOG). Rituximab, bendamustine hydrochloride, and bortezomib followed by rituximab and lenalidomide in treating older patients with previously untreated mantle cell lymphoma (E1411). http://www.clinicaltrials.gov/ ct2/show/NCT01415752?term=E1411&rank=1. Accessed May 7, 2012.

17. Kahl BS, Longo WL, Eickoff JC, et al. Maintenance rituximab following induction chemoimmunotherapy may prolong progression-free survival in mantle cell lymphoma: a pilot study from the Wisconsin Oncology Network. Ann Oncol. 2006;17:1418-1423.

18. Kahl BS, Li H, Smith MR, et al. The VcR-CVAD regimen produces a high complete response rate in untreated mantle cell lymphoma (MCL): first analysis of E1405—a phase II study of VcRCVAD with maintenance rituximab for MCL. Blood (ASH Annual Meeting Abstracts). 2009; 114:Abstract 1661.

19. Smith MR, Li H, Gordon L, et al. Phase II study of R-CHOP followed by 90Y-ibritumomab tiuxetan in untreated mantle cell lymphoma (MCL): 5 year follow-up of Eastern Cooperative Oncology Group E1499. Ann Oncol (ICML Annual Meeting Abstracts). 2011;22(suppl 4):Abstract 017.

20. Morschhauser F, Radford J, Van Hoof A, et al. Phase III trial of consolidation therapy with yttrium-90–ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008;26:5156-5164.

21. Kluin-Nelemans JC, Hoster E, Walewski J, et al. R-CHOP versus R-FC followed by maintenance with rituximab versus interferon-alfa: outcome of the first randomized trial for elderly patients with mantle cell lymphoma. Blood (ASH Annual Meeting Abstracts). 2011;118:Abstract 439.

22. Wang L, Martin P, Blum KA, et al. The Bruton’s tyrosine kinase inhibitor PCI-32765 is highly active as single-agent therapy in previously-treated mantle cell lymphoma (MCL): preliminary results of a phase II trial. Blood (ASH Annual Meeting Abstracts). 2011;118:Abstract 442.

23. Kahl B, Byrd JC, Flinn IW, et al. Clinical safety and activity in a phase 1 study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110 , in patients with relapsed or refractory non-Hodgkin lymphoma. Blood (ASH Annual Meeting Abstracts). 2010;116: Abstract 1777.

24. Jares P, Colomer D, Campo E. Genetic and molecular pathogenesis of mantle cell lymphoma: perspectives for new targeted therapeutics. Nature Review Cancer. 2007;7:750-762.

25. Hess G, Herbrecht R, Romaguera J, et al. Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009;27:3822-3829.

26. Renner C, Zinzani PL, Gressin R, et al. A multi-center phase II study (SAKK 36/06) of single agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma. Blood (ASH Annual Meeting Abstracts). 2010;116:Abstract 2803.

27. Meadows SA, Kashishian A, Johnson D, et al. CAL-101 (GS-1101), a specific inhibitor of phosphatidylinositol-3-kinase-delta (PI3K ), disrupts signals from the microenvironment, induces apoptosis, and enhances the antitumor activity of everolimus (RAD001), an inhibitor of mam-

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Improving Patient Outcomes in Mantle Cell Lymphoma Barbara Rogers, CRNP, MN, AOCN, ANP-BC Adult Hematology-Oncology Nurse Practitioner Fox Chase Cancer Center Philadelphia, PA

Introduction The treatment of mantle cell lymphoma (MCL) continues to evolve with the development of newer, more effective therapies. However, treatment-related adverse events remain a significant source of concern, as they may negatively impact clinical outcomes and quality of life. In this article, Barbara Rogers, CRNP, MN, AOCN, ANP-BC, answers questions concerning specific toxicities that may occur during treatment, including infection, myelosuppression, and hypersensitivity reactions. She also discusses the importance of individualizing management strategies to provide optimal patient care.

What steps are necessary to minimize infection in patients with MCL who undergo stem cell transplantation?

The National Comprehensive Cancer Network (NCCN) suggests highdose therapy with autologous stem cell transplant (ASCT) as consolidation for patients receiving first-line therapy for MCL and high-dose therapy with allogeneic SCT (allo-SCT) for consolidation in the second-line setting.1 Both of these approaches are myelosuppressive, with allo-SCT being associated with a much higher infection risk than ASCT.1 This risk may be lessened to some degree if a patient is treated with a nonmyeloablative allo-SCT. This type of transplant administers chemo radiotherapy with the intent of allowing for donor cell engraftment, with less of an emphasis on dose intensity. Based on emerging safety and efficacy data,2,3 nonmyeloablative alloSCTs may become the preferred transplant modality for patients with relapsed/refractory MCL when suitable donors are available.

Regardless of the type of transplant a patient receives, nurses should carefully monitor patients for signs and symptoms of infection during all phases of the process. Patients must receive prophylaxis for bacterial, viral, and fungal infections, in accordance with guidelines published by the Centers for Disease Control and Prevention, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation.4 Patient education about infection precautions should include the importance of good hygiene (especially frequent hand washing), food safety, and strategies for avoiding or minimizing exposure to potentially infectious people and pets.4 Following transplant, patients must also be reimmunized with childhood vaccinations, because antibody titers to vaccine-preventable diseases decrease 1 to 4 years post-transplant. Guidelines suggest a schedule of reimmunization that begins 1 year after allo-SCT or ASCT.4 At our institution, we try to follow these recommendations as closely as possible. There are times, however, when we may need to alter the schedule due to specific medical situations, such as patients who are extremely immunocompromised after transplant.

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How do you minimize and manage infusion reactions associated with the use of rituximab?

Similar to other monoclonal antibodies, rituximab is associated with infusion reactions that are caused primarily by cytokine release, rather than true allergic reactions.5 The incidence of mild-to-moderate reactions is approximately 77% with the first infusion of rituximab and tends to decrease with subsequent infusions.5,6 Certain factors may increase the risk of a reaction, including having a hematologic malignancy such as MCL (Table 1).6 Patient education is the first step in the effective management of rituximab-related infusion reactions. We always inform patients of potential signs and symptoms that may occur during their first infusion. Common symptoms are fever, chills, and rigors; less frequent (and more severe) reactions include angioedema, bronchospasm, and dyspnea.5 All patients receiving rituximab must be premedicated with acetaminophen and diphenhydramine prior to each infusion. If we anticipate that a patient is at very high risk for a reaction,6 we will also administer a steroid such as dexamethasone. Risk factors for more significant infusion reactions are very high white blood cell (WBC) counts or untreated bulky disease.6 In patients with high counts, we may divide the dose of rituximab over 2 days.

For example, we may administer 100 mg of the calculated dose on day 1 and the remainder of the dose on the following day. Alternatively, we may omit rituximab in the first cycle of treatment to allow for a decline of the WBC count, and add it during the second cycle instead.

We start the rituximab infusion slowly and monitor vital signs every 30 minutes. If a reaction occurs, we stop the infusion, perhaps give more steroid

Table 1. Risk Factors for Hypersensitivity Reactions6 Asthma diagnosis Atopic patients (ie, patients who tend to react to specific allergens, such as hay fever, skin irritations, and asthma) Circulating lymphocyte counts 25,000 mm3 (lymphoma or leukemia) Concomitant -adrenergic blocker therapy Concurrent autoimmune disease Female gender Higher than standard drug doses Iodine or seafood allergies Newly diagnosed, untreated patients Older age Patients with hematologic malignancies such as mantle cell lymphoma and chronic or small lymphocytic leukemia Personal history of drug allergy or previous immediate reaction to a medication Preexisting cardiac or pulmonary dysfunction Previous exposure to the drug Vogel WH. Infusion reactions: diagnosis, assessment, and management. Clin J Oncol Nurs.

2010;14:E10-E21. Reproduced with permission of the Clinical Journal of Oncology Nursing.

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CONSIDERATIONS IN LYMPHOMA

or diphenhydramine, and wait for recovery. A histamine-2 receptor antagonist may also be added as a precautionary measure. We then resume rituximab at a slower rate. When a patient has a severe, anaphylactic-like reaction, the infusion is usually discontinued and reinitiated on an alternate day.

In rare situations, we may need to halt rituximab therapy permanently.

What strategies can be used to manage hematologic toxicities associated with treatments for MCL?

Our approach to the management of neutropenia, anemia, and thrombocytopenia is dependent on the severity of the myelosuppression itself, as well as patient-specific factors. We always use pegfilgrastim when administering chemotherapy regimens that pose a high risk of neutropenia, such as rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-HyperCVAD). For older patients, who are at higher risk of neutropenic fever, we give neutrophil growth factors starting with the first cycle of treatment, in accordance with guidelines from the American Society of Clinical Oncology.7 However, younger, fit patients and those who are being treated with less aggressive chemotherapy combinations usually do not receive growth-factor support unless we see a need for it during treatment.

If a patient develops anemia, transfusion may be necessary. However, according to current NCCN recommendations, the decision to transfuse should not be based solely on red blood cell (RBC) count, but rather on patient-specific criteria.8 For example, patients with cardiac comorbidities are often transfused at a higher hemoglobin level than otherwise healthy individuals. We also use the erythropoiesis-stimulating agents (ESAs) epoetin alfa and darbepoetin alfa to treat anemia in some cases. Although these agents can be beneficial, as they help patients avoid transfusion, they are associated with serious risk, including increased mortality and tumor progression, thromboembolism, hypertension, and seizures.8 As a result, ESAs are contraindicated if the intention of treatment is to cure.

Treatment with standard chemotherapy can cause a decline in platelet count. If a patient experiences severe thrombocytopenia (platelet count <10,000 platelets/mm3 without bleeding or 10,000 platelets/mm3 with bleeding),9 we initiate a platelet transfusion. Dose reductions of certain agents may be helpful for reducing a patient’s risk of experiencing severe thrombocytopenia in future cycles of therapy.

In clinical practice, we have also learned that some drugs may be better tolerated if they are administered at a dose lower than what is listed in the package insert. For example, the approved dose of bendamustine for the management of non-Hodgkin lymphoma is 120 mg/m2.10 However, in a phase 3 trial of patients with mantle cell, indolent, and follicular lymphomas, Rummel and colleagues administered bendamustine at a dose of 90 mg/m2, in combination with rituximab (BR). This regimen was shown to be effective and well tolerated, with a reasonably good safety profile. As shown in Table 2, significant differences in grade 3/4 hematologic toxicities were observed between BR and a regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).11 It is important to remember, however, that there are clinical scenarios in which dose-reducing bendamustine may not be the best course of action, and the full dose will be needed to obtain adequate response.

The rate of recovery from hematologic toxicities varies, depending on the type of therapy the patient is receiving, as well as what he or she received in the past. With chemotherapy, the nadir occurs approximately 7 to 10 days after treatment. R-HyperCVAD/R-MA is associated with profound (grade 4) neutropenia and thrombocytopenia in spite of growth-factor support,12 and-

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Table 2. Grade 3/4 Myelosuppression in the Phase 3 StiL Trial of R-CHOP versus BR11 Toxicity

R-CHOP (N=253)

BR (N=260)

P Value

Neutropenia

46.5%

10.7%

<.0001

Leukocytopenia

38.2%

12.1%

<.0001

Use of G-CSF

20.0%

4.0%

<.0001

BR indicates bendamustine plus rituximab; G-CSF, granulocyte colony-stimulating factors; R-CHOP; rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

patients treated with this type of aggressive regimen are at greater risk of developing neutropenic fever. Hematologic toxicities seen with regimens such as BR and R-CHOP tend to be less severe, but still require careful monitoring and management strategies.11,13 With radioimmunotherapy, the rate of myelosuppression is usually delayed; blood cell and platelet counts typically do not decline until approximately 1 month after treatment. For example, following 90Y-ibritumomab tiuxetan therapy, nadir counts occur at about 7 to 9 weeks post treatment and last approximately 1 to 4 weeks before recovery begins.14 As a result, patients do not receive additional antilymphoma therapies for approximately 3 to 4 months following treatment.

Conclusion

Although advances in the treatment of MCL have led to improved outcomes, individuals who receive treatment with novel agents, with or without transplant, can potentially experience significant toxicities that can lead to greater morbidity and mortality. Nurses must be aware of evidence-based preventative and supportive care strategies for these toxicities so that patients can be promptly treated and continue with their therapy. ◆ References 1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™): Non-Hodgkin Lymphoma. Version 2.2012. http://www.nccn.org.

Accessed May 14, 2012.

2. Khouri IF, Lee MS, Saliba RM, et al. Nonablative allogeneic stem-cell transplantation for advanced/recurrent mantle-cell lymphoma. J Clin Oncol. 2003;21:4407-4412.

3. Tam CS, Bassett R, Ledesma C, et al. Mature results of the M.D. Anderson Cancer Center riskadapted transplantation strategy in mantle cell lymphoma. Blood. 2009;113:4144-4152.

4. Centers for Disease Control and Prevention; Infectious Diseases Society of America; American Society of Blood and Marrow Transplantation. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. MMWR Recomm Rep. 2000;49:1-125.

5. Lenz H-J. Management and preparedness for infusion and hypersensitivity reactions.

Oncologist. 2007;12:601-609.

6. Vogel WH. Infusion reactions: diagnosis, assessment, and management. Clin J Oncol Nurs.

2010;14:E10-E21.

7. Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline. J Clin Oncol. 2006;24:3187-3205 8. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™): Cancer- and Chemotherapy-Induced Anemia. Version 2.2012. http:// www.nccn.org. Accessed May 15, 2012.

9. Slichter SJ. Evidence-based platelet transfusion guidelines. Hematology Am Soc Hematol Educ Program. 2007:172-1788. Review.

10. Treanda [package insert]. Frazer, PA: Cephalon, Inc; 2008.

11. Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab is superior in respect of progression free survival and CR rate when compared to CHOP plus rituximab as first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: final results of a randomized phase III study of the StiL (Study Group Indolent Lymphomas, Germany). Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 405.

12. Romaguera JE, Fayad L, Rodriquez MA, et al. High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol. 2005;23: 7013-7023.

13. Lenz G, Dreyling M, Hoster E, et al. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol. 2005;23:1984-1992.

14. Witzig TE, White CA, Gordon LI, et al. Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-Hodgkin’s lymphoma. J Clin Oncol. 2003;21:1263-1270.

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CONTINUING EDUCATION

Pharmacologic Considerations in the Treatment of Mantle Cell Lymphoma Dwight Kloth, PharmD, FCCP, BCOP Director of Pharmacy, Fox Chase Cancer Center Philadelphia, PA

Introduction Historically, the treatment of mantle cell lymphoma (MCL) has relied on conventional chemotherapeutic agents, which, unfortunately, are not curative. Patients eventually relapse following initial treatment, and overall survival rates have remained quite variable,

of therapy to prolong survival while minimizing side effects? It is important to have an open dialogue with patients in order to review their treatment history, establish priorities, and ascertain which therapies offer the best chance of meeting therapeutic goals. For instance, if a patient expresses a desire to continue working at a job that requires great mental acuity, it may be prudent to avoid lenalidomide-based treatment, as this drug can cause significant drowsiness.2 Similarly, a patient’s ability to perform certain work-related tasks may be impaired by bortezomib-induced peripheral neuropathy.1 Consequently, it is imperative to consider the toxicity profile of any agent as part of the decision algorithm.

with most patients succumbing to the disease. In recent years, a number of newer therapies have been developed for MCL, leading to more durable responses in both the frontline and relapsed/refractory

What special requirements are necessary to administer radioimmunotherapy (RIT) to patients with MCL?

settings. With an ever-increasing array of choices, treatment decisions have become more complex, requiring careful consideration of numerous patient- and drug-related factors. In this article, Dwight Kloth, PharmD, FCCP, BCOP, answers questions related to the use of novel agents for MCL and provides his clinical perspectives on future directions in the treatment of the disease.

What are some of the pharmacologic issues that must be considered when using novel drugs in the relapsed/refractory setting for MCL?

We are fortunate to have several novel therapies available to treat patients with relapsed/refractory MCL. If we try 1 agent and it is not well tolerated or does not appear to be effective, we can usually offer the patient an alternative treatment. When choosing among the different agents, we must consider several factors. For example, the novel agents we are using with the greatest frequency in MCL—bendamustine, bortezomib, lenalidomide, and rituximab—have varied routes of administration. Bendamustine and rituximab can only be given by intravenous (IV) infusion, which lasts 60 minutes or longer. Bortezomib has traditionally been used as an IV drug but is increasingly being administered subcutaneously (SC). This new approach is based on a study in multiple myeloma patients that showed reduced neurotoxicity and similar therapeutic benefit with SC dosing.1 Lenalidomide is taken orally, which increases convenience but also raises issues concerning the teratogenic risk associated with this drug.2 Patients must be advised that the risk management program for lenalidomide is not trivial.

Prior to prescribing a high-cost oral agent, it is important to ascertain whether a patient has a prescription drug benefit plan, and what the tier level for the out-of-pocket copay will be, as reimbursement issues can have a significant impact on patients and their families. Individuals may have coverage for an IV drug administered by a healthcare provider (eg, Medicare Part B or a commercial insurer’s major medical plan), but not for an oral self-administered agent, and this may affect choice of therapy. Other considerations include the patients’ ability to travel to the clinic for IV infusions and how well they are able to comply with and adhere to an oral drug regimen.

Goals of therapy are another factor to consider when selecting treatments.

Are we trying to prepare the patient for stem cell transplantation? Is the aim

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JunE 2012 I VOL 5, nO 5

Clinical data regarding the use of RIT in MCL are somewhat limited.

However, 90Y-ibritumomab tiuxetan consolidation therapy after a regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone improved the quality of response in 57 previously untreated patients with stage III/IV MCL.3 The mechanism of action of RIT—radiation combined with a monoclonal antibody carrier—provides an interesting and effective way to target treatment right to the malignancy. The antibody binds to receptor sites on the tumor cell, and the radiation hits the cell where it is targeted. Radiation also hits neighboring tumor cells that may be inaccessible to the antibody due to penetration barriers—a phenomenon called radioactive crossfire.4 However, logistics can be a challenge with RIT. The half-life of the radiolabeled combination product makes this therapy extremely time sensitive,5 so everything has to be carefully staged and choreographed. The antibody must be radiolabeled by a nuclear-certified pharmacy in close geographic proximity to the treatment site; this needs to be done immediately before the scheduled time of treatment to ensure that radiation does not decay excessively. In addition, patients must have the necessary bone marrow reserves and hematologic status to undergo RIT (Table).4-7 Careful follow-up is needed postRIT, to prepare for the nadir of blood counts several weeks later.8 These issues almost always make it impractical for a small oncology practice to provide RIT to their patients. The therapy is usually coordinated and given by a nuclear medicine department and its affiliated pharmacy. These clinicians have the expertise to give RIT efficiently and safely, and to maintain continuity of care as patients return home and back to their oncology team.

Table. Bone Marrow Reserves and Hematologic Criteria for the Administration of Radioimmunotherapy4-7 • Bone marrow: - < 25% bone marrow involvement with lymphoma, assessed via biopsy - No other evidence of bone marrow impairment • Blood counts: - Platelet count 100,000 cells/mm3 - Neutrophil count 1500 cells/mm3

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CONSIDERATIONS IN LYMPHOMA

9

Figure. The central role of Btk in the B-cell fate.

apoptosis of non-Hodgkin lymphoma cell lines.11 The PI3-K pathway may have special relevance to MCL. It is part of a larger pathway—PI3K/Akt/mTOR (mammalian target of rapamycin)—involved in the transduction of signals from cell receptors to proteins that mediate cell cycling. These proteins include cyclin D1, which is overexpressed in MCL.12,13 Promising results with GS-1101 have been reported in a phase 1 study that included 16 heavily pretreated patients with relapsed/refractory MCL.11 ORR was 62%, with higher rates of response in the relapsed versus the refractory populations (73% and 40%, respectively). Median duration of response in MCL was 3 months (range, 1-8 months).11 Recent data show that GS-1101 is active in combination with the mTOR inhibitor everolimus, another agent that affects protein kinase pathways and interrupts translation of cyclin D1.12,13 Several investigative teams are now developing protocols with kinase inhibitors in combination with other drugs. These novel agents are an exciting development, because they are targeted to the B cell and to specific molecular pathways of MCL.9,12-14 The hope is that this kind of targeting will move us closer to our goal of prolonging survival in this difficult-to-treat population of patients. ◆

References Courtesy of Sabine Ponader, PhD.

Can you discuss the mechanism of action and clinical activity of the investigational agents ibrutinib (PCI-32765) and GS-1101 (formerly known as CAL-101)?

Ibrutinib (PCI-32765) is an inhibitor of Bruton’s tyrosine kinase (Btk), which is a key component of the B-cell receptor signaling pathway.9 This agent selectively and permanently inhibits Btk, which blocks B-cell activation and downstream signaling of the B-cell receptor (Figure). MCL cells are known to express Btk.9 Preliminary results of an ongoing phase 2 study of ibrutinib in MCL were recently reported.10 A total of 48 patients were enrolled, in cohorts of bortezomib-naive and bortezomib-exposed, with 24 patients evaluable for response.

The objective response rate (ORR) for both cohorts was 67% (16/24); ORR was 58% (7/12) in the bortezomib-naive cohort and 75% (9/12) in the bortezomib-exposed cohort. Treatment was well-tolerated; the most frequent grade 1/2 toxicities included fatigue, diarrhea, and nausea. Grade >3 toxicities considered potentially related to ibrutinib were observed in 11% of patients.10 The expression of phosphatidylinositol 3-kinase (PI3-K) P110 in cells of hematopoietic origin influences B-cell proliferation and survival.11 GS-1101 is a selective inhibitor of PI3-K signaling and has been shown in vitro to induce

1. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011;12:431-440.

2. Revlimid [package insert]. Summit, NJ: Celgene Corporation. October 2011.

3. Smith MR, Li H, Gordon L, et al. Phase II study of R-CHOP immunochemotherapy followed by 90Y-ibritumomab tiuxetan in untreated mantle cell lymphoma: 5-year Eastern Cooperative Oncology Group Study E1499. J Clin Oncol. In press.

4. Rao AV, Akabani G, Rizzieri DA. Radioimmunotherapy for non-Hodgkin’s lymphoma. Clin Med Res. 2005;3:157-165.

5. Wagner HN Jr, Wiseman GA, Marcus CS, et al. Administration guidelines for radioimmunotherapy of non-Hodgkin’s lymphoma with 90Y-labeled anti-CD20 monoclonal antibody.

J Nucl Med. 2002;43:267-272.

6. Zevalin [package insert]. Irvine, CA: Spectrum Pharmaceuticals, Inc. November 2011.

7. Bexxar [package insert]. Research Triangle Park, NC: GlaxoSmithKline. February 2012.

8. Wiztig TE, White CA, Gordon LI, et al. Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-Hodgkin’s lymphoma. J Clin Oncol. 2003;21:1263-1270.

9. Ponader S, Balasubramanian S, Pham LV, et al. Activity of Bruton’s tyrosine kinase (Btk) inhibitor PCI-32765 in mantle cell lymphoma (MCL) identifies Btk as a novel therapeutic target. Blood (ASH Annual Meeting Abstracts). 2011;118. Abstract 3688 and Poster.

10. Wang L, Martin P, Blum KA, et al. The Bruton’s tyrosine kinase inhibitor PCI-32765 is highly active as single-agent therapy in previously-treated mantle cell lymphoma (MCL): preliminary results of a phase II trial. Blood (ASH Annual Meeting Abstracts). 2011;118. Abstract 442.

11. Kahl B, Byrd JC, Flinn IW, et al. Clinical safety and activity in a phase 1 study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110 , in patients with relapsed or refractory non-Hodgkin lymphoma. Blood (ASH Annual Meeting Abstracts).

2010;116. Abstract 1777.

12. Meadows SA, Kashishian A, Johnson D, et al. CAL-101 (GS-1101), a specific inhibitor of phosphatidylinositol-3-kinase-delta (PI3K ), disrupts signals from the microenvironment, induces apoptosis, and enhances the antitumor activity of everolimus (RAD001), an inhibitor of mammalian target of rapamycin (mTOR), in mantle cell lymphoma (MCL). Blood (ASH Annual Meeting Abstracts). 2011;118. Abstract 3730.

13. O’Connor OA. Mantle cell lymphoma: identifying novel molecular targets in growth and survival pathways. ASH Education Book. 2007;2007:270-276.

14. Smith MR. Mantle cell lymphoma: advances in biology and therapy. Curr Opin Hematol.

2008;15:415-421.

Current and Emerging Treatment Strategies in Mantle Cell Lymphoma Continued from page 23 malian target of rapamycin (mTOR), in mantle cell lymphoma (MCL). Blood (ASH Annual Meeting Abstracts). 2011;118:Abstract 3730.

28. Goy A, Kahl B. Mantle cell lymphoma: the promise of new treatment options. Crit Rev Oncol Hematol. 2011;80:69-86.

29. Viallet J; Gemin X. Safety and efficacy of obatoclax mesylate (GX15-070MS) in combination with bortezomib for the treatment of relapsed or refractory mantle cell lymphoma (MCL). http://clinicaltrials.gov/ct2/show/NCT00407303. Accessed May 7, 2012.

30. Friedberg JW, Vose JM, Kelly JL, et al. The combination of bendamustine, bortezomib, and rit-

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uximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma.

Blood. 2011;117:2807-2812.

31. Fowler N, Kahl BS, Matous JV, et al. Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II vertical study. J Clin Oncol. 2011;29: 3389-3395.

32. Wang M, Fayad L, Wagner-Bartak N, et al. Oral lenalidomide plus 4 doses of rituximab induced prolonged remissions in relapsed/refractory mantle cell lymphoma: a completed phase I/II clinical trial. Ann Oncol. 2011;22(suppl 4):iv119. Abstract 109.

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The Patient’s Voice

Let the Truth Be Told About Pain!

By MMA

D

o you remember going to the pediatrician as a child for your vaccinations? Do you ever remember looking at the nurse as she readied the injection and asking her “Is this going to hurt?” Did you ever get back the true answer, something that would go a little like this: “Well, yes, kid, this is going to hurt. After all, usually when a needle sticks through your skin and then a medical substance gets pushed into your body, things kinda hurt. I honestly do my best to make it as painless as possible for you, but given the nature of injections and your own fear, this will definitely feel like more than a little ‘pinch.’ ” Of course, you almost never got the real answer. Back then, same as now, the truth about pain rarely gets told.

As a cancer patient, though, I want the truth to be told to me about pain.

After all, pain makes up an integral part of both my inpatient and outpatient hospital visits. From routine procedures, such as getting blood drawn and receiving injections, to more specialized procedures, such as bone marrow biopsies and catheter exchanges, I spend much of my treatment days undergoing procedures I consider painful.

Yet, only recently, after two and a half months of treatment, did a nurse ever outrightly tell me the truth about the pain associated with a procedure I had to

undergo. Lucky enough to be in a clinical trial related to a stem cell transplant, I needed to have some T cells harvested.

Since I did not have the proper catheter in place due to a prior exchange, the morning before my procedure I was told that I would need to have the cells harvested through a needle inserted into the veins in my arms. Yet, clearly, my defini-

with certain procedures. Rather, prior to this day, when I asked about pain, I would get answers such as, “Well, rather than extreme pain, patients tell me it feels like heavy pressure,” or, “Well, we are going to numb the local area so that you hopefully do not feel pain; if you feel any sharp pain, let us know and we will give you more numbing medicine.” In

Without humiliating me or making me feel like a bother, you gave me a clear plan to reduce my anxiety about the pain.

tion of a needle (ie, a small injection needle or one used to take blood) did not accurately depict what awaited me.

When I saw the size of the needle to be used for the cell harvest—a needle bigger than I had ever seen, except perhaps in a scene from a diabolical horror movie—I asked the nurse as she readied it, “Is this going to hurt?”

I did not expect her answer. After all, I had become accustomed, perhaps since childhood, to being told that it would not hurt all that much.

To be honest, it is not that no one during my treatment course has ever acknowledged the suffering associated

my mind, the message seemed clear: almost every other patient is able to tolerate the pain associated with this process without taking additional medicine; if you need some medicine to help you get through, you are somehow weaker, not as valiant, more of a bother than they are. In the end, after appearing to contemplate my decision for a few seconds, I always ask for the available relaxation/pain-killing medicine and I always get it. The aggravating part is that I first need to go through the process of being made to feel somehow weak because I am afraid of or do not want to feel the

pain; then, only after that, can I get my medicine.

This nurse, though, did not lie to me at all. “It is very painful,” she told me.

“Though everyone is different, most patients cry a bit, or at least let out a little scream when the needle goes in. I can easily get you some medicine to help you, though. We simply need to call down for the orders. The procedure may take an extra half hour or so to give us time for the medicine to take effect, but I think it will be better for you. Do you want me to do that?”

Thank you! Thank you! Thank you!

You told me the truth about pain! You spared me the physical agony related to the immediate procedure and the subsequent exhaustion that usually haunts me after a hurtful day of treatment. You shielded me from the embarrassment and emotional turmoil of crying and screaming in surprise at the real hurt that this needle would cause. Without humiliating me or making me feel like a bother, you gave me a clear plan to reduce my anxiety about the pain. You did not force me to take any medication, nor did you lead me to believe that I could not make it without the medication; you simply told me that this would hurt and that, if I decided (not you, or the experience of legions of other patients), I could get something that would help me handle the pain. l MMA is undergoing treatment for cancer. She wishes to use her initials.

Reader Poll ©iStockphoto.com/Slobodan Vasic

Do patients talk to you about pain? r Yes r No

Go to www.TheOncologyNurse.com to cast your vote and add your comments.

Please tell us what you think and what your patients are saying.

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JunE 2012 I VOL 5, nO 5

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Personalized Medicine in Oncology Personalizing Lung Cancer Care... involving anaplastic lymphoma kinase (ALK; 5%). Several associations were observed between genotypes and clinical characteristics. Many institutions across the country are developing their own unique version of this assay. This genotyping has significant utility in influencing treatment decisions and directing patients toward relevant clinical trials.

Continued from cover

One new subset of NSCLC is the presence of the ALK fusion oncogene, which was recently studied in a phase 1 clinical trial.2 The study looked at the ALK tyrosine kinase inhibitor crizotinib, which revealed significant activity in patients with ALK-positive NSCLC. On August 26, 2011, the US Food and Drug Administration (FDA)

granted accelerated approval to crizotinib for patients with locally advanced or metastatic NSCLC that is ALK-positive as detected by an FDA-approved test, Vysis ALK Break-Apart FISH Probe Kit.3 Crizotinib was initially developed as a MET inhibitor but was subsequently found to have inhibitory activity against the EML4-ALK fusion

Pushing Your Limits

protein.4 Currently, resistance mechanisms are being studied, and another class of drugs, heat shock protein inhibitors, may have a role in this subset of resistant patients.

The introduction of targeted treatment options provides patients with a more individualized approach to patient care. From the nursing perspective, the movement toward more individualized care brings with it both improved outcomes and challenges. We are able to offer patients treatment options with increased efficacy potential. As a nurse, I see this instill confidence in patients with their healthcare team and increase hopefulness for a response to treatment.

It also provides patients with time in

From the nursing perspective, the movement toward more individualized care brings with it both

Current activities at www.COEXM.com include:

To use 2D barcodes, download the ScanLife app: • Text “scan” to 43588 • Go to www.getscanlife.com on your smartphone’s web browser, and select “Download” • Visit the app store for your smartphone

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JunE 2012 I VOL 5, nO 5

and challenges.

which we hope that research will learn more about drug resistance and provide more treatment options. Along with the positive aspects associated with more individualized care, we also experience challenges. The recent research advances have been capitalized on by the media. Patients are able to easily find pieces of information on the Internet and television, but the harsh reality of success is dramatized.

Crizotinib is approved for ALK-positive NSCLC patients, who represent about 3% to 4% of the entire NSCLC population.5 EGFR mutations account for about 15% of the NSCLC population.

There is much work to be done before we are able to find specific mutations or markers that can help us direct individualized care for each patient. l

Scan Here to Register.

©iStockphoto.com/altaykaya

improved outcomes

References

COEKsize71112CE

1. Sequist LV, Heist RS, Shaw AT, et al. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol. 2011;22:26162624.

2. Shaw AT, Yeap BY, Solomon BJ, et al. Effect of crizotinib on overall survival in patients with advanced nonsmall-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011; 12:1004-1012.

3. National Cancer Institute. FDA approval for crizotinib. www.cancer.gov/cancertopics/druginfo/fda-crizo tinib. Accessed January 27, 2012.

4. Govindan R. Hope without hype: EML4-ALK inhibition for treatment of lung cancer. Lancet Oncol.

2011;12:983-984.

5. Shaw AT, Yeap BY, Mino-Kenudson M, et al.

Clinical features and outcome of patients with nonsmall-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009;27:4247-4253.

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Cancer Center Profile University of Arizona Cancer Center Continued from cover including cancer biology and development, cancer imaging technology, gastrointestinal cancer, therapeutic development, and cancer prevention and control. A newly developed program conducts research into the biobehavioral and social sciences to identify and evaluate interventions to improve the quality of cancer care and implement effective supportive strategies in caring for people with cancer.

Sandra Kurtin, RN, MS, AOCN, ANP-C, is a hematology/oncology nurse practitioner at the University of Arizona Cancer Center and a clinical assistant professor at the University of Arizona colleges of medicine and nursing. She answered our questions about the profession of oncology nursing.

What are you excited about right now in the cancer field?

Sandra Kurtin (SK): I am excited about the progress being made in diagnostic technologies and their application to the clinical management of patients with cancer. For example, high-resolution MRI with phases of arterial and venous contrast (functional MRIs) can now suggest certain malignancies and often exclude other potential diagnoses prior to any tissue biopsy or surgical intervention. This allows more effective treatment planning and eliminates unnecessary invasive procedures in some cases. In other cases, functional imaging and tissue analysis can predict early response or lack of benefit to treatment within days of the first dosing, potentially eliminating exposure to treatments that have limited potential benefit but considerable potential toxicity. This does present challenges to the healthcare team and to the patient—requiring very individualized treatment plans that may change based on these techniques.

Similarly, tissue diagnostics have provided a number of new therapies with activity in specific populations.

Whether we call them targeted therapies or tailored therapies, these treatments have particular benefit in patients with a specific tumor profile.

For example, patients with wild-type KRAS are known to have improved benefit from EGFR inhibitor agents,

“Oncology nurses are often the most common long-standing contact for patients and their caregivers. They must develop the knowledge and skills that will allow them to safely treat and support the patient.”

—Sandra Kurtin, RN, MS, AOCN, ANP-C

patients with ALK-1+ lung cancer may benefit from a new drug targeting this marker. Similarly, profiling cytogenetic and molecular markers in the hematologic malignancies allows risk stratification and risk-adapted treatment selection. The diagnostic process, both imaging and tissue analysis, will dictate the treatment plan. Thus, precision in the diagnostic process is critical to making the best treatment decisions.

and is the foundation for the patientprovider partnership. As patients move through their cancer experience, continued open and honest communication is key to helping the patient live within the constraints of his or her diagnosis. This support is best achieved with a multidisciplinary approach including providers, advanced practitioners, dietitians, social workers, pharmacists, genetic counselors, and others.

What approach does your institution take to treating people with cancer?

SK: Each patient is approached as an individual as opposed to a diagnosis or suspected diagnosis. This individualized approach to care is critical to building a sense of trust and confidence on the part of the patient and his or her family. The initial interactions with the patient and his or her caregivers are critical to building a partnership for ongoing management of the disease and any possible adverse events as a result of treatment. Careful review of the diagnostic evaluation, in some cases by multidisciplinary tumor boards, is routine in our institution. As mentioned previously, the diagnosis drives treatment selection. Discussion with the patient and his or her caregivers about the diagnosis, implications for survival, available treatment options, the risks and benefits of the treatment, and how the disease and potential treatment will affect their daily life is a critical step in creating trust

How does that translate to better outcomes for your patients?

SK: Open communication, and partnership with the patient and his or her caregivers allows for effectively setting expectations for treatment, potential adverse events, and reportable signs and symptoms. Early identification of adverse events and prompt intervention will reduce the severity of these events. An individualized multidisciplinary approach to the diagnosis, treatment planning, and ongoing support of patients improves patient outcomes.

How has the role of the oncology nurse changed over the past 5 years?

SK: The continued and robust scientific discoveries in the diagnosis, risk analysis, and risk-adapted treatment selection of cancer presents challenges to all healthcare professionals. It is imperative that oncology nurses remain engaged in the discussion of these advances as well as maintaining a working knowledge of key aspects of each development. The complexity in

the diagnosis and treatment of cancer will continue to grow. Oncology nurses are often the most common longstanding contact for patients and their caregivers. They must develop the knowledge and skills that will allow them to safely treat and support the patient, including educating the patient on these complex concepts.

This is most effectively done when the nurse has a good working knowledge.

The majority of oncology care is provided in the outpatient setting and the majority of patients with cancer are older, which requires an understanding of the needs of the older adult and effective strategies for safe outpatient management.

What inspired you to enter the field of oncology nursing?

SK: The courage, grace, resilience, and humor the patients exhibit each and every day is my inspiration. The continued progress being made and the excitement of offering new therapies to patients, in essence providing hope, is extremely rewarding. Knowing that I make a difference every day provides a sense of accomplishment. Being able to do something I love every day is priceless.

Any advice for nurses just entering the field?

SK: Be thankful. Oncology nursing is a unique area. There are many challenges and there will be difficult times. You must be willing to feel, but be cautious in allowing boundaries to be too open. Ask for assistance, seek out mentors, and be kind to your colleagues—we are all in this fight against cancer together. Read something every day, attend local meetings, visit websites, talk to members of the multidisciplinary team—this will make the challenge of staying current much more manageable. Oncology nursing is a gift, so Pass the Passion!

Any advice for nurses just entering If you weren't working in this field, what would you be doing?

SK: My plan in retirement is to be in charge of the mud puddle and the sandbox at my daughter’s future preschool. l

Take action: get YOUR cancer center profiled!

We are looking to interview oncology nurses from cancer centers around the country.

It’s an easy process—a short phone interview and you need to submit some photos.

Contact editorial@greenhillhc.com for more information. www.TheOncologynurse.com

JunE 2012 I VOL 5, nO 5

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Third Annual Navigation and Survivorship Conference PRELIMINARY AGENDA* Friday, September 14 12:45 – 1:00pm

1:00 – 2:00pm & 2:15 – 3:15pm

3:15 – 3:30pm 3:30 – 5:00pm

5:00 – 6:00pm 6:00 – 8:00pm

Welcome Conference Co-Chairs: Sharon Gentry, RN, MSN, AOCN, CBCN Lillie D. Shockney, RN, BS, MAS Pre-Conference Workshops Beginners Track • Core Principles of Navigation Nicole Messier, RN, BSN Pamela J. Vlahakis, RN, MSN, CBCN Members • Getting Excited about Research – Case Examples Linda Fleisher, PhD, MPH Elaine Sein, RN, BSN, OCN, CBCN • Panel Discussion: Building Optimal Community Outreach – Lay and Community Jean B. Sellers, RN, MSN (Moderator) Leah Leilani Beck, BS Jessica Denton, MSW • Implementing a Survivorship Program/Clinic Cynthia Waddington, RN, MSN, AOCN Break Administrators Track • Administering a Navigation Program Bonnie J. Miller, RN, BSN, OCN, FAAMA Elizabeth Whitley, PhD, RN Navigators Track • How Do Case Managers and Navigators Interface?

Nancy Skinner, RN-BC, CCM FREE TIME Welcome Reception/Posters in the Exhibit Hall

Saturday, September 15 7:30 – 8:30am 8:30 – 8:45am

Breakfast Symposium/Product Theater Welcome & Introductions Conference Co-Chairs 8:45 – 9:45am General Session 1: Navigation Update: 2012 Current Regulations – Navigation & Survivorship Care Plan Linda Ferris, PhD 9:45 – 10:00am Break 10:00 – 11:30am Disease-Site–Specific Breakouts Stand-Alone Sessions • Breast Cancer Navigation Mary Rooney, RN, BSN, OCN • Thoracic Oncology Navigation Pamela Matten, RN, BSN, OCN • GI Cancer Navigation Coralyn Martinez, MSN, RN, OCN • Colorectal Cancer Navigation Maura Kadan, RN, MSN, OCN • GYN Cancer Navigation Robin A. Atkinson, RN, BSN, OCN

Prostate Cancer Navigation Juli Aistars, RN, MS, APN, AOCN Rapid Fire Sessions with Panel • Head, Neck, & Neuro Navigation Heather Stern, RN, BSN, CNOR, OCN And • Hematology/Oncology Tina Scherer, RN, MSN, OCN Administrators Session • The Role of the Administrator Lisa Shalkowski, RN, BSN, MSM 11:45 – 1:00pm Lunch in the Exhibit Hall 1:15 – 2:15pm Advocacy Keynote TBD 2:15 – 3:15pm General Session 2: Best Practices in Survivorship Care Rehabilitation Julie Silver, MD 3:15 – 4:15pm General Session 3: Plenary Session Financial and Legal Issues for Our Cancer Patients David S. Landay, JD 4:15 – 5:00pm The Art of Exceptional Professional Performance – Making a Difference in Your Patients’ Lives Selinza Mitchell, RN 5:00 – 7:00pm Poster Award Reception in the Exhibit Hall Pamela Matten, RN, BSN, OCN 7:00pm Conclusion of Day – Networking FREE TIME •

Sunday, September 16 7:30 – 8:30am 8:30 – 9:30am

Breakfast Symposium/Product Theater General Session 4: Navigation in the Age of Personalized Cancer Care Sharon Gentry, RN, MSN, AOCN, CBCN Lillie D. Shockney, RN, BS, MAS 9:30 – 10:30am General Session 5: Best Practices in Addressing Health Inequities Lauren Kelley, MSW, MPA Adrienne Lofton, RN, MSN 10:30 – 10:45am Break 10:45 – 12:15pm Practice Setting – Panel Discussion with Moderator • Office-Based Roxanne Parker, RN, MSN, CPN (Moderator) • Academic Bonnie J. Miller, RN, BSN, OCN, FAAMA • Community Hospital–Based Karyl Blaseg, RN, MSN, OCN 12:15 – 1:15pm Lunch in the Exhibit Hall 1:30 – 2:30pm Clinical Survivorship Guidance Mandi Pratt-Chapman, MA Katherine Sharpe, MTS 2:30 – 2:45pm Conclusion/Final Remarks Conference Co-Chairs *Preliminary agenda, subject to change.

www.regonline.com/aonn2012

September 14-16, 2012 Phoenix, Arizona Arizona Grand

CONFERENCE REGISTRATION Register online: www.regonline.com/aonn2012 *Early Bird Rate: $295 Includes Membership throughSeptember 30, 2013.

Conference Registration: $345 Includes Membership through September 30, 2013. *Early bird expires August 1, 2012.

TARGET AUDIENCE CONFERENCE CO-CHAIRS Sharon Gentry, RN, MSN, AOCN, CBCN Breast Health Navigator Derrick L. Davis Forsyth Regional Cancer Center Winston-Salem, NC

This educational initiative is directed toward oncology nurse navigators, patient navigators, and social workers.

Lillie D. Shockney, RN, BS, MAS University Distinguished Associate Professor of Breast Cancer Adm Director, Johns Hopkins Clinical Breast Programs Adm Director, Johns Hopkins Cancer Survivorship Programs Depts of Surgery and Oncology Associate Professor, JHU School of Medicine, Depts of Surgery, Oncology and Gynecology Associate Professor, JHU School of Nursing Johns Hopkins Avon Foundation Breast Center Baltimore, MD

FACULTY* Juli Aistars, RN, MS, APN, AOCN

Roxanne Parker, RN, MSN, CPN

Robin A. Atkinson, RN, BSN, OCN

Mandi Pratt-Chapman, MA

Leah Leilani Beck, BS

Mary Rooney, RN, BSN, OCN

Karyl Blaseg, RN, MSN, OCN

Tina Scherer, RN, MSN, OCN

Jessica Denton, MSW

Elaine Sein, RN, BSN, OCN, CBCN

Linda Ferris, PhD

Jean B. Sellers, RN, MSN

Linda Fleisher, PhD, MPH

Lisa Shalkowski, RN, BSN, MSM

Maura Kadan, RN, MSN, OCN

Katherine Sharpe, MTS

Lauren Kelley, MSW, MPA

Julie Silver, MD

David S. Landay, JD

Nancy Skinner, RN-BC, CCM

Adrienne Lofton, RN, MSN

Heather Stern, RN, BSN, CNOR, OCN

Coralyn Martinez, MSN, RN, OCN

Pamela J. Vlahakis, RN, MSN, CBCN

Pamela Matten, RN, BSN, OCN

Cynthia Waddington, RN, MSN, AOCN

Nicole Messier, RN, BSN

Elizabeth Whitley, PhD, RN

Bonnie J. Miller, RN, BSN, OCN, FAAMA

AONN’s Third Annual Conference is the only meeting that gives you access to decision-makers and key practitioners involved in oncology navigation and survivorship. If your company provides any of the following services/products for the oncology healthcare community, this is the meeting for you.

*For full information visit www.aonnonline.org

• • • • •

Pharmaceutical/Biotech Genetic Laboratory Services Navigation Software Patient Advocacy Training

• • • • •

Patient Access Reimbursement Publishers Education Certification

CONTINUING EDUCATION INFORMATION Goal AONN’s Third Annual Navigation and Survivorship Conference will advance the role of navigation and survivorship in cancer care to ultimately improve the quality of patient care.

Objectives • Discuss the evolution of the role of navigation in healthcare • Assess strategies for navigating diverse patient populations by cancer type and environmental factors • Define methods for providing patient support and guidance in the age of personalized cancer care • Evaluate best practices regarding survivorship and psychosocial care

CALL FOR ABSTRACTS This is an opportunity to share research, programs, and results with your colleagues.

Submit your abstract via e-mail to Liz@aonnonline.org.

Abstract Deadline: August 1, 2012

SPONSORS This activity is jointly sponsored by AONN Foundation for Learning, Inc., Center of Excellence Media, LLC, and Medical Learning Institute, Inc.

CONFERENCE OVERVIEW AONN’s Third Annual Conference will continue to advance the navigation profession by expanding the scope of educational sessions, networking opportunities, and poster presentations. In addition, this year’s conference will address the evolving challenges of program improvement, the role of personalized medicine, and implementing best practices in navigation, survivorship, and psychosocial care.

REGISTERED NURSE DESIGNATION Medical Learning Institute, Inc. Provider approved by the California Board of Registered Nursing, Provider Number 15106, for up to 12.25 contact hours.

SOCIAL WORK DESIGNATION This activity is pending approval from the National Association of Social Workers. Contact hours for this continuing social worker education activity have been submitted to the National Association of Social Workers.

www.regonline.com/aonn2012

Genetic Counseling

Lobular Breast Cancer and “Abdominal Cancer”

By Cristi Radford, MS, CGC Sarasota Memorial Health Care System, Sarasota, Florida

Cristi Radford, MS, CGC

T

eresa is a 45-year-old female recently diagnosed with lobular breast cancer. She has 1 brother, aged 42 years, and 3 children, a 14-yearold son, a 12-year-old daughter, and a 10-year-old daughter. Her father is 65 years of age and has 2 sisters, aged 55 and 62, both of whom have children, and none are reported to have cancer.

Her paternal grandparents died in their 80s, and the stated cause was “old age.”

Teresa’s mother was reported to have had breast cancer in her late 40s and died from an “abdominal cancer” in her 50s. She had zero siblings. Teresa’s maternal grandmother died in her 60s, cause unknown, and her maternal grandfather died at age 79 in a car accident. He had a sister who died from “abdominal cancer” in her 60s. Ethnic background is reported to be a mix of Irish and English and consanguinity is denied. To Teresa’s knowledge, nobody has undergone risk-reducing procedures or had colonic polyps. Should genetic consultation be considered? What else would you want to know?

Background The majority of breast cancers are sporadic and not inherited. However, up to 10% of breast cancer cases are associated with germline mutations in highly penetrant genes, including BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11.

Distinguishing among the different inherited breast cancer syndromes is important because each has its own cancer risks. Thus, medical management for the patient and his or her at-risk family members varies significantly based on the syndrome. According to NCCN

Guidelines, referral to a cancer genetics professional is recommended for breast cancer survivors if any of the following criteria are met1: • Early-age–onset breast cancer • Triple-negative breast cancer • Two breast cancer primaries in a single individual • Breast cancer at any age, and – At least 1 close blood relative with breast cancer at age 50 or younger, or – At least 1 close blood relative with epithelial ovarian cancer at any age, or – At least 2 close blood relatives with breast cancer and/or pancreatic cancer at any age – From a population at increased risk

rants further evaluation for a genetic syndrome. She was diagnosed with breast cancer at a young age.

Additionally, she has multiple family members diagnosed with cancer, including her mother who was reported to have had both breast cancer and an “abdominal or stomach cancer.” Earlyonset cancer, multiple primary cancers, and multiple generations affected with cancer are features of hereditary cancer syndromes. You inquire if Teresa has seen a genetics professional. She states she cancelled a scheduled appointment because she had a negative result on a “BRACA test” performed by her primary care physician. You encourage Teresa to meet with a genetics professional, explaining that there are other cancer syndromes associated with breast cancer. You also encourage her to bring

When a cancer is reported using a generic term, such as abdominal, it is important to encourage the patient to obtain more information.

• A combination of breast cancer with 1 or more of the following: thyroid cancer, sarcoma, adrenocortical carcinoma, endometrial cancer, pancreatic cancer, brain tumors, diffuse gastric cancer, dermatologic manifestations and/or macrocephaly, or leukemia/lymphoma on the same side of family (especially if early onset) • Ovarian cancer • Male breast cancer Knowledge Applied to Teresa Teresa’s personal and family history war-

in a copy of her test results and to contact family members to obtain additional family history information.

Differentials Based on Teresa’s reported personal and family history, the most likely syndromes would be hereditary breast and ovarian cancer (HBOC) or hereditary diffuse gastric cancer (HDGC). HBOC is associated with mutations in the BRCA1/2 genes, while HDGC is associated with alterations in the CDH1 gene. Medical management differs significantly, as mutations in BRCA1/2

place a woman at high risk for breast and ovarian cancer as well as several other cancers. Mutations in the CDH1 gene place an individual at increased risk primarily for breast and gastric cancer.

Accurate family history information is essential in cancer risk assessment.

When a cancer is reported using a generic term, such as abdominal, it is important to encourage the patient to obtain more information. Teresa contacted family members prior to her appointment but stated she was unable to learn additional information. If family members are unsure of the type of cancer deceased individuals experienced, sometimes the death certificate will have additional information.

Medical records may be available if appropriate releases and documents are presented (state laws vary on who has the right to access or authorize release of records after death). Additional information was not available for Teresa’s maternal great aunt. However, with the assistance of her father and a genetics professional, some medical records were obtained for her mother. Per these records, her mother was diagnosed with diffuse gastric cancer at age 54, but pathology reports were not available for her mother’s breast cancer.

Additionally, a copy of her previous genetic testing was obtained, and she underwent sequencing of BRCA1 and BRCA2 with a 5-site rearrangement panel for BRCA1. All was negative.

Given Teresa’s diagnosis of lobular breast cancer, her mother’s diagnosis of breast cancer and diffuse gastric cancer, and her maternal great aunt’s diagnosis of “abdominal cancer,” an alteration in CDH1 is more likely than an alteration in BRCA1/2 detected by BART (BRACAnalysis Rearrangement Test).

Ultimately, Teresa undergoes analysis of the CDH1 gene and is found to have a mutation.

Get involved: have you ever wanted to write an article for TON? We’re interested in articles about the everyday issues that affect nurses—everything from chemotherapy safe handling to supportive care for patients to challenging cases.

Contact editorial@greenhillhc.com for information.

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Genetic Counseling Hereditary Diffuse Gastric Cancer There are 2 main categories of gastric cancer: intestinal and diffuse. The intestinal type is more common in the general population and more likely to be sporadic, while the diffuse type is less common and more likely to have inherited factors.2 It is estimated that 2% to 8% of gastric cancer is due to an inherited cancer syndrome, such as HDGC. CDH1 is the only gene known to be associated with HDGC. The typical pathology of HDGC is a poorly differentiated adenocarcinoma that infiltrates into the stomach wall causing thickening of the wall (linitis plastica) without forming a distinct mass. It is also called signet ring carcinoma due to the signet ring appearance of malignant cells.

In 1999, HDGC was defined as occurring in a family with either (1) two or more documented cases of diffuse gastric cancer in first- or second-degree relatives, with at least one diagnosed before the age of 50 years, or (2) three or more cases of documented diffuse gastric cancer in first- or second-degree relatives, independent of age of onset. Only about one-fourth of families meeting these criteria have a CDH1 mutation.3 The International Gastric Cancer Linkage Consortium broadened the above-stated clinical criteria as indications for genetic testing if any of the following were met4: (1) two gastric cancer cases in a family, one confirmed DGC before age 50 years; (2) three confirmed DGC cases in firstor second-degree relatives independent of age; (3) simplex case (ie, a single occurrence in a family) of DGC occurring before age 40 years; and (4) personal or family history of DGC and lobular breast cancer, one diagnosed before age 50 years. Of importance, most criteria are tailored to individuals of low geographic risk for gastric cancer and may be too broad for individuals in high-risk areas, such as East Asia, Eastern Europe, and parts of Central and South America.5 It is likely criteria will continue to evolve as more individuals are found to have CDH1 mutations.

The estimated lifetime risk for gastric cancer by age 80 years is 67% for men and 83% for women.6 The average age of onset of hereditary diffuse gastric cancer is 38 years, with a range of 14 to 69 years. More recent data suggest at least an 80% risk for both men and women.

Women also have up to a 39% risk for developing breast cancer, primarily of the lobular type.6 Colorectal cancer may also be associated. As at least half of the individuals with a clinical diagnosis of HDGC do not have a CDH1 mutation, it is likely other genes play a role in HDGC or there are unidentified mutations present in CDH1.7 HDGC is inherited in an autosomal dominant fashion. Thus, offspring of carriers have a 50% chance of also car-

www.TheOncologynurse.com

rying the mutation. Typically, testing does not begin until at least age 18 years unless the family history has early-onset cancers suggesting medical management is needed prior to age 18.

Clinical diagnosis of gastric cancer is difficult in the early stages of the disease because the symptoms are nonspecific.

Symptoms do not manifest until the disease is either locally advanced or metastatic. To date, there is no good screening for diffuse gastric cancer and

not develop metastases.2 At this time, the natural history of DGC is not well understood, making it extremely difficult to determine at what point an individual on a surveillance program should proceed with prophylactic gastrectomy.

Management is more challenging in families meeting clinical criteria but not having an identifiable CDH1 mutation or in families with a CDH1 variant of uncertain significance. For these individuals, annual endoscopy with multiple

To date, there is no good screening for diffuse gastric cancer and prophylactic

ily history. Risk-reducing bilateral mastectomy is also an option.

Take-Home Messages • Pathology of cancer—including breast cancer—can be important when determining a genetic testing strategy • Cancer reported as “abdominal” by patients and family members could be one of a variety of primary cancers (including ovarian, stomach, and colon) and should be factored into risk assessment • If a patient reports a negative BRCA test result but extensive personal and family history is present, consider referral to an expert in cancer genetics l

total gastrectomy is indicated for mutation carriers.

prophylactic total gastrectomy is indicated for mutation carriers. For individuals not electing prophylactic gastrectomy, annual endoscopy with multiple biopsies is a surveillance option. However, as the malignant cells infiltrate and spread under normal-looking mucosa, they are virtually invisible and multiple biopsies must be performed. Furthermore, analysis of gastrectomy specimens suggests that the majority of mutation carriers have microscopic foci of signet ring cells, and approximately 30% of CDH1 carriers do

biopsies is a screening option. All at-risk individuals electing endoscopy should be aware that multiple random biopsies may not detect cancer early.

Additionally, management of HDGC should include input from a multidisciplinary team consisting of individuals with expertise in gastric surgery, gastroenterology, pathology, and nutrition.4 Surveillance and screening for lobular breast cancer should include annual mammogram and breast MRI beginning at age 35 unless suggested earlier by fam-

References 1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Genetic/Familial High-Risk Assessment: Breast and Ovarian. Version 1.2012. http://www.nccn.org/professionals/physician_ gls/pdf/genetics_screening.pdf. Accessed May 22, 2012.

2. Lynch H, Lynch J, Shaw T. Hereditary gastrointestinal cancer syndromes. Gastrointest Cancer Res. 2011;4(supp 1):S9-S17.

3. Caldas C, Carneiro F, Lynch HT, et al. Familial gastric cancer: overview and guidelines for management. J Med Genet. 1999;36:873-880.

4. Fitzgerald RC, Hardwick R, Huntsman D, et al.

Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Med Genet. 2010;47:436-444.

5. Corso G, Marrelli D, Pascale V, et al. Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature. BMC Cancer. 2012;12:8.

6. Pharoah PD, Guilford P, Caldas C. Incidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology. 2001;121:1348-1353.

7. Kaurah P, MacMillan A, Boyd N, et al. Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric cancer. JAMA. 2007;297:2360-2372.

Reader Survey

Do you agree that the IOM report and the APRN Consensus Model should serve as guidelines for the future of the nursing profession?

In the April issue, we published Catherine Bishop’s article, “A New Look at Nursing Education and Practice.” We asked our online reading community what they thought of the IOM report and the APRN Consensus Model.

• 70% agreed that the IOM report and the APRN Consensus Model should serve as guidelines for the future.

• 30% did not agree that these should serve as guidelines.

Here’s a sample of the comments: • As an NP, I feel this would be a good guide tool so things are consistent across the nation for advanced practice.

• Direction is always a good place to start. However, there may need to be a more universal conversation regarding some of the issues with the actual working participants. But both bodies of work are a positive step forward.

• I have been a diploma nurse for 28 years. Why is it that bedside nurses are looked down on? [The] article almost exclusively looks at advanced practice nursing. The majority of us are bedside RNs….

Our sincere thanks to all who participated in this survey.

If you want to participate in this month’s survey, see page 28 for details.

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News Briefs

Tumors More Heterogeneous Than Previously Recognized

By Alice Goodman

R

esearchers have documented over time into different “branches.” diverse genetic changes in differIn an accompanying editorial, Dan ent parts of the same primary Longo, MD, deputy editor of the New tumor, suggesting that individual tumors harbor a complexity of genetic changes that has not been well appreciated (Gerlinger M, et al. N Engl J Med. 2012;366:883-892). This discovery has implications for personalized medicine directed at genetic changes identified in 1 biopsy of a primary tumor.

“Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor biopsy samples and may present challenges to personalized medicine and biomarker development,” wrote the authors. They noted that the extent of intratumoral heterogeneity is what was striking and surprising in this study.

England Journal of Medicine, wrote that these observations suggest that it is probably “too simple” to direct therapy

according to genetic tumor markers due to the heterogeneity observed within a single tumor. l

TREANDA® (bendamustine HCI) for Injection is his chemo.

This is his therapy.

The small study found more genetic differences than genetic similarities between biopsies taken from different parts of the same tumor.

The small study found more genetic differences than genetic similarities between biopsies taken from different parts of the same tumor. The authors also found differences in genetic changes between the primary tumor and local as well as distant metastases. The fact that the primary tumor has different genetic characteristics than metastases from that tumor has been documented in breast cancer, and there is currently a movement to recommend biopsies of metastases when they develop in addition to primary tumor biopsies.

The study analyzed cancer genomics in biopsy samples of a total of 30 biopsies from 4 primary tumors. Genomic analysis revealed that 26 of the 30 biopsies had different genetic expressions. The authors identified 118 different genetic mutations. About 40 were found in all the biopsies from the primary tumor and the metastases (ubiquitous mutations), and 53 mutations were shared. Twentyfive mutations were found only in a single biopsy (“private mutations”).

Furthermore, gene expression signatures associated with a good prognosis and also those associated with a poor prognosis were seen in different sites of the same primary tumor.

Likening the genetic changes to a trunk and branches of a tree, the authors said that some genetic changes were seen early in the “trunk,” while others evolved

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Conference News: ONS 37th Annual Congress

DVD Prepares Patients for Transplant

By Caroline Helwick

F

or patients with hematologic cancers, an educational DVD about the bone marrow transplant

process can explain complex concepts and facilitate discussions with nurses, according to representatives

of Be The Match (www.BeTheMatch. org/patients), a program of the National Marrow Donor Program,

which is based in Minneapolis, Minnesota.

At the 37th Annual Congress of the Oncology Nursing Society held in New Orleans, Louisiana, Elizabeth A. Murphy, RN, EdD, and Ellen M. Continued on page 38

Single-agent TREANDA tripled median PFS* 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.

PROGRESSION-FREE SURVIVAL (PFS): CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) Survival distribution function

TREANDA (n=153)

1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1

Chlorambucil (n=148)

18 months median PFS

6 months median PFS

P<.0001 HR†=0.27 (95% CI‡: 0.17, 0.43)

0

5

10

15

20

25

30

35

40

45

Months *TREANDA (95% CI: 11.7, 23.5) vs chlorambucil (95% CI: 5.6, 8.6). † HR=hazard ratio. ‡ CI=confidence interval.

• TREANDA was compared with chlorambucil in a randomized, open-label, phase 3 trial in treatment-naïve patients with Binet stage B or C (Rai stages I-IV) CLL who required treatment (N=301) • TREANDA is administered with a convenient dosing schedule – The recommended dose for TREANDA is 100 mg/m2 administered intravenously over 30 minutes on Days 1 and 2 of a 28-day treatment cycle, up to 6 cycles – In the phase 3 trial, patients received chlorambucil at a dose of 0.8 mg/kg orally on Days 1 and 15 (n=148) of a 28-day treatment cycle, up to 6 cycles • In the pivotal phase 3 trial, the most common non-hematologic adverse reactions (frequency ≥15%) were pyrexia (24%), nausea (20%), and vomiting (16%) (n=153). The most common hematologic abnormalities (frequency ≥15%) were anemia (89%), thrombocytopenia (77%), neutropenia (75%), lymphopenia (68%), and leukopenia (61%) (n=150) Important Safety Information • Serious adverse reactions, including myelosuppression, infections, infusion reactions and anaphylaxis, tumor lysis syndrome, skin reactions including SJS/TEN, other malignancies, and extravasation, have been associated with TREANDA. Some reactions, such as myelosuppression, infections, and SJS/TEN (when TREANDA was administered concomitantly with allopurinol and other medications known to cause SJS/TEN), have been fatal. Patients should be monitored closely for these reactions and treated promptly if any occur • Adverse reactions may require interventions such as decreasing the dose of TREANDA, or withholding or delaying treatment • TREANDA is contraindicated in patients with a known hypersensitivity to bendamustine or mannitol. Women should be advised to avoid becoming pregnant while using TREANDA

Discover the elements of efficacy and safety LEARN MORE AT WWW.TREANDA.COM Please see accompanying brief summary of full Prescribing Information.

©2012 Cephalon, Inc., a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd.

All rights reserved. TRE-2460 March 2012

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Conference News: ONS 37th Annual Congress DVD Prepares Patients for Transplant Denzen, MS, shared their experience with this teaching approach.

The Words of Experience. Stories of Hope (WOE) DVD is designed to help patients and caregivers understand the transplant process, to define the role of the medical team and caregiver, and to

Continued from page 37

provide strategies for preparing for transplant, with a focus on hospital life. In 2011, the WOE DVD won the gold Telly Award in the Health and Wellness category, competing with more than 14,000 entries. The process is described from the point of view of

previous transplant patients, who appear on camera discussing their experiences. â&#x20AC;&#x153;The WOE, which is aimed at young adults, focuses on the sharing of the patient and caregiver experience.

Patients consistently have told us that

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.

Brief Summary of Prescribing Information for Chronic Lymphocytic Leukemia 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.

CONTRAINDICATIONS: TREANDA is contraindicated in patients with a known hypersensitivity (eg, anaphylactic and anaphylactoid reactions) to bendamustine or mannitol. [See Warnings and Precautions] WARNINGS AND PRECAUTIONS: Myelosuppression. Patients treated with TREANDA are likely to experience myelosuppression. In the two NHL studies, 98% of patients had Grade 3-4 myelosuppression. Three patients (2%) died from myelosuppression-related 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 closely.

In the clinical trials, blood counts were monitored every week initially. Hematologic nadirs were observed predominantly in the third week of therapy. Hematologic nadirs may require dose delays if recovery to the recommended values have 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 â&#x2030;Ľ 1 x 109/L and the platelet count should be â&#x2030;Ľ 75 x 109/L. [See Dosage and Administration]. Infections. Infection, including pneumonia and sepsis, has been reported in patients in clinical trials and in post-marketing reports. Infection has been associated with hospitalization, septic shock and death. Patients with myelosuppression following treatment with TREANDA are more susceptible to infections.

Patients with myelosuppression following TREANDA treatment should be advised to contact a physician if they have symptoms or signs of infection. Infusion Reactions and Anaphylaxis. 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. Patients should be asked about symptoms suggestive of infusion reactions after their first cycle of therapy. Patients who experienced Grade 3 or worse allergic-type reactions were not typically rechallenged. Measures to prevent severe reactions, including antihistamines, antipyretics and corticosteroids should be considered in subsequent cycles in patients who have previously experienced Grade 1 or 2 infusion reactions. Discontinuation should be considered in patients with Grade 3 or 4 infusion reactions. Tumor Lysis Syndrome. Tumor lysis syndrome associated with TREANDA treatment has been reported in patients in clinical trials and in post-marketing 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 maintaining adequate volume status, 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. Skin Reactions. A number of skin reactions have been reported in clinical trials and post-marketing safety reports. These events have included rash, toxic skin reactions and bullous exanthema.

Some events occurred when TREANDA was given in combination with other anticancer agents, so the precise relationship to TREANDA is uncertain. 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. Therefore, patients with skin reactions should be monitored closely. If skin reactions are severe or progressive, TREANDA should be withheld or discontinued. 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. There are postmarketing reports of bendamustine extravasations resulting in hospitalizations from erythema, marked swelling, and pain. Precautions should be taken to avoid extravasations, including monitoring of the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of TREANDA. Use in Pregnancy. 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.

ADVERSE REACTIONS: 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. 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; Infections; Infusion Reactions and Anaphylaxis; Tumor Lysis Syndrome; Skin Reactions; Other Malignancies. Clinical Trials Experience in CLL. The data described below reflect exposure to TREANDA in 153 patients. TREANDA was studied in an active-controlled trial.

The population was 45-77 years of age, 63% male, 100% white, and had treatment naĂŻve CLL. 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. In the randomized CLL clinical study, 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 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 randomized CLL clinical study and 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 â&#x2030;Ľ 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 Chlorambucil (N=153) (N=143) System organ class Preferred term All Grades Grade 3/4 All Grades Grade 3/4 Total number of patients with at least 1 adverse reaction 121 (79) 52 (34) 96 (67) 25 (17) Gastrointestinal disorders Nausea 31 (20) 1 (<1) 21 (15) 1 (<1) Vomiting 24 (16) 1 (<1) 9 (6) 0 Diarrhea 14 (9) 2 (1) 5 (3) General disorders and administration site conditions Pyrexia 36 (24) 6 (4) 8 (6) 2 (1) Fatigue 14 (9) 2 (1) 8 (6) 0 Asthenia 13 (8) 0 6 (4) 0 Chills 9 (6) 0 1 (<1) 0 Immune system disorders Hypersensitivity 7 (5) 2 (1) 3 (2) 0 Infections and infestations Nasopharyngitis 10 (7) 0 12 (8) 0 Infection 9 (6) 3 (2) 1 (<1) 1 (<1) Herpes simplex 5 (3) 0 7 (5) 0 Investigations Weight decreased 11 (7) 0 5 (3) 0 Metabolism and nutrition disorders Hyperuricemia 11 (7) 3 (2) 2 (1) 0 Respiratory, thoracic and mediastinal disorders Cough 6 (4) 1 (<1) 7 (5) 1 (<1) Skin and subcutaneous tissue disorders Rash 12 (8) 4 (3) 7 (5) 3 (2) Pruritus 8 (5) 0 2 (1) 0

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Table 2: Incidence of Hematology Laboratory Abnormalities in Patients Who Received TREANDA or Chlorambucil in the Randomized CLL Clinical Study Chlorambucil TREANDA (N=141) (N=150) Grade 3/4 All Grades Grade 3/4 All Grades Laboratory Abnormality n (%) n (%) n (%) 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) In the randomized CLL clinical study, 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 significant deterioration does not occur. Post-Marketing 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. 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] OVERDOSAGE: The intravenous LD 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. DOSAGE AND ADMINISTRATION: 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 â&#x2030;ĽÂ Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to â&#x2030;¤Â Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) â&#x2030;ĽÂ 1 x 109/L, platelets â&#x2030;ĽÂ 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] 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. Reconstitution/Preparation for Intravenous Administration. t Aseptically SFDPOTUJUVUF FBDI 53&"/%" WJBM BT GPMMPXT t NH 53&"/%" WJBM "EE N- PG POMZ Sterile Water for Injection, USP t NH 53&"/%" WJBM "EE N- PG POMZ 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 VTFE t "TFQUJDBMMZ XJUIESBX UIF WPMVNF OFFEFE GPS UIF SFRVJSFE EPTF CBTFE PO NH N- DPODFOUSBUJPO BOE 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 0.2â&#x20AC;&#x201C;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 BENJYUVSF TIPVME CF B DMFBS BOE DPMPSMFTT UP TMJHIUMZ ZFMMPX TPMVUJPO t 6TF 4UFSJMF 8BUFS GPS *OKFDUJPO 641 GPS reconstitution and then either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride *OKFDUJPO 641 GPS EJMVUJPO BT PVUMJOFE BCPWF /P PUIFS EJMVFOUT IBWF CFFO TIPXO UP CF DPNQBUJCMF t 1BSFOUFSBM 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. 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.

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.

HOW SUPPLIED/STORAGE AND HANDLING: 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. Procedures for the proper handling and disposal of anticancer drugs should be considered. Several guidelines on the subject have been published. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate. 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 singleuse vial and NDC 63459-391-20 TREANDA (bendamustine hydrochloride) for Injection, 100 mg in 20 mL amber single-use vial. 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.

they want to hear about transplant from the patientâ&#x20AC;&#x2122;s perspective, and since they canâ&#x20AC;&#x2122;t always connect with other patients this is a way of doing that,â&#x20AC;? said Denzen.

The DVD is provided free of charge.

Patients own their copies and can share them with caregivers. â&#x20AC;&#x153;The DVD serves to reinforce what providers tell the patient, and they find it very helpful,â&#x20AC;? Murphy said.

DVDs are among the most effective formats for communicating healthrelated messages to patients, as they have demonstrated a consistent increase in short-term knowledge and have outperformed written materials, lectures, and individual counseling.

The benefits of DVDs are their familiar format, their ability to simplify complex concepts in a manner that is especially helpful to low-literate individuals, and their visual appeal, which increases interest and information retention, they said.

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Distributed by: Cephalon, Inc. Frazer, PA 19355 TREANDA is a trademark of Cephalon, Inc., or its affiliates. All rights reserved. Š2008-2012 Cephalon, Inc., or its affiliates.

TRE-2500 (Label Code: 00016287.06) This brief summary is based on TRE-006 TREANDA full Prescribing Information.

April 2012

Survey Proves Value of the DVD Patients who will be undergoing transplant watch WOE prior to the procedure. Nurses reiterate the benefits and main points of the DVD, answer questions, and clarify concepts. There are chapters on orientation, conditioning, transplant, engraftment, early recovery, and long-term recovery.

The effectiveness of the DVD as a teaching tool prior to transplant was assessed over 3 years via a mailed survey of 209 patients and their caregivers.

The survey assessed helpfulness, change in transplant knowledge, and change in anxiety regarding the transplant process after viewing the DVD. The DVD viewers indicated the following: â&#x20AC;˘ 99% would recommend the WOE DVD to someone in their situation â&#x20AC;˘ 95% gained a better understanding of the transplant process â&#x20AC;˘ 97% gained a better understanding of the caregiverâ&#x20AC;&#x2122;s role â&#x20AC;˘ 88% developed useful strategies for preparing for transplant â&#x20AC;˘ 60% had less anxiety (or no increase in anxiety) about the transplant process â&#x20AC;˘ Higher education level was associated with lower levels of anxiety Among the viewerâ&#x20AC;&#x2122;s comments: â&#x20AC;&#x153;The DVD collects information in one place and makes it more relevant and personal, with real people who speak directly to us,â&#x20AC;? and â&#x20AC;&#x153;It made me feel more in control and left me feeling hopeful.â&#x20AC;?

The WOE DVD has been viewed by more than 3000 transplant patients.

Copies can be ordered online (https:// secure.marrow.org/Contact/Materials/ Request_Patient_Materials.aspx). l

1:54 PM

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Conference News: ONS 37th Annual Congress

Online Education Effectively Prepares Patients for Chemotherapy

A

n online chemotherapy therapy education program based on Emmi Solutions is an effective way to educate patients and is a timesaver for oncology nurses, according to nurses from the Hillman Cancer Center at the University of Pittsburgh.

They described their program at the 37th Annual Congress of the Oncology Nursing Society held in New Orleans, Louisiana.

Their healthcare system was already using Emmi Solutions in other departments, and based on the success of those programs, the program was introduced into oncology, said Lynda Tunon, RN, MSN, OCN. The objective is to prepare patients for their first chemotherapy treatment by integrating interactive computer technology that reduces one-on-one teaching time while providing consistent education and maintaining nurse, physician, and patient satisfaction with the process, she said.

Patients and families can view the Emmi Solutions online program at home or in the office prior to their first treatment. The program was piloted in 1 oncology clinic for 3 months and then rolled out to 17 clinics in the outpatient cancer center.

The interactive program uses voice, image, and text to engage patients as active participants in their care. It emphasizes the personal nature of each patient’s treatment, the potential for side effects, and the management of those side effects during treatment and at home, Tunon said.

While patients generally view the program on their own computers, those without computers can use the one at the center, with assistance by office personnel as needed. The next stage of the program will incorporate iPads and other tablets, so that patients can view the program at any site in the office (such as in the infusion chair).

Program Frees Up Nurses for Other Things At the time of this report, 239 patients were registered for the program, 114 (48%) had started it and 104 (44%) had completed it. A patient survey revealed: • 91% of patients said the Emmi program answered questions they normally would have called their healthcare providers to discuss • 85% of patients felt the program explained risks they did not know about • 83% obtained “new information” from the program

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• 72% felt the program would change the way they manage their condition or prepare for their treatment Patients commented that the program gave them new insights into side effects and when to call their providers, lowered their stress levels, and answered questions they “didn’t

know they had.” Physicians felt that understanding and retaining the information was probably accomplished more effectively in the patient’s own home environment. Nurses felt that Emmi was a good starting point for discussion, and it clearly freed up time normally spent in patient education.

Prior to Emmi implementation, the average education time was 60 minutes. With patients viewing the program on their own, the average time spent on education by nurses is 30 minutes, Tunon reported. “Our nurses spend 50% less time in discussions with the patient,” she said.

Gloria Gotaskie, RN, MSN, a coauthor, stressed that nurses still have the most significant role in education, but with the online program “patients get the best of both worlds.” l —CH

Newsletter Series

YOUR QUESTIONS ANSWERED

™

™

Editor in Chief

Editor in Chief

Sagar Lonial, MD

Stephanie A. Gregory, MD

Professor Vice Chair of Clinical Affairs Department of Hematology and Medical Oncology Winship Cancer Institute Emory University School of Medicine

Topics include: • Newly Diagnosed Patients • Maintenance Settings • Transplant-Eligible and -Ineligible Patients • Retreatment Settings • Bone Health

The Elodia Kehm Chair of Hematology Professor of Medicine Director, Lymphoma Program Rush University Medical Center/Rush University

Topics include: • Mantle Cell Lymphoma • Follicular Lymphoma

These activities are supported by educational grants from Millennium: The Takeda Oncology Company and Celgene Corporation.

These activities are supported by educational grants from Millennium: The Takeda Oncology Company and Spectrum Pharmaceuticals.

ALL NEW CONTENT FOR 2012 Accreditation These activities will be accredited for physicians, nurses, and pharmacists.

For complete accreditation information, please refer to each activity.

This activity is jointly sponsored by Medical Learning Institute, Inc. and Center of Excellence Media, LLC.

COEAsize61512AskExperts

JunE 2012 I VOL 5, nO 5

39

Conference News: ASCO 2012 Annual Meeting

Abstracts of Interest From the 2012 American Society of Clinical Oncology Annual Meeting

By Caroline Helwick

Sriram Yennurajalingam, MD, at the ASCO 2012 Annual Meeting. Photo © ASCO/Phil McCarten 2012.

Patients with chemotherapy-induced nausea and vomiting (CINV) that persists in spite of recommended prophylaxis may be helped by the antipsychotic medication olanzapine. In a double-blind randomized trial of patients with breakthrough CINV after highly emetogenic chemotherapy, 71% of patients given olanzapine 10 mg orally for 3 days had no further vomiting, compared with 32% who received metoclopramide 10 mg orally 3 times a day for 3 days, and 67% versus 24% had no further nausea. Navari RM, et al. Abstract 9064.

ignorance about the late effects of common chemotherapy regimens for common cancers. The 2009 Survey of Physician Attitudes Regarding the Care of Cancer Survivors involved 1072 PCPs and 1130 oncologists.

Physicians were asked to select which of 5 late effects of 4 widely used breast and colorectal cancer drugs (doxorubicin, paclitaxel, oxaliplatin, and cyclophosphamide) they observed most often in their practices, or had seen reported. Among the PCPs, only 15% to 55% identified the common side effects with the drugs. While oncologists were much better—with 62% to 97% answering correctly—there was still some room for improvement, the authors suggested. Nakhlyudov L, et al.

Abstract 6008.

T-DM1 Prolongs Remission in Metastatic Breast Cancer

Glucocorticoid, Ginseng Reduce Cancer-Related Fatigue The use of dexamethasone for up to 15 days reduced cancer-related fatigue more effectively than placebo among patients with advanced cancer. The study randomly assigned 132 patients with documented fatigue to 4 mg dexamethasone twice a day or placebo for 14 days. On day 15, the dexamethasone group demonstrated significant improvements on measurements of fatigue, symptom distress, physical symptoms, and quality of life, while the placebo group did not improve over baseline. In a separate randomized study of 364 patients with fatigue, 8 weeks of ginseng (2000 mg ground Wisconsin ginseng root) also significantly improved fatigue scores, especially among patients currently on treatment. Yennurajalingam S, et al.

Abstract 9002; Barton DL, et al.

Abstract 9001.

Primary Care Providers Largely Unaware of Chemotherapy’s Late Effects A survey of primary care providers (PCPs) showed an alarming level of

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JunE 2012 I VOL 5, nO 5

Trastuzumab emtansine (T-DM1), the antibody-drug conjugate linking trastuzumab to a cytotoxic agent, significantly prolonged disease-free survival in previously treated metastatic breast cancer in the international phase 3 EMILIA trial. Compared with a standard regimen, T-DM1 reduced the risk of disease progression by 35%, improving progression-free survival (PFS) from 6.4 to 9.6 months (P <.0001).

Overall survival (OS) was numerically improved though the difference is not yet statistically significant. T-DM1 was also substantially better tolerated.

Blackwell K, et al. LBA1.

Intermittent AndrogenDeprivation Therapy Should Not Replace Continuous Treatment in Prostate Cancer Continuous androgen-deprivation therapy should remain the standard of care for the treatment of men with hormone-sensitive metastatic prostate cancer, according to the results of the phase 3 international SWOG 9346 trial. The 17-year study treated 3040 newly diagnosed patients with gose rlin and bicalutamide for 7 months.

Those who achieved PSA ≤4 ng/mL were randomly assigned to continuous treatment or intermittent treatment upon signs of progression. The intermittent approach was “not shown to be non-inferior to” continuous treatment.

Median OS was 5.8 years with continuous therapy and 5.1 years with intermittent therapy, and 7-year survival was 42% and 38%, respectively.

Hussain M, et al. Abstract 4.

Androgen Blockers Score Big in Prostate Cancer For the treatment of metastatic castration-resistant prostate cancer (CRPC), 2 drugs targeting the androgen receptor returned impressive results. In men who had not been treated yet with chemotherapy, abiraterone significantly improved radiographic PFS in the phase 3 COUAA-302 trial. Median PFS was 8.3 months with placebo, but has not been reached in the abiraterone group. The drug is currently approved for patients previously treated with chemotherapy, but these data suggest it would be effective earlier in the disease. The phase 3 AFFIRM trial of a similar drug, enzalutamide, in 1199 CRPC patients with prior docetaxel treatment, found a 4.8month OS improvement, and a 5.4month improvement in PFS (P <.0001).

Ryan CJ, et al. LBA4518; de Bono JS, et al. Abstract 4519.

Suzanne L. Topalian, MD, at the ASCO 2012 Annual Meeting. Photo © ASCO/Zach Boyden-Holmes 2012.

Antipsychotic Controls Breakthrough Nausea and Vomiting

promise for the treatment of anaplastic large cell lymphoma (ALCL), inflammatory myofibroblastic tumors, and aggressive forms of neuroblastoma in children, according to a study of 70 children whose cancer was refractory to standard therapies. The greatest activity, an 88% response rate, was for ALCL, though complete responses were observed in all 3 tumor types.

Responders have remained on therapy for up to 2 years without progression.

Mosse YP, et al. Abstract 9500.

Afatinib Delays Progression in Lung Cancer In the phase 3 LUX-Lung 3 trial of 345 patients with advanced non–small cell lung cancer of adenoma histology harboring the epidermal growth factor receptor (EGFR) mutation, singleagent treatment with the oral EGFR inhibitor afatinib delayed disease progression by more than 4 months over a relatively new first-line regimen, pemetrexed and cisplatin. Median PFS was 11.1 months with afatinib versus 6.9 months with standard therapy, a 42% reduction in risk (P = .0004). More strikingly, in patients with 2 common mutations, afatinib doubled the time in remission, from 6.9 months to 13.6 months (P <.0001). Afatinib blocks the EGFR pathway more thoroughly and permanently than current EGFRtargeted treatments, and also blocks the broader ErbB family of receptors. Yang J C-H, et al. LBA7500.

PD-1 Targeted Immune Therapy Active in Solid Tumors

Regorafenib Fills Unmet Needs in GI Tumors

In a phase 1 trial, the investigational drug BMS-936558 caused tumor shrinkage in about one-quarter of 296 patients with advanced melanoma (28% response rate), renal cancer (27%), and non–small cell lung cancer (18%). The antibody drug targets a key pathway in T cells called PD-1, which inhibits the body’s immune response to cancer. By blocking this pathway, BMS936558 may reactivate the immune system to attack the tumor. A subanalysis of the data hinted at a potential biomarker, a protein called PD-L1. One-third of patients expressing PD-L1 responded to this novel therapy. Topalian SL, et al.

Abstract CRA2509.

In both colorectal cancer and gastrointestinal stromal tumors (GIST) refractory to current therapies, the oral multikinase inhibitor regorafenib improved outcomes in phase 3 trials. In the CORRECT trial of 770 advanced colorectal cancer patients, OS was improved by 29% with regorafenib, versus placebo, from 5.0 to 6.4 months (P = .0052). In the study of 199 patients with GIST, regorafenib improved PFS from 0.9 months with placebo to 4.8 months, a 73% reduction in risk (P <.0001). Side effects were in line with other tyrosine kinase inhibitors. Van Cutsem E, et al. Abstract 3502; Demetri GD, et al. LBA10008.

Crizotinib Effective in Pediatric Cancers

In Breast Cancer, Older Drug Wins Out

Crizotinib, already proven effective in non–small cell lung cancer patients with ALK gene abnormalities, shows

In a phase 3 randomized trial of 799 patients, 2 newer and significantly more expensive drugs—nab-paclitaxel

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and ixabepilone—were not superior to standard weekly treatment with paclitaxel as first-line treatment for advanced breast cancer (most patients also received bevacizumab). Median PFS was 10.6 months for the paclitaxel arm, 9.2 months for nab-paclitaxel, and 7.6 months for ixabepilone. Weekly ixabepilone was significantly less effective than paclitaxel, and nab-paclitaxel was not superior to it. Grade 3 or 4 hematologic and nonhematologic toxicities were also lowest with paclitaxel, including peripheral neuropathy (16% vs 25% with either experimental arm).

The authors suggested that nab-paclitaxel be reserved for patients with sensitivity reactions to paclitaxel and those for whom corticosteroids are not advised. Rugo H, et al. CRA1002.

A. Hauschild, MD, at the ASCO 2012 Annual Meeting.

Photo © ASCO/Todd Buchanan 2012.

Conference News: ASCO 2012 Annual Meeting

Melanoma Treatment Options Further Expand Patients with advanced melanoma who harbor the BRAF mutation may soon have treatment options beyond

vemurafenib. In two phase 3 studies (METRIC and BREAK-3), the investigational BRAF inhibitor dabrafenib and the first-in-class MEK inhibitor trametinib, as single agents, essentially doubled the median PFS, compared with chemo therapy treatment (P <.0001 for both). But when the 2 were combined in an open-label phase 1/2 dose-finding study, the results were even better. Median PFS reached 7.4 months, and rose to 10.8 months among patients who were optimally dosed. Importantly, the combination was associated with less skin toxicity (14%) than is observed with vemurafenib alone. Hauschild A, et al. LBA8500; Robert C, et al.

LBA8509; Weber JS, et al. Abstract 8510.

For Metastatic Kidney Cancer, Patients Prefer Pazopanib In a study with a novel aim and design, patients with metastatic renal cell carcinoma were treated with 2 approved agents, then asked which treatment they preferred. Almost 50% more patients preferred pazopanib over sunitinib, citing less fatigue and better quality of life with this agent (the study did not evaluate efficacy). The PISCES study enrolled 169 patients assigned to one agent for 10 weeks, and to the other for 10 weeks after a 2-week washout period. At 22 weeks, 70% preferred pazopanib, 22% preferred sunitinib, and 8% had no preference (P <.001). Physicians also preferred pazopanib (61%) over sunitinib (22%) while 17% had no preference. Escudier BJ, et al. Abstract CRA4502. l

Prostate Cancer

Another Reason for Men With Prostate Cancer to Exercise

By Alice Goodman

E

xercise has been shown to reduce recurrence in men with prostate cancer, according to several studies. A new study shows that vigorous exercise for 1 hour 3 times per week upregulates the expression of genes that are unfavorable to cancer, providing a potential explanation for the mechanism by which exercise has anticancer effects.

These findings related to gene expression were reported in men with low-risk prostate cancer by senior author June Chan, MD, University of California San Francisco, at a Press Cast for the 2012 American Society of Clinical Oncology Genitourinary Symposium held in San Francisco, California. The study was presented at a poster session by lead author MJM Magbanua, MD, UCSF. “There are several studies showing that increments of exercise result in graded outcomes in terms of prostate cancer recurrence. In our study, we measured genetic expression in normal prostate tissue and saw, with vigorous exercise, upregulation of most of the genes we

Vigorous exercise was defined as jogging, brisk walking, swimming, or singles tennis— in other words, exercise that gets the heart rate up.

think kill cancer,” Chan said.

A previous study showed that 3 hours per week of vigorous physical exercise reduced all-cause mortality by 49% and prostate-specific mortality by 61% (Kenfield SA, et al. J Clin Oncol.

2011;29:726-732). A second study found that a brisk versus easy walking pace reduced the risk of prostate cancer progression by 48% (Richman EL, et al. Cancer Res. 2011;7:3889-3895).

Chan and coauthors sought to build on that work and identify potential mechanisms by which exercise influences the prostate gland.

The study included 70 men diagnosed with low-risk prostate cancer who were treated with active surveillance. These men were previously enrolled in a trial of nutritional supplements and provided biopsy tissue at baseline. Vigorous exercise was defined as jogging, brisk walking, swimming, or singles tennis—in other words, exercise that gets the heart rate up. In the men who reported vigorous exercise at least 3 times per week (n = 23), 184 genes were differently expressed in normal prostate tissue versus those who did not (n = 47).

Upregulated genes included known tumor suppressor genes, BRCA1 and BRCA2. Furthermore, gene-set analysis demonstrated that cell cycle and DNA repair pathways were positively modulated in the men who reported vigorous exercise at least 3 times a week versus those who exercised less.

A separate analysis found no affect on genes and pathways in men who reported engaging in any type of physical activity (but not vigorous exercise 3 times a week) versus no exercise.

Chan said that these findings suggest that a certain threshold of intensity or duration of exercise may be important in reducing the risk of prostate recurrence.

Because this is a small sample size, further study is needed. For now, the results suggest that participation in vigorous exercise for at least 3 hours per week may prevent or delay recurrence.

“This study was in low-risk men. I now advise all my low-risk patients to participate in vigorous exercise, and in general, after primary therapy, no matter what the patient’s performance status is, I suggest that they do whatever type of exercise they are able to,” said Nicholas Vogelzang, MD, Chair and Medical Director of the Developmental Therapeutics Committee of US Oncology. l

Visit our user-friendly Web site www.TheOncologyNurse.com In addition to Web-only exclusives, news coverage, journal articles, contests, and polling questions, you’ll have the opportunity to earn Continuing Education credits at NO CHARGE by participating in a number of activities offered!

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Amazing Asparagus

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By Karen Connelly, RD, CSO he mighty green spear of the asparagus is a wel- be of significant therapeutic benefit to their overall come sign of spring. This nutrient-packed veg- clinical outcome. etable has been harvested for more than 2500 While the study of medicinal plants is an exciting and years and has been highly regarded as a promoter of promising area of research, those studied are not usually health and wellness.1 Asparagus has been a staple for the edible type. The good news is that researchers are also many different people of different cultures around the studying active components of the common fruits and world for its taste as well as its proposed medicinal prop- vegetables we eat on a daily basis. Both Asparagus officierties. The ancient Greeks and Romans heralded aspara- nalis and Asparagus racemosus, in addition to various gus as the ultimate delicacy.1 The variety of vitamins, types of vegetables, beans, and herbs, have been found to minerals, and phytochemicals contained in asparagus contain a powerful phytonutrient called saponins. make it a vegetable not to be ignored. Take advantage of Saponins are naturally occurring steroid or triterpene glythis superb vegetable while it is at its peak this season. cosides found in plants, and have the ability to foam Thanks to the many different species of asparagus, its when shaken in water. The saponins found in the asparause and function can vary widely. Asparagus belongs to gus typically consumed in the United States are the lily family (Liliaceae) and as such is related to onions, asparanin A, sarsasapogenin, protodioscin, and a small leeks, and garlic.2 Two main amount of the saponin diosgenin. A species of asparagus have been 2009 research study isolated The variety of vitaresearched extensively: the asparanin A, a steroidal saponin wild asparagus type, Asparagus found in Asparagus officinalis, and mins, minerals, and racemosus, which has been culfound that it has an active cytotoxic tivated and used in India and component.4 Although the exact phytochemicals conmechanism of its cytotoxic activity is the Himalayas as a medicinal unknown at this time, asparanin A food, and Asparagus officinalis, tained in asparagus has been shown to induce cell cycle the most commonly consumed make it a vegetable arrest and trigger apoptosis in human type of asparagus in the United hepatocelluar carcinoma cells.4 States. One particular study not to be ignored.

Further research may look into how examined the antimicrobial this saponin might be used in the impact of medicinal plants, including Asparagus racemosus, on secondary infec- prevention of hepatocellular carcinoma or perhaps as a tions that occurred in treated immunocompromised treatment against this type of cancer.

Asparagus contains a wide variety of vitamins, mineroral cancer patients.3 The investigators determined that the secondary infections these oral cancer als, and phytochemicals. Due to this impressive nutrient patients developed were due to bacterial and fungal content, asparagus has anti-inflammatory and antioxispecies. They then isolated these microbial species dant properties. For example, asparagus is an excellent from the oral cancer patients and assessed the in source of folic acid; a 5.3-ounce serving of asparagus provitro antimicrobial activity of medicinal plants vides 60% of the recommended daily allowance for folic against them. The results of the study demonstrated acid.2 The benefits of folic acid are numerous: it is a that the medicinal plants, including Asparagus race- water-soluble B vitamin that helps in reducing the level mosus, did show antimicrobial activity against the of a chemical called homocysteine in the blood, which clinical isolates from the oral cancer cases. These when present in high levels has been linked to heart disfindings help validate the long history of using ease; folic acid also participates in protein metabolism, plants for medicinal purposes. This study also renews red blood cell and DNA production, and prevention of interest in testing the safety and efficacy of medici- neural tube defects in pregnancy.5 Asparagus also connal plants used against resistant strains of bacterial tains a very potent antioxidant called glutathione and fungal infections in cancer patients, which may (GSH). The role of GSH as an anticarcinogenic and antioxidant compound is significant to our overall health status. GSH is present in many cells of the body and helps support the immune system. GSH also detoxifies Ms Connelly is a Registered Dietitian and Certified Specialist carcinogenic compounds and neutralizes free radicals in Oncology Nutrition at the that occur due to environmental exposure or as the natSteeplechase Cancer Center in ural byproduct of certain metabolic processes. Asparagus Somerville, New Jersey. As is also a good source of thiamin, vitamin B6, and potassipart of her responsibilities, she um and is naturally free of fat and cholesterol and very provides nutrition counseling, low in sodium.2 Not only is asparagus a great choice for a group classes, and monthly low-fat diet, but it also fits very nicely into a calorie-concooking classes for patients trolled diet, with each spear contributing less than 4 caloand families. ries. Encourage patients to incorporate asparagus into

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their daily diet to reap all of these exceptional nutritional benefits.

In addition to the numerous nutritional benefits of asparagus mentioned above, it also boasts yet another well-known component by the name of fiber. Asparagus contains approximately 3 grams of fiber per cup, with about 2 grams of insoluble fiber and 1 gram of soluble fiber. Fiber in the diet is important for a variety of reasons. Insoluble and soluble fiber help promote bowel regularity, regulate blood sugar, maintain healthy cholesterol levels, and reduce the risk of certain types of cancer. In addition to soluble and insoluble fiber, asparagus also contains inulin. The National Cancer Institute defines inulin as “a naturally occurring, indigestible and nonabsorbable oligosaccharide produced by certain plants with prebiotic and potential anticancer activity. Inulin stimulates the growth of beneficial bacteria in the colon, including Bifidobacteria and Lactobacilli, thereby modulating the composition of microflora. This creates an environment that protects against pathogens, toxins and carcinogens, which can cause inflammation and cancer.

In addition, fermentation of inulin leads to an increase in short-chain fatty acids and lactic acid production, thereby reducing colonic pH, which may further control pathogenic bacteria growth and may contribute to inulin’s cancer protective properties.”6 As the definition explains, these attributes make inulin a very useful carbohydrate to include in the diet to help promote digestive health, as well as maintain good glycemic control for patients with diabetes, due to its unique process of metabolism by the body. Adding asparagus to the diet is an easy way for patients to naturally experience the many health benefits of prebiotics and probiotics without having to take a commercial supplement.

During the season, you can find asparagus in a variety of colors—green, purple, and white—at your local grocery store or farmers market. The differences in color have to do, in some part, with the way in which asparagus is harvested. Asparagus is naturally green, but if the developing shoots are covered with dirt and allowed to continue to grow without exposure to the sun, the resulting spears of asparagus are white. This type of asparagus may be found more easily in a gourmet store rather than at your local grocer. Purple asparagus offers an additional health benefit, as it contains anthocyanins, a group of phytochemicals that give the plant its purple color.

Asparagus is not only very nutritious but also very easy and quick to prepare, which may make it a more attractive vegetable choice for the hectic lifestyles many of us lead on a daily basis. Fresh asparagus spears can be steamed in a saucepan or upright in a double boiler in just 5 to 8 minutes. It can also easily be added to a stir-fry, omelets and frittatas, green salads, and whole-grain salads like quinoa. Purchase asparagus spears that are bright in color with firm, thin stalks and closed, compact tips. For best results, first trim the stems and wash in warm water,

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Nutri ion

Karen

with then wrap the entire spear in a moist towel and refrigerate. Another option for storage is, after washing and trimming the stems, stand them upright in a couple inches of cold water and then place them in the refrigerator. It is best to use fresh asparagus within 1 to 2 days of purchasing.

Asparagus may not always get the attention it deserves compared to other members of the vegetable family, but after listing all of its health benefits, perhaps asparagus will become a staple in many diets. This special vegetable is available from late April through mid to late June, so enjoy its delicate flavor and bountiful health benefits while they last. l References 1. Michigan Asparagus Advisory Board (MAAB).

FAQs: questions about asparagus. MAAB Web site. http://www.asparagus.org/maab/faq.html. Published 2000. Accessed May 7, 2012.

2. Michigan Asparagus Advisory Board. Nutrition information. MAAB Web site. http://www.asparagus. org/maab/nutrition.html. Published 2000. Accessed May 7, 2012.

3. Panghal M, Kaushal V, Yadav JP. In vitro antimicrobial activity of ten medicinal plants against clinical isolates of oral cancer cases. Ann Clin Microbiol Antimicrob.

2011;10:21.

4. Liu W, Huang XF, Qi Q, et al. Asparanin A induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Biochem Biophys Res Commun. 2009;381:700-705.

5. Murphy M. The Ohio State University Extension fact sheet: folate (folacin, folic acid). OSU Extension Web site. http://ohioline.osu.edu/hyg-fact/5000/ pdf/5553.pdf. Updated and revised 2004. Accessed May 7, 2012.

6. National Cancer Institute, National Institutes of Health. NCI drug dictionary: inulin. NCI Web site. http://www.cancer.gov/drugdictionary?CdrID=486745.

Recipe n Roasted Beet and Grilled Asparagus Salad With an Orange Tarragon Sour Cream Ingredients 1 bunch asparagus 1 tablespoon canola oil 1 tablespoon thyme 1 bunch beets 2 oranges, juice and zest 2 oranges, peeled, halved, and sliced 1 tablespoon fresh chopped tarragon 4 tablespoons low-fat sour cream 1 bunch leeks, cut into strips and blanched

1. Roast beets in a 350-degree oven for 45 minutes. Peel while still warm and let cool. Cut into slices.

2. Toss asparagus with canola oil and chopped thyme. Grill for 2 to 4 minutes. Let cool.

3. Combine orange juice, tarragon, and sour cream. Place in a plastic squirt bottle with a wide tip. Set aside.

4. Use squirt bottle to apply dressing to the plate. In the center of the plate alternate the beets and orange slices in a tight circle.

5. Tie asparagus in small bundles with leek strips. Place on top of beets and oranges.

6. Garnish with the orange zest.

Nutritional Information Yield: 4 servings

180 calories, 6 g total fat, 1.5 g saturated fat, 5 mg cholesterol, 70 mg sodium, 31 g total carbohydrate, 6 g dietary fiber, 17 g sugars, 5 g protein

®

BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE SANCUSO® (Granisetron Transdermal System) is indicated for the prevention of nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy regimens of up to 5 consecutive days duration.

DOSAGE AND ADMINISTRATION The transdermal system (patch) should be applied to clean, dry, intact healthy skin on the upper outer arm. SANCUSO should not be placed on skin that is red, irritated or damaged. Each patch is packed in a pouch and should be applied directly after the pouch has been opened. The patch should not be cut into pieces.

Adults Apply a single patch to the upper outer arm a minimum of 24 hours before chemotherapy. The patch may be applied up to a maximum of 48 hours before chemotherapy as appropriate. Remove the patch a minimum of 24 hours after completion of chemotherapy. The patch can be worn for up to 7 days depending on the duration of the chemotherapy regimen.

DOSAGE FORMS AND STRENGTHS SANCUSO is a 52 cm2 patch containing 34.3 mg of granisetron. The patch releases 3.1 mg of granisetron per 24 hours for up to 7 days.

CONTRAINDICATIONS SANCUSO is contraindicated in patients with known hypersensitivity to granisetron or to any of the components of the patch.

WARNINGS AND PRECAUTIONS Gastrointestinal The use of granisetron in patients may mask a progressive ileus and/or gastric distention caused by the underlying condition.

Skin Reactions In clinical trials with SANCUSO, application site reactions were reported which were generally mild in intensity and did not lead to discontinuation of use. The incidence of reactions was comparable with placebo. If severe reactions, or a generalized skin reaction occur (e.g. allergic rash, including erythematous, macular, papular rash or pruritus), the patch must be removed.

Exposure to Sunlight Granisetron may be affected by direct natural or artificial sunlight. Patients must be advised to cover the patch application site, e.g. with clothing, if there is a risk of exposure to sunlight throughout the period of wear and for 10 days following its removal because of a potential skin reaction.

ADVERSE REACTIONS Clinical Trials Experience The safety of SANCUSO was evaluated in a total of 404 patients undergoing chemotherapy who participated in two doubleblind, comparator studies with patch treatment durations of up to 7 days. The control groups included a total of 406 patients who received a daily dose of 2 mg oral granisetron, for 1 to 5 days.

Adverse reactions considered by the investigators as drug-related occurred in 8.7% (35/404) of patients receiving SANCUSO and 7.1% (29/406) of patients receiving oral granisetron. The most common adverse reaction was constipation that occurred in 5.4% of patients in the SANCUSO group and 3.0% of patients in the oral granisetron group.

Table 1 lists the treatment emergent adverse reactions that occurred in at least 3% of patients treated with SANCUSO or oral granisetron.

Table 1: Incidence of Adverse Reactions in Double-Blind, Active Comparator Controlled Studies in Cancer Patients Receiving Chemotherapy (Events ≥ 3% in either group) Body System Preferred Term

SANCUSO TDS N=404 (%)

Oral granisetron N=406 (%)

5.4

3.0

0.7

3.0

Gastrointestinal disorders Constipation Nervous system disorders Headache

DRUG INTERACTIONS Granisetron does not induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system in vitro. There have been no definitive drug-drug-interaction studies to examine pharmacokinetic or pharmacodynamic interaction with other drugs. However, in humans, granisetron hydrochloride injection has been safely administered with drugs representing benzodiazepines, neuroleptics and anti-ulcer medications commonly prescribed with antiemetic treatments. Granisetron hydrochloride injection also does not appear to interact with emetogenic cancer therapies. In agreement with these data, no clinically relevant drug interactions have been reported in clinical studies with SANCUSO. Because granisetron is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes (CYP1A1 and CYP3A4), inducers or inhibitors of these enzymes may change the clearance and hence, the half-life of granisetron. In addition, the activity of the cytochrome P-450 subfamily 3A4 (involved in the metabolism of some of the main narcotic analgesic agents) is not modified by granisetron hydrochloride in vitro. In in vitro human microsomal studies, ketoconazole inhibited ring oxidation of granisetron hydrochloride. However, the clinical significance of in vivo pharmacokinetic interactions with ketoconazole is not known. In a human pharmacokinetic study, hepatic enzyme induction with phenobarbital resulted in a 25% increase in total plasma clearance of intravenous granisetron hydrochloride. The clinical significance of this change is not known.

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Did You Know?

An estimated 2.5 million Americans travel outside the United States to receive medical treatment.

—Aesthet Surg J. 2011;31:694-697.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category B Reproduction studies with granisetron hydrochloride have been performed in pregnant rats at intravenous doses up to 9 mg/kg/day (54 mg/m2/day, about 24 times the recommended human dose delivered by the SANCUSO patch, based on body surface area) and oral doses up to 125 mg/m2/day (750 mg/m2/day, about 326 times the recommended human dose with SANCUSO based on body surface area). Reproduction studies have been performed in pregnant rabbits at intravenous doses up to 3 mg/kg/day (36 mg/m2/day, about 16 times the human dose with SANCUSO based on body surface area) and at oral doses up to 32 mg/kg/day (384 mg/m2/day, about 167 times the human dose with SANCUSO based on body surface area). These studies did not reveal any evidence of impaired fertility or harm to the fetus due to granisetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, SANCUSO should be used during pregnancy only if clearly needed.

Nursing Mothers It is not known whether granisetron is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when SANCUSO is administered to a nursing woman.

Pediatric Use Safety and effectiveness of SANCUSO in pediatric patients under 18 years of age have not been established.

Geriatric Use Clinical studies of SANCUSO did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, cautious treatment selection for an elderly patient is prudent because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Renal Failure or Hepatically-Impaired Patients Although no studies have been performed to investigate the pharmacokinetics of SANCUSO in patients with renal or hepatic impairment, pharmacokinetic information is available for intravenous granisetron.

OVERDOSAGE There is no specific antidote for granisetron overdosage. In the case of overdosage, symptomatic treatment should be given.

Overdosage of up to 38.5 mg of granisetron hydrochloride, as a single intravenous injection, has been reported without symptoms or only the occurrence of a slight headache. In clinical trials there were no reported cases of overdosage with SANCUSO. HOW SUPPLIED/STORAGE AND HANDLING SANCUSO (Granisetron Transdermal System) is supplied as a 52 cm2 patch containing 34.3 mg of granisetron. Each patch is printed on one side with the words “Granisetron 3.1 mg/24 hours”. Each patch is packaged in a separate sealed foil-lined plastic pouch.

SANCUSO is available in packages of 1 (NDC 42747-726-01) patch.

Store at 20˚-25˚C (68˚-77˚F); excursions permitted between 15˚-30˚C (59˚-86˚F). [see USP Controlled Room Temperature].

SANCUSO should be stored in the original packaging.

PATIENT COUNSELING INFORMATION See FDA-approved patient labeling.

Gastrointestinal Because the use of granisetron may mask a progressive ileus and/or gastric distention caused by the underlying condition, patients should be instructed to tell their physician if they have pain or swelling in their abdomen.

Skin Reactions Patients should be instructed to remove the patch if they have a severe skin reaction, or a generalized skin reaction (e.g. allergic rash, including erythematous, macular, papular rash or pruritus). When patients remove the patch, they should be instructed to peel it off gently.

Exposure to Sunlight Granisetron may be degraded by direct sunlight or exposure to sunlamps. In addition, an in vitro study using Chinese hamster ovary cells suggests that granisetron has the potential for photogenotoxicity.

Patients must be advised to cover the patch application site, e.g. with clothing, if there is a risk of exposure to sunlight or sunlamps throughout the period of wear and for 10 days following its removal.

FDA-Approved Patient Labeling Rx Only Manufactured by: Aveva Drug Delivery Systems Inc., Miramar FL 33025

Manufactured for: ProStrakan Inc., Bedminster NJ 07921 Copyright ©2008, ProStrakan Inc. All rights reserved.

SANCUSO and ProStrakan are trademarks owned by the ProStrakan group of companies Revised: 08/2008

5:28 PM

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SANCUSO速 (Granisetron Transdermal System): A recommendation from NCCN1 and ASCO2 In the treatment of CINV, she is now

armed & ready 5 full days of 5-HT3 protection in a single patch3 Visit www.sancuso.com to learn more about the only transdermal antiemetic patch for CINV. Please refer to the important safety information for sunlight warning.

Important safety information SANCUSO速 (Granisetron Transdermal System) is indicated for the prevention of nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy regimens of up to 5 consecutive days duration.4 SANCUSO is contraindicated in patients with known hypersensitivity to granisetron or to any of the components of the patch.4 Granisetron may mask a progressive ileus and/or gastric distention caused by the underlying condition.4 Mild application site reactions have occurred; remove the patch if severe reaction or a generalized skin reaction occurs.4 Patients should avoid direct exposure of application site to natural or artificial sunlight by covering with clothing while wearing the patch and for 10 days after removing it.4 The most common adverse reaction in patients receiving SANCUSO is constipation (5.4%).4 SANCUSO contains granisetron.4 Healthcare professionals should avoid prescribing any additional products that contain granisetron. No clinically relevant drug interactions have been reported in clinical studies with SANCUSO.4

References: 1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Antiemesis. V.1.2012. http://www.nccn.org/professionals/ physician_gls/pdf/antiemesis.pdf. Accessed December 13, 2011. 2. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2011;29(31):4189-4198. 3. Boccia RV, Gordan LN, Clark G, Howell JD, Grunberg SM; on behalf of the Sancuso Study Group. Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study. Support Care Cancer. 2011;19(10):1609-1617.

4. SANCUSO [package insert]. Bedminster, NJ: ProStrakan, Inc; 2008.

ONLY 速

www.prostrakan-usa.com www.sancuso.com SANCUSO is a registered trademark of ProStrakan, Inc. 息2012 ProStrakan, Inc. All rights reserved. Printed in U.S.A. SAN-2012-001 January 2012

Please see brief summary of Prescribing Information on adjacent page.

Keeps them covered