TON September 2013 by The Oncology Nurse

September 2013

www.TheOncologyNurse.com

Vol 6, No 8

Through the Eyes of an Advocate

Cancer Center Profile

The Medical Minute

The Cleveland Clinic Taussig Cancer Institute

By Peg Ford

The Expanding Role of APNs and NPs

“The doctor will be here in a minute,” the RN said to me and a patient who was in the recovery room. A few days before, I had received a phone call from a friend asking if I was available to accompany this woman, a mutual friend, to the hospital for an outpatient procedure. According to the instructions and figuring in the time to transport her there and back from the hospital, it would be no more than 3 hours. The patient, who had faced numerous recurrences of cancer over several years that involved chemotherapy, radiation, adverse reactions, etc, had been rushed

to the ER just a week earlier, dehydrated and vomiting uncontrollably. We were, obviously, concerned about what this brave woman was facing at this juncture, as she had been in remission until this episode. Arriving at the hospital, the outpatient admission went smoothly as did the standard procedure of checking vitals, while we sat in the examination room awaiting the doctor. The patient told me that her referring doctor’s office had faxed all her records to this facility. However, when the resident entered and Continued on page 17

The Patient’s Voice Iyaad Hasan, CNP, APN/PA Director at the Cleveland Clinic Taussig Cancer Institute, is involved with the Community Outreach Program. Outreach services include screening and education about cancer prevention and risk factors.

My Prostate Cancer Story: Receiving the News By John Nickel

he Taussig Cancer Institute at the Cleveland Clinic in Ohio employs more than 250 highly skilled doctors, nurses, and other healthcare professionals who provide advanced cancer care to more than 14,000 patients with cancer each year. The Taussig Cancer Institute is involved in translational research and clinical trials and collaborates internationally with other centers to ensure that patients have access to the latest advances in cancer treatment. Taussig is committed to providing a range of support programs to help patients navigate their treatment course and associated issues. Continued on page 22

’d been meaning to wash my car for days, and was pleased to see I had just enough time to fit that little task in before sunset. Just as I’d finished and hopped into the driver’s seat to move the car back into the garage, my cell phone rang. It was my urologist, Dr G. As he started to speak, in that first instant, 2 thoughts flashed through my mind: First, when the doctor’s office calls, it’s always a nurse or administrative person, not the

News Briefs

his month’s column focuses on recent reports in the literature pertaining to prostate cancer. The studies summarized below cover such topics as the first radioisotope to show a survival benefit in men with bone metastases, the importance of an accurate biopsy reading by a pathologist who specializes in urology specimens,

Drug Shortages. . . . . . . . . . . . . . . . .

the inappropriate use of intensity-modulated radiotherapy by physicians who self-refer patients for radiation, overuse of imaging modalities in men with lowrisk prostate cancer, and data suggesting that acute kidney injury is associated with current use of androgen deprivation therapy.

Continued on page 12

inside

Prostate Cancer in the News By Alice Goodman

doctor himself. And second, they don’t call after office hours—probably 4:45 at the latest. It was 6:30. This was odd. After a pleasant hello, the conversation began like this: Dr G: I just got back the results of your prostate biopsy from the lab, and I’m sorry to tell you, you have prostate cancer. Me: Um, uh, okay...

Surveys Confirm Drug Shortages Are a Persistent Problem

Multiple Myeloma . . . . . . . . . . . .

Novel Agents Emerge in Initial Therapy, Refractory Setting

Prostate Cancer

Technology Brings No Upward Shift in Treatment of Local Prostate Cancer. . . . . . . . . . . . . . . . . . .

Abiraterone in Untreated Metastatic Castration-Resistant Prostate Cancer. . . . . . . . . . . . . . . . . . . Enzalutamide Promising in Hormone-Naive Prostate Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Side Effects Management . .

Superior Efficacy Shown for Novel Fixed-Dose Antiemetic Combination

19 19 20

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Editorial Board EDITOR-IN-CHIEF

Beth Faiman,

Shannon Hazen, RN, BSN, OCN

PhD(c), MSN, APRNBC, AOCN

Novant Health Presbyterian Cancer Center Charlotte, NC

Catherine Bishop,

Patricia Irouer Hughes, RN, MSN,

Cleveland Clinic Taussig Cancer Institute Cleveland, OH

DNP, NP, AOCNP

Melinda Oberleitner, RN,

Karla Wilson,

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

City of Hope National Medical Center Duarte, CA

Jayshree Shah, NP

Pharmacy John F. Aforismo,

DNS, APRN, CNS

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Johns Hopkins Kimmel Cancer Center/Sibley Infusion Washington, DC

BSN, OCN

Deena Damsky Dell, MSN, RN-BC,

Taline Khoukaz,

Gary Shelton,

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

NYU Clinical Cancer Center New York, NY

AOCN, LNC

Fox Chase Cancer Center Philadelphia, PA

Wendy DiSalvo,

DNP, APRN, AOCN Genentech New London, NH

Denice Economou,

RN, MN, CNS, AOCN City of Hope National Medical Center Duarte, CA

Constance Engelking, RN,

MS, CNS, OCN

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

Amy Ford, RN,

BSN, OCN Biodesix, Inc. Dallas, TX

Piedmont Healthcare Rex, GA

NP, MSN, ACNP-C

MSN, NP, ANP-BC, AOCNP

Sandra E. Kurtin,

Lori Stover, RN,

Arizona Cancer Center Tucson, AZ

Western Pennsylvania Cancer Institute Pittsburgh, PA

Ann McNeill,

Joseph D. Tariman,

RN, MS, AOCN, ANP-C

MSN, RN, NP-C, OCN

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Kena C. Miller, RN, MSN, FNP

Roswell Park Cancer Institute Buffalo, NY

Patricia Molinelli, MS, RN, APN-C, AOCNS

Somerset Medical Center Somerville, NJ

BSN

PhD, APRN, BC

Northwestern University Myeloma Program Chicago, IL

Jacqueline Marie Toia, RN, MS, DNP

Northwestern University Myeloma Program Chicago, IL

Pamela Hallquist Viale, RN, MS,

CS, ANP, AOCN Saratoga, CA

RN, MSN, FNP-C, CPON

BSc Pharm, RPh, FASCP RJ Health Systems International, LLC Wethersfield, CT

Nutrition Karen Connelly, RD, CSO

Somerset Medical Center Somerville, NJ

Patient Advocacy Peg Ford

Ovarian Cancer Alliance San Diego, CA

Social Work Carolyn Messner, DSW, MSW, LCSW-R, BCD CancerCare New York, NY

Genetic Counseling Cristi Radford, MS, CGC

Ambry Genetics Sarasota, FL

Managed Care and Pharmaceutical Management Burt Zweigenhaft, BS

OncoMed Onco360 Great Neck, NY

Sharon S. Gentry, RN, MSN, AOCN

Novant Health Derrick L. Davis Cancer Center Winston-Salem, NC

Ellen A. Neylon, MSN, FNP-BC, CCRP, OCN

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

Cassandra J. Hammond, RN,

Dolores “Jeff” Nordquist, RN, MS,

Avid Education Partners, LLC Sharpsburg, MD

Mayo Clinic Rochester, MN

MSN, CRNP

www.TheOncologyNurse.com

CS, FNP

Connie Visovsky, RN, PhD, APRN

University of South Florida College of Nursing Tampa, FL

Rita Wickham,

PhD, RN, AOCN

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

Isabell Castellano, RN

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

Jeanne Westphal, RN

Meeker County Memorial Hospital Litchfield, MN

September 2013 I VOL 6, NO 8

From The Editor PUBLISHING STAFF Senior Vice President, Sales & Marketing Philip Pawelko phil@greenhillhc.com

Group Director, Sales & Marketing John W. Hennessy john@greenhillhc.com Publisher Russell Hennessy russell@greenhillhc.com Editorial Director Kristin Siyahian kristin@greenhillhc.com Managing Editor Kristen Olafson kristen@greenhillhc.com Copy Editors Mollie Friedman Peggy Roeske Editorial Assistant Jennifer Brandt Production Manager Stephanie Laudien

eptember is National Prostate Cancer Awareness Month. The presidential proclamation noting this included the following statement encouraging “all Americans to lend their support to family, friends, and neighbors whose lives have been touched by prostate cancer. Let us celebrate the compassion and perseverance of health care providers, researchers, and dedicated advocates. Beth Faiman, PhD(c), Together, we can raise awareness, MSN, APRN-BC, AOCN support research, improve care, and Editor-in-Chief reduce the impact of this disease on our citizens and our Nation.” This month’s issue of The Oncology Nurse-APN/PA (TON) provides updates on the latest research and treatment for prostate cancer. The Patient’s Voice column gives us the perspective of a man who “receives the news” that he has prostate cancer. His article shows us how many patients carefully analyze our verbal and nonverbal communication for cues as they try to understand

and process a frightening situation. Also, the column is a good reminder that common terminology to us (for example, Gleason score) can be completely unknown to patients. In her Through the Eyes of an Advocate column, Peg Ford tells us about her experience escorting a friend to the hospital for an outpatient procedure. The friend had survived several recurrences of cancer and her latest symptoms had everyone worried. Unfortunately, things at the hospital conspired against a smooth process—medical records had not been received and the doctor was delayed in coming to speak with the patient after the procedure was over. What should have taken a total of 3 hours ended up taking 6½ hours. Peg notes that “The patient is too often the stakeholder whose needs are not fully considered in a system that is groaning from unrealistic burdens and stresses.” It is a system where the “medical minute” is becoming all too unrealistic for all involved— patients and healthcare providers. The “medical minute” is this month’s TON reader poll. See below for information and be sure to visit our website, www.TheOncologyNurse, to give us your perspective. l

Reader Poll

President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Director, Human Resources Blanche Marchitto

Have you had to explain “the medical minute” to patients?

Associate Editorial Director, Projects Division Terri Moore

o Yes

Director, Quality Control Barbara Marino

o No

Quality Control Assistant Theresa Salerno Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Creative & Design Assistant Lora LaRocca Director, Digital Media Anthony Romano Web Content Managers David Maldonado Anthony Travean Digital Programmer Michael Amundsen Senior Project Manager Andrea Boylston Project Coordinators Deanna Martinez Jackie Luma Executive Administrator Rachael Baranoski Office Coordinator Robert Sorensen

1249 South River Road - Ste 202A Cranbury, NJ 08512 phone: 732-656-7935 fax: 732-656-7938

September 2013 I VOL 6, NO 8

©iStockphoto.com/Slobodan Vasic

eg Ford talks about her recent experience with “the medical minute” (see article on cover). She accompanied a friend for an outpatient procedure that was supposed to take about a total of 3 hours, including transportation time to and from the hospital.

Even though nothing went “wrong” during the procedure, the whole process took 6½ hours—a very difficult situation for a cancer survivor in a weakened condition. Have you experienced similar situations? What do you say to patients when these situations occur?

Go to www.TheOncologyNurse.com to answer the question and add your comments.

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, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Telephone: 732.656.7935. Fax: 732.656.7938. Copyright ©2013 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®, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. E-mail: editorial@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, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. 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 mentioned 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.

www.TheOncologyNurse.com

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Drug Shortages

Surveys Confirm Drug Shortages Are a Persistent Problem By Caroline Helwick

ecent surveys of oncologists and hematologists show that drug shortages persist, that practitioners are adapting in ways that often raise the cost of cancer care, and that

most have no guidance to aid in decision making in the face of these shortages. A survey of 250 physicians, by investigators at the University of Pennsylvania, Philadelphia, showed that 83% encoun-

tered shortages of curative and palliative chemotherapy agents between March and September of 2012. Many reported that shortages affected the quality and cost of patient care, as they were forced

IS NOW

LynxCME is the new home of COEXM activities CONTINUING EDUCATION 6th Annual

Visit our NEW website

MAY 2013 • VOLUME 6 • NUMBER 2

CONSIDERATIONS in

Multiple Myeloma

™

www.lynxcme.com

ASK THE EXPERTS: Maintenance Settings PUBLISHING STAFF Group Director, Sales & Marketing John W. Hennessy john@greenhillhc.com Editorial Director Susan A. Berry susan@coexm.com Senior Copy Editor BJ Hansen Copy Editors Dana Delibovi Rosemary Hansen Grants/Project Associate Susan Yeager The Lynx Group President/CEO Brian Tyburski Chief Operating Officer Pam Rattanonont Ferris Vice President of Finance Andrea Kelly Director of Human Resources Blanche Marchitto Associate Editorial Director, Projects Division Terri Moore

LETTER

FROM THE

EDITOR-IN-CHIEF

Over the past decade, significant progress has been made in the management of multiple myeloma, including new standards of care and the development and approval of several novel, effective agents. Despite this progress, more work needs to be done and numerous questions remain regarding the application and interpretation of recent clinical advances. In this sixth annual “Considerations in Multiple Myeloma” newsletter series, we continue to explore unresolved issues related to the management of the disease and new directions in treatment. To ensure an interprofessional perspective, our faculty is comprised of physicians, nurses, and pharmacists from leading cancer institutions, who provide their insight, knowledge, and clinical experience related to the topic at hand. In this second issue, experts from Dana-Farber Cancer Institute answer questions related to the management of patients in the maintenance setting.

to learn more!

Sincerely, Sagar Lonial, MD Professor Vice Chair of Clinical Affairs Department of Hematology and Medical Oncology Winship Cancer Institute Emory University School of Medicine Atlanta, GA

Director, Quality Control Barbara Marino Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Creative & Design Assistant Lora LaRocca Director, Digital Media Anthony Romano Web Content Managers David Maldonado Anthony Travean

FACULTY Kenneth C. Anderson, MD Director, Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics Kraft Family Professor of Medicine Harvard Medical School Dana-Farber Cancer Institute, Boston, MA

Tina Flaherty, ANP-BC, AOCN Nurse Practitioner Division of Hematologic Malignancies Dana-Farber Cancer Institute Boston, MA

Houry Leblebjian, PharmD, BCOP Clinical Pharmacy Specialist in MARCH 2013 • VOLUME 4 • NUMBER 2 Hematology/Oncology Dana-Farber Cancer Institute Boston, MA

Digital Programmer Michael Amundsen Senior Project Manager Andrea Boylston Project Coordinators Deanna Martinez Jackie Luma

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

Executive Administrator Rachael Baranoski Office Coordinator Robert Sorensen

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

Center of Excellence Media, LLC 1249 South River Road - Ste 202A Cranbury, NJ 08512

Discussions in Personalized Treatment for Lymphoma: Do We Have Consensus? CONTRIBUTING FACULTY Chair Stephanie A. Gregory, MD

AONNAsize SaveTheDate_31413_Layout 1 6/7/13 12:27 PM Page 1

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

Sonali M. Smith, MD

Associate Professor Section of Hematology/Oncology Director, Lymphoma Program The University of Chicago Medical Center Chicago, IL

Mitchell R. Smith, MD, PhD Director of Lymphoid Malignancies Program Taussig Cancer Institute Cleveland Clinic Cleveland, OH

Steve M. Horwitz, MD

Assistant Attending Medical Oncologist Lymphoma, Cutaneous Lymphomas, T-Cell Lymphoma Memorial Sloan-Kettering Cancer Center New York, NY

Supported by an educational grant from Celgene Corporation

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

Fourth Annual Navigation

Memphis, Tennessee • The Peabody Memphis

NOVEMBER 15-17, 2013 CONFERENCE CO-CHAIRS Lillie D. Shockney, RN, BS, MAS AONN Program Director University Distinguished Service Associate Professor of Breast Cancer Departments of Surgery and Oncology Administrative Director, Johns Hopkins Clinical Breast Programs Administrative Director, Johns Hopkins Cancer Survivorship Programs Department of Surgery and Oncology Associate Professor, JHU School of Medicine Departments of Surgery, Oncology, and Gynecology Associate Professor, JHU School of Nursing Johns Hopkins Avon Foundation Breast Center Baltimore, MD

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

www.AONNonline.org AONNAsize31413

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to substitute more expensive drugs for cheaper generics. “Drug shortages are affecting the treatment of curable malignancies. We don’t know the extent to which adaptations forced by these shortages led to adverse clinical outcomes for patients,” said Keerthi Gogineni, MD, of the Abramson Cancer Center in Philadelphia, at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO).1 Shortages have also interfered with patient participation in clinical trials, slowing the pace of research progress, she added. “We were surprised by the large number of oncologists who had to make changes in how they care for patients due to drug shortages,” she said at a press briefing at ASCO. “Unfortunately, cancer drug shortages are likely to persist, but doctors are adapting to this new reality as best they can. We need more uniform guidance to ensure that the modifications in treatment are being made in the most educated and ethical way.” Gogineni and colleagues distributed the survey to 454 oncologists and hematologists in the United States randomly selected from the ASCO membership; 250 responded and 214 surveys were analyzed. About two-thirds practiced in community-based private settings while one-third practiced in academic settings. The data reflect drug shortage experiences from March 2012 to March 2013. Shortages were most commonly reported for leucovorin, liposomal doxorubicin, 5-fluorouracil (5-FU), bleomycin, and cytarabine. More Than 80% of Patients Had Treatment Altered The respondents were asked about the impact of drug shortages over the previous 6 months. In response, 94% reported that their patients’ treatment had been affected and for 83% they were unable to provide standard chemotherapy. About 13% said that shortages had prevented enrollment in clinical trials or had suspended participation in them. The physicians adapted to shortages in various ways, including changing the treatment regimen (78%), substituting drugs partway through therapy (77%), delaying treatment (43%), “rationing” treatment to certain patients (37%), omitting doses (29%), reducing doses (20%), and referring patients to other practices (17%). Most providers (70%) indicated that they lacked institutional guidelines or committees to advise them in these difficult treatment decisions; academic physicians had more help. Clinical trial Continued on page 8

September 2013 I VOL 6, NO 8

www.TheOncologyNurse.com

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Important Safety Information About ARIMIDEX® • ARIMIDEX is only for postmenopausal women. ARIMIDEX can cause fetal harm when administered to a pregnant woman. Before starting treatment with ARIMIDEX, pregnancy must be excluded. ARIMIDEX is contraindicated in patients with demonstrated hypersensitivity to ARIMIDEX or any of its excipients. Observed reactions include anaphylaxis, angioedema, and urticaria (see CONTRAINDICATIONS section of full Prescribing Information) • In women with preexisting ischemic heart disease 465/6186 (7.5%), an increased incidence of ischemic cardiovascular events occurred with ARIMIDEX (17%) vs tamoxifen (10%). In this patient population, angina pectoris was reported in 25/216 (11.6%) vs 13/249 (5.2%) and myocardial infarction was reported in 2/216 (0.9%) vs 8/249 (3.2%) patients receiving ARIMIDEX and tamoxifen, respectively • Compared to baseline, ARIMIDEX showed a mean decrease in both lumbar spine and total hip bone mineral density. Tamoxifen showed a mean increase in these measurements. Nine percent of patients receiving ARIMIDEX had an elevated serum cholesterol vs 3.5% of patients receiving tamoxifen • In the early breast cancer (ATAC) study, the most common (occurring with an incidence of >10%) side effects occurring in women taking ARIMIDEX included: hot ﬂashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, insomnia, headache, peripheral edema and lymphedema, regardless of causality • In the advanced breast cancer studies, the most common (occurring with an incidence of >10%) side effects occurring in women taking ARIMIDEX included hot ﬂashes, nausea, asthenia, pain, headache, back pain, bone pain, increased cough, dyspnea, pharyngitis, and peripheral edema. Joint pain/stiffness has been reported in association with the use of ARIMIDEX

• Clinical and pharmacokinetic results suggest that tamoxifen should not be administered with ARIMIDEX. Estrogen-containing therapies should not be used with ARIMIDEX as they may diminish its pharmacologic action

Approved Uses ARIMIDEX is indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. ARIMIDEX is indicated for the ﬁrst-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer and for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with estrogen receptor-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to ARIMIDEX.

Please see brief summary of full Prescribing Information on next page. If you can’t afford your medication, AstraZeneca may be able to help. For more information, please visit www.AstraZeneca-us.com You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch, or call 1-800-FDA-1088. References: 1. Source: IMS NPA Monthly, February 2001-December 2012.

Drug Shortages

Surveys Confirm Drug Shortages... Continued from page 6 participation was affected in some way 11% of the time.

Photo by © ASCO/Todd Buchanan 2013.

nab-paclitaxel for paclitaxel. “This is adding to healthcare costs,” Gogineni emphasized. Costly Substitutions Levoleucovorin costs about Nearly 60% of physicians 30 times more than leucovorin substituted more expensive and capecitabine costs about agents when cheaper gener140 times more than 5-FU for Richard L. ics were not available. This 1 cycle of colon cancer treatSchilsky, MD included levoleucovorin for ment. There are also “hidden leucovorin, capecitabine for 5-FU, and costs” in terms of additional hours

spent by staff trying to manage these shortages, she said. ASCO Survey: Only Small Improvements Seen ASCO also surveyed its members in October and November 2012 (n = 390) and again in March and April 2013 (n = 462) to assess the impact of shortages over those 6 months and

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INDICATIONS AND USAGE Adjuvant Treatment ARIMIDEX is indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. First-Line Treatment ARIMIDEX is indicated for the ﬁrst-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer. Second-Line Treatment ARIMIDEX is indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to ARIMIDEX.

RECOMMENDED DOSE The dose of ARIMIDEX is one 1 mg tablet taken once a day. For patients with advanced breast cancer, ARIMIDEX should be continued until tumor progression. ARIMIDEX can be taken with or without food. No dosage adjustment is necessary for patients with renal impairment or for elderly patients. No changes in dose are recommended for patients with mild-to-moderate hepatic impairment. ARIMIDEX has not been studied in patients with severe hepatic impairment.

CONTRAINDICATIONS ARIMIDEX may cause fetal harm when administered to a pregnant woman and offers no clinical beneﬁt to premenopausal women with breast cancer. ARIMIDEX is contraindicated in women who are or may become pregnant. ARIMIDEX is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. Observed reactions include anaphylaxis, angioedema, and urticaria.

WARNINGS AND PRECAUTIONS In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events was observed with ARIMIDEX in the ATAC trial (17% of patients on ARIMIDEX and 10% of patients on tamoxifen). Consider risk and beneﬁts of ARIMIDEX therapy in patients with pre-existing ischemic heart disease. Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving ARIMIDEX had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline. Consider bone mineral density monitoring in patients treated with ARIMIDEX. During the ATAC trial, more patients receiving ARIMIDEX were reported to have elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively).

ADVERSE REACTIONS Serious adverse reactions with ARIMIDEX occurring in less than 1 in 10,000 patients are: 1) skin reactions such as lesions, ulcers, or blisters; 2) allergic reactions with swelling of the face, lips, tongue, and/or throat. This may cause difficulty in swallowing and/or breathing; and 3) changes in blood tests of the liver function, including inflammation of the liver with symptoms that may include a general feeling of not being well, with or without jaundice, liver pain or liver swelling. In the early breast cancer (ATAC) study, the most common (occurring with an incidence of >10%) side effects occurring in women taking ARIMIDEX included: hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, insomnia, headache, peripheral edema and lymphedema, regardless of causality. In the advanced breast cancer studies, the most common (occurring with an incidence of >10%) side effects occurring in women taking ARIMIDEX included: hot flashes, nausea, asthenia, pain, headache, back pain, bone pain, increased cough, dyspnea, pharyngitis and peripheral edema. Ischemic Cardiovascular Events Between treatment arms in the overall population of 6186 patients, there was no statistical difference in ischemic cardiovascular events (4% ARIMIDEX vs. 3% tamoxifen). In the overall population, angina pectoris was reported in 71/3092 (2.3%) patients in the ARIMIDEX arm and 51/3094 (1.6%) patients in the tamoxifen arm; myocardial infarction was reported in 37/3092 (1.2%) patients in the ARIMIDEX arm and 34/3094 (1.1%) patients in the tamoxifen arm. In women with preexisting ischemic heart disease 465/6186 (7.5%), the incidence of ischemic cardiovascular events was 17% in patients on ARIMIDEX and 10% in patients on tamoxifen. In this patient population, angina pectoris was reported in 25/216 (11.6%) patients receiving ARIMIDEX and 13/249 (5.2%) patients receiving tamoxifen; myocardial infarction was reported in 2/216 (0.9%) patients receiving ARIMIDEX and 8/249 (3.2%) patients receiving tamoxifen. Bone Mineral Density Findings Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving ARIMIDEX had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline. Because ARIMIDEX lowers circulating estrogen levels it may cause a reduction in bone mineral density. A post-marketing trial assessed the combined effects of ARIMIDEX and the bisphosphonate risedronate on changes from baseline in BMD and markers of bone resorption and formation in postmenopausal women with hormone receptor-positive early breast cancer. All patients received calcium and vitamin D supplementation. At 12 months, small reductions in lumbar spine bone mineral density were noted in patients not receiving bisphosphonates. Bisphosphonate treatment preserved bone density in most patients at risk of fracture. Postmenopausal women with early breast cancer scheduled to be treated with ARIMIDEX should have their bone status managed according to treatment guidelines already available for postmenopausal women at similar risk of fragility fracture. Cholesterol During the ATAC trial, more patients receiving ARIMIDEX were reported to have an elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively). A post-marketing trial also evaluated any potential effects of ARIMIDEX on lipid profile. In the primary analysis population for lipids (ARIMIDEX alone), there was no clinically significant change in LDL-C from baseline to 12 months and HDL-C from baseline to 12 months. In secondary population for lipids (ARIMIDEX+risedronate), there also was no clinically significant change in LDL-C and HDL-C from baseline to 12 months. In both populations for lipids, there was no clinically significant difference in total cholesterol (TC) or serum triglycerides (TG) at 12 months compared with baseline. In this trial, treatment for 12 months with ARIMIDEX alone had a neutral effect on lipid profile. Combination treatment with ARIMIDEX and risedronate also had a neutral effect on lipid profile. The trial provides evidence that postmenopausal women with early breast cancer scheduled to be treated with ARIMIDEX should be managed using the current National Cholesterol Education Program guidelines for cardiovascular risk-based management of individual patients with LDL elevations. Second-Line Therapy ARIMIDEX was tolerated in two controlled clinical trials (i.e., Trials 0004 and 0005), with less than 3.3% of the ARIMIDEX-treated patients and 4.0% of the megestrol acetate-treated patients withdrawing due to an adverse reaction. The principal adverse reaction more common with ARIMIDEX than megestrol acetate was diarrhea.

September 2013 I VOL 6, NO 8

The incidences of the following adverse reaction groups potentially causally related to one or both of the therapies because of their pharmacology, were statistically analyzed: weight gain, edema, thromboembolic disease, gastrointestinal disturbance, hot flushes, and vaginal dryness. These six groups, and the adverse reactions captured in the groups, were prospectively defined. The results are shown in the following table. Table 1 – Number (n) and Percentage of Patients with Pre-specified Adverse Reactions in Trials 0004 and 0005 ARIMIDEX 1 mg ARIMIDEX 10 mg Megestrol Acetate 160 mg (N=262) (N=246) (N=253) Adverse Reaction Group N (%) N (%) N (%) Gastrointestinal Disturbance 77 (29) 81 (33) 54 (21) Hot Flushes 33 (13) 29 (12) 35 (14) Edema 19 (7) 28 (11) 35 (14) Thromboembolic Disease 9 (3) 4 (2) 12 (5) Vaginal Dryness 5 (2) 3 (1) 2 (1) Weight Gain 4 (2) 10 (4) 30 (12)

Post-Marketing Experience These adverse reactions are reported voluntarily from a population of uncertain size. Therefore, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. The following have been reported in post-approval use of Arimidex: • Hepatobiliary events including increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-GT, and bilirubin; hepatitis; • Rash including cases of mucocutaneous disorders such as erythema multiforme and StevensJohnson syndrome; • Cases of allergic reactions including angioedema, urticaria and anaphylaxis; • Myalgia, trigger ﬁnger and hypercalcemia (with or without an increase in parathyroid hormone).

DRUG INTERACTIONS Co-administration of anastrozole and tamoxifen in breast cancer patients reduced anastrozole plasma concentration by 27%. However, the coadministration of anastrozole and tamoxifen did not affect the pharmacokinetics of tamoxifen or N-desmethyltamoxifen. At a median follow-up of 33 months, the combination of ARIMIDEX and tamoxifen did not demonstrate any efﬁcacy beneﬁt when compared with tamoxifen in all patients as well as in the hormone receptor-positive subpopulation. This treatment arm was discontinued from the trial [see Clinical Studies (14.1) in Full Prescribing Information ]. Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with anastrozole. Estrogen-containing therapies should not be used with ARIMIDEX as they may diminish its pharmacological action.

USE IN SPECIFIC POPULATIONS Pregnancy PREGNANCY CATEGORY X ARIMIDEX may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. ARIMIDEX is contraindicated in women who are or may become pregnant. If ARIMIDEX is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus and potential risk for pregnancy loss. Nursing Mothers It is not known if anastrozole is excreted in human milk. Because many drugs are excreted in human milk and because of the tumorigenicity shown for anastrozole in animal studies, or the potential for serious adverse reactions in nursing infants, 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 Clinical studies in pediatric patients included a placebo-controlled trial in pubertal boys of adolescent age with gynecomastia and a single-arm trial in girls with McCune-Albright Syndrome and progressive precocious puberty. The efﬁcacy of ARIMIDEX in the treatment of pubertal gynecomastia in adolescent boys and in the treatment of precocious puberty in girls with McCune-Albright Syndrome has not been demonstrated. Geriatric Use In studies 0030 and 0027 about 50% of patients were 65 or older. Patients ≥65 years of age had moderately better tumor response and time to tumor progression than patients <65 years of age regardless of randomized treatment. In studies 0004 and 0005 50% of patients were 65 or older. Response rates and time to progression were similar for the over 65 and younger patients. In the ATAC study 45% of patients were 65 years of age or older. The efficacy of ARIMIDEX compared to tamoxifen in patients who were 65 years or older (N=1413 for ARIMIDEX and N=1410 for tamoxifen, the hazard ratio for disease-free survival was 0.93 [95% CI: 0.80, 1.08]) was less than efficacy observed in patients who were less than 65 years of age (N=1712 for ARIMIDEX and N=1706 for tamoxifen, the hazard ratio for disease-free survival was 0.79 [95% CI: 0.67, 0.94]). The pharmacokinetics of anastrozole are not affected by age. Renal Impairment Since only about 10% of anastrozole is excreted unchanged in the urine, the renal impairment does not inﬂuence the total body clearance. Dosage adjustment in patients with renal impairment is not necessary [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3) in Full Prescribing Information]. Hepatic Impairment The plasma anastrozole concentrations in the subjects with hepatic cirrhosis were within the range of concentrations seen in normal subjects across all clinical trials. Therefore, dosage adjustment is also not necessary in patients with stable hepatic cirrhosis. ARIMIDEX has not been studied in patients with severe hepatic impairment [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3) in Full Prescribing Information].

OVERDOSAGE Clinical trials have been conducted with ARIMIDEX, up to 60 mg in a single dose given to healthy male volunteers and up to 10 mg daily given to postmenopausal women with advanced breast cancer; these dosages were tolerated. A single dose of ARIMIDEX that results in life-threatening symptoms has not been established. There is no specific antidote to overdosage and treatment must be symptomatic. In the management of an overdose, consider that multiple agents may have been taken. Vomiting may be induced if the patient is alert. Dialysis may be helpful because ARIMIDEX is not highly protein bound. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated. These highlights do not include all the information needed to use ARIMIDEX safely and effectively. See full Prescribing Information for ARIMIDEX. To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca Pharmaceuticals LP at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch ARIMIDEX is a registered trademark of the AstraZeneca group of companies. © 2009 AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850. All rights reserved. Rev 5/13 2633500 5/13

to determine whether recent legislative and regulatory efforts to address the problem are working. Results of the second survey suggested that chemotherapy drug shortages have eased slightly, but oncologists still need to substitute drugs. Moreover, respondents expressed growing concern over the shortage of drugs used in supportive care, such as antiemetics, pain medications, and basic intravenous fluids and electrolytes, reported Richard L. Schilsky, MD, chief medical officer of ASCO.2 The most commonly reported substitutions were levoleucovorin for leucovorin (cited by 38% of respondents giving examples) and capecitabine for 5-FU (12%), comparable to what Gogineni reported from her survey. “The cost implications of these are significant,” Schilsky agreed. In addition to critical chemotherapy substitutions, other substitutions include oral formulations for intravenous agents in nearly a dozen drugs. In supportive care, a few of the substitutions used are ganciclovir for acyclovir, Lomotil for atropine, and methylprednisolone and prednisone for dexamethasone. The second survey also found: • 59% of respondents were aware of ongoing drug substitutions in their community in 2013, versus 70% in 2012 • 17% said the situation is worse now, while 16% said the situation is unchanged, and 9% said some shortages improved but others worsened • More than one-third (37%) in both surveys had no institutional policy for drug allocation during a shortage The Cancer and Leukemia Group B (CALGB) clinical trials group reported that 23 study protocols have been affected by drug shortages, he said. CALGB is delaying registration of new patients, borrowing drugs from neighboring institutions, substituting alternative drugs, and omitting drugs in short supply. According to Schilsky, while the US Food and Drug Administration has stop-gap measures in place to ease the situation, “Permanent solutions will require enhancing the business model of generic drug manufacturing.” l References

1. Emanuel EJ, Shuman K, Chinn D, et al. Impact of oncology drug shortages. J Clin Oncol. 2013;31(suppl):Abstract CRA6510. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL. 2. Schilsky RL. Improvising when standard therapy is not available. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

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News Briefs News Briefs continued from cover

Radium-223 Improves Survival in Castration-Resistant Prostate Cancer Radium-223 (Xofigo), a radioactive isotope, improved survival in men with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases, according to results of a randomized, phase 3, double-blind, placebo-controlled pivotal trial. The study was halted early, when an interim analysis showed a clear survival benefit for radium-223. Updated results of the trial were published in the New England Journal of Medicine. Radium-223 homes to the bone, where it emits alpha particles that cause DNA damage, sparing normal tissue. The drug has a half-life of 11.4 days, which is much shorter than other alpha-emitting isotopes. Radium-223 was approved by the US Food and Drug Administration earlier in 2013 based on this study, which is the first to show a survival benefit for an alpha-emitting isotope in CRPC. The trial enrolled 921 participants randomized 2:1 to receive radium-223 intravenously every 4 weeks for 6 cycles or placebo in combination with the best available standard care. Best available standard care included radiotherapy, antiandrogen therapy, estrogen, estramustine, and ketoconazole; men who were taking antiandrogen therapy at baseline continued it during the trial. Median age was 71 years; 94% were white; 87% were Eastern Cooperative Oncology Group (ECOG) performance status 0-1; 58% had previously received docetaxel; 54% were taking opioids for pain relief; 44% were taking nonopioids for pain relief. Overall survival (OS) was the primary end point. At the time of the interim analysis, when 314 deaths had occurred, median OS was significantly in favor of radium-223: 14 months versus 11.2 months, respectively (P = .002). An updated analysis in the New England Journal of Medicine, when 528 deaths were reported, confirmed that radium-223 achieved a significant OS benefit, with a median OS of 14.9 months for patients treated with radium-223 versus 11.3 months for the placebo group (P <.001). Patients treated with radium-223 were 30% less likely to die: 54% died versus 64% in the placebo group (P <.001). Median time to first symptomatic skeletal event—a key secondary end point—was significantly improved with radium-223: 15.6 months versus 9.8 months, respectively (P <.001). Adverse events, including grade 3 or 4 adverse events, serious adverse events, and drug discontinuations due to adverse events, were numerical-

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ly lower in the group treated with radium-223. The most commonly reported adverse events (at least 5%

hematologic laboratory abnormalities were anemia, thrombocytopenia, and neutropenia.

Radium-223 was approved by the US Food and Drug Administration earlier in 2013 based on this study.

MD, University of Pennsylvania, Philadelphia, wrote that the properties of radium-223, including its half-life and safety, make it an important new anticancer weapon. They noted that it is not clear what the ultimate role of radium-223 will be; perhaps it will be combined with other agents to further improve outcomes. Additional trials combining radium-223 with other drugs, including docetaxel, are being planned. Reference

frequency) with radium-223 included nausea, diarrhea, vomiting, and peripheral edema. The most common

In an accompanying editorial in the New England Journal of Medicine, Neha Vapiwala, MD, and Eli Glatstein,

Parker C, Nilsson S, Heinrich D, et al; ALSYMPCA Investigators. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213-223.

News Briefs continued on page 10

Gleason Scoring May Provide Better Management and Prognosis The Gleason score (GS) assigned at a comprehensive guided prostate biopsy at a referring institution. Patients cancer center allowed better biochemical failure risk were treated with radiation therapy alone (no androgen stratification and prognostic information for patients deprivation therapy) between 1994 and 2007. Pathology treated with external-beam radiotherapy compared with slides of all patients diagnosed at a referring institution were the GS of the referring institution. A confirmatory reviewed at FCCC by an oncologic pathologist with special second pathologic review (SPR) at a dedicated compre- expertise in GU pathology. Follow-up comprised serial proshensive cancer center by a pathologist who specializes tate-specific antigen (PSA) determinations every 6 months in genitourinary (GU) malignancies led to a change in and annual digital rectal examinations. Biochemical failure overall GS grouping in 13% of patients. An SPR per- was determined by the American Society for Radiation formed at Fox Chase Cancer Center (FCCC) changed Oncology definition (PSA nadir plus 2 ng/mL). the National Comprehensive Cancer Network risk group Median follow-up was 64 months, and median folassignment in 144 men (9%): 92 low-up PSA interval was 6.2 men (64%) to lower risk and 52 months. Median age of patients Several studies, as well (36%) to higher risk. was 68 years. About 80% had “These changes all have the stage T1/2 prostate cancer and as anecdotal reports, potential to alter management and PSA <10 ng/mL. note discordance rates prognosis. The GS assigned based on Overall, the GS assigned by the SPR provided greater prognosFCCC upgraded 8% of patients of up to 40% between tication of biochemical failure risk. and downgraded 6% of patients the GS assigned by a Patients may benefit from national compared with the GS assigned by standards encouraging an SPR at a their referring institution. Among general pathologist and comprehensive cancer center,” wrote patients originally assigned to GS the GS subsequently the authors. Natasha C. Townsend, 6 by the referring institution, 8% MD, of FCCC, was lead author. At were upgraded to the intermediassigned by a GU present, nationwide standards do not ate category (ie, GS 7). A greater pathology specialist. call for an SPR at a comprehensive impact was observed in patients cancer center. originally assigned to GS 7 by This retrospective study, pubthe referring institution; 20% were lished in the July 2013 issue of the Journal of the National downgraded by FCCC to GS 6 and 2% upgraded to GS Comprehensive Cancer Network, is the largest regarding 8-9. The authors note that the greatest impact of an SPR by the impact of an SPR on the GS and the only report on FCCC was in the group of men originally assigned to GS 8-9: the impact of an SPR on the GS in patients treated with 58% were downgraded to GS 6 (12%) or GS 7 (88%). radiotherapy. The data show an improvement in overall prediction Several studies, as well as anecdotal reports, note dis- of biochemical failure with the GS assigned by FCCC cordance rates of up to 40% between the GS assigned by a compared with the GS assigned by the referring institugeneral pathologist and the GS subsequently assigned by tion. “Overall, these data support a routine SPR, prefa GU pathology specialist. Taken together, studies to date erably at a dedicated comprehensive cancer center with suggest that central review by a specialist in GU pathology a pathologist specializing in the diagnosis of prostate will provide a more accurate estimate of the GS than that cancer,” the authors wrote. assigned by general pathologists. The retrospective study included 1649 men diagnosed Reference Townsend NC, Ruth K, Al-Saleem T, et al. Gleason scoring at a comprehensive with prostate cancer based on a transrectal ultrasound– cancer center: what’s the difference? J Natl Compr Canc Netw. 2013;11(7):812-819.

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News Briefs News Briefs continued from page 9

Campaign Reduces Unnecessary Tests for Low-Risk Prostate Cancer The rate of unnecessary cancer imaging scans for low-risk prostate cancer was drastically reduced by a joint campaign in Sweden aimed at curtailing those tests. Such tests account for a significant proportion of healthcare funds in the United States. The campaign was initiated in 2000 by the Swedish County Councils and the National Prostate Cancer Register of Sweden to reduce inappropriate diagnostic imaging in men with this cancer. Men diagnosed with low-risk prostate cancer are unlikely to harbor metastases. Despite guidelines and quality measures from various policy organizations and professional societies that stipulate that extensive cancer scans for metastases are discouraged for these patients, many physicians continue to order these scans, said lead author Danil V. Makarov, MD, assistant professor at NYU Langone Medical Center, New York City.

The authors note that imaging is important to detect metastases in men with high-risk prostate cancer. However, most prostate cancer is diagnosed at an early stage, when it is unlikely to have spread.

records of almost 100,000 Swedish men diagnosed with prostate cancer from 1998 to 2009. Imaging rates at institutions in Sweden were published and compared with best practices, giving providers an incentive not to be cited for ordering

In the US, inappropriate prostate cancer imaging ranges from 22% to 62%, depending on the geographic region, according to a study published in 2012. The study was a collaboration between Makarov; his colleague at NYU, Stacy Loeb, MD; investigators at Memorial Sloan-Kettering Cancer Center; and Swedish investigators at Uppsala University Hospital and the Karolinska Institute. The authors examined the

unnecessary imaging tests for low-risk prostate cancer. These data were also presented at urology meetings in Sweden. During the study period, the percentage of inappropriate scans among patients with low-risk prostate cancer dropped from 45% at the beginning of

the campaign to 3% at the end. But the rate of appropriate scans for high-risk patients also dropped from 63% to 47% over the study period. Makarov said that it is important to emphasize the appropriate use of scans, along with the inappropriate use. He believes that the Swedish campaign demonstrates that targeted educational efforts can reduce the number of inappropriate tests. Such efforts could be implemented at urology conferences and in collaboration with the government, he suggested. In the US, inappropriate prostate cancer imaging ranges from 22% to 62%, depending on the geographic region, according to a study published in 2012. Reference

Makarov DV, Loeb S, Ulmert D, et al. Prostate cancer imaging trends after a nationwide effort to discourage inappropriate prostate cancer imaging. J Natl Cancer Inst. 2013;105(17):1306-1313.

Medicare Report on Costly Radiation Therapy for Prostate Cancer Another study reveals the growing use of expensive treatment for prostate cancer. In July 2013, the Government Accountability Office (GAO) released a report, “Medicare: Higher Use of Costly Prostate Cancer Treatment by Providers Who Self-

Refer Warrants Scrutiny,” requested by bipartisan leaders in Congress. The report focused on specialty urology groups’ use of intensity-modulated radiation therapy (IMRT) from 2006 to 2010. The report showed that IMRT utilization among

self-referring groups increased by 456% over the study period. IMRT utilization among non–self-referring physicians decreased by 5%, in line with national recommendations calling for judicious use of IMRT for treating prostate cancer.

Hormone Therapy and Kidney Damage The risk of acute kidney injury was increased in men levels may also affect blood vessels in the kidney and cause with nonmetastatic prostate cancer treated with androgen estrogen deficiency, leading to adverse effects on renal deprivation therapy (ADT), according to a retrospective tubular function. This association has not been well studied analysis reported online in the Journal of the American previously, the authors noted. Medical Association. Current use of ADT more than douThe renal effects of ADT were analyzed in a nestbled the odds of acute kidney injury ed case-control study of men with compared with men who did not nonmetastatic prostate cancer. receive ADT. The highest rate of The study was based on a nationADT will remain a acute kidney damage was reportal hospital database that included mainstay of treatment ed with combined use of gonado10,250 men followed up for a mean tropin-releasing hormone (GnRH) of 4.1 years. Of these men, 232 for nonmetastatic agonists and antiandrogens. Effects developed acute kidney injury at a prostate cancer, but were also seen with estrogen, other rate of 5.5 per 1000 patient-years; combination therapies, and GnRH 40 men (17.2%) never received ADT. these findings should monotherapy. Controls were 2721 patients who did raise concern about ADT will remain a mainstay of not develop acute kidney injury. treatment for nonmetastatic prosOverall, current ADT use increased potential effects on tate cancer, but these findings should the likelihood of developing acute the kidney. raise concern about potential effects kidney injury by 2.48 compared with on the kidney. Hormonal therapy controls. The association was conshould be used judiciously to avoid sistently elevated, with the highest potentially serious adverse events, the authors noted. odds during the first year of treatment with ADT. Past ADT is widely used to treat men with prostate can- treatment with ADT did not increase the risk of acute cer, but can lead to serious adverse events. For example, kidney injury. metabolic disturbances induced by the hypogonadal state achieved by ADT are known to increase the risk of heart Reference Lapi F, Azoulay L, Niazi MT, et al. Androgen deprivation therapy and risk of acute disease and diabetes. Reducing testosterone to castrate kidney injury in patients with prostate cancer. JAMA. 2013;310(3):289-296.

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The number of IMRT services performed by limited urology groups increased by 609%, while use by true multispecialty groups decreased 3.8%. Along with these trends, IMRT spending by self-referral groups increased by approximately $138 million, compared with a $91 million decrease in non–self-referral groups. These increases in IMRT utilization among self-referring practices were not attributable to patient preferences, age, geographic area, or patients’ health status. The report concludes that financial incentives were a major factor responsible for increased referrals for IMRT. Moreover, financial incentives were responsible for self-referral groups not ordering other appropriate but less expensive treatments, such as brachytherapy, prostatectomy, and active surveillance when appropriate. These factors result in higher costs to Medicare and beneficiaries, and the costs when driven by providers’ financial interest are difficult to justify, states the GAO report. Congress is currently considering a law called “Promoting Integrity in Medicare Act of 2013” that addresses the findings of the GAO to improve patient care and save billions of dollars in Medicare funds. l Reference

US Government Accountability Office. Medicare: Higher Use of Costly Prostate Cancer Treatment by Providers Who Self-Refer Warrants Scrutiny. July 2013. http://www.gao. gov/products/GAO-13-525. Accessed August 5, 2013.

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Noteworthy Numbers

Prostate Cancer Sources 1. http://www.cancer.org/cancer/prostatecancer/detailed guide/prostate-cancer-key-statistics. 2. http://www.pcf.org/site/c.leJRIROrEpH/b.5802027/k. D271/Prostate_Cancer_Risk_Factors.htm. 3. http://www.pcf.org/site/c.leJRIROrEpH/b.8481037/ k.1EF4/AfricanAmerican_Men__Risk_Factors.htm. 4. http://www.cancer.org/cancer/prostatecancer/detailed guide/prostate-cancer-risk-factors. 5. http://www.wcrf.org/cancer_statistics/data_specific_ cancers/prostate_cancer_statistics.php.

As the second leading cause of cancer-related deaths among men in the United States, prostate cancer is expected to cause approximately 29,720 deaths during 2013.1 In recognition of National Prostate Cancer Awareness Month, let’s examine these prostate cancer statistics.

According to the Prostate Cancer Foundation, the average age at the time of prostate cancer diagnosis is 69 years. Moreover, 1 in 14 men between the ages of 60 and 69 years receive a prostate cancer diagnosis.2

occur in more developed countries, with the highest rates of diagnosis in

Australia and New Zealand, Western Europe, and North America.5 S:7.25”

NOW RECRUITING

Investigators

Prostate cancer is less common in men younger than 40 years, with 1 in 10,000 men affected.2

Study of the long-term safety and efficacy of darbepoetin alfa in anemic patients with Non-Small Cell Lung Cancer (NSCLC) receiving chemotherapy

Overall, approximately 238,590 men in the US will be diagnosed with prostate cancer in 2013.1

Phase 3 study with approximately 3,000 subjects at 500 study sites globally

The American Cancer Society states that the ratio of men who will die from prostate cancer is 1:36.1

KEY ELIGIBILITY CRITERIA*

PRIMARY ENDPOINT

• Stage IV NSCLC

• Overall survival

• Receiving 1st-line myelosuppressive

SECONDARY ENDPOINTS

chemotherapy

African American men in the US are almost 2.5 times as likely to die from prostate cancer as white men.3 The rate of prostate cancer is less in Asian American and Hispanic men than in non-Hispanic white men. The reasons behind these racial and ethnic differences are unclear.4

• Hemoglobin (Hb) ≤ 11 g/dL

transfusion or Hb ≤ 8.0 g/dL S:9.75”

Darbepoetin alfa 500-mcg Q3W

2:1 Randomization (darbepoetin alfa:placebo)

End of Treatment Period

End of Investigational Product

Long-term Follow-up

Placebo Q3W

Week 1

Disease progression or end of chemotherapy treatment

*Complete inclusion/exclusion criteria and additional study details can be found in the protocol. ECOG = Eastern Cooperative Oncology Group; Q3W = once every 3 weeks.

Cory Docken/Getty Images

For more information, please email Study-20070782@amgen.com or call 1-866-965-0782. Products under investigational study have not been approved by the FDA for the use under investigation in this trial.

According to the World Cancer Research Fund International, about 7 in 10 prostate cancer cases (72%) www.TheOncologyNurse.com

• Incidence of ≥ 1 red blood cell (RBC)

• ECOG score ≤ 1

Week 0

Compared with men in the US whose risk for prostate cancer is 17%, men who live in rural China have less risk (2%) of developing prostate cancer. Yet, the risk for prostate cancer increases for Chinese men if they move to a more western-style culture, reports the Prostate Cancer Foundation.2

• Progression-free survival

AOCO3X0071_Recruitment782_AdAsize_r3.indd 1

72140-R2-V1

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September 2013 I VOL2/12/13 6, NO9:38 8 AM 11

The Patient’s Voice

My Prostate Cancer Story... Continued from cover Dr G: It was a Gleason 7—a 4 plus 3. Me: Gleason 7? What’s that? Is it bad? Dr G: Well, it’s not the worst... Dr G then explained that he’d submitted orders for additional tests, and that the next day I should call to set up a session with the counselor, and to make appointments for a CT scan and a bone scan. I repeated this brief checklist, assured him I’d make the calls, and hung up so that he could wrap up his long day and go home. It all seemed straightforward enough at the time, just a couple of things to take care of tomorrow, and then we’ll go from there. In a strange way, I almost felt relief. This dreaded disease that had killed my dad, that I’d feared all my adult life, finally I no longer had to worry about getting it—because I had it. Like a bully who keeps threatening to beat you up, the wait was over, the fight was on. And in my corner I had decades of technology and cutting-edge medicine, as well as my doctor, who spoke confidently and who clearly had a plan to take it on. “Alright, I’ve got cancer,” I thought, “and now I’ll deal with it.”

I did beat myself up with one question: Why did I wait so long to get another PSA test?!

believe I could get prostate cancer, what with my excellent health and at my age (58). Like everyone else, I pretty much thought that prostate cancer only happened to older men—and besides that, it was no big deal regardless, because we guys always hear that if we live long enough everyone B:8.75” gets it and something T:8.125” else will kill us first anyway, so no need

to be too concerned. Who knew that prostate cancer also comes in an aggressive, life-threatening version? Not me. So it had been 2 full years since my first PSA, which itself was borderline suspicious (a 3.3), yet I’d barely given it another thought. I was only tested because my seasonal allergies were acting up (completely unrelated—the can-

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Important Safety Information

ADVERSE REACTIONS: Peripheral T-Cell Lymphoma The most common Grade 3/4 adverse reactions (>5%) regardless of causality in Study 3 (N=131) were thrombocytopenia (24%), neutropenia (20%), anemia (11%), asthenia/fatigue (8%), and leukopenia (6%), and in Study 4 (N=47) were neutropenia (47%), leukopenia (45%), thrombocytopenia (36%), anemia (28%), asthenia/fatigue (19%), pyrexia (17%), vomiting (9%), and nausea (6%). Infections were the most common type of serious adverse event reported in Study 3 (N=131) and Study 4 (N=47). In Study 3, 25 patients (19%) experienced a serious infection, including 6 patients (5%) with serious treatment-related infections. In Study 4, 11 patients (23%) experienced a serious infection, including 8 patients (17%) with serious treatment-related infections. The most common adverse reactions regardless of causality in Study 3 (N=131) were nausea (59%), asthenia/fatigue (55%), thrombocytopenia (41%), vomiting (39%), diarrhea (36%), and pyrexia (35%), and in Study 4 (N=47) were asthenia/fatigue (77%), nausea (75%),

Cutaneous T-Cell Lymphoma The most common Grade 3/4 adverse reactions (>5%) regardless of causality in Study 1 (N=102) were infections (11%) and asthenia/fatigue (8%), and in Study 2 (N=83) were lymphopenia (37%), infections (33%), neutropenia (27%), leukopenia (22%), anemia (16%), asthenia/fatigue (14%), thrombocytopenia (14%), hypophosphatemia (10%), vomiting (10%), dermatitis/exfoliative dermatitis (8%), hypermagnesemia (8%), hyperuricemia (8%), hypocalcemia (6%), nausea (6%), and pruritus (6%). Infections were the most common type of serious adverse event reported in both Study 1 (N=102) and Study 2 (N=83) with 8 patients (8%) in Study 1 and 26 patients (31%) in Study 2 experiencing a serious infection. The most common adverse reactions regardless of causality in Study 1 (N=102) were nausea (56%), asthenia/fatigue (53%), infections (46%), vomiting (34%), and anorexia (23%) and in Study 2 (N=83) were nausea (86%), asthenia/fatigue (77%), anemia (72%), thrombocytopenia (65%), ECG ST-T wave changes (63%), neutropenia (57%), lymphopenia (57%), infections (54%), anorexia (54%), vomiting (52%), hypocalcemia (52%), hyperglycemia (51%), hypoalbuminemia (48%), leukopenia (46%), dysgeusia (40%), and constipation (39%). DRUG INTERACTIONS: • ISTODAX is metabolized by CYP3A4. Avoid concomitant use with strong CYP3A4 inhibitors and potent CYP3A4 inducers if possible • Caution should also be exercised with concomitant use of moderate CYP3A4 inhibitors and P-glycoprotein (P-gp, ABCB1) inhibitors • Physicians should carefully monitor prothrombin time (PT) and International Normalized Ratio (INR) in patients concurrently administered ISTODAX and warfarin sodium derivatives USE IN SPECIFIC POPULATIONS: • Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother • Patients with moderate and severe hepatic impairment and/or patients with end-stage renal disease should be treated with caution

Please see full Prescribing Information, including WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS.

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WARNINGS AND PRECAUTIONS: • Treatment with ISTODAX has been associated with thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; therefore, monitor these hematological parameters during treatment with ISTODAX and modify the dose as necessary • Serious and sometimes fatal infections have been reported during treatment and within 30 days after treatment with ISTODAX and the risk of life threatening infections may be higher in patients with a history of extensive or intensive chemotherapy • Electrocardiographic (ECG) changes have been observed with ISTODAX • In patients with congenital long QT syndrome, a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, appropriate cardiovascular monitoring precautions should be considered, such as monitoring electrolytes and ECGs at baseline and periodically during treatment • Ensure that potassium and magnesium are within the normal range before administration of ISTODAX • Tumor lysis syndrome has been reported during treatment with ISTODAX. Patients with advanced stage disease and/or high tumor burden should be closely monitored and appropriate precautions taken, and treatment should be instituted as appropriate • ISTODAX may cause fetal harm when administered to a pregnant woman. Advise women to avoid pregnancy while receiving ISTODAX. If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus (Pregnancy Category D)

thrombocytopenia (72%), neutropenia (66%), anemia (62%), leukopenia (55%), pyrexia (47%), anorexia (45%), vomiting (40%), constipation (40%), and diarrhea (36%).

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But as soon as I hung up, questions and doubts and panic started filling my mind. “Wait, I’m seeing a counselor? Why a counselor? Does everyone get sent to a counselor? How bad is this?! Okay, it’s ‘not the worst,’ but... What the heck is a Gleason 7? And what’s a CT scan? Is that the same as a CAT scan? I’ve heard of a CAT scan... (Hmmm, actually, I don’t really know what a CAT scan is either...) And a bone scan? Bone scan, bone scan, BONE SCAN?! Oh God, that can only mean one thing, the cancer is in my bones! Can they fix it in my bones?” And suddenly, after a few scant moments of this runaway internal dialogue, I’d convinced myself there was no doubt: I was going to die. In 30 seconds I’d gone from triumph to death! But it soon toggled back to optimism, and mostly stayed there. I did beat myself up with one question: Why did I wait so long to get another PSA test?! I would have been a lot more confident about what these upcoming scans were going to show had I been diagnosed a year sooner. Sure, I was busy. Everyone is busy, but how

could I let something so important slip for so long when I knew my risk factors? Was it just bad prioritizing? Had I deliberately avoided the follow-up PSA, maybe in some way not wanting to get the result (as if nothing could be wrong as long as I didn’t know about it)? If so, bad strategy! But I think mainly I just wasn’t all that concerned. I didn’t really

The Patient’s Voice cer had absolutely no symptoms, but the allergies got me in for a doctor visit). Turns out my primary care physician had retired, and his successor wanted to run a set of tests for a current baseline on some things, including a PSA test. When it came back at 11.2, he knew that this big jump up from my previous result was a serious red flag. (And as an aside, now whenever I read an article criticizing the PSA test for its fallibil-

There are a lot of men who believe the PSA test helped save their life, and I’m among them. ities, I shake my head. I understand it’s not perfect, but it’s one simple and useful tool available to us, especially to

get that starting-point result for future comparisons. So aren’t we better off having that piece of data? There are a lot of

men who believe the PSA test helped save their life, and I’m among them.) When I learned of the cancer diagnosis, my wife and I already had a long-awaited 10-day trip to England planned. Although I couldn’t go in for the bone scan before we left, Dr G assured me that the trip wouldn’t affect an ultimate surgery date, so off we went. And I, a compulsive worrier, somehow Continued on page 14

INDICATIONS THE FIRST AND ONLY • Treatment of peripheral T-cell lymphoma (PTCL) in patients DRUG APPROVED IN BOTH who have received at least one prior therapy PTCL AND CTCL • Treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.

RECHARGE THE POSSIBILITIES

www.istodax.com Please see Important Safety Information on adjacent page. Please see Brief Summary of full Prescribing Information on following pages.

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My Prostate Cancer Story... Continued from page 13 managed to enjoy myself and not worry. How? Until I was asked to write this article, I hadn’t really thought about whether my surprisingly positive outlook had been influenced by the way the news was delivered. And I started to wonder, how do doctors decide

exactly what to say? There’s surely no “one size fits all”—that is, every patient and situation must be different. Personally, I wanted straight answers, no unnecessary grim details to ponder, and a little reassurance. A doctor friend once told me that

even if he has bad news, he always starts by saying he has good news. This might work for him, because he honestly sees the bright side, but it seems to me that the brief high expectation would invite disappointment. I see the benefit in being positive, reassuring a

Only

ISTODAX® (romidepsin) for injection For intravenous infusion only The following is a brief summary only; see full prescribing information for complete product information. 1 INDICATIONS AND USAGE ISTODAX is indicated for: • Treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy. • Treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy. These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated. 2 DOSAGE AND ADMINISTRATION 2.1 Dosing Information The recommended dose of romidepsin is 14 mg/m2 administered intravenously over a 4-hour period on days 1, 8 and 15 of a 28-day cycle. Cycles should be repeated every 28 days provided that the patient continues to benefit from and tolerates the drug. 2.2 Dose Modification Nonhematologic toxicities except alopecia • Grade 2 or 3 toxicity: Treatment with romidepsin should be delayed until toxicity returns to ≤Grade 1 or baseline, then therapy may be restarted at 14 mg/m2. If Grade 3 toxicity recurs, treatment with romidepsin should be delayed until toxicity returns to ≤Grade 1 or baseline and the dose should be permanently reduced to 10 mg/m2. • Grade 4 toxicity: Treatment with romidepsin should be delayed until toxicity returns to ≤Grade 1 or baseline, then the dose should be permanently reduced to 10 mg/m2. • Romidepsin should be discontinued if Grade 3 or 4 toxicities recur after dose reduction. Hematologic toxicities • Grade 3 or 4 neutropenia or thrombocytopenia: Treatment with romidepsin should be delayed until the specific cytopenia returns to ANC ≥1.5×109/L and/or platelet count ≥75×109/L or baseline, then therapy may be restarted at 14 mg/m2. • Grade 4 febrile (≥38.5°C) neutropenia or thrombocytopenia that requires platelet transfusion: Treatment with romidepsin should be delayed until the specific cytopenia returns to ≤Grade 1 or baseline, and then the dose should be permanently reduced to 10 mg/m2. 2.3 Instructions for Preparation and Intravenous Administration ISTODAX should be handled in a manner consistent with recommended safe procedures for handling cytotoxic drugs. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Hematologic Treatment with ISTODAX can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; therefore, these hematological parameters should be monitored during treatment with ISTODAX, and the dose should be modified, as necessary [See Dosage and Administration (2.2) and Adverse Reactions (6)]. 5.2 Infection Serious and sometimes fatal infections, including pneumonia and sepsis, have been reported in clinical trials with ISTODAX. These can occur during treatment and within 30 days after treatment, and the risk of life threatening infections may be higher in patients with a history of extensive or intensive chemotherapy [See Adverse Reactions (6)]. 5.3 Electrocardiographic Changes Several treatment-emergent morphological changes in ECGs (including T-wave and ST-segment changes) have been reported in clinical studies. The clinical significance of these changes is unknown [See Adverse Reactions (6)]. In patients with congenital long QT syndrome, patients with a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment. Potassium and magnesium should be within the normal range before administration of ISTODAX [See Adverse Reactions (6)]. 5.4 Tumor Lysis Syndrome Tumor lysis syndrome (TLS) has been reported to occur in 1% of patients with tumor stage CTCL and 2% of patients with Stage III/IV PTCL. Patients

patient who’s overly concerned, and certainly not painting an overly bleak picture, but I think that people generally want to keep their expectations under control, and hope things will turn out better than expected. In my case, I don’t know if Dr G’s

with advanced stage disease and/or high tumor burden should be closely monitored, appropriate precautions should be taken, and treatment should be instituted as appropriate. 5.5 Use in Pregnancy There are no adequate and well-controlled studies of ISTODAX in pregnant women. However, based on its mechanism of action and findings in animals, ISTODAX may cause fetal harm when administered to a pregnant woman. In an animal reproductive study, romidepsin was embryocidal and resulted in adverse effects on the developing fetus at exposures below those in patients at the recommended dose of 14 mg/m2/week. If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus [See Use in Specific Populations (8.1)]. 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Cutaneous T-Cell Lymphoma The safety of ISTODAX was evaluated in 185 patients with CTCL in 2 single arm clinical studies in which patients received a starting dose of 14 mg/m2. The mean duration of treatment in these studies was 5.6 months (range: <1 to 83.4 months).

Common Adverse Reactions Table 1 summarizes the most frequent adverse reactions (> 20%) regardless of causality using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 3.0). Due to methodological differences between the studies, the AE data are presented separately for Study 1 and Study 2. Adverse reactions are ranked by their incidence in Study 1. Laboratory abnormalities commonly reported (> 20%) as adverse reactions are included in Table 1. Table 1. Adverse Reactions Occurring in >20% of Patients in Either CTCL Study (N=185) Study 1 Study 2 (n=102) (n=83) Grade 3 Grade 3 Adverse Reactions n (%) All or 4 All or 4 Any adverse reaction 99 (97) 36 (35) 83 (100) 68 (82) Nausea 57 (56) 3 (3) 71 (86) 5 (6) Asthenia/Fatigue 54 (53) 8 (8) 64 (77) 12 (14) Infections 47 (46) 11 (11) 45 (54) 27 (33) Vomiting 35 (34) 1 (<1) 43 (52) 8 (10) Anorexia 23 (23) 1 (<1) 45 (54) 3 (4) Hypomagnesemia 22 (22) 1 (<1) 23 (28) 0 Diarrhea 20 (20) 1 (<1) 22 (27) 1 (1) Pyrexia 20 (20) 4 (4) 19 (23) 1 (1) Anemia 19 (19) 3 (3) 60 (72) 13 (16) Thrombocytopenia 17 (17) 0 54 (65) 12 (14) Dysgeusia 15 (15) 0 33 (40) 0 Constipation 12 (12) 2 (2) 32 (39) 1 (1) Neutropenia 11 (11) 4 (4) 47 (57) 22 (27) Hypotension 7 (7) 3 (3) 19 (23) 3 (4) Pruritus 7 (7) 0 26 (31) 5 (6) Hypokalemia 6 (6) 0 17 (20) 2 (2) Dermatitis/Exfoliative dermatitis 4 (4) 1 (<1) 22 (27) 7 (8) Hypocalcemia 4 (4) 0 43 (52) 5 (6) Leukopenia 4 (4) 0 38 (46) 18 (22) Lymphopenia 4 (4) 0 47 (57) 31 (37) Alanine aminotransferase increased 3 (3) 0 18 (22) 2 (2) Aspartate aminotransferase increased 3 (3) 0 23 (28) 3 (4) Hypoalbuminemia 3 (3) 1 (<1) 40 (48) 3 (4) Electrocardiogram ST-T wave changes 2 (2) 0 52 (63) 0 Hyperglycemia 2 (2) 2 (2) 42 (51) 1 (1) Hyponatremia 1 (<1) 1 (<1) 17 (20) 2 (2) Hypermagnesemia 0 0 22 (27) 7 (8) Hypophosphatemia 0 0 22 (27) 8 (10) Hyperuricemia 0 0 27 (33) 7 (8)

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The Patient’s Voice seemingly candid response that a Gleason 7 is “not the worst” was off the top of his head, but as I reflect on it now it was maybe the perfect answer for me: It at once conveyed that this was a serious thing, but also I figured if I worked and battled it through, I’d come out alright. I’m reminded of a Mark Twain quote, “Eat a live frog first thing in the morning and

As I moved past my initial panic, worry was replaced by its best antidote: positive action. nothing worse will happen to you the rest of the day.” Dr G’s calling me that night with the diagnosis and a plan for the next

Serious Adverse Reactions Infections were the most common type of SAE reported in both studies with 8 patients (8%) in Study 1 and 26 patients (31%) in Study 2 experiencing a serious infection. Serious adverse reactions reported in > 2% of patients in Study 1 were sepsis and pyrexia (3%). In Study 2, serious adverse reactions in > 2% of patients were fatigue (7%), supraventricular arrhythmia, central line infection, neutropenia (6%), hypotension, hyperuricemia, edema (5%), ventricular arrhythmia, thrombocytopenia, nausea, leukopenia, dehydration, pyrexia, aspartate aminotransferase increased, sepsis, catheter related infection, hypophosphatemia and dyspnea (4%). Most deaths were due to disease progression. In Study 1, there were two deaths due to cardiopulmonary failure and acute renal failure. In Study 2, there were six deaths due to infection (4), myocardial ischemia, and acute respiratory distress syndrome. Discontinuations Discontinuation due to an adverse event occurred in 21% of patients in Study 1 and 11% in Study 2. Discontinuations occurring in at least 2% of patients in either study included infection, fatigue, dyspnea, QT prolongation, and hypomagnesmia. Peripheral T-Cell Lymphoma The safety of ISTODAX was evaluated in 178 patients with PTCL in a sponsor-conducted pivotal study (Study 3) and a secondary NCI-sponsored study (Study 4) in which patients received a starting dose of 14 mg/m2. The mean duration of treatment and number of cycles in these studies were 5.6 months and 6 cycles. Common Adverse Reactions Table 2 summarizes the most frequent adverse reactions (≥ 10%) regardless of causality, using the NCI-CTCAE, Version 3.0. The AE data are presented separately for Study 3 and Study 4. Laboratory abnormalities commonly reported (≥ 10%) as adverse reactions are included in Table 2. Table 2. Adverse Reactions Occurring in ≥10% of Patients with PTCL in Study 3 and Corresponding Incidence in Study 4 (N=178) Study 3 Study 4 (N=131) (N=47) Grade 3 Grade 3 Adverse Reactions n (%) All or 4 All or 4 Any adverse reactions 127 (97) 86 (66) 47 (100) 40 (85) Gastrointestinal disorders Nausea 77 (59) 3 (2) 35 (75) 3 (6) Vomiting 51 (39) 6 (5) 19 (40) 4 (9) Diarrhea 47 (36) 3 (2) 17 (36) 1 (2) Constipation 39 (30) 1 (<1) 19 (40) 1 (2) Abdominal pain 18 (14) 3 (2) 6 (13) 1 (2) Stomatitis 13 (10) 0 3 (6) 0 General disorders and administration site conditions Asthenia/Fatigue 72 (55) 11 (8) 36 (77) 9 (19) Pyrexia 46 (35) 7 (5) 22 (47) 8 (17) Chills 14 (11) 1 (<1) 8 (17) 0 Edema peripheral 13 (10) 1 (<1) 3 (6) 0 Blood and lymphatic system disorders Thrombocytopenia 53 (41) 32 (24) 34 (72) 17 (36) Neutropenia 39 (30) 26 (20) 31 (66) 22 (47) Anemia 32 (24) 14 (11) 29 (62) 13 (28) Leukopenia 16 (12) 8 (6) 26 (55) 21 (45) Metabolism and nutrition disorders Anorexia 37 (28) 2 (2) 21 (45) 1 (2) Hypokalemia 14 (11) 3 (2) 8 (17) 1 (2) Nervous system disorders Dysgeusia 27 (21) 0 13 (28) 0 Headache 19 (15) 0 16 (34) 1 (2) Respiratory, thoracic and mediastinal disorders Cough 23 (18) 0 10 (21) 0 Dyspnea 17 (13) 3 (2) 10 (21) 2 (4) Investigations Weight decreased 13 (10) 0 7 (15) 0 Cardiac disorders Tachycardia 13 (10) 0 0 0

steps helped me stay calm and optimistic in the long run. It seemed completely honest, so I immediately trusted him and

Continued on page 16

Serious Adverse Reactions Infections were the most common type of SAE reported. In Study 3, 25 patients (19%) experienced a serious infection, including 6 patients (5%) with serious treatment-related infections. In Study 4, 11 patients (23%) experienced a serious infection, including 8 patients (17%) with serious treatment-related infections. Serious adverse reactions reported in ≥ 2% of patients in Study 3 were pyrexia (7%), pneumonia, sepsis, vomiting (5%), cellulitis, deep vein thrombosis, (4%), febrile neutropenia, abdominal pain (3%), chest pain, neutropenia, pulmonary embolism, dyspnea, and dehydration (2%). In Study 4, serious adverse reactions in ≥ 2 patients were pyrexia (17%), aspartate aminotransferase increased, hypotension (13%), anemia, thrombocytopenia, alanine aminotransferase increased (11%), infection, dehydration, dyspnea (9%), lymphopenia, neutropenia, hyperbilirubinemia, hypocalcemia, hypoxia (6%), febrile neutropenia, leukopenia, ventricular arrhythmia, vomiting, hypersensitivity, catheter related infection, hyperuricemia, hypoalbuminemia, syncope, pneumonitis, packed red blood cell transfusion, and platelet transfusion (4%). Deaths due to all causes within 30 days of the last dose of ISTODAX occurred in 7% of patients in Study 3 and 17% of patients in Study 4. In Study 3, there were 5 deaths unrelated to disease progression that were due to infections, including multi-organ failure/sepsis, pneumonia, septic shock, candida sepsis, and sepsis/cardiogenic shock. In Study 4, there were 3 deaths unrelated to disease progression that were due to sepsis, aspartate aminotransferase elevation in the setting of Epstein Barr virus reactivation, and death of unknown cause. Discontinuations Discontinuation due to an adverse event occurred in 19% of patients in Study 3 and in 28% of patients in Study 4. In Study 3, thrombocytopenia and pneumonia were the only events leading to treatment discontinuation in at least 2% of patients. In Study 4, events leading to treatment discontinuation in ≥ 2 patients were thrombocytopenia (11%), anemia, infection, and alanine aminotransferase increased (4%). 6.2 Postmarketing Experience No additional safety signals have been observed from postmarketing experience. 7 DRUG INTERACTIONS 7.1 Coumadin or Coumadin Derivatives Prolongation of PT and elevation of INR were observed in a patient receiving ISTODAX concomitantly with warfarin. Although the interaction potential between ISTODAX and Coumadin® (a registered trademark of BristolMyers Squibb Pharma Company) or Coumadin derivatives has not been formally studied, physicians should carefully monitor PT and INR in patients concurrently administered ISTODAX and Coumadin or Coumadin derivatives [See Clinical Pharmacology (12.3)]. 7.2 Drugs that Inhibit or Induce Cytochrome P450 3A4 Enzymes Romidepsin is metabolized by CYP3A4. Although there are no formal drug interaction studies for ISTODAX, strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) may increase concentrations of romidepsin. Therefore, co-administration with strong CYP3A4 inhibitors should be avoided if possible. Caution should be exercised with concomitant use of moderate CYP3A4 inhibitors. Co-administration of potent CYP3A4 inducers (e.g., dexamethasone, carbamazepine, phenytoin, rifampin, rifabutin, rifapentine, phenobarbital) may decrease concentrations of romidepsin and should be avoided if possible. Patients should also refrain from taking St. John’s Wort. 7.3 Drugs that Inhibit Drug Transport Systems Romidepsin is a substrate of the efflux transporter P-glycoprotein (P-gp, ABCB1). If ISTODAX is administered with drugs that inhibit P-gp, increased concentrations of romidepsin are likely, and caution should be exercised. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category D [See Warnings and Precautions (5.5)]. There are no adequate and well-controlled studies of ISTODAX in pregnant women. However, based on its mechanism of action and findings in animals, ISTODAX may cause fetal harm when administered to a pregnant woman. In an animal reproductive study, romidepsin was embryocidal and resulted in adverse effects on the developing fetus at exposures below those in patients at the recommended dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus. Romidepsin was administered intravenously to rats during the period of organogenesis at doses of 0.1, 0.2, or 0.5 mg/kg/day. Substantial resorption or post-implantation loss was observed at the high-dose of 0.5 mg/kg/day, a maternally toxic dose. Adverse embryo-fetal effects were Cosmos Communications

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felt I was getting the whole truth, no sugar coating, nothing held back that might blindside me later. I’d eaten the frog. And in the next few days as I moved past my initial panic, worry was replaced by its best antidote: positive action. Whatever I needed to do, I was going to do it. And my wife was a huge help, researching and

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My Prostate Cancer Story... Continued from page 15 filtering useful information for me. We had a mission. As difficult as it all was, there were some amazing positives. In my mind, I figured if my bone scan was okay, I would definitely live. And probably for the first time, I felt like that was

plenty! I could accept any of the other possible long-term consequences, but I really wanted to live. I suppose this is an experience that can’t readily be simulated—to believe there’s a strong likelihood you’re about to die, and to look at what that means. I still wanted

noted at romidepsin doses of ≥0.1 mg/kg/day, with systemic exposures (AUC) ≥0.2% of the human exposure at the recommended dose of 14 mg/m2/week. Drug-related fetal effects consisted of folded retina, rotated limbs, and incomplete sternal ossification.

seen in mice after 4 weeks of drug administration at higher doses. Seminal vesicle and prostate organ weights were decreased in a separate study in rats after 4 weeks of daily drug administration at 0.1 mg/kg/day (0.6 mg/m2/day), approximately 30% the estimated human daily dose based on body surface area. Romidepsin showed high affinity for binding to estrogen receptors in pharmacology studies. In a 26-week toxicology study in rats, atrophy was seen in the ovary, uterus, vagina and mammary gland of females administered doses as low as 0.1 mg/kg/dose (0.6 mg/m2/dose) following the clinical dosing schedule. This dose resulted in AUC0-inf. values that were 0.3% of those in patients receiving the recommended dose of 14 mg/m2/dose. Maturation arrest of ovarian follicles and decreased weight of ovaries were observed in a separate study in rats after four weeks of daily drug administration at 0.1 mg/kg/day (0.6 mg/m2/day). This dose is approximately 30% the estimated human daily dose based on body surface area

8.3 Nursing Mothers It is not known whether romidepsin 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 ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use The safety and effectiveness of ISTODAX in pediatric patients has not been established. 8.5 Geriatric Use Of the approximately 300 patients with CTCL or PTCL in trials, about 25% were > 65 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects; however, greater sensitivity of some older individuals cannot be ruled out. 8.6 Hepatic Impairment No dedicated hepatic impairment study for ISTODAX has been conducted. Mild hepatic impairment does not alter pharmacokinetics of romidepsin based on a population pharmacokinetic analysis. Patients with moderate and severe hepatic impairment should be treated with caution [See Clinical Pharmacology (12.3)]

16 HOW SUPPLIED/STORAGE AND HANDLING Keep out of reach of children. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published1-4 [See References (15)]. 17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling. 17.1 Instructions • Nausea and Vomiting Nausea and vomiting are common following treatment with ISTODAX. Prophylactic antiemetics are recommended to be used in all patients. Advise patients to report these symptoms so that appropriate treatment can be instituted [See Adverse Reactions (6)]. • Low Blood Counts Patients should be informed that treatment with ISTODAX can cause low blood counts and that frequent monitoring of hematologic parameters is required. Patients should be instructed to report fever or other signs of infection, significant fatigue, shortness of breath, or bleeding [See Warnings and Precautions (5.1)]. • Infections Patients should be informed that infections may occur during treatment with ISTODAX. Patients should be instructed to report fever, cough, shortness of breath with or without chest pain, burning on urination, flu-like symptoms, muscle aches, or worsening skin problems [See Warnings and Precautions (5.2]. • Tumor Lysis Syndrome Patients at risk of tumor lysis syndrome (i.e, those with advanced stage disease and/or high tumor burden) should be monitored closely for TLS and appropriate measures taken if symptoms are observed [See Warnings and Precautions (5.4)]. • Use in Pregnancy If pregnancy occurs during treatment with ISTODAX, female patients should be advised to seek immediate medical advice and counseling. [See Warnings and Precautions (5.5)]. • Patients should be instructed to read the patient insert carefully.

8.7 Renal Impairment No dedicated renal impairment study for ISTODAX has been conducted. Based upon the population pharmacokinetic analysis, renal impairment is not expected to significantly influence drug exposure. The effect of end-stage renal disease on romidepsin pharmacokinetics has not been studied. Thus, patients with end-stage renal disease should be treated with caution [See Clinical Pharmacology (12.3)] 10 OVERDOSAGE No specific information is available on the treatment of overdosage of ISTODAX. Toxicities in a single-dose study in rats or dogs, at intravenous romidepsin doses up to 2.2 fold the recommended human dose based on the body surface area, included irregular respiration, irregular heart beat, staggering gait, tremor, and tonic convulsions. In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., clinical monitoring and supportive therapy, if required. There is no known antidote for ISTODAX and it is not known if ISTODAX is dialyzable. 12 CLINICAL PHARMACOLOGY 12.2 Pharmacodynamics Cardiac Electrophysiology The effect of romidepsin on the heart-rate corrected QTc/QTcF was evaluated in 26 subjects with advanced malignancies given romidepsin at doses of 14 mg/m2 as a 4-hour intravenous infusion, and at doses of 8, 10 or 12 mg/m2 as a 1–hour infusion. Patients received premedications with antiemetics. No large changes in the mean QTc interval (> 20 milliseconds) from baseline based on Fridericia correction method were detected in the trial. Small increase in mean QT interval (< 10 milliseconds) and mean QT interval increase between 10 to 20 milliseconds cannot be excluded because of the limitations in the trial design. Romidepsin was associated with a delayed concentration-dependent increase in heart rate in patients with advanced cancer with a maximum mean increase in heart rate of 20 beats per minute occurring at the 6 hour time point after start of romidepsin infusion for patients receiving 14 mg/m2 as a 4-hour infusion. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been performed with romidepsin. Romidepsin was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Romidepsin was not clastogenic in an in vivo rat bone marrow micronucleus assay when tested to the maximum tolerated dose (MTD) of 1 mg/kg in males and 3 mg/kg in females (6 and 18 mg/m2 in males and females, respectively). These doses were up to 1.3-fold the recommended human dose, based on body surface area.

to visit Australia and such, but things like that wouldn’t make the list. What I actually thought about was how my wife was going to miss me, just having me around, making her laugh, walking together, taking road trips, making a salad (she doesn’t like making salads),

Manufactured for: Celgene Corporation Summit, NJ 07901 Manufactured by: Ben Venue Laboratories, Inc. Bedford, OH 44146 or Baxter Oncology GmbH Halle/Westfalen, Germany ISTODAX® is a registered trademark of Celgene Corporation © 2010-2012 Celgene Corporation. All Rights Reserved. U.S. Patents: 4,977,138; 7,608,280; 7,611,724 ISTBAXPI.004/PPI.004 03/12

Based on non-clinical findings, male and female fertility may be compromised by treatment with ISTODAX. In a 26-week toxicology study, romidepsin administration resulted in testicular degeneration in rats at 0.33 mg/kg/dose (2 mg/m2/dose) following the clinical dosing schedule. This dose resulted in AUC0-inf. values that were approximately 2% the exposure level in patients receiving the recommended dose of 14 mg/m2/dose. A similar effect was Cosmos Communications

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taking out the recycling, replacing her windshield wipers, feeding the cats, so many things to take care of each day. And my son, I didn’t want him to be sad. I wanted to be there for him, for a long time to come. That’s all that really mattered. The day after we got back from England, I had that bone scan, the moment of truth. The tech was a middle-aged woman, pleasant, very professional. I chatted nervously. She was nice, but stayed on task, no particular frivolity. After running the scan, she left to take a look at it to determine if the images were clearly readable. When she returned, she told me we were through, that I’d done a good job of staying still, and a physician would read the scan and call me in a few days. I thanked her and started walking down the hallway, then turned to give her a wave goodbye. She waved back and I saw she was smiling, a big, radiant smile. Suddenly I was overwhelmed by the sense that she must have known what the scan showed, and it made her happy. I couldn’t be certain, but I knew in that moment that I was going to live. As I turned and continued down the hall toward the exit door, I started to cry.

Two long days later I received the official word: my bones were indeed clear.

Two long days later I received the official word: my bones were indeed clear. In brief retrospect I realized, too, there had been other unintentional previews of my cancer story, which probably helped me to prepare for, and therefore cope with, the news. Even when the nurse called to set up my initial visit with Dr G, I noticed she seemed almost too nice, as if my chart showed something clearly worrisome. Likewise, I could tell from Dr G’s calm delivery of the cancer diagnosis that he felt confident he could remove it. So knowing that I had operable cancer, I began part 2 of my life. These were bonus days, a gift, and I felt so very fortunate and grateful to have them. I’d always thought that our purpose on this planet was to contribute in a positive way to the world around us. Now, much more vividly than before, I felt compelled to be a better person, to do things that mattered, to put myself out there and make a difference. A lot had happened in 3 weeks. l

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Through the Eyes of an Advocate

The Medical Minute Continued from cover asked about her extensive medical history, I could see the look of fear in her eyes, especially when she informed the resident that everything had been faxed to the office, and he responded that they had nothing! When he left the room to check if by chance the fax was received, I discovered an unfortunate issue: her referring doctor was in a different medical system not affiliated with this hospital, and therefore her medical records/charts were not available—hence the need for the fax. I sensed she was almost in a panic as she glanced at the clock with only 20 minutes before her scheduled procedure. I gently suggested that going forward, she should get a copy of all her tests, records, and scans so she could hand carry them as a precaution to ensure this would never happen again. Fax machines in doctors’ offices are often running behind, and the staff, I am certain, do their best, but they surely must be frustrated in their attempts to get vital information between medical offices and facilities. The resident returned to inform us that nothing had been received, but he took the time to assure the patient that her doctor was one of the best. As I was concerned about getting her home as soon as possible because of her fragile condition, my last question to him was about the length of the procedure, which he said was 20 minutes to about an hour if they needed to take a biopsy. When they came to escort her, without delay and right on time, I hugged and assured her that I would be in recovery when she woke. After I was ushered into the recovery unit, it was not long before the patient opened her weary eyes that I recognized the look of “What happened? Am I okay?” I held her hand and spoke words of encouragement that it was over and we would be heading home shortly, as we waited for the doctor to appear and give us some word. I looked at my watch and breathed a sigh of relief: we were right on schedule and I was thinking I could get her home and just miss the afternoon rush hour! The RN was working on the chart paperwork

and keeping her eye on my friend as I noticed other patients being visited by their doctors and released. Each time I looked up thinking this was her doctor, but no, it wasn’t. I looked at my watch when the RN asked where my friend lived; she shook her head as she realized that if the doctor was delayed any longer, we would be caught in rush hour traffic. At the same time, I could see how anxious the patient was becoming, as her fear of waiting for news, any news, was dragged on. The RN, bless her, went to see about the delay and returned and said, compassionately, “The doctor went in to do another procedure.” What!!! There

of the time or had never considered what was involved or the toll on the patient’s health, energy, and nerves, as possibly he never had someone ask him to explain the situation. I know now I missed a golden opportunity to communicate, to reach an understanding and become aware, and I certainly was not a good advocate for the patient that day. I got my friend in the car and on the road right in the middle of heavy rush hour traffic. Of course, as they say in Murphy’s law, “Anything that can go wrong, will go wrong.” There was an accident on the Coronado Bridge, which meant driving through heavy

“The patient is too often the stakeholder whose needs are not fully considered in a system that is groaning from unrealistic burdens and stresses.” Peg Ford

was nothing the RN could do, and we became the last ones in the unit that day. She did check a couple of more times. Once, she came back saying, “It will only be a moment.” I responded, “A moment, or do you mean a medical moment?” She took a deep breath but her eyes gave her away. When the doctor finally arrived, he gave no indication of the reason for the delay, nor any apology. He spoke to us for less than 10 minutes and then he was gone. I hesitated to ask why he was delayed for 2 reasons: my concern was getting my friend home as quickly as possible and I did not want to upset her by confronting the doctor with the question. Perhaps I took the easy way out and missed an opportunity to understand what actually happened and reinforced that it was okay to keep a patient waiting. Perhaps the doctor was unaware

traffic further south on the freeway to Imperial Beach to retrace our trip back up the Strand, adding additional miles and time to get her home. I assisted her up the stairs to her condo—6½ hours after picking her up for a procedure that took less than an hour! She was shaken, in a more weakened condition, drained of any energy, and visibly scared as she said that she couldn’t remember anything the doctor said to us. I told her we would talk in the morning, that she should go to bed and get some much needed sleep. Since then, I have mentioned the situation to several people who nodded their heads, recalling incidents when this happened to them or to others they knew, which seemed to be the norm rather than the exception. I have heard from ovarian cancer survivors who wait by their telephones with

trepidation as they anticipate word from their doctor’s office on the results (which regrettably can be delayed for days) of their CA-125 blood test: “Is it climbing, am I facing a recurrence of the most lethal gynecologic cancer, why have they not called me?” On the day of my friend’s procedure, what was the reason for the doctor’s delay or for deciding to do another procedure rather than speaking to her for 10 minutes before going in? Too many procedures scheduled for the doctor? It seems the system for far too many reasons is demanding more and more from the medical community, who are making every effort to keep up the pace, a pace that is unfair to everyone involved. The patient is too often the stakeholder whose needs are not fully considered in a system that is groaning from unrealistic burdens and stresses. Conceivably, and maybe in the not-too-distant future, all electronic medical records will be made available to any doctor or medical facility for instant access to any patient’s records, and then the need for fax machines will be just a memory. If credit bureaus and financial institutions are all connected electronically, perhaps a similar program could be designed for the medical world? What can the patient community do to raise these issues and in what manner? This was such a striking incident that I hope I will remember to discuss it, when I meet with policymakers and others in the healthcare industry, as it is an important matter that needs to be addressed. I have heard and read numerous reports that the healthcare system is unsustainable in regard to costs that, in my opinion, are not only related to dollars and cents but also to the most important commodity—the health, energy, and welfare of our healthcare providers. This situation that so adversely affects patients is but one terrible strain resulting from the unmanageable demands on our healthcare providers. 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 information. www.TheOncologyNurse.com

September 2013 I VOL 6, NO 8

Multiple Myeloma

Novel Agents Emerge in Initial Therapy, Refractory Setting By Wayne Kuznar

dvances in the understanding of the biology of multiple myeloma (MM) and the identification of new drugs have resulted in improved management of MM, including patients who are refractory to proteasome inhibitors and immunomodulatory agents. An update on initial therapy was offered by Donna E. Reece, MD, director of the Program for Multiple Myeloma and Related Diseases, Princess Margaret Cancer Centre, Toronto, Ontario, Canada, at the 2013 American Society of Clinical Oncology Annual Meeting. Myeloma consists of at least 7 subtypes based on cytogenetics and molecular features. The highest-risk subtypes by fluorescence in situ hybridization are t(4;14), t(14;16), del(17p), and chromosome 1 abnormalities; all are recognized as adverse prognostic factors. An evolving treatment algorithm recommends treating younger patients, particularly those with standard-risk disease, with regimens based on novel agents such as thalidomide, bortezomib, and lenalidomide before autologous

stem cell transplant (ASCT). After ASCT, bortezomib-based therapies have increased the median progression-free survival (PFS) to 3 years compared with 2 years achieved with older regimens such as VAD (vincristine, doxorubicin, and dexamethasone) or thalidomide plus dexamethasone induction, Reece said. Bortezomib-containing regimens as induction also yield better response rates and overall survival (OS) compared with these older regimens. The inclusion of bortezomib, particularly in a 3-drug regimen, seems important for high-risk disease, as indicated by the recent integrated analysis of the 4 phase 3 studies of bortezomib induction. Thalidomide as a single agent or in conjunction with corticosteroids as postASCT maintenance improved both PFS and OS in a meta-analysis of 7 phase 3 clinical trials. Lenalidomide maintenance has been assessed in 2 phase 3 trials, demonstrating significant prolongation of PFS and time to progression. “Advantages of consolidation [moderately intensive combination therapy

given for several cycles after recovery from ASCT] compared with long-term maintenance therapy include a finite period of treatment and, potentially, a lower and more predictable cost,” said Reece. In the future, consolidation with a 3-drug combination would ideally be integrated into therapy, particularly in the high-risk setting. In elderly patients, the addition of a novel agent to melphalan and prednisone results in a better antimyeloma effect, although the incidence of grade 3/4 toxicity is relatively high. Lenalidomide plus weekly dexamethasone is also a promising regimen in elderly patients. Double-Refractory MM More frequent use of proteasome inhibitors and immunomodulatory agents as part of initial therapy and in the maintenance setting has contributed to drug resistance, which portends a poor prognosis. New therapeutic strategies are needed in this population, said Robert Z. Orlowski, PhD, MD, professor in the Department of Lymphoma/Myeloma,

Prostate Cancer

Technology Brings No Upward Shift in Treatment of Local Prostate Cancer

he rate of therapy for localized prostate cancer does not increase in markets with higher penetration of robotic surgical technology and intensity-modulated radiation therapy (IMRT), according to an examination of trends using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. Lead investigator Florian Rudolf Schroeck, MD, MS, presented the analysis in poster format at the 2013 American Society of Clinical Oncology Annual Meeting. “The major concern with diffusion of technology is that people might shift their treatment recommendations, either consciously or subconsciously, toward treating more people than they did before they had the new technology,” said Schroeck. An expansion of the population treated would result not only in an increase in costs but also more men experiencing treatment-related morbidity. “But we found that new technology does not spur additional therapy of prostate cancer,” he said. His group categorized markets as low, medium, or high technological capacity based on the number of physicians who provided robotic prostatectomy and IMRT. Technology penetration was characterized separately for each hospital referral region and year. Using the SEER-Medicare linked database, they identified 59,043 patients with locoregional prostate cancer who were treated or managed expectantly from 2003 to 2007. The use of radiotherapy, radical prostatectomy, or observation was obtained from Medicare claims using Healthcare Common Procedure Coding System (HCPCS) and International Classification of Diseases, Ninth

September 2013 I VOL 6, NO 8

Revision, Clinical Modification (ICD-9-CM) codes. Multinomial logistic regression was performed to examine the association of technology penetration with receipt of prostatectomy, radiotherapy, or no local therapy. Over time, technological capacity increased. “There was no shift in the overall number of men who got treated, but what we do see is a shift in what kind of treatment they get,” said Schroeck, a fellow in urologic oncology and health services research at the University of Michigan, Ann Arbor. With more robotic technology, patients received more prostatectomy at the expense of radiotherapy. Among all age groups, the adjusted number of men receiving treatment per 1000 diagnosed was not significantly different in the lowand high-technology markets. Markets with high robotic prostatectomy penetration compared with low penetration had higher use of prostatectomy (175 vs 141 per 1000; P = .004) but a lower use of radiotherapy (584 vs 613 per 1000; P = .046). “It seems like patients are moved to some extent from the radiotherapy group to prostatectomy, but we are not expanding the pool of patients that get treated,” he said. “It makes a lot of sense too, because the urologists are the ones seeing the prostate cancer patients first and they’re the ones who have access to the robot.” l —WK Reference

Schroeck FR, Kaufman SR, Jacobs BL, et al. The impact of technology diffusion on treatment for prostate cancer. J Clin Oncol. 2013;31(suppl):Abstract 5044. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

MD Anderson Cancer Center, Houston, Texas. Carfilzomib, Pomalidomide Potent analogues of existing MM drugs, such as carfilzomib and pomalidomide, have demonstrated clinical efficacy in the double-refractory setting, resulting in the recent approval of both drugs. Carfilzomib in patients with relapsed or refractory MM was associated with an overall response rate (ORR) of 15.4%, with a median duration of response of 7.8 months. Median OS was 15.6 months in the overall population and 11.9 months in the double-refractory subgroup. Pomalidomide has been shown to be active against double-refractory MM in several phase 2 and phase 3 trials. The ORR was 31%, PFS was 3.8 months, and OS was 13.8 months in patients with relapsed/refractory MM who were randomized to pomalidomide with weekly dexamethasone. In a phase 3 trial, patients were randomly assigned to either pomalidomide and low-dose dexamethasone or single-agent high-dose dexamethasone. In patients with double-refractory disease, median PFS in the pomalidomide arm was 3.2 months versus 1.7 months in the high-dose dexamethasone arm (P <.001), and median OS was not reached in the pomalidomide arm, whereas median OS in the high-dose dexamethasone arm was 7.4 months (P <.001), said Orlowski. KSP Inhibitor A novel strategy targets kinesin-spindle protein (KSP), said Orlowski. ARRY520 is a potent, highly selective KSP inhibitor that was studied in a phase 2 trial as both a single agent (cohort 1) and in combination with low-dose dexamethasone (cohort 2). After a median treatment time of 3.9 months, the ORR rate was 22%, and the median duration of response was 5.4 months. In cohort 1, 53% had disease refractory to bortezomib, and 75% had disease refractory to lenalidomide. Of 32 patients in cohort 1 with assessable response, ORR was 16% (5 partial responses). Daratumumab Daratumumab is an investigational human monoclonal antibody that has received breakthrough therapy designation from the US Food and Drug Administration for the treatment of patients with MM who have received at least 3 prior lines of therapy or who are double refractory to a proteasome inhibitor and an immunomodulatory agent. A phase 1/2 dose escalation study in 32 patients with relapsed MM showed at least a minimal response in 8 of the 12 patients who received 4 mg/ kg or higher of daratumumab, with no major safety issues. l

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Prostate Cancer

Abiraterone in Untreated Metastatic Castration-Resistant Prostate Cancer Longer-Term Analysis of Pivotal Trial Confirms Safety and Efficacy By Alice Goodman

biraterone plus prednisone reduces the risk of disease progression and delays the time to opiate use and chemotherapy versus prednisone alone in men with metastatic castration-resistant prostate cancer (mCRPC) who had not received chemotherapy for metastatic disease, according to a long-term analysis of the COU-AA-302 trial presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting. Treatment with abiraterone plus prednisone was safe, and no new safety concerns emerged with longer follow-up. Abiraterone plus prednisone received expanded approval from the US Food and Drug Administration in December 2012 for men with chemotherapynaive mCRPC, based on updated interim results of COU-AA-302. “Building on an increased understanding of the continued relevance of the androgen signaling pathway in CRPC, abiraterone impairs androgen synthesis by selective inhibition of the CYP17 enzyme complex and is now approved for the treatment of mCRPC across the spectrum of disease states,” said lead author Dana Rathkopf, MD, of Memorial Sloan-Kettering Cancer Center in New York City. Rathkopf presented updated safety and efficacy results from COU-AA-302 at ASCO. The study evaluated 1082 men with asymptomatic or mildly symptomatic progressive mCRPC not treated with prior chemotherapy. They were randomized to receive abiraterone plus prednisone versus prednisone alone. The phase 3 multinational, randomized, double-blind, placebo-controlled study was conducted at 151 sites in 12 countries, enrolling patients from April 2009 to June 2010. Median duration of follow-up was 27.1 months. An interim analysis showed that abiraterone plus prednisone significantly improved radiographic progression-free survival (rPFS; P <.0001). A nonsignificant trend was seen for improved overall survival (OS) with abiraterone treatment. Results of the longer-term analysis were similar to those reported at the interim analysis. Abiraterone significantly improved rPFS versus prednisone alone, reducing the risk of disease progression by 48%: median of 16.5 months versus 8.2 months, respectively (P <.0001). OS was a median of 35.3 months in the abiraterone-treated group versus 30.1 months in the pred-

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nisone-alone group (not significant). Significant differences favoring abiraterone plus prednisone were observed for time to opiate use (P = .0002), time to chemotherapy initiation (P <.0001), time to deterioration in Eastern Cooperative Oncology Group (ECOG) performance status (P = .0052), and time to prostate-specific

antigen (PSA) progression (P <.0001). The percentage of grades 3 and 4 adverse events was low, despite more than 2 years of exposure to abiraterone. The cumulative incidence of all grades of adverse events was similar across both treatment groups. Rates of infection were high in both groups; the majority of grades 1 and 2 infections

were of the upper respiratory tract and upper urinary tract. l Reference

Rathkopf DE, Smith MR, De Bono JS, et al. Long-term safety and efficacy analysis of abiraterone acetate (AA) plus prednisone (P) in metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy (COU-AA-302). J Clin Oncol. 2013;31(suppl):Abstract 5009. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

Enzalutamide Promising in Hormone-Naive Prostate Cancer

romising results were obtained with enzalutamide monotherapy in patients with hormone-naive prostate cancer. The drug prevented biochemical failure in more than 90% of patients enrolled in a phase 2 trial, and enzalutamide appears to have an improved adverse event profile compared with standard androgen deprivation therapy (ADT). A phase 3 trial will be needed to determine the role of enzalutamide vis-à-vis standard ADT. Enzalutamide, an oral androgen receptor antagonist, is approved by the US Food and Drug Administration for the treatment of metastatic castration-resistant prostate cancer that progresses on docetaxel. The phase 2 trial, reported at the 2013 American Society of Clinical Oncology Annual Meeting, sought to evaluate the role of this novel agent earlier in the course of disease. “Enzalutamide monotherapy achieved high PSA responses and PSA declines in men with hormonenaive prostate cancer. We believe the results of this trial compare favorably with ADT. By contrast with ADT, patients treated with enzalutamide had stable bone mineral density (BMD) and only modest changes in serum triglycerides. The effects seen in this phase 2 trial are consistent with those seen with potent ADT inhibition, and support the role of enzalutamide as monotherapy in prostate cancer,” stated Matthew R. Smith, MD, Dana-Farber Cancer Institute and Massachusetts General Hospital in Boston. ADT is considered the mainstay of treatment for recurrent or metastatic prostate cancer, but men find the side effects difficult to tolerate, including frequent hot flashes, fatigue, loss of libido and erectile function, gynecomastia, increased risk of BMD loss, decreased muscle mass, and decreased insulin sensitivity. Some of these side effects are risk factors for diabetes mellitus and cardiovascular disease. It would be desirable to have an effective therapy with fewer adverse events, Smith told listeners. The study included patients with hormone-naive prostate cancer for which ADT is indicated. At baseline, patients had testosterone levels ≥230 ng/mL, prostate-specific antigen (PSA) ≥2 ng/mL, and a life expectancy of at least 12 months. The men received enzalutamide monotherapy for 25 weeks; then an analysis of primary efficacy was performed. Patients deemed eligible could continue on therapy. The study included 67 men, with a median age of 73 years,

median body mass index (BMI) 26.2 kg/m2, median baseline PSA 18.2 ng/mL, and median duration of prostate cancer since diagnosis of 1 year; 51% had a Gleason score of 7, and 24% had a Gleason score ≥8 at entry. At study entry, 39% had metastasis, and more than one-third had prior prostatectomy. Enzalutamide monotherapy achieved marked and rapid PSA declines in 92.5% of patients; median PSA decrease was –99.6%; and 62/67 (92.5%) achieved the primary end point of PSA decline ≥80% at week 25, regardless of the presence of metastasis at baseline. Four of 5 patients deemed nonresponders were actually withdrawals prior to evaluating response. Among 16 patients evaluable for objective responses with measurable disease, complete response plus partial response was 50%. Although BMD declines of 3% to 4% are observed during the first year of ADT, no significant changes in BMD were found after 25 weeks of treatment with enzalutamide. In fact, slight increases in BMD were observed at the femoral neck and other sites. After 25 weeks of enzalutamide monotherapy, mean BMI decreased by 4.2%, and body fat increased by 6.9%. Moderate increases were seen in serum triglycerides (6.5%) and total cholesterol levels (4.6%), but Smith noted that these are smaller increases than occur with ADT. Discussant’s Comments The study was positive, with a high rate of PSA decline and an improved side effect profile for enzalutamide compared with ADT, said formal discussant Michael Carducci, MD, of the Johns Hopkins School of Medicine in Baltimore, Maryland. Enzalutamide is 1 of 6 new drugs approved for metastatic castration-resistant prostate cancer, and the use of each of these drugs will also be studied earlier in the course of disease, Carducci continued. He said that advances in survival will come from learning how to optimize sequencing of the new drugs as well as older therapies. The emphasis will be on how best to combine agents. Several studies are under way to examine this question. l —AG Reference

Smith MR, Borre M, Rathenborg P, et al. Efficacy and safety of enzalutamide (ENZA) monotherapy in hormone-naive prostate cancer (HNPC). J Clin Oncol. 2013;31(suppl):Abstract 5001. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

September 2013 I VOL 6, NO 8

Side Effects Management

Superior Efficacy Shown for Novel Fixed-Dose Antiemetic Combination By Caroline Helwick

novel fixed-dose combination of netupitant and palonosetron, referred to as NEPA, was found to be highly effective in preventing chemotherapy-induced nausea and vomiting in 2 studies presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting. “NEPA, a fixed-dose combination of netupitant, a new NK1 receptor antagonist, and palonosetron, a 5-HT3 receptor antagonist, targets dual antiemetic pathways and has been shown to uniquely work synergistically in vitro,” said principal investigator Matti S. Aapro, MD, of the Clinique de Genolier in Switzerland.1 Netupitant is believed to work by blocking the action of substance P, an endogenous neurotransmitter (high concentrations of which are found in the vomiting center of the brain stem) that can stimulate the vomiting reflex. NEPA was developed to improve the convenience of administering guideline-based antiemetic prophylaxis, according to David Ettinger, MD, who reviewed the 2 studies at a poster discussion session. The optimal dose of NEPA was initially determined in a study led by Paul Hesketh, MD, of the Lahey Hospital & Medical Center in Burlington, Massachusetts.2 At ASCO, Aapro presented a late-breaking abstract examining the efficacy of NEPA at a fixed dose of 300 mg, which had proved most effective in the earlier study. The dose-finding study was a randomized, double-blind comparison of 3 oral

Table Complete Response Rates1 Outcome

NEPA 300 mg (%) Palonosetron (%) (N=724) (N=725) P Value

Delayed emesis (25-120 h)

76.9

69.5

.001

Acute emesis (0-24 h)

88.4

85.0

.047

Overall CR (0-120 h)

74.3

66.6

.001

Overall (including no significant nausea)

64.0

58.0

.020

Abbreviations: CR, complete response; NEPA, netupitant plus palonosetron.

doses of NEPA (netupitant 100, 200, or 300 mg plus palonosetron 0.5 mg), compared with palonosetron 0.5 mg alone, in 694 previously untreated patients receiving cisplatin-based, highly emetogenic chemotherapy. The antiemetics were all given on day 1, and all patients received oral dexamethasone on days 1 to 4. An exploratory arm included aprepitant plus ondansetron and dexamethasone. The primary end point was complete response (ie, no emesis and no rescue medication). “Each NEPA dose resulted in superior complete response rates compared with palonosetron,” Hesketh reported. Complete responses were observed in 89.6% of patients receiving NEPA at the most effective dose of 300 mg, compared with 76.5% of the palonosetron group (P = .004). The percentage of patients protected from acute emesis was 98.5% with NEPA compared with 89.7% with palonosetron (P = .007). Delayed emesis protection was observed

in 90.4% versus 80.1%, respectively (P = .018), and overall complete protection (no emesis, no significant nausea) in 83.0% versus 69.9% (P ≤.05). Late-Breaking Abstract: NEPA 300 mg in Patients Receiving Anthracyclines Aapro presented findings from a multinational, randomized, double-blind study assessing the efficacy of a single oral dose of NEPA 300 mg versus palonosetron 0.5 mg in 1455 chemotherapy-naive patients receiving anthracycline-based (moderately emetogenic) chemotherapy; 98% were female and 97% had breast cancer. In addition to NEPA or palonosetron, dexamethasone was given on day 1 in a dose of 12 mg to patients on the NEPA arm and 20 mg to those receiving palonosetron. The primary end point of this study was complete response during the delayed phase (ie, 25 to 120 hours post chemotherapy).

“NEPA showed superior complete response rates as compared to palonosetron during the delayed, acute, and overall phases,” Aapro reported (Table). “NEPA was also superior to palonosetron during the delayed/overall phases for complete protection, no emesis, and no significant nausea.” The most frequently reported study drug–related adverse events for NEPA included headache (3.3%) and constipation (2.1%), the majority being mild to moderate. Severe adverse events were rare (0.7%). Ettinger, the Alex Grass Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, said these were “good studies” that showed NEPA 300 mg to be more efficacious and more convenient than its comparators. He suggested that future studies compare NEPA plus dexamethasone with the guideline-recommended antiemetic regimen of aprepitant/palonosetron/dexamethasone. l References

1. Aapro MS, Rossi G, Rizzi G, et al. Phase III study of NEPA, a fixed-dose combination of netupitant (NETU) and palonosetron (PALO), versus PALO for prevention of chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC). J Clin Oncol. 2013;31(suppl):Abstract LBA9514. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL. 2. Hesketh PJ, Rossi G, Rizzi G, et al. Efficacy of NEPA, a novel combination of netupitant (NETU) and palonosetron (PALO), for prevention of chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC). J Clin Oncol. 2013;31(suppl):Abstract 9512. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

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CONQUERING THE ANCER CARE C The publishers of The Oncology CONTINUUM CONQUERING Nurse-APN/PA, The Oncology GHHC Conq Cancer Care Cont THE ANCER C I Pharmacist, and Personalized C O N T C ARE INUUM Medicine in Oncology are e h t g n i uer I q n o C proud to present our 2nd annual are r e c C n a CC O N T I N U U M Conquering the Cancer Care Continuum series. Conquering t Upcoming topics include: Cancer Carehe I CONTI N SECOND ANNUAL

SECON

D ISSUE ™ IN THE 2013 SE RIES SE C O N D ANN UAL

Changing the Image of Palliative Care Lillie D. Shockney, RN, BS, MAS

vention and relief of suffering by means of early identiam enthusiastic about this 6-part series titled Confication and impeccable assessment and treatment of quering the Cancer Care Continuum. Each edition of pain and other problems, physical, psychosocial, and CCCC will address an important topic in oncology ES RI SE spiritual.” (http://www.who.int/cancer/ management and offer expert stakeE 2013 TH IN UE ISS palliative/en/). Topics will IRD commentaries. THholder For too long, however, the image of include: palliative care, pain manageNU AN - AL O ND ™ palliative care has been tied exclusively SE Ccare, ment, hospice comprehensive to end-of-life care and focused solely on treatment planning, survivorship care, pain control. and the role of biosimilars in supportLillie D. Sho ckney, RN , BS, MA The articles that follow provide a ive care. In this issue, we address palS n part 2 of clear understanding of the intent of liative care. our Conqu series, the ering the Ca palliative care today, with the primary Palliation in cancer care is a topic focus is on ncer Care ma Continuum pai goal ending its identification that commonly makes people (medical well tic improvements n managem ent inabilitysolely .ofDe as surgic in ph spite drato overco provideddie for wh theile dying. providers as well as patients) uncom- we still hav al procedures des armaceasuticancer me it effe cal agecare nts, as igned ctivel in gre ea p con monly res Instead, palliative be pon asso- at pain. Family y, fearing they wil fortable. I recently had the opportunity cessful on beh long way to go to be to hel ™tro l pain, care should l memb d tha sucLillie D.alf Shockney, RN, of our nes patients. I was rec theirforlov ciated with quality-of-lifescare alled t their greatest fea ers, too, comto speak with members of our palliative MAS ly wa r is having one in gre tching a few utes of an entBS, to witold, blackcare team at Johns Hopkins and learned ern min- cancer patients and survivors, no mat- ease the at pain witho and ut a wa movie. A -white we suf cowboy ter what theirst-clinical outcome. that the word “palliative” comes from the fear these fering. Family me y to byword had a gun“palliare,” wil mb been sho slin , and t patients may not tell you about the sidewitness bef l be the final image ers tor att which means to disguise or cloak. Centuries ago, this ger word as Your cancer em ore their s they pted to rem the town docove m hisAlthough effects treatment they are experiencing or about their Many organiza loved one dies. was used for the drapes that covered afro casket. theofbul che let tions have oped me the woun st, another discomfort cow asu develdue we continue to drape coffins—most memorably withma the ded tice guidel rement tools an e to their cancer diagnosis or its treatment. n a bottle boy gav to drink d pracines for whisk In of many cases they may simply assume that the discomflag—the drape is no longer referred to this and term.a helping hisby teeth. I’m knife to bite betwe ey providers the purpose of sure back fort “comes effective age pain The World Health Organizationwamodified s how peoits origin the day enwith the disease.” However, with the imple coped this in medicine and the power of science,itsit treatmassociated with canly manprovements inal definition of palliative care as quo follows: “Palliative r to nu cer and en mb them with pain – liprovide you t. The following harthe d toquality art to anymore. Do not wait for your patients care is an approach that improves life and doesn’t somethhave call bite onof. Th icles with a we ing asking him to ma is is far fro alth of back BS, MAS Today him teinitiate he symptoms; be proac-tion associated m rised their to a discussion all pat problems as- . I wro ckney, RN, of patients and their families facing the ide said t sank and guidel with the inforhow surpabout ien hear Lillie D. Sho ts wh andal. se talMy that o ent r tive of hospithrough enviro est thatat the time you are planer initiate soon and thisrequ discussion sociated withthe life-threatening thenm prethat thoughines. They also pro tools a to even next edition illness, entafte He did an inp , ond me. wheth atient aterall and tion he to bring to you s. This be of the info sure that tful care be taken mote Lillirma or resp meitto e D. Sho a clinic visrateitd all for un wastor t is my privilege cer Care Continuum serie ons, their doc all to ckn ney reite of en it I ey, RN, , by pho with ut the long jour us addres Can opti cancer pat askne. pain me ed to com talk are BS, MA abo s wit weasu Conquering the ses specifically on hospice Hopeme Hill Healthcare Communications, told e �� Green ple te a had endLLC focu ured togetherS experien ients the pain the h our read. of wheth rement toolhad thaand issue, which cin important to t prohis 30. er vidwife he es som to be vitally to relieve g and impleme y are nosis at age gree. Pat they are presen e exp ial diag will be nt ways is one I believe tlye in resof her it. Pain ste i iherpaiinit ien n clinph n, and time, psy s addressed here on sio als away ripti what to cir ts have trosinc ysical en s of descto ubl wh ch way his fully, concept it soc er e, at on olo s, d debett ho cle ial gic du tnes Base wever, intlimited aler and rance an (a hap al well-b tuaI lly abs pain was n and erpreting ely ill. e or adopted as newterminally ill cancer bad in the py faccal ent for som d can make quali eing, and con a ditio grav y sad facshe an cause the morning ver e) ifwas supporting our r families. ent that theirthe doctord adequate treatme patients. Accur ty of life viry evidno but t so bad thei ate assess ment ne doctor. 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And that drug wrote to me ught ts is the you in rea ning valuable inf but expressed metastatic brea fear of pai step ormation is not a well as dev ssessing you oncan ing herby wife, Mary, had gressed to her liver, that nnow (He plac elo and r ice. pin cur suf o hosp r ren g p fering and ed more effe future pat call cer that had ctive ways t patients as n. She was ei ients hav the re eispecial program befotiv and now brai to help you Lilli elyofmanag e quality of life heard this termainfec lungs, bone, D.ping andeslee e not r Sh ital som had by oc ed. hosp hav kn Q ey, RN, BS, ing pain I began to expl care, he currently in the awake, confused at ©ther ef.)3As 201 MA ice S Gre was hosp enefits of alth Hil He ckney, RN, more than she “had still lie, my car, e“Lil the key ben land Lillie D. Sho weight, but Comm said l unicati untifou BS, MAS times, losing chemotherapy he I ons, LLC very upset old. s got year 8 rth g and issue of Co doctor 2 sons, 6 been receivin nquering die. We have then told him that she wrote that the Colast theotCa wife cann yesterday.” He e.” I for the ntinuumt hser nce Care s thiad n care of her would work with dresse raise themr alon mee imies nin e and cansnot sitIua who had take Treat g Thro ice staff and to com said omeand methat ir mTh ugs.hHethe nt hosp then. asked him Planildren for losingtio ld die but Fotollo next step go wou 4 years had wiabo talk ng utare se chnhileCancer ds who al of the team therap e w Ca h t a e room r re a for p e 2 her andy frien r er C p in ke ontinuu is optimal tco im him to artplac morning t would ling y ng icles imthe m.ily membersemphasiou e, to pro s. fam cologis rol tify medical zed theme on e he iden t taki of y him all vid ns were help e insighraise these boys. I There are – adclinical that usu ad discussiothe that s tofas t som now said ph int type gis him e or row arm e co a o thes help doct in er acolo ks a me would f. 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Introduc tion to O ncology Pain Ma nagem ent

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r on paper ent is ted. And the on or electron re is a new prescription kle in the ically – wrinin treatment ins plann by the pharm tructions to be filled – what wil l this treatm ing process acologist or ent cost? W These ind pharmacist. patients ha ividuals, ex ill ve to pay ou perts in dru t manageme of their treatm pocket for g nt, i ent? Is the cost of tre mization, are nteraction, and opt ment worth at atiintegral to the clinic the oncology care team. al outcome to be achiev You will s ed? No pa soon read tie learn why. lea Lilli nts ve their fam e D. Shoc want to and kney, RN ily in deep debt, , although we And speaki BS, MAS and ha ng of the tea that the pat era of person ve entered an excitin m, it is cri tically impo g ient, and cer alized medic rtant tain family cases, be con of these ne ine, the cos compared members in w drugs is t sidered me with treatm incredibly some mbers of the ning team. ents we ha high to in the We should ve been acc past. Even not be doing treatment planwe must be n ust pri om or treatmen been daunti things to a ed doing thing patient; t regimen ng from a s with a pat patients, of s have cost perspe ient. Thou Everyone course, are ctive. gh the wa not expert many have s on oncol the right tre nts to make sure tha desperatel ogy care, t the patien atment at y tried to sort by tur the t be gets way. Now ning to the come expe right time clinicians rts off a Internet an and in the for themselv must realize d trying to right treatment’s es what tre determine that treatm sake is ne atment wo ent for ver wise an uld be bes Thoughtfu t for their d not the l de mission. and patients cisions about treatm en , oncologist s, pharmaco t are a must, logists, pa © 2013 Gr lliative een Hill He althcare Co mmunicatio ns, LLC

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Cancer Center Profile

The Cleveland Clinic Taussig Cancer Institute... Continued from cover cells and disease has led to greater success rates of cancer treatment, especially in the delivery of oral chemotherapies. Oral chemotherapy agents have fewer side effects, and patients can take the medication in the comfort of their home. Drugs like Gleevec, Cytoxan, and Xeloda have changed the way therapy is delivered. Although I am excited, I feel that nursing will have to take the lead in increasing patient adherence to these medications.

The Oncology Nurse-APN/PA spoke with Iyaad Hasan, CNP, who wears several hats at the Taussig Cancer Institute in his position as APN/PA Director.

Can you describe your role at Taussig? Iyaad Hasan (IH): I have administrative and clinical duties. There are over 40 APNs [advanced practice nurses] and PAs [physician assistants] who work at Taussig Cancer Institute. My role is to make sure they are credentialed, productive, but are supported by me to help develop their career as an APN. On the clinical side, I direct the Tobacco Cessation Program with Taussig. Smokers have more treatment-related complications, and smoking reduces the success rates of treatments by 40%. Our main goal in getting patients to stop smoking tobacco is to maintain high clinical outcomes and lower readmission rates. The program focuses on giving the patient the best chances of success through behavior modification strategies and providing pharmacology intervention. I am currently involved in an effort to develop and expand our survivorship services beyond our excellent program for breast cancer patients. Taussig wants to offer survivorship programs to patients with head and neck cancer, colorectal cancer, and prostate cancer—3 cancer types with many survivors. Our vision is to have survivorship services for every type of cancer, including late-stage or metastatic disease patients, who are often ignored because they have a short life expectancy. One great initiative that I am part of is our Community Outreach Program. Once a week I work with our Langston Hughes Center that serves the uninsured or underserved. At the clinic, I screen and educate patients on

The Cleveland Clinic Taussig Cancer Institute provides world-class care to patients and offers a variety of community outreach programs that promote cancer prevention and screening.

cancer risk factors and prevention. If a patient needs a cancer screening test, I refer him or her to our Taussig Cancer Navigation Program to work with them to obtain free or affordable screenings.

What is your greatest challenge? IH: My biggest challenge is maximizing the scope of practice of the APNs within Taussig. As we move into healthcare reform, the role of the APN will increase. The Affordable Care

sent a good opportunity for APNs to expand their roles in oncology clinical care. Although patients and physicians are becoming more exposed to APNs, they still do not understand their function and roles. This leaves many APNs not practicing within their scope and not stratified with their positions. So my constant challenge is to continue to ensure that APNs are practicing within their scope. I feel that the situation regarding APNs will change with more education and engagement

“Physicians and the healthcare industry in general have a better appreciation of the potential of our value.” Iyaad Hasan, CNP

Act will provide more opportunity for Americans to get health and cancer screenings. Thus, more cancers will be identified, which will drive up the patient volume. In addition, a shortage of oncologists is projected over the next decade. Both of these factors pre-

by healthcare facilities, but for now, it is a constant challenge.

What are you excited about in the field of oncology right now? IH: The advent of better understanding of the molecular basis of cancer

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. 22

September 2013 I VOL 6, NO 8

How has the role of the oncology nurse practitioner changed in the past 5 years? IH: As previously stated, the projected shortage of oncologists has opened the eyes of a lot of healthcare professionals, and the scope of NPs is expanding in oncology. Physicians and the healthcare industry in general have a better appreciation of the potential of our value. APNs’ scope and formularies have increased, our research findings have been published, and there has been better reimbursement from third-party payers. These are all indicators of increased awareness and acceptance of APNs. It is an exciting time to be an oncology NP, especially with the new healthcare reform. What inspired you to become an oncology NP? IH: I was attracted to this profession because of the emphasis on health promotion and disease prevention. NPs have moved to an autonomous role as providers of patient care. We can help shape patients’ decisions to improve their health as well as educate them on cancer prevention and screening. What advice would you give to someone just entering the profession? IH: Many people in this field are ambitious and want to rush to show their potential as an independent provider. My main advice would be to take it slow and try to learn about the cancers, but most of all, hone in to learning how to manage the whole patient. Try to look at the overall health of a patient and help meet that patient’s needs. Cancer is not the only factor that affects a person’s general health. What would you be if you weren’t an oncology NP? IH: I would do international work on health promotion and disease prevention. Patients all over the world, especially cancer patients, need empowerment and education on maintaining optimal health. NPs are in the perfect spot to take care of teaching patients how to help themselves. l www.TheOncologyNurse.com

Fourth Annual Navigation and Survivorship Conference Memphis, Tennessee â&#x20AC;˘ The Peabody Memphis

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

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Now enrolling

Investigating ABT-199 (GDC-0199) in Chronic Lymphocytic Leukemia Phase II Open-Label Study of the Efficacy and Safety of ABT-199 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia Harboring the 17p Deletion N=100

ABT-199 is an investigational agent that has not been approved by regulatory agencies for the use under investigation in this trial. Primary Endpoint

Secondary Endpoints

• Overall response rate

• • • • • • • •

Complete remission rate Partial remission rate Duration of response Progression-free survival Time to progression Overall survival Percentage of patients who move on to stem-cell transplant Safety and tolerability of ABT-199

Key Inclusion Criteria • Adult patients ≥18 years of age • Diagnosis of CLL that meets 2008 IWCLL NCI-WG criteria (relapsed/refractory after receiving ≥1 prior line of therapy and 17p deletion) • ECOG performance score of ≤2 • Adequate bone marrow function • Adequate coagulation, renal, and hepatic function, per laboratory reference range

NCT#01889186 Reference: ClinicalTrials.gov.

To learn more about this study, please visit www.ClinicalTrials.gov.