TON October 2013 by The Oncology Nurse

OCTOBER 2013

www.TheOncologyNurse.com

VOL 6, NO 9

BREAST CANCER

CANCER CENTER PROFILE

The University of Arizona Cancer Center Coordinating Care for Patients With Breast Cancer

Additional Analyses of Eribulin Study Find Quality of Life, Survival Benefits By Caroline Helwick

urther analyses of Study 301, which compared eribulin to capecitabine in the treatment of advanced breast cancer, showed greater improvements in quality of life (QOL) with eribulin, and overall survival (OS) benefits in subsets of patients. The open-label, randomized, phase 3 Study 301 compared the therapies in 1102 women with locally advanced or metastatic breast cancer previously treated

The breast team nurses at the University of Arizona Cancer Center (left to right): Elisa Bracamonte, RN (imaging); Beth High, RN, BSN, OCN, CBCN, CBPN-IC (med onc); Kelly Smith, RN, BSN, OCN (rad onc); Magdalena Szatko-Honory, RN, BSN (med onc); Annette Whinery, RN, BSN (high risk); Melissa Denogean, RN, BSN, CPHON (clinical leader); Kathryn Clarke, RN, MSN, FNP-C, AOCNP (med onc); and Cynthia M. Figueroa, RN, BSN (surg onc). Another team member, Patty Anderson, RN, BSN, CWOCN (reconstruction), is not pictured.

he University of Arizona Cancer Center is a National Cancer Institute (NCI)-designated comprehensive cancer center, providing excellence in patient care as well as a focus on the development and delivery of therapies to reduce cancer-associated morbidity and mortality. The center is 1 of 2 NCI-designated comprehensive cancer centers in the 5-state region comprising Arizona, Colorado, Nevada, New Mexico, and Utah. Continued on page 31

ONCOLOGY PHARMACY SAFETY

Chemotherapy: Every Step You Take, Every Move You Make…

I Get By With a Little Help From My Friends: The Role of the Support Group in Breast Cancer Survivorship By Carolyn Comeau

“Wow, those meetings must be sober events.” I’ve gotten this and other similar comments regularly over the past 6½ years since I received my diagnosis of stage III breast cancer in 2007. Fortunately for me and many other women, the assumption couldn’t be less accurate.

Mind you, my support group meetings aren’t nonstop laugh riots, but neither are they gloom-and-doom fests. My sisters help me gain perspective as I navigate the road of the survivor. I think the Merriam-Webster Dictionary Continued on page 7

INSIDE

Thomas H. Connor, PhD Research Biologist, National Institute for Occupational Safety and Health

Continued on page 22

THE PATIENT’S VOICE

Christine Roussel, PharmD, BCOP Clinical Pharmacy Manager, Doylestown Hospital Pharmacy

his article describes sources of workplace contamination with hazardous drugs and how healthcare workers may be exposed to hazardous drugs during the course of their duties. For a description of some of the hazards associated with working with antineoplastic drugs in the pharmacy and discussion of some

with no more than 2 regimens, including anthracyclines and taxanes. Median OS was numerically but not significantly improved with eribulin in the overall population: 15.9 versus 14.5 months (hazard ratio [HR] = 0.88; P = .056). The additional analyses of Study 301 were presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.1,2

of the published recommendations for their safe handling, see the article by Roussel and Connor in the May 2013 issue of The Oncology Pharmacist.1 Measurement of surface contamination is currently the only indication of the amount of environmental contamination in areas where hazardous drugs

THROUGH THE EYES OF AN ADVOCATE. . . . . . . . . . . . . . . . . . . . . . . . . .

Project LEAD: An Innovative Science Program for Advocates COMPLIMENTARY CE. . . . . . . . . . . .

NUTRITION IN FOCUS. . . . . . . . . . . .

Considerations in Multiple Myeloma Ask the Experts: The Role of Transplantation

Malnutrition in Patients With Cancer

EMPOWERING PATIENTS AND SURVIVORS. . . . . . . . . . . . . . . . . . . . . . .

Survivorship Is a Matter of Perspective

VOTE NOW The 2013

ONE Award Make Your Choice at www.TheOncologyNurse.com/award

See Our 4 Finalists on Page 12

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.

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

OCTOBER 2013 I VOL 6, NO 9

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

President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Director, Human Resources Blanche Marchitto Associate Editorial Director, Projects Division Terri Moore Director, Quality Control Barbara Marino

ctober is National Breast Cancer Awareness Month. The September 30, 2013, presidential proclamation acknowledging this points out that “This disease touches every corner of the United States—in 2013 alone, more than 230,000 women and over 2,000 men will be diagnosed with breast cancer, and tens of thousands will die from it.” The proclamation states Beth Faiman, PhD(c), that during this month “we salute MSN, APRN-BC, AOCN the women and men who dedicate Editor-in-Chief themselves to prevention, detection, and treatment; we show our support for every individual and every family struggling with breast cancer; and we pause to remember those we have lost.” We at The Oncology Nurse-APN/PA (TON) recognize all that you do to educate and treat those who have breast cancer or who are at risk of developing breast cancer. In this month’s issue, we bring you some of the latest research news as well as present the voices of those who have confronted breast cancer. Carolyn Comeau, a woman diagnosed with stage III breast cancer in 2007, tells us about her support group, the “Young and the Breastless,” and shares how this remarkable group of women helped her through some very tough times. Carolyn also points out that “there’s no ‘right’ way to ‘do’ cancer” and that “Support groups come in all shapes and sizes, and,

as with that elusive pair of comfortable and chic jeans, I advise trying on a few before you commit to the purchase.” Carolyn’s insights and her unique voice can help us help our patients with cancer think about how a support group might be beneficial. Angela Long, founder of Breast Investigators, discusses the different ways people define and use the word survivor. She notes that some people are uncomfortable with the word while others may view it as a badge of honor. It’s a perspective that’s valuable for all oncology professionals to keep in mind. As Angela states, “although cancer takes so much from us, it cannot take our right to define ourselves.” We’ll be hearing more from Angela in future issues of TON. Project LEAD is an amazing 5-day intensive program for breast cancer advocates that covers the basics of cancer biology, genetics, epidemiology, research design, and advocacy. Peg Ford, very active in education and advocacy in the area of ovarian cancer, wanted to become “the best informed cancer research advocate” she could be and decided to apply to Project LEAD. It will come as no surprise to readers of Peg’s Through the Eyes of an Advocate column that she was accepted. Peg tells us about her experience at the Project LEAD course and encourages other advocates to apply and participate. As always, we hope the information in this issue benefits your practice and your patients. Please contact us at editorial@greenhillhc.com with any comments or suggestions. We love to hear from readers! l

READER POLL

Quality Control Assistant Theresa Salerno Director, Production & Manufacturing Alaina Pede

Do you talk to patients about the possibility of joining a support group?

Director, Creative & Design Robyn Jacobs Creative & Design Assistant Lora LaRocca

o Yes

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

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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.

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eO seri Vie nc es w olo on the gy line Nu a rse t .co m

2ND ANNUAL

ONQUERING THE C CANCER CARE CONTINUUM

™

A 6-part series The publishers of The Oncology Nurse-APN/PA, The Oncology Pharmacist, and Personalized Medicine in Oncology are proud to present our 2nd annual Conquering the Cancer Care Continuum series. Upcoming topics include:

NEXT ISSUE

• Palliation • Pain management • Hospice care • Treatment planning • Survivorship care • Biosimilars in supportive care

FIRST ISSUE IN THE 2013 SERIES

CONQUERING THE CANCER CARE CONTINUUM CONQUERING THE A C N C E R I C O N T C ARE IN 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 SERIES 13 spiritual.” (http://www.who.int/cancer/ management and offer expert stake20 E TH INTopics UE ISS palliative/en/). D holder commentaries. will IR TH For too long, however, the image of include: palliative care, pain manageNU AL AN ND O ™ palliative care has been tied exclusively SE Ccare, comprehensive ment, hospice 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.ofDe inabilitysolely as surgical in pharm spite drato overco ace cal care procedure for wh theile dying. providers as well as patients) uncom- we still hav me it effe die agents, provided s designed asuticancer ctivel in gre ea as 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 sucD.alf Shockney, of our pat RN, nesscare I wasLillie theirforlov ien ciated with quality-of-life alled t their greatest fea ers, too, comto speak with members of our palliative recentBS, ts. MAS ly wa r is one in gre tch ute at pain wit having to witcare team at Johns Hopkins and learned ern s of an old, black- ing a few min- cancer patients and survivors, no mat- ease hout a wa and-white the suf movie. A west-clinical outcome. cowboy ter what their that the word “palliative” comes from the fear these fering. Family me y to byword a gun“palliare,” will be the mb slinger, and had been shot ers final image tor att patients may not tell you about the sidewitness before which means to disguise or cloak. Centuries ago, this word as theYour em towncancer s they pted to rem their 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 pracof ine and wh s isk In many cases they may simply assume that the discomfor flag—the drape is no longer referred to by this term. a ey knife helping his teeth. providers the purpose of e between I’m sure bac to bit effective age pain with the disease.” However, with the imThe World Health Organizationwamodified k infort s how peoits origly manassociate the “comes day this ple coped provements in medicine and the power of science,itsit treatment. Th d with cancer an inal definition of palliative care as quo follows: “Palliative r to nu mb them with pain – lid e fol pro harthe d toquality to anymore. not wait for your patients vide you with a lowing articles care is an approach that improves life and doesn’t somethhave bite onof. Th toDocall him ing ng ma wealth of aski is is far fro back BS, MAS Today him teinitiate he symptoms; be proac-tion associated inform I wroto rised a discussion about their . all problems asckney, RN, of patients and their families facing the ide surp Sho sank pat t al. D. an wit how ien hear d guideline Lillie h these too hospitalMy ts wh and said that o ent enviro est thatat the time you are planafter tive s. ls er Th requ soon and initiate this discussion sociatedyou withthe life-threatening through the pret edition ofillness, nm tha a ey did even nex ent to t though also pro He an inp , ond me. wheth atient aterall and tion he to bring to 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 ckney, I reite it with journey , by pho Can opti RN, cancer pat of us address wit enaskne. pain me ed to com talk are about the long BS,ther weasu Conquering the ses specifically on hospice HopeMAS me Hill Healthcare Communications, told e �� Green ple te a had endLLC focu ured toge experien ients the pain the h our of wheth rement toolhad nt to read. thaand issue, which cing and t prohis y are er they are vitally importa age 30. vidwife he at be s es to im to nosi som eve ple rel pre gre diag beli e be ieve it. Pa ment wa ial expressio e. Patien sentlye in is one I i iys n clinph in steals essed here will sinc herpaiinit her ts have of n, addr tim s on and e, cept ripti wh of tro aw psycholo s at to circle ay social ubl his descto what defully, con it ysical enduran e,dho onwe Base and better way alertness,tua (a hap ver ce and can gical well-bein , intlimi pain was erpted n and e or adopted as newterminally ill cancer I lly absent for g, and reting make qu bad in the py faccal con a ditio gravely ill. y sad facshe som ali an cause the morning ver e) ifwas supporting our r families. ent that theirthe doctord adequate treatme patients. Accur ty of life viry took a evidno was but t ght thei so ate pai me doc and thou bad en n I an ass nt tor pill before t for effect ing essment now be- f that he need to that . Fur patients himcom years ago gett He be priori ive pain himsel ing the cancer viewed by thermore, is thitold ties for all ma I recall several Bill. swinf his so distressetod seeling anyone dur field. as orm of us wo nagea man named on act to theer after I feel and someti ing their d itatidiffi rking in rnet and e-mail from ly re- g this next confident mes visit? Somecultualrega foun via the Inte rdin you will fin provok Certainly it is not. timnes it is, atio had found me ing that his young d these art t he is ing and contai one of the brief convers whawil stat that cer icle me nin And to l gre pat s ass cancan y. te g tho st ate ients is the val Mar wro aist you in st fearsfor exp metastatic brea reassessin uable information ught fear of pai step webut ressed is not a drug oncan ll(He as dev herby g your cur ing wife, Mary, had gressed to her liver, that nnow andplac suffer ren pro ed- hospice. future pat eloping more effe ing and call cer that had ctive ways t patients as n. She was ei ients hav the special program before eie quality and now brai Lilliesleeping rd this term fectively lungs, bone, of life by to help your had not hea n to explain some ofmanaged. Q hospital and D. Shockney, RN having pai bega I , BS, MAS currently in the awake, confused at n ef©ther , he .)3As 201 Greenefits was hospice care RN, of Hil ey, still l ckn He more than she ben “had althcar Co lie, my the key Lillie D. Sho weight, but mmunicati l t and said, e“Lil untifou MAS times, losing chemotherapy he got very upse 8 years old. I ons, LLC rth issue of BS, g doctor been receivin Conquering ot die. We have 2 sons, 6 and him that she wrote that the Colast the Cancer alone.” I then told wife cann yesterday.” He for the ntinuumt hser s thiad n care of her would work with dresse raise them Care staff and Iua mee imies not and nin e can s sit who had take Tr g com ice T to eatment hosp tio ir mTh hrougs.hHethe said omeand asked him Planlosing then. Followiabo next step go n n for the Ca would die but that 4 years had ng utare ds who al of the team these childre a while ncer Ca room to talk re tin rapy frien paon 2 erkefor preC outco is optimal y art ld ling him tore morning in her onthe uum.ily members and me icl e, to pro ims. roltewou medical identify fam hasized the im the cologis taking places of the empere him vid were . I Th ns help e boys cli e ins that usually ussio nic ad thes disc are igh – adsaidphthat into ducks in a row nowsom giss ofas a me e type armacolo e considerat doctor al ld help him traise wou local whenever thes was tvery brief. The the ugh ly mb all to ions that bee absTho “going he pli wasthe heof en ance of getting , power of attorney,netc. soer , have histor t mu port bu king na but this time no ltid t wor ry can this er to iscilong team worki no longer i ce directive, will iiwent on he realized that 5 and then ng ed, rem van husb elm treatments were to izz.” co ain rwh lla The just wa the ove so. Patients nt to know t findboratively was obviously hosp render rec she died in but I can’ he about the put my wife on soon. Though ndati drug Hercept ommeabou t how pros and con treatm d the of treatmen onseff--abou did have to happen very entme anything write, “I foun t s t, risks and s?” met Can you tell plar,nn lungop benefits, wh anding tio the ns. drug Hospizz. are live the ir n, Go qu brai day ality of life ne is for at s, or fective this drug will be wh oncology spe they should be, when treatment ons, LLC ile on as well as aft cialists me n Hill Healthcare Communicati rely passed er treatm – eithe comple © 2013 Gree

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Personaliz ed Treatm ent Plann ing

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 of pocke manageme their treatm t 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 tients want learn why. leave their Lillie D. Sh and to ockney, family in RN, deep debt, although we And speaki BS, MAS and have enter ng of the tea ed an excitin that the pat era of person 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 treatment ve pa bee st. no pla n accustom t be doing we must be Even prior nn been daunti things to a ed treatment doing thing patient; ng from a regimens s with a pat patients, of cost perspe have 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 t atm the y car tried to be sort by tur ent at the patient get e, way. Now ning to the come expe right time s 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 decision mission. s about tre and patients atmen , oncologist s, pharmaco t are a must, logists, pa © 2013 Gr lliative een Hill He althcare Co mmunicatio ns, LLC

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THROUGH THE EYES OF AN ADVOCATE

Project LEAD: An Innovative Science Program for Advocates By Peg Ford

ould I have a chance to be accepted, as I did not technically qualify as a “breast cancer activist,” was the thought that raced through my mind as I viewed the following description on the National Breast Cancer Coalition (NBCC) website? “The Project LEAD® Institute is a fiveday intensive science course for breast cancer advocates covering the basics of cancer biology, genetics, epidemiology, research design and advocacy. This course provides a foundation of scientific knowledge upon which participants can strengthen and empower themselves as activists. Taught by a renowned research faculty, this is a unique opportunity for those interested in learning more about working as an NBCC research advocate.” Project LEAD is a registered trademark of the National Breast Cancer Coalition Fund, a 501(c)(3) tax-deductible nonprofit organization. Over the last few years, several of my fellow advocates from the breast cancer community had mentioned Project LEAD (LEAD = Leadership, Education & Advocacy Development), suggesting that I look into the program. As well, I noticed that several organizations and scientific programs had Project LEAD listed on their applications. I decided to apply this past July and was accepted! I felt it was timely for me to apply because of the necessity to learn about the connection with the BRCA1/2 mutations and learn, as a woman, about the science of breast cancer. With the recent declaration by Angelina Jolie of her health issues related to BRCA mutation and her family history, including her mother who survived breast cancer but passed away from ovarian cancer, I held the hope that I had a chance to be accepted. Since my life-threatening ovarian cancer health scare in 2007, I have noticed the growing awareness, first, in the breast and ovarian communities, of the connection due to BRCA mutations, the launching of the FORCE organization (for breast and ovarian cancer), and now the highly visible national and international increased public awareness, which I foresee will only focus more attention on evidence-based research and guidance. As I am determined to become the best informed cancer research advocate, I felt strongly that I would benefit from NBCC’s Project LEAD program, which would increase my education and understanding of the science of carcinogenesis, biology, and epidemiology in general, and breast cancer because of the overlapping subject areas and advocacy involvement. As well, I planned to go back to my con-

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stituencies and share how important the course was for me, to hopefully encourage more to pursue opportunities to learn and expand the collaboration between the 2 communities. In addition, as I have many contacts within the academic medical structure on a local, state, national, and international level, I felt Project LEAD’s great leadership program would only support improved confidence and knowledge about cancer research to help me further engage with researchers. I approach my advocacy efforts with a focus not only on ovarian cancer, but also on cancer research in general. As I see science

oped this 6-module course specifically for consumer advocates, as well as one I had taken back in 2009 when I became a consumer reviewer for the Cochrane Gynaecological Cancer Review Group in the United Kingdom. I know Kay Dickersin from having attended the Cochrane Colloquiums in Keystone, Colorado, in 2010, and in Madrid, Spain, in 2011, as well as joining the Consumers United for Evidence-based Healthcare (CUE) organization. Project LEAD: what an incredible program! It was certainly intense and an incredible learning opportunity absolutely. I found the program to be current

Peg Ford (left) with Annette Bar-Cohen, Executive Director of the Center for National Breast Cancer Coalition (NBCC) Advocacy Training. Annette has overall responsibilities for all of NBCC’s educational programs, including Project LEAD.

moving toward precision medicine, with more and more genetic mutations and pathways connecting treatment to various cancer disease types, it will not be long before, to be truly effective as an advocate, you will need to learn and expand your knowledge about the interconnected consequences of cancer research. From the acceptance notice with prereadings to the hefty binder I received on arrival, I realized that the description of an intense, packed 5 days was appropriate, and the 12- to 14-hour days with homework each night were a reality. Part of the preparation was the Cochrane Collaboration online course “Understanding Evidence-based Healthcare: A Foundation for Action” written by Professor Kay Dickersin, of the Johns Hopkins Bloomberg School of Public Health and a longtime Project LEAD faculty member, and Musa Mayer, NBCC advocate. They devel-

and well designed, and the area of focus amazed me. Each morning, we started the day with a moment of silence to honor a fallen hero, to remind us of the importance of carrying the torch forward. The topics covered on the agenda were enlightening and educational. I was immersed from the start in: • Introduction to basic science • Biology of cancer • Principles of genetics • Immunology 101 • Structure and function of DNA and RNA, protein, translation, and mutations • Development of cancer at the molecular level • Introduction to epidemiology • From bench to clinic: issues and controversies in breast cancer • Risk factors • Evidence-based healthcare • Research seminar in the genomics of screening

• Critical appraisal skills • Evaluating science information presented in the media • Systematic review and meta-analysis One great aspect was the added benefit of the formation of smaller study groups with a facilitator/mentor, where we worked to understand the nuances and concepts of the lectures. The faculty members were outstanding and had the ability to explain complex scientific theories to a lay audience with such ease and grace. I never got the impression they had to struggle to have us understand the lectures or found it difficult in any way to grasp the teachings. Since its inception in 1991, NBCC has an accomplished record of bringing about exceptional research funding to the worldwide scientific community, shaping new collaborations to design research and set priorities, expanding access to information and care to underserved women, and implementing unmatched training programs to prepare advocates to work side-byside with scientists, policymakers, and healthcare providers. NBCC’s initiative, Breast Cancer Deadline 2020, is a formative action and undertaking to know how to end breast cancer by January 1, 2020! The strategic plan is impressive, involving all stakeholders, researchers, advocates, the patient community, policymakers, and healthcare providers. If any group has the passion, leadership, and determination, NBCC is the organization to achieve this mission. Check the website for further details and how to get involved in this important mission: www.BreastCancerDeadline2020.org. For certain, having attended this program will enable me to be a better cancer research advocate. I have such gratitude for the opportunity to participate this year. I realize the gift I was given and wish to acknowledge NBCC as well as the companies (the Avon Foundation for Women, Cancer Treatment Centers of America, and Novartis Oncology), which in part funded the program with their generous grants. And, finally, I feel it is very important for women’s cancer advocates to bond, work together, and create opportunities to combine our efforts for the benefit of all women. Without question, it would be tremendously appreciated and valued if sponsors would step forward to not only continue to support this vital project, but perhaps fund an expansion of Project LEAD for more advocates from all cancer disease tracks. l

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I Get By With a Little Help From My Friends... Continued from cover hit the proverbial bull’s-eye, because its definition of “support” includes, as a noun, a “thing that bears the weight of something or keeps it upright,” and as a verb, “to keep from fainting, yielding, or losing courage.” My support group has personified these qualities and much, much more. Despite the sad statistic that more than 232,000 women will be diagnosed with invasive breast cancer in 2013 in the United States (ww5.komen.org/ breastcancer/statistics.html), one can feel awfully alone when one is first diagnosed. The unknowns and the fear that accompany this life-changing news are enough to drive one crazy—or at least cause serious sleep loss. But there’s a super statistic too: the growth of breast cancer support groups points to the happy fact that there is a growing need for survivor services, because there are a growing number of survivors.

Breastless,” or Y&B for short (who says we don’t have a sense of humor?!) comes in. Aside from being a group of women to whom you don’t have to explain much (unfortunately, they understand), they’re allies who welcome newbies into the fold, share

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NOW RECRUITING

Investigators Study of the long-term safety and efficacy of darbepoetin alfa in anemic patients with Non-Small Cell Lung Cancer (NSCLC) receiving chemotherapy Phase 3 study with approximately 3,000 subjects at 500 study sites globally KEY ELIGIBILITY CRITERIA*

PRIMARY ENDPOINT

• Stage IV NSCLC

• Overall survival

• Receiving 1st-line myelosuppressive

SECONDARY ENDPOINTS

chemotherapy

• Progression-free survival

• Hemoglobin (Hb) ≤ 11 g/dL

• Incidence of ≥ 1 red blood cell (RBC) transfusion or Hb ≤ 8.0 g/dL

• ECOG score ≤ 1

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one I’d seen just a few months before at a holiday party, whom, I’m ashamed to say, I was afraid to talk to and avoided. In fact, when I first took my place at the local restaurant’s table these warriors graced, I could barely speak.

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Despite the sad statistic that more than 232,000 women will be diagnosed with invasive breast cancer in 2013 in the United States, one can feel awfully alone when one is first diagnosed.

Darbepoetin alfa 500-mcg Q3W

2:1 Randomization (darbepoetin alfa:placebo)

End of Investigational Product

End of Treatment Period

Long-term Follow-up

Placebo Q3W

Week 0

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.

For more information, please email Cory Docken/Getty Images

Support groups help with, first and foremost, the questions that everyone from the newly diagnosed to the seasoned survivor has: What do ductal carcinoma in situ, invasive ductal carcinoma, inflammatory breast cancer, triple negative breast cancer, HER2/ neu-positive status (and countless other terms reminiscent of an especially terrifying Latin class) mean? Whom do I listen to first (concerned loved ones, nurse navigator, oncologist, radiologist, or acupuncturist)? How do I internalize and comprehend this diagnosis myself, let alone explain it to family, friends, and acquaintances? How will I handle chemotherapy, radiation, and other treatments? How can I start healing, emotionally and physically, from surgery? Should I undergo reconstructive surgery? How do I begin to make the daunting ascent out of this experiential abyss and attempt to sculpt a “new normal” life? This is exactly where my support group, dubbed the “Young and the

their feelings and experiences, and plain-old disseminate hope. When I went to my first support group meeting, I was newly diagnosed, had 2 young children, and was, to put it mildly, petrified. Breast cancer equaled death. It meant bald women, like the

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.

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I Get By With a Little Help From My Friends... Continued from page 7 I clearly remember sputtering, “Is this the…the…meeting?” semicoherently. I couldn’t even utter the words “breast cancer” out loud. After sitting down, I got the first 2 syllables of my first name out before I broke down sobbing. They didn’t stare at me aghast, as I would have; they put their arms around me, shared their amazing stories, and enveloped me in understanding, which was so validating and desperately needed! Cancer survivors definitely deal with a very real form of PTSD; like veterans or crime victims, breast cancer survivors benefit from the therapeutic gifts of sharing their experiences and developing coping skills unique to their realities. My support group has also been an amazing example of the “pay it forward” principle. One day it occurred to me that I was no longer the “new one.” I, along with the others, were now ushering in frightened women who sought connection with others who understood. Support groups come in all shapes and sizes, and, as with that elusive pair of comfortable and chic jeans, I advise trying on a few before you commit to the purchase. What makes a support group able to successfully serve its members? Like a succulent culinary dish, it requires essential ingredients, with no substitutions allowed.

Support groups come in all shapes and sizes, and, as with that elusive pair of comfortable and chic jeans, I advise trying on a few before you commit to the purchase.

The first is a skilled facilitator. My group’s is like a mother to us; she was the staff social worker from my oncologist’s practice, but then she retired. We loved her so much, and she us, that she stayed with us even after her professional career ended—a true gift. She sees to it that new members feel welcome, helps keep us focused and (loosely) organized, invites speakers to meet-

ings who discuss everything from clinical trials to integrative healing modalities, and, possibly most importantly, ensures

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that the group is a safe and nonjudgmental place to share. That said, there’s no “right” way to

ISTODAX® (romidepsin) for injection is indicated for treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy. This indication is based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.

RECHARGE THE POSSIBILITIES

• Efficacy and safety evaluated in the largest prospective single-arm PTCL study (Study 3, N=131)1 • Studied in a pretreated, histologically diverse PTCL population1 • Patients could be treated until disease progression at their discretion and that of the investigator1

Important Safety Information WARNINGS AND PRECAUTIONS • Treatment with ISTODAX® (romidepsin) 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. 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, 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 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)

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%).

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“do” cancer. No member should feel obligated to contribute in a certain way or a required amount during a meeting.

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THE PATIENT’S VOICE Our breast cancer journeys are as different as our individual selves, and so too are our internal lives and struggles. Another requirement that’s decidedly simple sounding is the chance for

members to witness survivorship up close, to really see what it looks like. I assert that what women need most when they’re first diagnosed is simply witnessing other women who’ve been

in the same place and come from relatable life circumstances. In my case, I needed, quite simply, to see women who were alive. In Asheville, North Carolina, where I live, my support

group formed because more and more younger women, often with young children, were being diagnosed. The only support group that existed years Continued on page 10

Demonstrated efficacy in PTCL after at least 1 prior therapy in Study 3a1

15% ~60% 25%

(19/130) Complete Response Rate (CR+CRu) by independent central review (95% CI: 9.0, 21.9) • Similar complete response rates in the 3 major PTCL subtypes (NOS, AITL, ALCL)

9.2 months

(11/19) of Complete Responses (CR+CRu) exceeded • Follow-up was discontinued in the remaining 8 patients prior to 9.2 months (33/130) Objective Response Rate (CR+CRu+PR) by independent central review (95% CI: 18.2, 33.8)

1.8 months a

(~2 cycles) median time to Objective Response

Efficacy based on 130 patients with histological confirmation by independent central review.1

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

DRUG INTERACTIONS • Monitor prothrombin time and International Normalized Ratio in patients concurrently administered ISTODAX (romidepsin) and warfarin sodium derivatives • Romidepsin is metabolized by CYP3A4 Monitor patients for toxicity related to increased romidepsin exposure and follow dose modifications for toxicity when ISTODAX is initially co-administered with strong CYP3A4 inhibitors Avoid co-administration of ISTODAX with rifampin and other potent inducers of CYP3A4 • Exercise caution with concomitant use of ISTODAX and P-glycoprotein (P-gp, ABCB1) inhibitors

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 Brief Summary of Full Prescribing Information, including WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS, on the following pages. Reference: 1. ISTODAX [package insert]. Summit, NJ: Celgene Corp; 2013.

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I Get By With a Little Help From My Friends... Continued from page 9 ago had a membership that consisted primarily of postmenopausal women who more than likely had adult children helping them through their breast cancer experiences. Younger women with young children have very different needs in terms of support, so a younger survivors group

was born. Members could then talk to each other about issues unique to them, like how to explain a cancer diagnosis and treatment to children at varying developmental levels, how one’s marriage might be affected, and, very importantly, how to ask for and receive help, from emotional

support to meals and child care. As a result of our accepting philosophy, my group’s “all over the place” politically, religiously, and in many other ways. Nevertheless, we respect each other’s views and communication styles, and we honor each other’s experiences as singular and equally T:7”

valuable. We offer suggestions and advice in nonpushy ways, and, not unlike a 12-step meeting, we encourage members to “take what you like and leave the rest.” Each member is acutely aware that everyone’s case is different; hence, we rarely, if ever, utter or hear the words “You should.”

Only

monitored, appropriate precautions should be taken, and treatment should be instituted as appropriate.

ISTODAX® (romidepsin) for injection For intravenous infusion only The following is a Brief Summary of the Prescribing Information for the peripheral T-cell lymphoma indication only; see Full Prescribing Information for complete product information.

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. 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

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1 INDICATIONS AND USAGE ISTODAX is indicated for: • Treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy. This indication is 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. 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 with advanced stage disease and/or high tumor burden should be closely

THE PATIENT’S VOICE Our typical conversational hallmarks more often sound like this: “What helped me in that situation was…” or “Have you considered…?” Now back to the decidedly nonsober mood of the meetings. I’m happy to report that there are, consistently, lots of laughs and hugs! Sure, we have times of happy and sad tears, but our group shares a special humor because

we have walked the same path, albeit via different routes. And hugs are not only healing, they’re free! There’s a palpable joy that emanates from a group of people who have dealt with or are still dealing with the specter of breast cancer. My own experiences, as well as conversations with many survivors, reveal that, especially after the shock

of diagnosis and the intensity of the treatment phase (for some, treatment will never end), we are often left very confused about what to do next. We frequently reassess everything about our lives, from our careers and volunteer commitments to our friendships. I’ve been the lucky recipient of an extraordinary combination of guided peer support, interaction in a nonclin-

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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%).

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 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. 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.

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.

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)]. 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. 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 © 2010-2013 Celgene Corporation. All Rights Reserved. U.S. Patents: 4,977,138; 7,608,280; 7,611,724 ISTBSPTCL.005 06/13

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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%). 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 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 Cytochrome P450 3A4 Enzymes Romidepsin is metabolized by CYP3A4. Strong CYP3A4 inhibitors increase concentrations of romidepsin. In a pharmacokinetic drug interaction trial the strong CYP3A4 inhibitor ketoconazole increased romidepsin (AUC0-∞) by approximately 25% [See Clinical Pharmacology (12.3)]. Monitor for toxicity related to increased romidepsin exposure and follow the dose modifications for toxicity [see Dosage and Administration (2.2)] when romidepsin is initially co-administered with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole). 7.3 Drugs that Induce Cytochrome P450 3A4 Enzymes Avoid co-administration of ISTODAX with rifampin. In a pharmacokinetic drug interaction trial with co-administered rifampin (a strong CYP3A4 inducer), romidepsin exposure was increased by approximately 80% and 60% for AUC0-∞ and Cmax, respectively [See Clinical Pharmacology (12.3)]. Typically, co-administration of CYP3A4 inducers decrease concentrations of drugs metabolized by CYP3A4. The increase in exposure seen after co-administration with rifampin is likely due to rifampin’s inhibition of an undetermined hepatic uptake process that is predominantly responsible for the disposition of ISTODAX. It is unknown if other potent CYP3A4 inducers (e.g., dexamethasone, carbamazepine, phenytoin, rifabutin, rifapentine, phenobarbital, St. John’s Wort) would alter the exposure of ISTODAX. Therefore, the use of other potent CYP3A4 inducers should be avoided when possible. 7.4 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.

ical setting, and simply talking with women who “get it.” After all, even our loved ones either don’t understand our experiences fully—how can they?—or we worry about boring or alarming them with what may seem like endless “cancer talk.” I’ve got some stories, too, of valuable lessons learned from long-term survivors and women living with cancer and how this is an instance in life when it decidedly does not pay to compare myself to others. My support group serves to remind me, every time I start feeling sorry for myself (and I believe that everyone, cancer or not, deserves to indulge in the occasional “pity party”; I think it’s therapeutic!), that my worst day is someone else’s best, that every member knows the anguish of awaiting test results, and that loyalty and love are priceless.

I remember that, when I was fairly new in my group, we all participated in a wonderful Relay for Life event at a local high school, whose beautiful campus is nestled in the mountains that define our region. At this point, I was healing from 2 surgeries, was smackdab in the middle of chemotherapy, and was pretty much shell-shocked. As we walked, my support group sisters, literally and figuratively, held me up as my emotions overcame me: the throngs of perfect strangers cheering us on, the concentrated energy of so many fighting for a cure, the natural beauty surrounding us. Amazingly, at the end of the Relay laps, we looked up to see a stunning double rainbow! Was it a mere coincidence? I think not! As Margaret Meade so aptly said, “Never underestimate the power of a few committed people to change the world. Indeed, it is the only thing that ever has.” My Y&B posse, for me, has been just such a lovingly committed group of “Wonder Women.” I’ve gained healing, wisdom, and strength since my diagnosis, all made priceless by the gift of connection. l

OCTOBER 2013 I VOL 6, NO 9

Oncology Nurse Excellence Award Finalists Vote Now for Your Choice www.TheOncologyNurse.com/award It was a difficult process, but we have selected 4 finalists from among the peers you nominated for the Third Annual Oncology Nurse Excellence (ONE) award. All the nominees were outstanding, but these 4 individuals stood out for their display of leadership and compassion and for their commitment to evidence-based practices. Now it’s your turn. After you read about each finalist, please go to www.TheOncologyNurse.com/award and tell us your pick for the ONE award. We will announce the readers’ choice at the Fourth Annual Academy of Oncology Nurse Navigators Meeting on November 15, 2013, in Memphis, Tennessee (http://aonnonline.org/).

Libby Daniels, RN, OCN

I Libby Daniels, RN, OCN

Lexington Medical Center West Columbia, South Carolina

n a very personal way, Libby Daniels made a lasting impression on the colleague who nominated her. “Libby’s exceptional knowledge and patient skills became even more evident to me when the oncology experience became personal after my grandfather was diagnosed with stage IV lung cancer,” the colleague shares. “Libby heard about my grandfather’s diagnosis, and even though he was not one of her patients, she immediately offered her assistance…Libby has been there for my whole family around the clock offering information, guidance, or just a listening ear—clearly illustrating that being an oncology nurse navigator is a way of life to her and not just a job. Some might say that oncology nursing is her ‘calling,’ and I would certainly agree.” Libby has been a nurse for almost 29

years. She actually began her career in healthcare as a pharmacy technician. There was a nursing shortage at the time, and she was still deciding what she really wanted to do with her life. She worked at the local drugstore and the pharmacist

Libby shares that she has “shed lots of tears” both alone and with her patients. was growing old and getting sick, and Libby would take care of him during and after her shifts. When she realized how much she enjoyed caring for her first “patient,” she decided to go into nursing. She enrolled in nursing school, and as she says, “It was just the right fit.”

Today, Libby is a general cancer nurse navigator, and she helps patients who are newly diagnosed with cancer on their journey through the treatment process by acting as their advocate, helping them to set up appointments, coordinating their care, and generally acting as their “go-to” person. She develops friendships with each one of her patients who are willing to accept her help as their navigator, and she says she’s learned something new from each patient that she’s cared for—something she’s been able to, in turn, use to care for her next new patient. Libby shares that she has “shed lots of tears” both alone and with her patients, and she feels that opening herself up in that way helps make a strong connection between her and the patient in front of her.

Elizabeth Hatcher, RN, BSN

F Elizabeth Hatcher, RN, BSN George Washington University Cancer Institute Washington, DC

OCTOBER 2013 I VOL 6, NO 9

inalist Elizabeth Hatcher is the Special Projects Coordinator and Survivorship Patient Navigator at the George Washington University (GWU) Cancer Institute, where her role spans education, research, practice management, and patient care with a focus on improving the quality of life for survivors who have completed active treatment. “Liz plays a vital role in the GWU cancer program by educating survivors to prepare them for the transition to the posttreatment phase of the cancer care continuum,” according to her colleagues. “She also develops and implements innovative education programs to empower cancer survivors to stay healthy and get the follow-up care they need, and she is researching best practices for—and the impacts of—these programs.” Liz’s mother is a nurse, so the influ-

ence to be a nurse herself had been prominent in her life since childhood. Although Liz studied psychology in college and had a short career in that field, she eventually realized that she really did want to be a nurse. She quit her job to go back to school, and graduated in 2010 with her bachelor’s degree in nursing; she is currently a part-time graduate student at GWU working on her master’s degree in nursing. In addition to navigating posttreatment cancer survivors through the healthcare system and directing them to needed posttreatment services, Liz has also implemented a new self-management program for breast cancer survivors, and drawn on her undergraduate psychology background for the provision of psychosocial support to these survivors through one-on-one

care planning as well as by cofacilitating a breast cancer support group. Liz has also developed content and presented to more than 85 administrative leaders at national conferences on navigation and survivorship, including the International Cancer Education Conference in both 2011 and 2012, and she has trained more than 100 patient navigators on survivorship issues as part of local and national training initiatives. Liz feels very lucky to have found a role at GWU that has allowed her to accomplish so much in such a short amount of time. One of the main lessons she’s learned so far is to not be afraid of trying new things. While it may not work out perfectly, if it improves the lives of patients with cancer, it is worth the effort.

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the

ONE Award

Susan Scherer, RN, BSN, OCN

ike all of our finalists, Susan Scherer is an oncology nurse navigator. But she is also a stroke survivor. At age 36, Susan’s right vertebral artery dissected spontaneously, leading to an aneurysm. After a lengthy recovery process, her family moved to Florida, where she found a role as neuromedical nurse at Moffitt Cancer Center, and spent 8 years of her 12-year nursing career specializing in neurooncology, critical care, and endocrine cancers. Having once been one herself, Susan found a particular affinity for the neurology patients, being able to relate to the challenges of recovering and rehabilitating from a neurological event. She was recruited by Marc Chamberlain, MD, a well-respected neurooncologist, to be his nurse. She worked with Dr Chamberlain for almost 6 years in neurooncology and neurosurgery. Eventually, she moved on to work with patients with endocrine cancers, and kept her ICU skills up to date by doing

extra work in Moffitt’s version of an emergency room. During her time at Moffitt, Susan’s 46-year-old brother-in-law was diagnosed with a brain tumor. With her neuro background, Susan assumed the role of oncology nurse navigator for her family. After her brother-in-law passed away, she made the decision to leave Moffitt and, in 2012, she founded RN

and seeking evidence-based holistic or alternative approaches in their cancer care. The nurses also provide help in facilitating and coordinating ancillary services including palliative care, hospice, advance directives and living wills, nutrition, physical therapy support, home healthcare, and insurance/ financial assistance. And, because they are based in Florida, RNCG nurses

As Susan sees it, nursing is not a job, it is a calling, and founding RNCG has been a large and important part of answering that call. Cancer Guides (RNCG). Providing oncology nursing services using a concierge model, the certified oncology nurses of RNCG assist patients with everything from seeking a second opinion and understanding their diagnosis, treatment plans, medications, and side effects to researching clinical trials

also coordinate cancer care for patients who are seasonal residents and need assistance in continuing their out-ofstate cancer treatments. As Susan sees it, nursing is not a job, it is a calling, and founding RNCG has been a large and important part of answering that call.

Susan Scherer, RN, BSN, OCN RN Cancer Guides Tampa, Florida

Anna Cathy Williams, RN, BSN, PHN

ncology nurse Anna Cathy Williams is a senior research specialist in the Division of Nursing Research and Education at the City of Hope Comprehensive Cancer Center, which is one of the 41 institutions designated by the National Cancer Institute as a national comprehensive cancer center. A nurse for 29 years, Anna Cathy has been with City of Hope for 28 of them, serving in roles such as staff nurse, charge nurse, triage nurse, and, now, oncology nurse. “She is fiercely committed to her patients’ needs,” writes the colleague who nominated her. “She is a strong advocate for the patients’ quality-of-life concerns, such as pain relief, psychosocial support, or sexuality concerns. Over the past 3 years, she has led our patient accrual in our lung cancer project, in which she

has personally served more than 200 patients with lung cancer.” Anna Cathy has a unique perspective on the role of an oncology nurse navigator—she, and nearly every member of her immediate family, are cancer

Anna Cathy is navigating almost 100 patients with cancer through their various stages of the cancer journey. survivors. She herself had breast cancer, melanoma, and basal cell cancer; her grandmother had colon cancer; her mother had ovarian and breast cancer;

her niece had neuroendocrine cancer; 2 of her sisters had cervical cancer; and her nephew is currently battling a glioblastoma. Starting at City of Hope in 1985 as a staff nurse, today Anna Cathy identifies and recruits patients with cancer into clinical research studies and implements interventions for experimental studies. Currently she is navigating almost 100 patients with cancer through their various stages of the cancer journey, following 40 of those patients closely with daily or weekly check-ins depending on where they are in their treatment courses. While she wishes she had all of the answers all of the time for her patients, she’s found that just the power of the presence of a nurse navigator helps patients with cancer in ways that cannot be underestimated or overvalued.

Anna Cathy Williams, RN, BSN, PHN City of Hope Duarte, California

Sponsored by

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OCTOBER 2013 I VOL 6, NO 9

CONTINUING EDUCATION 6th Annual

OCTOBER 2013 • VOLUME 6 • NUMBER 4

CONSIDERATIONS in

Multiple Myeloma

™

ASK THE EXPERTS: The Role of Transplantation 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 Rattananont Ferris Vice President of Finance Andrea Kelly Director, Human Resources Blanche Marchitto Associate Editorial Director, Projects Division Terri Moore Director, Quality Control Barbara Marino

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 6th 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 fourth issue, experts from Abramson Cancer Center answer questions related to the use of transplantation in patients with MM. 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

Quality Control Assistant Theresa Salerno

FACULTY

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

Edward A. Stadtmauer, MD Professor of Medicine Chief, Hematologic Malignancies Abramson Cancer Center University of Pennsylvania Philadelphia, PA

Patricia A. Mangan, MSN, CRNP Coordinator Bone Marrow and Stem Cell Transplant Program Abramson Cancer Center University of Pennsylvania Philadelphia, PA

Alex Ganetsky, PharmD, BCOP Hematology/Oncology Clinical Pharmacy Specialist Abramson Cancer Center University of Pennsylvania Philadelphia, PA

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

OCTOBER 2013 I VOL 6, NO 9

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CONSIDERATIONS IN MULTIPLE MYELOMA Sponsors This activity is jointly sponsored by Medical Learning Institute Inc and Center of Excellence Media, LLC. Commercial Support Acknowledgment This activity is supported by educational grants from Onyx Pharmaceuticals and Millennium: The Takeda Oncology Company. Target Audience The activity was developed for physicians, nurses, and pharmacists involved in the treatment of patients with multiple myeloma (MM). Purpose Statement The purpose of this activity is to enhance competence of physicians, nurses, and pharmacists concerning the treatment of MM. Physician Credit Designation The Medical Learning Institute Inc designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of the Medical Learning Institute Inc and Center of Excellence Media, LLC. The Medical Learning Institute Inc is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Registered Nurse Designation Medical Learning Institute Inc Provider approved by the California Board of Registered Nursing, Provider Number 15106, for 1.0 contact hour. Registered Pharmacy Designation The Medical Learning Institute Inc is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Completion of this application-based activity provides for 1.0 contact hour (0.1 CEU) of continuing pharmacy education credit. The Universal Activity Number for this activity is 0468-9999-13-022-H01-P. Learning Objectives Upon completion of this activity, the participant will be able to: • Discuss existing and emerging therapeutic options for patients with newly diagnosed or relapsed/refractory MM and how to tailor therapy for individual patients • Describe the pharmacokinetics and pharmacodynamics of novel

agents when integrating these agents into treatment regimens for MM • Evaluate adverse event management strategies for patients with MM receiving novel therapies and multidrug regimens Disclosures Before the activity, all faculty and anyone who is in a position to have control over the content of this activity and their spouse/life partner will disclose the existence of any financial interest and/or relationship(s) they might have with any commercial interest producing healthcare goods/services to be discussed during their presentation(s): honoraria, expenses, grants, consulting roles, speakers’ bureau membership, stock ownership, or other special relationships. Presenters will inform participants of any off-label discussions. All identified conflicts of interest are thoroughly vetted by Medical Learning Institute Inc for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations. The associates of Medical Learning Institute Inc, the accredited provider for this activity, and Center of Excellence Media, LLC, do not have any financial relationships or relationships to products or devices with any commercial interest related to the content of this CME/CPE/CE activity for any amount during the past 12 months. Planners’ and Managers’ Disclosures Dana Delibovi, Medical Writer, has nothing to disclose. She does not intend to discuss non-FDA-approved or investigational use for any products/devices. William J. Wong, MD, MLI Reviewer, has nothing to disclose. Shannon Woerner, RN, MSN, MLI Reviewer, has nothing to disclose. Shelly Chun, PharmD, MLI Reviewer, has nothing to disclose. Faculty Disclosures Sagar Lonial, MD, is on the advisory board for and is a Consultant to Bristol-Myers Squibb, Celgene Corporation, Millennium: the Takeda Oncology Company, Novartis, Onyx Pharmaceuticals, and sanofi-aventis. He does not intend to discuss any non–FDA-approved or investigational use for any products/devices. Edward A. Stadtmauer, MD, is a consultant to Celgene Corporation, Millennium: the Takeda Oncology Company, and Onyx Pharmaceuticals. He does not intend to discuss non-FDA-approved or investigational use for any products/devices. Patricia A. Mangan, MSN, CRNP, is on the advisory board for sanofi-aventis and the speaker’s bureau for Celgene Corporation, Millennium: The Takeda Oncology Company, and Onyx Pharma-

ceuticals. She does not intend to discuss any non-FDA-approved or investigational use for any products/devices. Alex Ganetsky, PharmD, BCOP, is on the advisory board for Cephalon. He does intend to discuss either non-FDA-approved or investigational use for the following product/device: cyclophosphamide. Disclaimer The information provided in this CME/CPE/CE activity is for continuing education purposes only and is not meant to substitute for the independent medical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition. Recommendations for the use of particular therapeutic agents are based on the best available scientific evidence and current clinical guidelines. No bias toward or promotion for any agent discussed in this program should be inferred. Instructions for Credit There is no fee for this activity. To receive credit after reading this CME/CPE/CE activity in its entirety, participants must complete the pretest, posttest, and evaluation. The pretest, posttest, and evaluation can be completed online at www.mlicme.org/P13008D.html. Upon completion of the evaluation and scoring 70% or better on the posttest, you will immediately receive your certificate online. If you do not achieve a score of 70% or better on the posttest, you will be asked to take it again. Please retain a copy of the certificate for your records. For questions regarding the accreditation of this activity, please contact Medical Learning Institute Inc at 609-333-1693 or cgusack@mlicme.org. For pharmacists, Medical Learning Institute Inc will report your participation in this educational activity to the NABP only if you provide your NABP e-Profile number and date of birth. For more information regarding this process or to get your NABP e-Profile number, go to www.mycpemonitor.net. Estimated time to complete activity: 1.0 hour Date of initial release: October 15, 2013 Valid for CME/CPE/CE credit through: October 15, 2014 SCAN HERE to Download the PDF or Apply for Credit. To use 2D barcodes, download the ScanLife app: • Text “scan” to 43588 • Go to www.getscanlife.com on your smartphone’s Web browser, and select “Download” • Visit the app store for your smartphone

The Role of Transplantation in Improving Patient Outcomes in Multiple Myeloma Edward A. Stadtmauer, MD

Professor of Medicine, Chief, Hematologic Malignancies Abramson Cancer Center, University of Pennsylvania Philadelphia, PA

Introduction With the advent of upfront transplantation, survival rates among patients with multiple myeloma (MM) have improved dramatically. Ongoing debate continues, however, on the utility of early transplantation, given the increasing efficacy of multidrug induction regimens that include such novel, molecularly targeted agents as bortezomib and lenalidomide. In this article, Edward A. Stadtmauer, MD, shares his insights and experience regarding the clinical pathway from induction, to high-dose melphalan therapy and transplantation, to posttransplant maintenance in transplant-eligible patients with MM.

Should all transplant-eligible patients receive early high-dose therapy and autologous stem cell transplantation (HDT/ASCT), or can transplantation be delayed in some cases? This is a very interesting and important question—particularly here in the United States. Most centers in the rest of the world that have the capability

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for transplantation have concluded that induction therapy to achieve remission, followed by consolidation with 1 or 2 cycles of high-dose melphalan and ASCT, followed by some form of maintenance therapy, are the steps that lead to the best outcomes among transplant-eligible patients.1 In the United States, however, some debate exists regarding the timing of HDT/ASCT. According to some experts, in the era of very effective initial treatment with novel agents, it may be possible to delay transplantation until first relapse with no untoward effect on patient survival.2,3 Recent data showing high response rates and similar survival for early versus delayed transplant provide support for this view (Figure).3 In clinical practice, prudent individualization of care dictates that not all transplant-eligible patients with MM should receive upfront HDT/ASCT as part of initial treatment. Nevertheless, all potentially transplant-eligible individuals should be evaluated for the procedure. Although not every patient needs to consult with a transplant specialist, the oncology team should inform every patient that HDT/ASCT is one of many options that may fit into his or her treatment plan. Let’s not be too quick to minimize the positive impact of the new chemotherapies for myeloma on patient outcomes. A major miracle has occurred over the last decade with the increased likelihood of deep durable remissions for patients with MM.4 A decade ago, we were pleased if half of our patients responded to initial therapy and, with good supportive care, survived for an additional 2 or 3 years. We now expect that more than 90% of our patients will respond to therapy and will survive for many years or even for decades. Contributing to this improvement is the use of such agents as thalidomide,

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CONTINUING EDUCATION

Patients (%)

Figure. Comparable OS with early vs delayed transplantation in patients treated with novel agent-based initial therapy.3 100 90 80 70 60 50 40 30 20 10 0

Table. Significant Improvement in PFS/TTP with Lenalidomide Maintenance vs Placebo Following HDT/ASCT17,18 Number of patients

Parameter

Lenalidomide

Placebo

McCarthy et al17

460

TTP

<.001

Attal et al18

614

PFS

<.001

Study 82.0% 72.7% 73.4%

67.8%

86.0%

Early ASCT Delayed ASCT

63.6%

Median duration (months)

P value

HDT/ASCT indicates high-dose therapy/autologous stem cell transplantation; PFS, progression-free survival; TTP, time to progression. 4-year OS

OS from diagnosis, TD initial treatment

OS from diagnosis, RD initial treatment

All between-group (early vs delayed ASCT) differences nonsigniﬁcant; P≥.3. ASCT indicates autologous stem cell transplantation, OS, overall survival; RD, lenalidomide plus dexamethasone; TD, thalidomide plus dexamethasone.

lenalidomide, and bortezomib, and, more recently, pomalidomide and carfilzomib. We cannot ignore, however, the fact that widespread use of HDT/ASCT even before these agents were widely available had generated improved survival across the MM population. Well-designed clinical trials have demonstrated that compared with nontransplant approaches, the incorporation of 1 or 2 cycles of high-dose melphalan and ASCT into first-line therapy is associated with both prolonged remission and improved overall survival (OS).5-7 Thus, although the results are very promising for initial multidrug therapy that includes novel agents,8,9 evidence continues to support the use of early transplantation. For example, an Italian study randomized patients to 1 of 2 treatment arms: (1) induction followed by either 1 or 2 doses of high-dose melphalan and ASCT or (2) induction followed by treatment with lenalidomide, melphalan, and a corticosteroid with no ASCT. Then, patients were once again randomly assigned to maintenance therapy with lenalidomide or observation. A substantial prolongation of time to relapse was reported among patients who received HDT/ASCT, despite the use of lenalidomide both in induction and maintenance.10,11 More clinical evidence is warranted to determine the conditions under which HDT/ASCT might be delayed. Currently, clinical trials in France and the United States are comparing early versus late transplantation; within the next 5 years, we hope to have data available that can help with this decision-making.12 Currently, however, upfront transplantation remains the standard of care for eligible patients with MM,13 which generally means an individual who is 70 years of age or younger has adequate organ function and good performance status, and is responding well to initial therapy. Are the high initial response rates seen with novel agents translating into improved outcomes following transplantation? Definitely. Data show that a complete response (CR) or very good partial response (VGPR) following induction with novel agents trends toward prolonged survival following HDT/ASCT.14 With some of the current induction regimens, at least two-thirds of patients achieve VGPR and one-third to onehalf of patients achieve CR,8,9,15 which is predictive of a favorable outcome following HDT/ASCT. VGPR has been defined by the Intergroupe Francophone du Myélome (IFM) and the International Myeloma Working Group as a 90% decrease in serum monoclonal component level or, in the subset of patients with BenceJones MM, a urine monoclonal component lower than 100 mg/24 hours.16 In clinical practice, however, our definition of response is multifactorial, including the serum monoclonal component level but also taking into account symptomatic response. When treatment is initiated in a patient, we want to rapidly reduce or reverse the symptoms that led to a diagnosis of active MM— that is, painful bone lesions, renal dysfunction, low blood counts, fatigue, and infections. Our goal is to protect patients from permanent organ dysfunction, prevent fractures, and offer a substantial improvement in quality of life. Fortunately, current initial treatments allow us to achieve these goals in the

great majority of patients. An ancillary benefit is that patients feel well and are fit to proceed to stem cell harvest and transplantation. Data show that effective induction resulting in deep remission prior to HDT/ASCT is clearly a good strategy. This does not translate, however, into an obligation to do everything possible to pound the patient into remission prior to harvesting his or her stem cells. Philosophically, we need moderation, and we need to know our patients. If a patient shows a modest response to therapy but is experiencing organ dysfunction or serious treatment-related adverse events, we cannot be overzealous about moving on to transplantation. If patients are feeling well and their symptoms have improved to a certain degree, but they have only a 50% reduction in measurable disease, we do not have to keep driving them into a deeper remission before we proceed to transplantation. Such patients may have disease that is somewhat resistant to the proteasome inhibitors, immunomodulators, and/or corticosteroids used for induction. It is likely that the best treatment for these individuals will be highdose melphalan, an alkylating agent, and ASCT. We do not delay treatment in such patients. In fact, a useful approach is to intensify the stem cell mobilization technique with chemotherapy using cyclophosphamide alone or multichemotherapy regimens (such as combinations of doxorubicin, etoposide, and cisplatin) in order to attempt to get these patients into a deeper remission while collecting their stem cells, in preparation for HDT/ASCT. What is the role played by the use of novel agents as consolidation and maintenance therapy following HDT/ASCT? Even though we now have excellent regimens for induction therapy and evidence-based protocols for HDT/ASCT, the vast majority of patients with MM will nonetheless eventually experience disease progression. This suggests that despite all that we do up front, residual disease still remains a key issue. A major recent finding is that we can improve duration of remission and survival by providing continuous therapy (also called posttransplant maintenance therapy) with regimens that are based on molecularly targeted agents. Data from clinical trials reveal that following HDT/ASCT, a maintenance course of lenalidomide, at a dose range of 5 to 15 mg daily for 1 year or more improves patient outcomes compared with placebo.17,18 The use of lenalidomide maintenance in the posttransplant population was associated with significant improvement in the primary end points of progression-free survival (PFS) or time to progression (TTP) (Table).17,18 OS was also significantly improved in one trial among patients who received lenalidomide maintenance.17 In this study, at a median follow-up of 34 months, 35 patients (15%) who received lenalidomide maintenance had died, compared with 53 patients (23%) in the placebo group (P=.03).17 These studies were designed to continue lenalidomide treatment to either intolerable toxicity or disease progression, and thus provide robust evidence that lenalidomide is generally well tolerated and effective as maintenance therapy. In one of the trials,17 TTP was improved to the extent that the study was unblinded at a median follow-up of 18 months, and patients receiving placebo who did not experience progressive disease were allowed to cross over to lenalidomide. Despite the crossover, however, patients who initially received lenalidomide maintenance benefited more in terms of PFS and OS than did those who received placebo.17 Continuous treatment with lenalidomide is associated with certain toxicities—in particular, cytopenias, gastrointestinal effects, and fatigue.17,18 More worrisome is the finding of an increased incidence of second primary malignancies (SPMs)—predominantly hematologic—among patients who receive lenalidomide maintenance. In the Cancer and Leukemia Group B 100104 and IFM

Continued on page 21 16

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CONSIDERATIONS IN MULTIPLE MYELOMA

Patient-Centered Nursing Care in the Transplant Setting Patricia A. Mangan, MSN, CRNP

Coordinator, Bone Marrow and Stem Cell Transplant Program Abramson Cancer Center, University of Pennsylvania Philadelphia, PA

Introduction In the setting of high-dose therapy/autologous stem cell transplantation (HDT/ASCT) for multiple myeloma (MM), nurses encourage patients through the process while providing supportive care for myelotoxicity and other adverse events associated with treatment. In this article, Patricia Mangan, MSN, CRNP, describes the advantages and disadvantages of early versus delayed HDT/ASCT. Ms. Mangan also advocates for multidisciplinary psychosocial support for the patient undergoing ASCT, utilizing a team that encompasses clinicians—social workers, nurses, and nurse navigators—as well as patient support groups. Finally, she offers her perspectives on older transplant recipients—a special population that must be selected judiciously and treated with extreme caution.

What are some of the advantages and disadvantages of early versus delayed transplantation in patients with MM? The main advantage of early transplantation is a robust evidence base. When we incorporate transplantation into initial therapy when myeloma disease is active, it offers patients very good outcomes and improves the likelihood of survival.1-3 Another advantage of early transplantation is that it facilitates easier collection of stem cells. With a delayed transplant, we are prolonging the time that patients receive drugs that can hinder the harvest of peripheral stem cells. One of these drugs is lenalidomide, which in some studies has been associated with a decline in peripheral stem cell collection when used for an extended period of time.4-7 Delaying transplant also increases the likelihood that a patient may be treated with melphalan, an alkylating agent that is generally contraindicated pre-ASCT because it interferes with stem cell harvest. Granted, we can sometimes solve this problem by collectTable 1. Evidence-Based Transplant Recommendations9 • Patients: Active, symptomatic myeloma eligible for transplantation - Sufficient liver, renal, pulmonary, cardiac function to tolerate high-dose therapy (melphalan)

ing stem cells early and cryopreserving them for transplantation later on. This is an option that appeals to many patients, because it provides them with a kind of “transplant insurance.” Moreover, even if the stored cells are not used for ASCT, they can be administered later in the course of therapy to manage cytopenias associated with the use of myelosuppressive agents. Conversely, if we do not perform early stem cell collection in a patient or if too many cells are lost during a very long period of preservation, we may face the difficult task of late stem cell harvest. Early rather than late transplantation also makes sense for patients who are on the older end of the eligibility range. Someone who is 68 years of age at the time of MM diagnosis may have organ function and performance status sufficient to allow HDT/ASCT. Two years later, however, at the time of relapse, this same patient may no longer be eligible for transplantation. Thus, delaying transplant deprives such patients of a treatment that may improve survival.

Early rather than late transplantation also makes sense for patients who are on the older end of the eligibility range. Of course, some disadvantages to early transplantation exist as well. The HDT/ASCT process requires hospitalization and exposes patients to significant treatment-related toxicities—especially risk for infection and organ dysfunction from HDT.2 The patient’s family, employment, and quality of life (QoL) all can be adversely affected, too. It takes approximately 3 months for individuals to recover from a transplant. Patients undergoing transplantation are not usually acutely ill for 3 months, but they can experience a considerable amount of fatigue. At 1 year posttransplant, patients are generally functioning well again,8 but recovery during that year is a gradual process. When we weigh the advantages and disadvantages, the balance favors early transplantation in those individuals with good organ function up to the age of 70 years; this has become the standard of care. At our center, we follow current evidence-based recommendations (Table 1)9 and offer early transplantation to eligible patients; we believe this provides the best outcome in terms of QoL and prolonged disease remission. What strategies do you use to guide your transplant-eligible patients through the process? Do you utilize a multidisciplinary approach to patient education and counseling? The overarching goal of patient education in the MM population must be

• Induction: Antimyeloma therapy that does not contain melphalan • Collection: Stem cell harvest sufficient for 2 transplants • HDT/ASCT - Patients who have ≥ partial response to induction—HDT/ASCT upfront (Category 1* evidence) or perform allogeneic transplant in clinical trial or continue antimyeloma therapy until best response - Patients who do not respond to induction—HDT/ASCT upfront (Category 1 evidence) • Posttransplant - Response or stable disease—Maintenance therapy or second tandem transplant or observation - Progression—Salvage, including additional transplantation if patient remains a candidate *Category 1 = the most robust clinical evidence from randomized trials. HDT/ASCT indicates high-dose therapy/autologous stem cell transplantation.

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Table 2. Patient Concerns in Anticipation of HDT/ASCT10-12 • Fear of being overwhelmed physically, emotionally, psychologically10 • Concern over missing work, losing productivity, job security10 • Inability to cover out-of-pocket costs of HDT/ASCT; concerns exacerbated by lack of open discussion of cost10 • Expectation of unmanageable, dangerous symptoms or adverse events during the process10* • Worries about family relationships and support11 • Sense of isolation11 *May be a mythical belief or exaggerated fear, since nursing practice for infection control is very consistent, and 72% of nurses surveyed report having institution-wide policies for transplantation nursing care.12 HDT/ASCT indicates high-dose therapy/autologous stem cell transplantation.

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Figure. Stem cell reinfusion with reduced-intensity melphalan (MEL100) conditioning vs standard therapy with melphalan plus prednisone (MP) in older patients (55 to 74 years; n=142).14

Median overall survival (months)

56 MP (standard Tx) MEL100 17.7

Median event-free survival (months)

Treatment groups: MEL100 = 2 to 3 courses of vincristine, doxorubicin, and dexamethasone, followed by stem cell harvest, melphalan dosed at 100 mg/m2, stem cell reinfusion, and 2 additional cycles of melphalan 100 mg/m2 at 2-month intervals post–stem cell reinfusion; MP = melphalan (6 mg/m2) and prednisone (60 mg/m2) administered for six 7-day courses at 4-week intervals.

to alleviate fears about transplantation. Many patients, regardless of their willingness to undergo HDT/ASCT, have a preconceived, negative notion of transplantation. They are burdened by worries, concerns, and sometimes myths about the experience (Table 2).10-12 For a few individuals, anxiety may be so great that they elect to postpone or avoid transplantation despite their oncologist’s recommendation. If we determine that early transplant is appropriate, we invite the patient to our center to meet with the transplant team, which includes a physician, a nurse, and a social worker or nurse navigator. If possible, we have patients and families speak with other patients who have undergone transplant. We utilize our waiting room as one of the best opportunities for patients to talk very casually. Myeloma support groups have sprung up across the country, and they provide new patients with a valuable opportunity to meet others who have undergone HDT/ASCT. Creating patient-to-patient rapport need not always be formal.

HDT/ASCT is often successful in this older population, but careful selection of patients and diligent monitoring throughout the process is critical for success. The International Myeloma Foundation and the Multiple Myeloma Research Foundation provide excellent online and printed materials. That being said, we tend to caution patients that online information may not always be accurate and can lead them astray. The multidisciplinary team, including the support group, is a much better source of information. In our role as nurse educators, we need to remember that the patient is not the only person who needs support. Caregivers benefit from help as well. Getting to know the family and friends involved in a patient’s care enables nurses to ascertain the needs of each individual. Many patients rely on loved ones to help them navigate through the HDT/ASCT process—from traveling to the transplant center to sharing ideas and feelings. Finally, nurses can encourage patients a great deal by always keeping the focus on the overarching goal of extending survival while maintaining QoL. Focusing on this goal helps to alleviate a lot of the stress involved in trans-

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plant decision-making, because you retain the perspective that the purpose of transplantation is a longer, more productive life. What are some of the special considerations in older patients undergoing transplantation? Today, patients with MM who are between 60 and 70 years of age and in otherwise good health are usually candidates for transplantation. HDT/ ASCT is often successful in this older population, but careful selection of patients and diligent monitoring throughout the process is critical for success. In selecting patients, a person’s overall performance status is very important.13 We need to ask: How frail is the patient? Can he or she perform the activities of daily life independently? Does he or she require considerable assistance moving around the house or yard? The answers to these questions can help to determine a patient’s ability to tolerate HDT/ASCT. The next step in patient selection is assessment of comorbidities and organ function. Patients 60 years of age or older are at increased risk for chronic diseases, such as type 2 diabetes, cardiovascular disease, and chronic obstructive pulmonary disease. These conditions reduce organ function and can advance a patient’s physiologic age beyond their chronological age. Once we decide to proceed to transplantation in an older patient, we may have to stratify risk and, if warranted, use a slightly lower dose of melphalan for conditioning. The dose is still high and effective, but it is scaled back a bit to get these older patients through the procedure more easily. One study has demonstrated the efficacy of a reduced-intensity, high-dose conditioning regimen of melphalan dosed at 100 mg/m2 in elderly patients (instead of the usual dose of 200 mg/m2), followed by stem cell reinfusion (Figure).14 As with any transplant candidate, older patients require individualized care. Although all patients with MM share the common goal of prolonged survival with good QoL, each one is unique and has his or her own path to that goal. As nurses, it is our job to help each patient walk that path. ♦ References

1. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516-2520. 2. Attal M, Harousseau J-L, Stoppa A-M, et al; Intergroupe Français du Myélome. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med. 1996;335:91-97. 3. Fermand J-P, Katsahian S, Divine M, et al. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol. 2005;23:9227-9233. 4. Nazha A, Cook R, Vogl DT, et al. Stem cell collection in patients with multiple myeloma: impact of induction therapy and mobilization regimen. Bone Marrow Transplant. 2011; 46:59-63. 5. Cavallo F, Bringhen S, Milone G, et al. Stem cell mobilization in patients with newly diagnosed multiple myeloma after lenalidomide induction therapy. Leukemia. 2011;25:1627-1631. 6. Kumar S, Dispenzieri A, Lacy MQ, et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia. 2007;21:2035-2042. 7. Bhutani D, Zonder J, Valent J, et al. Evaluating the effects of lenalidomide induction therapy on peripheral stem cells collection in patients undergoing autologous stem cell transplant for multiple myeloma. Support Care Cancer. 2013;21:2437-2442. 8. Grulke N, Albani C, Bailer H. Quality of life in patients before and after haematopoietic stem cell transplantation measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire QLQ-C30. Bone Marrow Transplant. 2012;47:473-482. 9. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Multiple Myeloma, Version 2.2013. http://www.nccn. org. Accessed June 2, 2013. 10. Sheldon LK, Kazmi M, Klein C, Berry DL. Concerns of stem cell transplant patients during routine ambulatory assessment. Patient Prefer Adherence. 2013;7:15-20. 11. Stephens M. The lived experience post-autologous haematopoietic stem cell transplant (HSCT): a phenomenological study. Eur J Oncol Nurs. 2005;9:204-215. 12. Bevans M, Tierney DK, Bruch C, et al. Hematopoietic stem cell transplantation nursing: a practice variation study. Oncol Nurs Forum. 2009;36:E317-E325. 13. Palumbo A, Bringhen S, Ludwig H, et al. Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood. 2011;118:4519-4529. 14. Palumbo A, Triolo S, Argentino C, et al. Dose-intensive melphalan with stem cell support (MEL100) is superior to standard treatment in elderly myeloma patients. Blood. 1999;94:1248-1253.

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CONSIDERATIONS IN MULTIPLE MYELOMA

Pharmacologic Considerations in the Transplant Setting for Myeloma Alex Ganetsky, PharmD, BCOP

Hematology/Oncology Clinical Pharmacy Specialist Abramson Cancer Center, University of Pennsylvania Philadelphia, PA

Introduction Over the past 2 decades, research has delineated the molecular biology of multiple myeloma (MM). These discoveries have given clinicians the ability to stratify risk in the disease and have also led to the development of more effective antimyeloma agents. Frontline regimens that include these novel targeted therapies produce high rates of response prior to high-dose therapy/autologous stem cell transplantation (HDT/ASCT). Induction therapy plus HDT/ASCT consistently yields favorable outcomes. In this article, Alex Ganetsky, PharmD, BCOP, describes the current paradigm for risk stratification and treatment selection in MM.

What is the role of risk stratification in the selection of induction therapy for transplant-eligible patients? Risk stratification is a relatively new approach that derives from a more thorough knowledge of myeloma biology. Historically, we had a limited understanding of the pathophysiology of the disease and didn’t realize just how heterogeneous it was. As a result, most patients were treated very similarly. In the past 10 to 15 years, however, there have been significant advances in our understanding of the molecular biology of MM, with a corresponding advent of new molecularly targeted drugs and combination regimens.1 We are now moving toward the goal of stratifying initial therapy based on the risk associated with different molecular characteristics of myeloma cells. Cytogenetics—which can identify chromosomal abnormalities predictive of risk—is critically important in patient stratification.2,3 Currently, cytogenetic testing is conducted via conventional karyotyping and fluorescence in situ hybridization (FISH) testing. This testing identifies standard and high levels of risk on the basis of specific mutations. According to current, evidence-based guidelines and consensus, patients with MM have a worse prognosis when their myeloma cells display the following abnormalities: deletion of chromosome 13 [del(13q)], deletion at the locus of the tumor suppressor gene p53 [del(17p13)], the chromosomal translocations t(4;14) and t(14;16), and an amplification at chromosome 1q21.4 FISHdetected del(17p), t(4;14), and t(14;16) have been associated with a particularly high level of risk,3-6 although there is some evidence that t(14;16) may not confer as high a risk as the other 2 abnormalities.6 While data have suggested that translocation t(11;14) may have a positive prognostic impact,7 evidence for this is not yet sufficient. Clinicians must err on the side of caution whenever a cytogenetic abnormality is detected in a patient with MM. Some experts assert that any cytogenetic abnormality may indicate higher-risk disease.5 In assessing risk, we also evaluate tumor burden and extramedullary disease, as high tumor burden and the finding of malignant plasma cells in soft tissue/visceral organ sites both confer a poorer prognosis.5,6,8 Whether a clinician relies on Durie-Salmon or International Staging System criteria to stage a patient, both methods link a greater tumor burden to a higher stage.4 We also look at a patient’s age, renal and other organ function, and overall health status in rounding out our risk assessment. Once we stratify a patient’s risk, we can use this information to select induction therapy. This is far from an exact science, but risk assessment does give us a good deal of guidance. For a transplant-eligible patient with standard-risk myeloma—most impor-

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tantly, with normal cytogenetic findings—we may select an effective but not exceedingly aggressive therapy. We might consider patient preferences for an oral regimen or their concerns regarding adverse events (AEs). Oftentimes, in this patient type, we will use 4 cycles of lenalidomide and low-dose dexamethasone (Rd) before proceeding to HDT/ASCT. There is good clinical evidence for this regimen from a randomized trial, which showed that four 28-day cycles of Rd (oral lenalidomide 25 mg/day on days 1-21 plus low-dose dexamethasone 40 mg on days 1, 8, 15, and 22) produced better 1-year survival with lower toxicity than a regimen of the same length and lenalidomide dose but incorporating high-dose dexamethasone (40 mg on days 1-4, 9-12, and 17-20), referred to as the RD regimen.9 Overall, 1-year survival was 96% with Rd, compared with 87% with RD (P=.0002). After 4 cycles of treatment, the incidence of grade 3 or higher AEs was 35% with Rd and 52% with RD (P<.001). For a clinician who prefers to use a bortezomib-based regimen, acceptable induction therapy for the patient at standard risk is cyclophosphamide, bortezomib, and dexamethasone (CyBorD). Historically, this regimen included twice-weekly intravenous (IV) bortezomib, but a clinical trial has shown that CyBorD using only once-weekly bortezomib also had good efficacy with manageable toxicity. Among patients whose CyBorD included once-weekly IV bortezomib (1.5 mg/m2 on days 1, 8, 15, and 22), overall response rates (ORRs) and rates of very good partial response or better (≥VGPR) to induction were comparable to those seen with CyBorD that included twice-weekly IV bortezomib (1.3 mg/m2 on days 1, 4, 8, and 11): ORR 93% versus 88% and ≥VGPR 60% versus 61%, respectively. In addition, grade 3 or higher AEs were lower in the once-weekly bortezomib cohort than in the twice-weekly cohort (37% vs 48%, respectively).10 In a patient with intermediate-risk disease (ie, with some cytogenetic abnormalities but negative for del[17p13] or t[4;14]), CyBorD and Rd remain good choices. At this time, although we have markers that enable us to stratify patients into risk groups, we do not have the ability to make certain treatment recommendations for each group—with the possible exception of 2 high-risk groups: patients who exhibit t(4;14) and those who exhibit del(17p13).6 Bortezomib-based therapy is appropriate in these patients, because data suggest that this agent improves outcomes in patients with t(4;14). Studies have shown that the addition of bortezomib to induction therapy enhances survival in patients with t(4;14).11,12 Recent evidence also suggests that lenalidomide has some ability to mitigate the effect of t(4;14) but with less favorable effect than bortezomib.13 Thus, bortezomib is an especially prudent choice for the t(4;14) population. Results have been somewhat mixed, however, regarding the ability of bortezomib to overcome the adverse effect of del(17p13). For example, data from a 2010 trial suggested that outcomes in patients with this high-risk feature could not be improved with 4 cycles of bortezomib-based therapy prior to HDT/ASCT (with no maintenance).12 However, recent data from the HOVON-65 trial reported that patients with del(17p13) attained significantly higher rates of progression-free survival (PFS) and overall survival (OS) when bortezomib was included in their pretransplant induction and posttransplant maintenance regimens (Figure).14 Lenalidomide, on the other hand, has not been shown to improve poor prognosis associated with del(17p13).15 However, as an effective antimyeloma agent, it can be part of a multidrug combination for high-risk patients. Aggressive 3-drug regimens that contain bortezomib are appropriate as induction for high-risk patients. One of these regimens—lenalidomide, bortezomib, and dexamethasone (RVD)—has shown very good results in newly diagnosed patients.16 In a phase 1/2 trial, RVD produced a 97% rate of 18month OS, with promising survival rates reported in the small number of patients with FISH-detected del(17p) and t(4;14).16 There may be no gain in adding a fourth drug to the regimen, as shown by a recent trial in which cyclophosphamide added to RVD provided no advan-

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Figure. 3-year overall survival in 37 patients with del(17p13) treated with and without bortezomib in the HOVON-65 trial.14

Plerixafor + G-CSF

Placebo + G-CSF

P Value

Patients achieving collection of ≥6 × 106 CD34+ cells/kg in ≤2 days

71.6%

34.4%

<.001

Median number of apheresis days required to collect ≥6 × 106 CD34+ cells/kg

1 day

4 days

<.001

Injection site reaction

20.4%

3.3%

Diarrhea

18.4%

5.3%

Nausea

16.3%

7.3%

Bone pain

9.5%

7.9%

Fatigue

8.2%

3.3%

69%*

Patients (%)

70 60 50 40

Incidence of most common adverse events:

30 17%

Treatment without bortezomib

Bortezomib-based treatment

*P=.028. Treatment without bortezomib: 3 cycles of induction with vincristine 0.4 mg IV on days 1-4; doxorubicin 9 mg/m2 IV on days 1-4; and dexamethasone 40 mg PO on days 1-4, 9-12, and 17-20/HDT/ ASCT/2 years of thalidomide maintenance (50 mg/day PO). Bortezomib-based treatment: Bortezomib 1.3 mg/m2 IV on days 1, 4, 8, and 11; doxorubicin 9 mg/m2 IV on days 1-4; and dexamethasone 40 mg PO on days 1-4, 9-12, and 17-20/HDT/ASCT/2 years of bortezomib maintenance (1.3 mg/m2 IV once every 2 weeks). HDT/ASCT indicates high-dose therapy/autologous stem cell transplantation; IV, intravenously; PO, orally.

tage in response or 1-year PFS compared with RVD or CyBorD in transplant-eligible patients; all patients received bortezomib maintenance therapy.17 A caveat here is that individuals in this study were predominantly classified as standard risk; data are not sufficient to predict the utility of a 4-drug regimen in high-risk MM. What strategies can be used to optimize stem-cell mobilization prior to transplant? There are 3 key strategies for stem cell mobilization. The first and historical strategy is to use growth factor support with filgrastim. The second is combination therapy with growth factor and chemotherapy. The third is combination therapy with growth factor plus the chemokine receptor CXCR4 antagonist plerixafor. There are advantages and disadvantages to each approach. First, if you mobilize with growth factor alone, you can do this in the outpatient setting. Toxicity is low; the most common AE associated with filgrastim is bone pain,18 which is relatively manageable. Also, the timing for apheresis is more predictable with this method. The disadvantages of mobilizing with growth factor alone are that stem cell yields are lower than with the other 2 methods, more apheresis sessions are required, and there is no antitumor effect. The second type of mobilization strategy—growth factor plus chemotherapy—produces a higher stem cell collection yield than does growth factor alone.19 This technique also provides cytoreduction of the malignancy via the chemotherapy drug. For MM, the most common chemotherapeutic agent to use for mobilization is cyclophosphamide. One of the disadvantages of this second strategy is that there is actually quite a bit of variability in peak CD34+ cell counts, which renders timing of apheresis sessions unpredictable. Another issue is that adding chemotherapy increases toxicity. Nevertheless, a recent retrospective study reported that the combination of chemotherapy plus a growth factor produced higher CD34+ cell yields and required fewer days of apheresis than did the use of a growth factor alone.20 Although rates of febrile neutropenia were higher with the chemotherapy–growth factor combination than with growth factor alone (17% vs 2%; P<.05), rates of other AEs were comparable between groups. Cost for chemotherapy plus growth factor mobilization was significantly higher than for growth factor alone, predominantly because of hospital admissions in the former group; febrile neutropenia often requires immediate hospitalization for a few days for IV antibiotics. The final mobilization strategy—growth factor plus plerixafor—has been shown to improve stem cell collection.21 In a phase 3 trial, the combination of these agents significantly increased the likelihood that patients with MM would achieve adequate stem cell harvest in 2 days or less of apheresis com-

Table. Stem-Cell Mobilization with Plerixafor + G-CSF vs Placebo + G-CSF: Efficacy and Tolerability21

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G-CSF indicates granulocyte colony-stimulating factor; NR, not reported.

pared with growth factor alone (Table).21 Plerixafor is very well tolerated; the most common AEs are gastrointestinal complaints, fatigue, and subcutaneous injection site reaction (Table). The disadvantages of plerixafor are timing of administration (it must be given 11 hours prior to initiation of apheresis)22 and cost. There have actually been a few studies to address these 2 disadvantages. A recent study suggested that the drug can be given 17 hours prior to apheresis with no untoward effect, which would improve the convenience factor.22 Costs of plerixafor can be contained by using it selectively, with a risk-adapted approach, in which preemptive plerixafor is given to patients with low CD34+ cell counts on day 4 of apheresis.23 At our center, we use multiple approaches, based on the patients’ needs. Patients with active myeloma who can benefit from additional cytoreductive therapy are good candidates for mobilization with growth factor plus chemotherapy. Patients in ≥VGPR who appear to have good cellularity in bone marrow may be candidates for mobilization with growth factor alone. In patients suspected to be poor mobilizers (ie, heavily pretreated, with poor cellularity on a bone marrow exam, or with low peripheral CD34+ cell counts), we like to administer filgrastim plus plerixafor. The next step in mobilization may be to combine all 3 strategies: growth factor, chemotherapy, and plerixafor. This approach has been studied in a small trial and was found safe in poor mobilizers.24 ♦ References

1. Lombardi L, Poretti G, Mattioli M, et al. Molecular characterization of human multiple myeloma cell lines by integrative genomics: insights into the biology of the disease. Genes Chromosom Cancer. 2007;46:226-238. 2. Stewart AK, Fonseca R. Prognostic and therapeutic significance of myeloma genetics and gene expression profiling. J Clin Oncol. 2005;23:6339-6344. 3. Kumar SK, Mikhael JR, Buadi FK, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines. Mayo Clin Proc. 2009;84:1095-1110. 4. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 2.2013. http://www.nccn.org. Accessed June 2, 2013. 5. Munshi NC, Anderson KC, Bergsagel L, et al; on behalf of the International Myeloma Workshop Consensus Panel 2. Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood. 2011;117: 4696-4700. 6. Chng W-J, Dispenzieri A, Chim CS, et al; on behalf of the International Myeloma Working Group. IMWG consensus on risk stratification in multiple myeloma [published online ahead of print August 26, 2013]. Leukemia. doi:10.1038/leu.2013.247. 7. Fonseca R, Barlogie B, Bataille R, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004;64:1546-1558. 8. Usmani SZ, Heuck C, Mitchell A, et al. Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents. Haematologica. 2012;97:1761-1767. 9. Rajkumar SV, Jacobus S, Callander NS, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11:29-37. 10. Reeder CB, Reece DE, Kukreti V, et al. Once- versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood. 2010;115:3416-3417. 11. Cavo M, Tacchetti P, Patriarca F, et al; for the GIMEMA Italian Myeloma Network.

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CONSIDERATIONS IN MULTIPLE MYELOMA

Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376:2075-2085. 12. Avet-Loiseau H, Leleu X, Roussel M, et al. Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p). J Clin Oncol. 2010;28:4630-4634. 13. Kalff A, Spencer A. The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications and current clinical strategies. Blood Cancer J. 2012;2:e89. 14. Neben K, Lokhorst HM, Jauch A, et al. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012;119:940-948. 15. Reece D, Song KW, Fu T, et al. Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood. 2009;114:522-525. 16. Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116:679-686. 17. Kumar S, Flinn I, Richardson PG, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012;119:4375-4382.

18. Pulsipher MA, Chitphakdithai P, Miller JP, et al. Adverse events among 2408 unrelated donors of peripheral blood stem cells: results of a prospective trial from the National Marrow Donor Program. Blood. 2009;113:3604-3611. 19. Pusic I, Jiang SY, Landua S, et al. Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation. Biol Blood Marrow Transplant. 2008;14:1045-1056. 20. Sung AD, Grima DT, Bernard LM, et al. Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF vs G-CSF alone [published online ahead of print June 10, 2013]. Bone Marrow Transplant. doi:10.1038/bmt.2013.80. 21. DiPersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009;113:5720-5726. 22. Harvey RD, Kaufman JL, Johnson HR, et al. Temporal changes in plerixafor administration and hematopoietic stem cell mobilization efficacy: results of a prospective clinical trial in multiple myeloma. Biol Blood Marrow Transplant. 2013;19:1393-1395. 23. Chen AI, Bains T, Murray S, et al. Clinical experience with a simple algorithm for plerixafor utilization in autologous stem cell mobilization. Bone Marrow Transplant. 2012;47:1526-1529. 24. Attolico I, Pavone V, Ostuni A, et al. Plerixafor added to chemotherapy plus G-CSF is safe and allows adequate PBSC collected in predicted poor mobilizer patients with multiple myeloma or lymphoma. Biol Blood Marrow Transplant. 2012;18:241-249.

The Role of Transplantation in Improving Patient Outcomes in Multiple Myeloma Continued from page 16 2005-02 studies, approximately 8% of patients who received lenalidomide maintenance developed SPMs, compared with 3% to 4% of those who received placebo. Fortunately, many types of SPMs are treatable. Furthermore, development of an SPM does not appear to erode the significant survival benefit derived from continuing or utilizing lenalidomide maintenance.17,18 Based on the strength of this evidence, lenalidomide is emerging as a standard of care for posttransplant maintenance therapy in patients with MM. Thalidomide maintenance, although effective, is limited by the development of neurotoxicity and fatigue.19 In a recent study in which our center participated, only about 15% of the patients who were assigned to thalidomide were able to continue taking the agent for 1 year.20 Bortezomib also has demonstrated efficacy as maintenance therapy following HDT/ASCT, with particular utility in patients with the high-risk cytogenetic abnormality deletion 17p (del 17p).21,22 Bortezomib is usually dosed once every 2 weeks as maintenance therapy; in the HOVON-65 trial, the agent was administered for approximately 2 years.21 The appropriate duration of this maintenance program has not been as well studied as the program for lenalidomide; however, 1 year of bortezomib maintenance is a reasonable estimate for treatment duration. The use of bortezomib with thalidomide plus a corticosteroid as induction prior to HDT/ASCT and as consolidation/maintenance following remission both in transplant-eligible and -ineligible patients improved outcomes compared with thalidomide plus dexamethasone or bortezomib plus prednisone.15,23 These results further suggest that bortezomib in combination with an immunomodulator may be useful as maintenance therapy following HDT/ASCT. ♦ References

1. Cavo M, Rajkumar SV, Palumbo A, et al; International Myeloma Working Group. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. Blood. 2011;117:6063-6073. 2. Dunavin NC, Wei L, Elder P, et al. Early versus delayed autologous stem cell transplantation in patients receiving novel therapies for multiple myeloma. Leuk Lymphoma. 2013;54:1658-1664. 3. Kumar S, Lacy MQ, Dispenzieri A, et al. Early versus delayed autologous transplantation following IMiD-based induction therapy in patients with newly diagnosed multiple myeloma. Cancer. 2012;118:1585-1592. 4. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516-2520. 5. Attal M, Harousseau J-L, Stoppa A-M, et al; Intergroupe Français du Myélome. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med. 1996;335:91-97. 6. Fermand J-P, Katsahian S, Divine M, et al. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol. 2005;23:9227-9233. 7. Child JA, Morgan GJ, Davies FE, et al; Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348:1875-1883. 8. Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combina-

tion therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116:679-686. 9. Jakubowiak AJ, Dytfeld D, Griffith KA, et al. Treatment outcome with the combination of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) for newly diagnosed multiple myeloma (NDMM) after extended follow-up. J Clin Oncol (ASCO Annual Meeting Abstracts). 2013;31(suppl):Abstract 8543. 10. Palumbo A, Cavallo F, Hardan I, et al. Melphalan/prednisone/lenalidomide (MPR) versus high-dose melphalan and autologous transplantation (MEL200) in newly diagnosed multiple myeloma (MM) patients <65 years: results of a randomized phase III study. Blood (ASH Annual Meeting Abstracts). 2011;118:Abstract 3069. 11. Boccadoro M, Cavallo F, Gay FM, et al. Melphalan/prednisone/lenalidomide (MPR) versus high-dose melphalan and autologous transplantation (MEL200) plus lenalidomide maintenance or no maintenance in newly diagnosed multiple myeloma (MM) patients. J Clin Oncol. 2013;31(suppl);Abstact 8509. 12. US National Institutes of Health. ClinicalTrials.gov. Study comparing conventional dose combination RVD to high-dose treatment with ASCT in the initial myeloma up to 65 years (IFM/DCFI2009) [NCT01191060]. http://clinicaltrials.gov/show/NCT01191060. Accessed September 27, 2013. 13. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Multiple Myeloma. Version 2.2013. http://www.nccn.org. Accessed June 2, 2013. 14. Harousseau J-L, Attal M, Avet-Loiseau H, et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol. 2010;28:4621-4629. 15. Cavo M, Tacchetti P, Patriarca F, et al; for the GIMEMA Italian Myeloma Network. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376:2075-2085. 16. Harousseau J-L, Avet-Loiseau H, Attal M, et al. Achievement of at least a very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: long-term analysis of the IFM 99-02 and 99-04 trials. J Clin Oncol. 2009; 27:5720-5726. 17. McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1770-1781. 18. Attal M, Lauwers-Cances V, Marit G, et al; IFM Investigators. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1782-1791. 19. Attal M, Harousseau J-L, Leyvraz S, et al; Inter-Groupe Francophone du Myélome (IFM). Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289-3294. 20. Krishnan A, Pasquini MC, Logan B, et al. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 2011;12:1195-1203. 21. Sonneveld P, Schmidt-Wolf IG, van der Holt B, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. J Clin Oncol. 2012;30:2946-2955. 22. Neben K, Lokhorst HM, Jauch A, et al. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood. 2012;119:940-948. 23. Mateos MV, Oriol A, Martínez-López J, Gutiérrez N. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood. 2012;120:2581-2588.

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OCTOBER 2013 I VOL 6, NO 9

BREAST CANCER

Additional Analyses of Eribulin Study... Continued from cover New Findings on Quality of Life in Study 301 Study 301 included QOL as a secondary end point, exploring patients’ experience of symptoms, functions, and overall well-being. The analysis found significantly greater improvements in QOL among patients treated with eribulin, reported Javier Cortes, MD, of Vall d’Hebron University Hospital in Barcelona, Spain. QOL was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQC30) and the breast cancer–specific supplementary measure (QLQ-BR23), administered at baseline, 6 weeks, and 3, 6, 12, 18, and 24 months after the start of treatment (or until progressive disease or treatment change) and at unscheduled visits. End points included the absolute change from baseline for Global Health Status (GHS), overall QOL, and for each functional domain and symptom score. Functional domains and symptoms were standardized into a scale from 0 (worst) to 100 (best). An increase in scores indicated improvement in functional domains and deterioration of symptoms. GHS and overall QOL scores were low at baseline for both arms (approximately 55), but they improved to a significantly greater degree for patients receiving eribulin than for those receiving capecitabine, with an estimated treatment effect of 6.52 (P = .048), Cortes reported. “Over time, GHS and overall QOL scores improved in both arms but significantly more so for eribulin, suggest-

ing subjective patient benefit,” he said. Patients receiving eribulin also had significantly better cognitive functioning (P <.001), whereas emotional functioning significantly improved for patients receiving capecitabine (P = .033). The estimated treatment effect for cognitive functioning was quite large, 15.33. The treatment effect for capecitabine with regard to emotional functioning was 3.29. “Changes in symptoms appeared to mirror the adverse event profiles of the 2 drugs,” Cortes indicated. “As expected, advantages in parameters linked to gastrointestinal effects were observed with eribulin, while advantages in parameters related to hair loss were observed with capecitabine.”

in international clinical trials to assess the QOL of patients with breast cancer. The QLQ-C30 includes 5 functional scales, 3 symptom scales, and 1 GHS scale. The QLQ-BR23 is a specific questionnaire containing 23 items measuring functioning and symptoms related to breast cancer. Overall Survival Improvements While the primary analysis of OS did not meet the predefined criterion for statistical significance in Study 301, the investigators hypothesized that significant differences might be observed within certain patient subgroups. The 1102 patients were randomized to receive eribulin or capecitabine as their first- (20.0%), second- (52.0%),

“As expected, advantages in parameters linked to gastrointestinal effects were observed with eribulin, while advantages in parameters related to hair loss were observed with capecitabine.” Javier Cortes, MD

Symptom changes favoring eribulin included improvements in nausea and vomiting (P = .032) and diarrhea (P = .001), while systemic adverse effects (P <.001) and upset related to hair loss changes (P = .023) favored capecitabine. Change in body image was improved more with capecitabine (P <.01). Pain was comparable between the treatments at baseline and diminished at each visit. The EORTC QLQ-C30 and QLQBR23 questionnaires are widely used

or third-line treatment (27.2%) for advanced disease. The median number of treatment cycles was 6 for eribulin and 5 for capecitabine. “A significant trend favoring improved overall survival with eribulin compared with capecitabine, consistent with the results of the overall population, was maintained over most patient subgroups, including those receiving study treatment as their first-, second-, or third-line regimen for advanced disease,” according to

Peter A. Kaufman, MD, of the Norris Cotton Cancer Center at DartmouthHitchcock Medical Center, Lebanon, New Hampshire, who presented the study at ASCO. Some patient subgroups seemed to have a greater benefit in survival with eribulin compared with capecitabine. In particular, median OS was improved by eribulin in patients with the following characteristics: • Human epidermal growth factor receptor 2 (HER2) negative (15.9 vs 13.5 months: HR = 0.84; P = .03) • Estrogen receptor negative (14.4 vs 10.5 months: HR = 0.78; P = .02) • Triple negative (14.4 vs 9.4 months: HR = 0.70; P = .01) Also deriving relatively more benefit from eribulin were patients who were Latin American, had nonvisceral disease only, had more than 2 organs involved, had progressed more than 6 months after their last chemotherapy, and had received an anthracycline and/or taxane in the metastatic setting (versus the neoadjuvant or adjuvant setting), Kaufman said. l References

1. Cortes J, Awada A, Kaufman PA, et al. Quality of life (QoL) in patients (pts) with locally advanced or metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes who received eribulin mesylate or capecitabine: a phase III, open-label, randomized study. J Clin Oncol. 2013;31(suppl):Abstract 1050. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL. 2. Kaufman PA, Cortes J, Awada A, et al. A phase III, open-label, randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes: subgroup analyses. J Clin Oncol. 2013;31(suppl):Abstract 1049. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.

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NUTRITION IN FOCUS

Malnutrition in Patients With Cancer: An Often Overlooked and Undertreated Problem By Abby C. Sauer, MPH, RD Abbott Nutrition

atients with cancer face many challenges, including eating well to maintain a good nutritional status and avoid weight loss and malnutrition. Research shows that the majority of patients with cancer suffer from nutritional deficits, and up to 85% of patients with certain cancer types experience some form of weight loss and/or malnutrition during their cancer treatment.1 For some patients, the nutritional deficits can progress to cancer cachexia, a specific form of malnutrition characterized by loss of lean body mass, muscle wasting, and impaired immune, physical, and mental function.2 Poor nutritional status and weight loss can lead to poor outcomes for patients, including decreased quality of life, decreased functional status, increased complication rates, and treatment disruptions.1,3,4 Fortunately, early nutrition intervention can improve patients’ nutritional status and help patients to maintain body weight, maintain lean body mass, better tolerate treatment, and improve quality of life.3,5-8 Therefore, all healthcare professionals who care for patients with cancer need to recognize the signs of malnutrition and provide early and effective nutrition intervention to improve outcomes. The continuum of cancer includes diagnosis, treatment, recovery, and survivorship. Each stage in this continuum is associated with specific nutritional challenges to patients. Changes in nutritional status may begin prior to diagnosis, when physical and psychosocial issues commonly have a negative impact on appetite and food intake. At cancer diagnosis, half of patients present with some form of nutritional deficit.9 Nutritional status also often declines further during cancer treatment due to various treatment-related side effects such as anorexia, mucositis, and nausea and vomiting. The incidence of malnutrition and weight loss in people with cancer ranges from 31% to 87%.1 Patients with cancer of the lung, esophagus, stomach, colon, rectum, liver, and pancreas are at greatest risk.10 Weight loss has been found to lead to poor outcomes, with as little as a 5% weight loss predicting decreased response to therapy and decreased survival.1 Malnutrition also leads to numerous negative outcomes, including decreased quality of life, increased complication rates, decreased treatment tolerance, and increased mor-

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Figure Impact of Malnutrition3 Cancer-Related Malnutrition

Increased Infection Rate

Increased Risk of Postoperative Complications

Reduced Tolerance/ Response to Treatment

Increased Cost

Reduced Performance Status

Social Burden

Decreased Quality of Life

Reprinted from Clinical Nutrition, 26(3), Marín Caro MM, Laviano A, Pichard C, Nutritional intervention and quality of life in adult oncology patients, pg. 292, 2007, with permission from Elsevier. www.sciencedirect.com/science/journal/02615614

tality (Figure).3 Of people who die from cancer, up to half have been malnourished.11 Furthermore, up to 20% of patients die from the effects of malnutrition rather than from the cancer itself.12 In addition to malnutrition and weight loss, patients with cancer often experience loss of lean body mass, or muscle mass. Loss of muscle mass can result in outcomes that are similar to those of malnutrition and include decreased immunity, increased infections, increased

an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment.”2 Its pathophysiology is characterized by a negative protein and energy balance driven by a combination of reduced food intake and abnormal metabolism.2 Due to the high prevalence of nutritional issues in these patients, nutrition screening, assessment, and intervention are crucial to preventing or

The continuum of cancer includes diagnosis, treatment, recovery, and survivorship. Each stage in this continuum is associated with specific nutritional challenges to patients. skin breakdown, decreased healing, and increased mortality.13 A study of patients with head and neck cancer who were starting treatment with concurrent chemotherapy and radiation found that weight loss began 1 week after the start of treatment.14 On average, the subjects lost almost 15 pounds over the course of treatment, and of that weight loss, lean body mass accounted for 71.7%.14 In some patients, malnutrition can progress to cancer cachexia, which is “a multifactorial syndrome defined by

minimizing the development of malnutrition. Many studies have demonstrated that maintaining a good nutritional status through nutrition intervention can help individuals with cancer improve outcomes including3,6-8,15-17: • Increase energy and protein intake • Maintain and gain body weight • Improve quality of life • Improve strength and energy levels • Manage treatment-related side effects • Avoid dose reduction and treatment delays

• Reduce unplanned hospital admissions Nutrition intervention in patients with cancer can involve many strategies, including diet education and oral nutritional supplementation. The goals of nutritional support in patients with cancer are numerous and include maintaining an acceptable weight and preventing or treating malnutrition, leading to better tolerance of treatment and its side effects, more rapid healing and recovery, reduced risk of infection during treatment, and enhanced overall survival.3,18,19 Research has demonstrated that nutritional intervention in patients with cancer can result in positive outcomes. A recent systematic review and meta-analysis of oral nutritional interventions in malnourished patients with cancer showed that nutritional intervention, including nutritional counseling and oral nutritional supplementation, was associated with statistically significant improvements in weight and energy intake compared with routine care and had a beneficial effect on some aspects of quality of life.17 Another recent study showed that patients undergoing chemoradiotherapy for esophageal cancer who had participated in a nutrition intervention program experienced better outcomes than those who had received usual care. The patients receiving nutrition intervention had greater treatment completion rates and fewer unplanned hospital admissions; those who were admitted to hospital had shorter length of stay compared to the patients receiving usual care.7 Additionally, expert nutrition groups including the American Society for Parenteral and Enteral Nutrition (ASPEN) and the European Society for Clinical Nutrition and Metabolism (ESPEN) have both issued clinical guidelines for nutritional treatment of patients with cancer. These guidelines state that patients with cancer should undergo nutrition screening and assessment and receive early nutrition intervention to improve outcomes.18,19 Research and expert recommendations support a preventive, rather than therapeutic, approach that encompasses nutrition screening as early as possible and treatment of nutritional problems through nutrition intervention.2,12,18,19 The entire healthcare team needs to work together to identify cancer Continued on page 24

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NUTRITION IN FOCUS

Malnutrition in Patients With Cancer… Continued from page 23 patients at risk of malnutrition early in order to plan the best possible intervention and follow-up during cancer treatment and progression.20 Poor nutritional status, weight loss, and malnutrition are common in patients

with cancer. These nutritional challenges significantly increase morbidity and mortality in these patients, and severe cases can lead to cancer cachexia. Early nutrition screening and intervention is vital to help these patients prevent this

nutritional decline and to better tolerate their treatment regimen. Research has demonstrated that early nutrition intervention in patients with cancer, including oral nutritional supplementation, improves outcomes such as nutritional

EMPOWERING PATIENTS AND SURVIVORS

Survivorship Is a Matter of Perspective By Angela Long “Words have meaning and names have power.”

Author Unknown

he word survivor has come to be widely identified and associated with words such as courage, heroine, brave, and fighter. Thus, it might surprise many that this socially endeared title is often debated in the breast cancer community. I have read numerous opinions regarding this topic in the breast cancer blogosphere and have talked to many women “cancer survivors” who are uncomfortable with the label. Some believe that the word is too limiting. Some believe that it is too arrogant. Some women are confused as to when survivorship begins. Some women question whether their stage of diagnosis gives them “rights” to the title at all. So many questions and so much discomfort regarding the use of this word begs the question, who created this title and who decides when and to whom it applies? The National Cancer Institute defines an individual as a cancer survivor from the time of diagnosis, through the balance of his or her life. Whether one who has been diagnosed with cancer defines or sees himself or herself as a survivor is solely a matter of perspective, based on each individual’s personal experience. When we examine the controversy around the use of the word survivor, we must remember that each person’s experience is unique and that therefore it is unlikely that one title will fit all. Most people associate the words breast cancer survivors with individuals who have had to endure treatment such as chemotherapy, radiation, mastectomy, targeted therapy, and/or breast reconstruction. These people are believed to have suffered all the side effects that go along with such treatments. After their treatment is complete, they are considered “cured” of the disease. They are celebrated as survivors! Yet there are many who do not like the term survivor for various reasons. A popular quote from Maya Angelou says, “My mission in life is not merely to survive, but to thrive; and to do so with some passion, some compassion, some humor, and some style.” Those who share this attitude do not like to refer to themselves as merely survivors. They prefer the term Thriver or SurThriver—terms that put an emphasis on the quality of life they have come to believe is of the utmost importance. While some feel the survivor title deemphasizes the importance of quality of life, others feel critical of a title that designates them as heroes of a battle they never chose to fight. Some feel it implies that those who have survived are somehow superior to those who have lost their battle to cancer. Beth L. Gainer expresses this position well in her blog “Calling the Shots,” when she says, “The problem is that on a subliminal level (or

OCTOBER 2013 I VOL 6, NO 9

maybe not too subliminal), there’s a blame game going on: those who survive did something heroic; those who don’t survive seemingly just weren’t tough enough.” Even for those accepting of the title of survivor, there is the question of exactly when it applies and the degree to which it is specific to the disease stage at diagnosis. Newly diagnosed cancer patients commonly question whether survivorship begins at diagnosis, after surgery, after treatment, or after their fifth year. Those who have been diagnosed with early-stage breast cancer are often referred to as the “lucky” ones. An early-stage diagnosis hopefully results in less invasive treatment options along with survival and cure rates that near 100%. In spite of their “good fortune” of catching their cancer early, having a less grueling treatment regimen than those with a later-stage diagnosis leaves some women feeling that they have not “earned” the title of survivor. The recent recommendation by the Journal of the American Medical Association that some early-stage diagnoses no longer be referred to as cancers can only further confuse cancer patients as to when and with whom the survivor title applies. While there are many sources of discomfort with the title survivor, it is those with an advanced-stage diagnosis who may struggle most with the label. Their view of survivorship is understandably different. They have a cancer that doctors say cannot be cured, but only controlled. Because of their pending fate due to their cancer diagnosis, some may struggle to identify themselves as survivors. I recently heard a woman diagnosed with stage IV breast cancer refer to herself as a survivor. She stopped mid-sentence and said, “Yes, I still call myself a survivor because I’m still here,” as if referring to herself as a survivor needed defending. In search of a more accurate representation of their experience, the metastatic community has coined the term metavivor. As a breast cancer survivor, I have never had a strong reaction to the title. I use it and will continue to do so because I know it is easy for others to understand. Regardless of my own position, I listen and care about the concerns and viewpoints of others regarding this topic. As the opening quote implies, I believe that a name has the power to shape not only how others see us, but more importantly how we see ourselves. Survivor is a single word used to represent a diverse array of people and their experiences with a disease that, according to the National Cancer Institute, “is not just one disease but many diseases.” We should bear in mind that, although cancer takes so much from us, it cannot take our right to define ourselves. l Angela Long is the founder and creator of Breast Investigators. Breast Investigators serves as a comprehensive resource guide to help those affected by breast cancer readily gain access to quality information, care, assistance, and support. Visit www. BreastInvestigators.com.

status, weight, treatment tolerance, and quality of life. A multidisciplinary approach among all healthcare professionals involved in cancer care is necessary to identify at-risk patients early in the process and provide appropriate and effective nutritional interventions, so that malnutrition does not remain an overlooked, underrecognized, and undertreated problem. l References

1. DeWys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med. 1980;69:491-497. 2. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12:489-495. 3. Marín Caro MM, Laviano A, Pichard C. Nutritional intervention and quality of life in adult oncology patients. Clin Nutr. 2007;26:289-301. 4. Andreyev HJN, Norman AR, Oates J, et al. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies? Eur J Cancer. 1998;34:503-509. 5. Isenring EA, Capra S, Bauer JD. Nutrition intervention is beneficial in oncology outpatients receiving radiotherapy to the gastrointestinal or head and neck area. Br J Cancer. 2004;91:447-452. 6. Bauer J, Capra S, Battistutta D, et al. Compliance with nutrition prescription improves outcomes in patients with unresectable pancreatic cancer. Clin Nutr. 2005;24:998-1004. 7. Odelli C, Burgess D, Bateman L, et al. Nutrition support improves patient outcomes, treatment tolerance and admission characteristics in oesophageal cancer. Clin Oncol. 2005;17:639-645. 8. Nayel H, el-Ghoneimy E, el-Haddad S. Impact of nutritional supplementation on treatment delay and morbidity in patients with head and neck tumors treated with irradiation. Nutrition. 1992;8:13-18. 9. Halpern-Silveira D, Susin LR, Borges LR, et al. Body weight and fat-free mass changes in a cohort of patients receiving chemotherapy. Support Care Cancer. 2010;18:617-625. 10. Capra S, Ferguson M, Ried K. Cancer: impact of nutrition intervention outcome—nutrition issues for patients. Nutrition. 2001;17:769-772. 11. Capra S, Bauer J, Davidson W, et al. Nutritional therapy for cancer-induced weight loss. Nutr Clin Pract. 2002;17:210-213. 12. Ottery FD. Cancer cachexia: prevention, early diagnosis, and management. Cancer Pract. 1994;2:123-131. 13. Demling RH. Nutrition, anabolism, and the wound healing process: an overview. Eplasty. 2009;9. www. eplasty.com/index.php?option=com_content&view= article&id=272&catid=170:volume-09-eplasty-2009. Accessed September 9, 2013. 14. Silver HJ, Dietrich MS, Murphy BA. Changes in body mass, energy balance, physical function, and inflammatory state in patients with locally advanced head and neck cancer treated with concurrent chemoradiation after low-dose induction chemotherapy. Head Neck. 2007;29:893-900. 15. Bozzetti F. Nutritional support of the oncology patient. Crit Rev Oncol Hematol. 2013;87:172-200. 16. Isenring EA, Bauer JD, Capra S. Nutrition support using the American Dietetic Association Medical Nutrition Therapy protocol for radiation oncology patients improves dietary intake compared with standard practice. J Am Diet Assoc. 2007;107:404-412. 17. Baldwin C, Spiro A, Ahern R, et al. Oral nutritional interventions in malnourished patients with cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2012;104:371-385. 18. August DA, Huhmann MB; American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors. ASPEN clinical guidelines: nutrition support therapy during adult anticancer treatment and in hematopoeitic cell transplantation. JPEN J Parenter Enteral Nutr. 2009;33:472-500. 19. Arends J, Bodoky G, Bozzetti F, et al. ESPEN Guidelines on Enteral Nutrition: non-surgical oncology. Clin Nutr. 2006;25:245-259. 20. Santarpia L, Contaldo F, Pasanisi F. Nutritional screening and early treatment of malnutrition in cancer patients. J Cachexia Sarcopenia Muscle. 2011;2: 27-35.

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Chemotherapy: Every Step You Take… Continued from cover are prepared, administered to patients, or otherwise handled (such as receiving areas, in transit throughout the facility, and waste storage areas) (Table 1). Although limited associations have been demonstrated between surface contamination and actual worker exposure,2 surface contamination is the most commonly used metric for evaluation of the workplace for hazardous drugs (Table 22-12). Workplace contamination with hazardous drugs in the United States and other countries has remained fairly constant over the past decade or more, indicating that worker exposure probably has not changed considerably over that time, despite efforts to reduce or eliminate environmental contamination. The introduction of Class II biological safety cabinets (BSCs) for the preparation of hazardous drugs in the 1980s substantially reduced the potential for worker exposure,13 but BSCs did not prove to be as efficient at reducing contamination as first believed.4 The recent use of isolators has not been widespread in the United States, nor have they proven to offer more protection to workers than do BSCs, as contamination from the inside surfaces of the isolator may be transferred to the outside of syringes and infusion bags.14 Use of robotic systems to prepare hazardous drugs may reduce environmental contamination and worker exposure to these drugs; however, their high cost makes them prohibitive for all but large cancer centers.15 The addition of closed-system drug transfer devices (CSTDs) for the preparation and administration of hazardous drugs has been shown to reduce surface contamination and possibly worker exposure, but they do not totally eliminate it.5,6,10,11 Recent research has shown that even when all of these controls are used in healthcare settings, the potential for exposure to antineoplastic and other hazardous drugs cannot be completely eliminated.2,10,11,16-22 Despite improvements in engineering controls and other attempts to reduce environmental contamination, hazardous drugs are still being released into the work environment and subsequently workers are being exposed to them. Therefore, for the foreseeable future, as the number of patients requiring treatment with hazardous drugs increases,23,24 contamination of the workplace with hazardous drugs and/or worker exposure to hazardous drugs will be an issue that does not have an immediate solution. Surface Contamination and Wipe Sampling for Hazardous Drugs Wipe sampling for surface contamination has been used in many industrial settings to measure materials such as

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Table 1 Common Locations in the Pharmacy Where Antineoplastic Drugs Have Been Detected Locations where high levels of contamination are seen: Working surface of BSC Surfaces inside the compounding isolator Leading edge (airfoil) of BSC Floor in front of BSC Locations where lower levels of contamination are seen: Floor in pharmacy Countertops Storage bins and trays Storage shelves Inside and outside pass-through windows Waste containers Keyboards Door handles Shoes of pharmacy employees Employee telephones Abbreviation: BSC, biological safety cabinet.

pesticides, lead, asbestos, etc. Sampling for hazardous drugs usually involves a battery of a small number of drugs for which sampling and analytic methods have been developed (Table 3). Methodology allows measurement as low as picogram amounts, but most values are reported as ng/cm2. The method for surface sampling typically follows this approach: an appropriate solvent is applied to a specified area; the surface is wiped with a swab; then the swab is extracted with a solvent and analyzed using either gas chromatography-tandem mass spectrometry or liquid chromatography-tandem mass spectrometry

the drugs that they can analyze. Some provide kits for sampling that can be shipped to the laboratory for analysis. It is important for individual institutions to test their own workplace for hazardous drug contamination, rather than make assumptions about their facilities and staff. Pharmacy and other healthcare provider management may worry about the employee perception of these results or the risk incurred by searching for such data. It is not uncommon to question the point of testing, or the greater worry about what the action plan will be if contamination is detected and whether this opens up an

Measurement of surface contamination is currently the only indication of the amount of environmental contamination in areas where hazardous drugs are prepared, administered to patients, or otherwise handled. (GC-MS/MS or LC-MS/MS).25 Values typically seen in pharmacies range from <1 ng/cm2 to a few hundred ng/cm2 (Table 2 provides specific contamination levels detected in studies from the US). Although there are no standards for surface contamination with hazardous drugs, and an action level has not been validated, <1 ng/cm2 is a value to aim for in the pharmacy.26 Table 3 also lists laboratories that provide analysis of hazardous drug wipe samples and

institution to litigation. While standard assays and established acceptable levels of workplace contamination have yet to be formally established, the latest revision of USP Chapter 797 (2008) includes a recommendation that surface sampling for hazardous drugs be tested for at baseline and every 6 months or more frequently for larger-volume facilities.26 It is recommended that surface sampling be conducted in a targeted manner, such as the surfaces of the

BSC, floor beneath the BSC, counters adjacent to primary engineering controls, counters where final compounded hazardous drug products are placed, and patient administration areas. Evaluation of facility controls should include the type of engineering control in use and to what extent the device is vented to the outside, where exhausting 100% of the filtered air is most appropriate based on volume and the extent of contamination.27 All employees’ techniques and knowledge should be evaluated, and retraining should be conducted as appropriate. Poor technique by one individual can lead to an area of concentrated drug on a surface that can, in turn, lead to worker uptake weeks after that drug was originally mishandled. Workflow processes including waste disposal could also be a contributor to contamination. Each institution should consider a self-evaluation of its workflow. Following simple recommendations, such as discarding all waste including syringes into a sealable plastic bag within the BSC while compounding, can dramatically reduce contamination. Once the contaminated waste is contained, it can then be removed from the engineering control and put into chemotherapy disposal bins. Otherwise, if the waste is open (ie, used syringes) during the transfer process, small droplets can contaminate the gown of the compounder, the floor, and the lid of the chemotherapy disposal container.28 Drug Vial Contamination The reporting of external contamination on drug vials is an important reminder that safe handling of hazardous drugs by healthcare workers begins with receiving. Studies in the United States,7 France,29 Germany,30 Switzerland,31 and Japan32 all show the high frequency of external vial contamination, with more than one study reporting contamination on 100% of samples. Favier and colleagues detected 2.4 µg of hazardous drug on the external surface of a single vial and 1.5 µg of hazardous drug on the plastic overwrap of a 25-vial package.29 Connor and colleagues measured 12 µg (cisplatin), 69 µg (cyclophosphamide), and 630 µg (5-fluorouracil) on vials in a multicenter study.7 Fleury-Souverain and colleagues detected traces of cytotoxic drugs different from the active ingredient in the vial on 35% of vials analyzed,31 and Schierl and colleagues reported cross-contamination on 54% of the vials tested.30 Connor, FleurySouverain, Schierl, and their respective colleagues all noted a reduction in contamination on the external surface of vials coated in plastic shrink-wrap.7,30,31 These studies highlight the imporContinued on page 29

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ONCOLOGY PHARMACY SAFETY Table 2

US Studies of Surface and Drug Vial Contamination With Hazardous Drugs

Authors

Study Description

Drugs Evaluated

Summary

McDevitt et al, 19933

Evaluated incidence and extent of contamination for both surfaces and air at 1 hospital’s outpatient cancer center

Surface Samples 18% pharmacy surfaces + for CP 14% nursing surfaces + for CP

Connor et al, 19994

Evaluated surface contamination in 6 cancer treatment centers

CP, IF, 5-FU

Connor et al, 20025

Evaluated surface conCP, IF, 5-FU tamination prior to and every 4 weeks after the implementation of a CSTD in a highvolume outpatient cancer center. CSTD used for compounding CP and IF. Standard compounding technique used for 5-FU as a control group

Air Samples 3/73 air samples + for CP 75% of pharmacy + for CP, IF, or 5-FU 65% of administration area + for CP, IF, or 5-FU

Max Contamination Values (ng/cm2 for surface; ng/L for urine) Comment CP surface = 35 ng/cm2

CP air = 0.407 µg/m3 CP = 65.66 ng/cm2 IF = 459.0 ng/cm2 5-FU = 208.59 ng/cm2

Almost 100% of samples had detectable surface contaminated with CP, IF, and/ or 5-FU

Levels of contamination were higher in pharmacy samples. Site with the highest compounding volume had considerably more contamination than other sites The pharmacy underwent construction in which the BSCs and other equipment were replaced, yet after 2 months of construction and cleaning, some areas of the floor were still positive for 5-FU and IF. CP spill was still detected 6 months later on the floor

There was a decline in the level of contamination for CP and IF over the 24-week periods of CSTD use, with a few spikes in contamination throughout the study Compounding with 5-FU did not include the use of a CSTD, and the level of 5-FU contamination increased during the study period There was a CP spill at the beginning of the study, and the elevated CP contamination from the spill was still detected 6 months later

Wick et al, 20036

Connor et al, 20057

Surface sampling and employee urine analysis performed preimplementation and 6 months postimplementation of CSTD in hospital pharmacy

CP, IF

Data from 3 studies: CP, IF, 5-FU, Cis Examined contamination of chemotherapy drug vials and evaluated a new vial-cleaning technique in a multicenter study

Baseline 17/17 surfaces + for CP 11/17 surfaces + for IF 6/8 employee urine + for CP 2/8 employee urine + for IF 6 Months Post-CSTD Implementation 7/21 surfaces + for CP 15/21 surfaces + for IF 0/8 employee urine + for CP 0/8 employee urine + for IF 5-FU Vials 7% (4/54 vials) + for 5-FU 5-FU mean = 209,280 ng/vial 5-FU max = 630,560 ng/vial CP Vials 89% (48/54 vials) + for CP CP median = 1468 ng/vial CP max = 69,819 ng/vial IF Vials (n=36) Variability between lots 100% (6/6) + for IF in one lot # IF mean = 1660 ng/vials 2 lots had no IF detected 3 lots had a mix of + and –

Max Values Pre-CSTD Surface CP >100 ng/cm2 IF >100 ng/cm2 Employee Urine CP >100 ng/L IF >100 ng/L

IF was last mixed more than 3 weeks prior to the baseline urine analysis, of which 25% of staff were positive for IF uptake

Post-CSTD CP = 80 ng/cm2 IF >100 ng/cm2 Max Contamination on Vials 5-FU = 630,560 ng/vial CP = 69,819 ng/vial IF = 1705 ng/vial Cis = 256 ng/vial

Vial contamination was widespread, with large variability between lots for certain medications. This study includes a summary table of European studies of vial contamination

Cis Vials (n=368) “Almost all vials” + for Cis 1st Cleaning Technique CP median = 32 ng/vial CP max = 245 ng/vial Table 2 continued on page 28

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ONCOLOGY PHARMACY SAFETY Table 2 continued from page 27

Table 2

US Studies of Surface and Drug Vial Contamination With Hazardous Drugs (continued )

Authors

Study Description

Drugs Evaluated

Summary

Max Contamination Values (ng/cm2 for surface; ng/L for urine) Comment

2nd Cleaning Method CP median = 7 ng/vial CP max = 79 ng/vial

Connor et al, 20057 (continued)

2nd Cleaning Method Plus Plastic Wrap on Vial CP median = 4 ng/vial CP max = 146 ng/vial Harrison et al, 20068

CP, 5-FU Evaluated surface contamination in 3 pharmacies for CP and 5-FU to compare 3 methods for compounding HDs: standard HD techniques while within a BSC for both CP and 5-FU; the addition of a CSTD to compounding within a BSC for CP only; use of a CSTD while compounding on a counter for 5-FU (not within a BSC)

8% (28/342) surfaces + for 5-FU throughout all phases of the study and all sites

CP = 35.72 ng/cm2 5-FU = 18.8 ng/cm2

Authors concluded that due to the high incidence of CP surface contamination (95%) compared with the overall incidence of 5-FU surface contamination (8%), it is difficult to assess whether compounding 5-FU on a counter using a CSTD yields comparable incidence and magnitude of surface contamination compared with compounding CP in a BSC with or without the use of a CSTD

Surface Max CP = 0.037 ng/cm2 IF = 0.737 ng/cm2

CSTD reduced the incidence of surface contamination and percentage of employees with CP detected in their urine. However, despite these reductions, a noncompounding employee had both IF and CP detected in their urine

Incidence of surface samples positive for 5-FU was significantly less during the control phase in which CSTDs were used, despite that 5-FU was compounded on a counter and not in a BSC 95% (324/342) surface samples + for CP Both incidence of contaminated surfaces and level of contamination were decreased during the phase where CSTDs were used

Authors note that compounding outside of a BSC was limited to immediate-use sterile products when a proper facility was not available Nyman et al, 20079

Evaluation of new cancer CP, IF facility that has exclusively used a CSTD for 6 months, plus data for 6 months of CSTD at old facility. Surface sampling of pharmacy, nursing, and patient areas; urine sampling of employees including pharmacists, technicians, and nurses

Connor et al, 20102

Sessink et al, 201010

Surface sampling and employee urine analysis from 7 pharmacies and 10 nursing/patient areas at 3 university-based hospitals

CP, IF, paclitaxel, 5-FU, cytarabine

Surface contamination evaluated in 22 US hospital pharmacies pre- and post-CSTD implementation

CP, IF, 5-FU

Prior to Implementation 71% (5/7) employee urine + CP 6 Months Post-CSTD at Old Facility 33% (7/21 surfaces) + for CP 71% (15/21 surfaces) + for IF 6 Months After Opening New Facility, CSTD Used Exclusively 21% (7/34 surfaces) + for CP 12% (4/34 surfaces) + for IF 9% (1/11) employee urine + CP 9% (1/11) employee urine + IF (+ employee was not involved in compounding) IF detected on floor in patient room 60% (86/143 surfaces) + for HD 32% surfaces + for >1 HD 40% surfaces + for CP 3/68 employee urine + for HD

Surface Max CP = 143 ng/cm2 5-FU = 910 ng/cm2 Max not provided for other HDs

HD refers to all hazardous drugs tested for

Employee Urine CP = 0.079 ng/L Paclitaxel = 0.01 ng/L

Surface Samples Pre-CSTD Implementation 78% + for CP 54% + for IF 33% + for 5-FU

Surface Max CP = 158.0 ng/cm2 IF = 14.19 ng/cm2 5-FU = 228.7 ng/cm2

CSTD reduced incidence and magnitude of surface contamination of the 3 drugs tested

Surface Sampling Post-CSTD 68% + for CP 45% + for IF 20% + for 5-FU Reduction in quantity of contamination detected

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ONCOLOGY PHARMACY SAFETY Table 2

US Studies of Surface and Drug Vial Contamination With Hazardous Drugs (continued ) Max Contamination Values (ng/cm2 for surface; ng/L for urine) Comment

Authors

Study Description

Drugs Evaluated

Summary

Sessink et al, 201311

Evaluated surface contamination in pre- and post-CSTD implementation in 30 hospitals

Pre-CSTD Implementation 83% for all surfaces Median CP = 0.22 ng/cm2

Compared 2 brands of CSTDs for effects on surface contamination at a hospital cancer center. CSTD #1 in place prior to study. Facility decontaminated after staff had adjustment period to CSTD #2, and new baseline created

CP, 5-FU

Clark and Sessink, 201312

CP max = 44.17 ng/cm2

Post-CSTD Implementation 80% for all surfaces Median CP = 0.03 ng/cm2 CSTD #1 (in place prior to study) 7/12 samples + for CP (max of 1.33 ng/ cm2) No 5-FU detected

CSTDs significantly reduced the concentration of surface contamination, but use of CSTDs showed little to no change in the incidence of contaminated surfaces

CP = 1.33 ng/cm2 5-FU = 0.40 ng/cm2

Start CSTD #2 Then Decontamination With NaOH 7/12 samples + for CP (CP max = 0.09 ng/cm2) 1/12 samples + 5-FU (5-FU max = 0.040 ng/cm2) CSTD #2 (1-year post) No CP detected No 5-FU detected

Abbreviations: BSC, biological safety cabinet; Cis, cisplatin; CP, cyclophosphamide; CSTD, closed-system transfer device; 5-FU, 5-fluorouracil; HD, hazardous drug; IF, ifosfamide; max, maximum; –, negative; +, positive.

Chemotherapy: Every Step You Take… Continued from page 26 tance of wearing gloves during handling of vials when performing noncompounding activities such as unloading shipping containers and managing stock. Vials become contaminated during manufacturing from lack of cleaning, incomplete cleaning, improper vial washing, contamination by broken vials during transportation, or contact with contaminated surfaces or employees’ hands.7 Globally, manufacturers must improve their procedures to provide the healthcare industry with products free from external contamination. If the external surfaces of drug vials are contaminated, the result is a continuous source of contamination, and it can be assumed that hazardous drug contamination can be spread to pharmacy surfaces, storage shelves, and bins, as well as employees’ hands. In light of external drug vial contamination, healthcare workers should consider the process of cleaning compounding supplies prior to entry into a cleanroom. USP Chapter 797 recommends sterile 70% isopropyl alcohol (IPA) delivered from a spray bottle or other suitable delivery method to compounding supplies prior to entering the buffering room; then transferred to a clean and properly sanitized metal cart.26 However, the vials themselves should not be sprayed directly with alcohol, as this may produce an aerosol of the drug that could lead to inhalation, and excess contaminated disinfecting solution could then drip off the vials, thus transferring

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Christine Roussel, PharmD, BCOP

Thomas H. Connor, PhD

contamination to other surfaces. The best practice is to spray the wipe materials and then use them to wipe the vials. The contaminated wipes should then be disposed of as hazardous waste. Alcohol solubilizes hazardous drugs and is not known to decontaminate drugs through chemical degradation like bleach does. The use of alcohol to sanitize areas where chemotherapy is compounded has been shown to spread contamination.28 Therefore, even cleaning procedures for these vials must be thoroughly evaluated to minimize the inadvertent spread of contamination.

a direct relationship with worker uptake of hazardous drugs, it is important to think about how workplace contamination leads to systemic exposure. Dermal absorption is a principal route of chemical exposure for nonvolatile chemicals, often exceeding respiratory exposure.33 Nonvolatile antineoplastic drugs can persist for several weeks on work surfaces, functioning as sources of worker contamination for long periods of time.5,6 In addition to a chemical’s local effects on the skin, including contact dermatitis and irritation, skin exposure to chemicals can function as a pathway to the bloodstream for hazardous chemicals to enter the body. The skin has 2 basic layers, the epidermis and the dermis, providing protection against chemical absorption.33

Skin Absorption of Hazardous Drugs Although the magnitude of surface contamination has yet to be proven to have

Chemicals can diffuse passively across the stratum corneum, reaching the blood vessels in the dermis where significant dermal exposure can produce detectable blood levels. The rate and magnitude of skin absorption can be affected by many occupational factors. Organic solvents such as alcohol, as found in hand sanitizer, can “defat” the skin, damaging the external layer and allowing increased chemical absorption. Wearing gloves for extended periods of time can increase the water content of the stratum corneum, both from perspiration and trapping normal skin water evaporation, thus increasing absorption of hydrophilic chemicals. Frequent hand washing with strong detergents throughout the workday can also lead to skin damage in healthcare settings. Increased moisture, skin irritation, damage from exposure to harsh chemicals, small cuts, or skin tears alter the physical barrier function of the skin and allow for increased chemical permeability. If chemical penetration did occur through a glove, due to prolonged contact of the chemical on the external surface or from a tear in the glove, the glove would function as an occlusive dressing, increasing chemical absorption through increasing temperature, friction, and contact between the glove and skin. Dermal uptake has been postulated to be the major route of exposure to antineoplastic drugs in workplace settings.34-37 Inhalation appears to be the second Continued on page 30

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ONCOLOGY PHARMACY SAFETY

Chemotherapy: Every Step You Take… Continued from page 29 most common route, with oral (handto-mouth) and accidental injection with sharps less common. Although a few antineoplastic drugs have been shown to have the ability to produce vapors, most antineoplastic drugs have very low vapor pressures.38,39 Numerous studies from the United States and countries around the world have documented surface contamination with antineoplastic drugs in areas where they are used.40 Uptake of Hazardous Drugs As stated previously, it is difficult to directly relate worker exposure to surface contamination with hazardous drugs. However, Connor and colleagues were able to detect cyclophosphamide in the urine of 2 pharmacists working in an area that had high levels of surface contamination with this drug.2 Both pharmacy and nursing personnel have been shown to have measurable amounts of antineoplastic drugs in their urine as a result of working where the drugs are handled. As with wipe samples, analysis is available for determining a battery of drugs in the urine of healthcare workers. Interestingly, in some studies, specific antineoplastic drugs have been measured in the urine of workers not directly involved with their preparation, suggesting indirect or incidental exposure from contact with contaminated surfaces. Uptake of these drugs by pharmacists and nurses has been well documented in more than 50 studies in the world literature.40 Analysis of the urine for hazardous drugs is usually done strictly on a research basis, as there are no standards for the amount of drugs in the urine and what the consequences might be concerning workers’ health. However, it does indicate that the workplace environment is contaminated with the drugs or that the worker may not have good technique, indicating the need for better engineering controls and cleaning procedures of the pharmacy and/or retraining of the worker. Although findings of hazardous drugs can be alarming to the worker, the OSHA Technical Manual states, “Results of biologic monitoring which have been voluntarily conducted by an employer should not be used as a basis for citations. In fact OSHA promotes the use of biologic monitoring of employees as a useful means of minimizing exposure and for evaluating effectiveness of control measures.”33 Summary Surface contamination with hazardous drugs, in particular, antineoplastic drugs, is usually present in pharmacies and all areas where the drugs are handled. Most work surfaces and drug vials have been demonstrated to be contaminated with antineoplastic drugs in numerous stud-

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Table 3 Laboratories That Test for Hazardous Drugs and Some Commonly Tested Drugs Laboratory

Drugs

Exposure Control B.V. www.exposurecontrol.nl

Cyclophosphamide, ifosfamide, 5-fluorouracil, methotrexate, etoposide, mitomycin C, platinum-containing compounds

RJ Lee Group www.rjlg.com

Cyclophosphamide, ifosfamide, 5-fluorouracil, methotrexate, cisplatin, carboplatin, oxaliplatin

ChemoGlo, LLC www.chemoglo.com

Cyclophosphamide, ifosfamide, 5-fluorouracil, paclitaxel, docetaxel

BVNA www.us.bureauveritas.com/ labs/ChemoAlert

Cyclophosphamide, ifosfamide, 5-fluorouracil, paclitaxel, methotrexate, doxorubicin, daunorubicin, idarubicin, cisplatin, carboplatin, cytarabine, imatinib, capecitabine

ies from the United States and internationally. Although other routes (inhalation, oral, needlesticks) may be factors in uptake of these drugs, the dermal route appears to be the most common. Uptake has been well documented by the presence of some antineoplastic drugs in the urine of healthcare workers. A prospective gap analysis of the work environment and compounding process, including surface analysis for hazardous drugs, is a good

While appropriate facility design and proper equipment are critical, so is a strong employee training program with continuing education.

starting point. While appropriate facility design and proper equipment are critical, so is a strong employee training program with continuing education. Components of employee education should include a hazard communication document, with didactic and demonstrative components and spill kit training. Access to proper personal protective equipment and a “safety culture” can promote employee compliance.41 l Disclaimers The findings and conclusions of this presentation have not been formally disseminated by NIOSH and should not be construed to represent any agency determination or policy. Mention of company names or products does not constitute endorsement by the National Institute for Occupational Safety and Health.

References

1. Roussel C, Connor TH. Chemotherapy and pharmacy: a toxic mix? Oncol Pharmacist. 2013;6:32-33. 2. Connor TH, DeBord G, Pretty JR, et al. Evaluation of antineoplastic drug exposure of health care workers at three university-based US cancer centers. J Occup Environ Med. 2010;52:1019-1027. 3. McDevitt JJ, Lees PS, McDiarmid MA. Exposure of hospital pharmacists and nurses to antineoplastic agents. J Occup Med. 1993;35:57-60. 4. Connor TH, Anderson RW, Sessink PJ, et al. Surface contamination with antineoplastic agents in six cancer treatment centers in the United States and Canada. Am J Health Syst Pharm. 1999;56:1427-1432. 5. Connor TH, Anderson RW, Sessink PJ, et al. Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and ifosfamide in an i.v. admixture area. Am J Health Syst Pharm. 2002;59:68-72. 6. Wick C, Slawson MH, Jorgenson JA, et al. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health Syst Pharm. 2003;60:2314-2320. 7. Connor TH, Sessink PJ, Harrison BR, et al. Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: results of three studies. Am J Health Syst Pharm. 2005;62:475-484. 8. Harrison BR, Peters BG, Bing MR. Comparison of surface contamination with cyclophosphamide and fluorouracil using a closed-system drug transfer device versus standard preparation techniques. Am J Health Syst Pharm. 2006;63:1736-1744. 9. Nyman H, Jorgenson J, Slawson MH. Workplace contamination with antineoplastic agents in a new cancer hospital using a closed-system drug transfer device. Hosp Pharm. 2007;42:219-225. 10. Sessink PJ, Connor TH, Jorgenson JA, et al. Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device. J Oncol Pharm Pract. 2010;17:39-48. 11. Sessink PJM, Trahan J, Coyne JW. Reduction in surface contamination with cyclophosphamide in 30 US hospital pharmacies following implementation of a closed-system drug transfer device. Hosp Pharm. 2013;48:204-212. 12. Clark BA, Sessink PJM. Use of a closed system drug-transfer device eliminates surface contamination with antineoplastic agents. J Oncol Pharm Pract. 2013;19:99-104. 13. Anderson RW, Puckett WH, Dana WJ, et al. Risk of handling antineoplastic agents. Am J Hosp Pharm. 1982;39:1881-1887. 14. Vyas N, Yainnakis D, Turner A, et al. Occupational exposure to anti-cancer drugs: a review of effects of new technology [published online ahead of print August 22, 2013]. J Oncol Pharm Pract. doi: 10.1177/1078155213498630. 15. Seger AC, Churchill WW, Keohane CA, et al. Impact of robotic antineoplastic preparation on safety, workflow, and costs. J Oncol Pract. 2012;8:344-349. 16. Schierl R, Bohlandt A, Nowak D. Guidance values for surface monitoring of antineoplastic drugs in German pharmacies. Ann Occup Hyg. 2009;53:1-9. 17. Siderov J, Kirsa S, McLauchlan R. Reducing workplace cytotoxic surface contamination using a closed-system drug transfer device. J Oncol Pharm Pract. 2010;16:19-25. 18. Yoshida J, Koda S, Nishida S, et al. Association between occupational exposure levels of antineoplastic drugs and work environment in five hospitals in Japan. J Oncol Pharm Pract. 2010;17:29-38. 19. Davis J, McLauchlan R, Connor TH. Exposure to

hazardous drugs in healthcare: an issue that will not go away. J Oncol Pharm Pract. 2011;17:9-13. 20. Turci R, Minola C, Sottani C, et al. Occupational exposure to antineoplastic drugs in seven Italian hospitals: the effect of quality assurance and adherence to guidelines. J Oncol Pharm Pract. 2011;17:320-332. 21. Chu WC, Hon C-Y, Danyluk Q, et al. Pilot assessment of the antineoplastic drug contamination levels in British Columbia hospitals pre- and post-cleaning. J Oncol Pharm Pract. 2012;18:46-51. 22. Kopp B, Schierl R, Nowak D. Evaluation of working practices and surface contamination with antineoplastic drugs in outpatient oncology health care settings. Int Arch Occup Environ Health. 2013;86:47-55. 23. Howlader N, Noone AM, Krapcho M, et al, eds. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute. Bethesda, MD, http://seer.cancer. gov/csr/1975_2010/, based on November 2012 SEER data submission, posted to the SEER website, April 2013. 24. World Health Organization. WHO cancer control programme. http://www.who.int/cancer/en/. Accessed September 10, 2013. 25. Turci R, Sottani C, Spagnoli G, et al. Biological and environmental monitoring of hospital personnel exposed to antineoplastic agents: a review of analytical methods. J Chromatog B. 2003;789:169-209. 26. US Pharmacopeial Convention. USP revised chapter (797) pharmaceutical compounding—sterile preparations. http://www.pbm.va.gov/linksother resources/docs/USP797PharmaceuticalCompounding SterileCompounding.pdf. Accessed September 10, 2013. 27. Centers for Disease Control and Prevention. NIOSH Publications and Products. Preventing occupational exposure to antineoplastic and other hazardous drugs in health care settings. http://www.cdc.gov/ niosh/docs/2004-165/. Accessed September 10, 2013. 28. Sessink PJ, Anzion RB, Van den Broek PH, et al. Detection of contamination with antineoplastic agents in a hospital pharmacy department. Pharm Weekbl Sci. 1992;14:16-22. 29. Favier B, Gilles L, Ardiet C, et al. External contamination of vials containing cytotoxic agents supplied by pharmaceutical manufacturers. J Oncol Pharm Pract. 2003;9:15-20. 30. Schierl R, Herwig A, Pfaller A, et al. Surface contamination of antineoplastic drug vials: comparison of unprotected and protected vials. Am J Health Syst Pharm. 2010;67:428-429. 31. Fleury-Souverain S, Nussbaumer S, Mattiuzzo M, et al. Determination of the external contamination and cross-contamination by cytotoxic drugs on the surfaces of vials available on the Swiss market [published online ahead of print May 14, 2013]. J Oncol Pharm Pract. doi: 10.1177/1078155213482683. 32. Naito T, Osawa T, Suzuki N, et al. Comparison of contamination levels on the exterior surfaces of vials containing platinum anticancer drugs in Japan. Biol Pharm Bull. 2012;35:2043-2049. 33. US Department of Labor, Occupational Safety & Health Administration. OSHA Technical Manual; Section II: Chapter 2, Occupational Skin Exposure. https://www.osha.gov/dts/osta/otm/otm_ii/otm_ii_2. Updated June 24, 2008. Accessed September 10, 2013. 34. Kromhout H, Hoek F, Uitterhoeve R, et al. Postulating a dermal pathway for exposure to antineoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys. Ann Occup Hyg. 2000;44:551-560. 35. Fransman W, Vermeulen R, Kromhout H. Occupational dermal exposure to cyclophosphamide in Dutch hospitals: a pilot study. Ann Occup Hyg. 2004;48:237-244. 36. Fransman W, Vermeulen R, Kromhout H. Dermal exposure to cyclophosphamide in hospitals during preparation, nursing and cleaning activities. Int Arch Occup Environ Health. 2005;78:403-412. 37. Fransman W, Huizer D, Tuerk J. Inhalation and dermal exposure to eight antineoplastic drugs in an industrial laundry facility. Int Arch Occup Environ Health. 2007;80:396-403. 38. Connor TH, Shults M, Fraser MP. Determination of the vaporization of solutions of mutagenic antineoplastic agents at 23 and 37 degrees C using a desiccator technique. Mutat Res. 2000;470:85-92. 39. Kiffmeyer TK, Kube C, Opiolka S, et al. Vapor pressures, evaporation behavior and airborne concentrations of hazardous drugs: implications for occupational safety. Pharm J. 2002;268:331-337. 40. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Occupation exposure to antineoplastic agents. http://www.cdc.gov/niosh/topics/antineoplas tic/. Updated April 13, 2012. Accessed September 10, 2013. 41. Polovich M, Clark PC. Factors influencing oncology nurses’ use of hazardous drug safe-handling precautions. Oncol Nurs Forum. 2012;39:E299-E309.

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CANCER CENTER PROFILE

The University of Arizona Cancer Center Continued from cover Programs at the University of Arizona Cancer Center cover cancer biology, imaging technology, development of therapeutics, and cancer prevention and control. More recently, the center has added a biobehavioral and social sciences program aimed at improving the delivery and quality of care for patients and providing support to them throughout the continuum of cancer care. The Oncology Nurse-APN/PA spoke with Beth High, RN, BSN, OCN, CBCN, CBPN-IC, Breast Oncology Nurse Coordinator, about her role at the University of Arizona Cancer Center in Tucson.

Can you describe the various duties that come with your title? Beth High (BH): Although I am a certified Breast Navigator, my job title is Nurse Coordinator. Basically, the roles for a navigator and a coordinator are similar, but in our institution, instead of meeting the patient at the time of diagnosis and navigating her through the cancer continuum, I meet the patient when she has her initial visit with the medical oncologist. As Nurse Coordinators on the breast medical oncology team, my colleague, Magdalena, and I typically attend the first appointment with the patient when the oncologist discusses systemic therapy. Knowing the treatment plan helps us to provide education on therapies, side effects, and what to expect in the future. Our patients can put a face to their nurse’s name when they call on the phone with questions and concerns. One of our main roles is Telephone Triage for patients needing symptom management. Our NP [nurse practitioner] is available to us for prescribing medications and for advice on complicated issues. We also coordinate with personnel in many other services such as pharmacy, social work, nutrition, pain and palliative care, survivorship clinic, and hospice, to name a few. A fair portion of our time is spent assisting patients with FMLA [Family and Medical Leave Act] and disability documents and, unfortunately, insurance issues. We are lucky to have an associate who is great at obtaining prior authorizations! What is the approach to cancer care at your institution? BH: Our top-notch academic Breast Health program is not all under one roof, but we function as a well-oiled multidisciplinary machine! When a patient is at the Imaging Center, she is assisted by an expert nurse who guides her through the diagnostic process of imaging and biopsy. A patient with a cancer diagnosis is then

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handed off to a nurse experienced in breast surgery. That nurse may collaborate with the nurse who is knowledgeable about reconstruction. I encounter the patient in the neoadjuvant or adjuvant setting and continue to follow her through systemic treatments and beyond. If radiation therapy is part of the treatment plan, patients will be cared for by a nurse certified in radiation oncology. Communication between the highly specialized Nurse Coordinators is essential for keeping patients on track during each phase of cancer care. Additionally, I frequently engage with the infusion nurses when their assessment uncovers an unmet need or problem that I can facilitate solving. Don’t let me forget to mention the research nurses who coordinate our patients on

deal from the oncologists, the patients, and especially Katy Clarke, our Breast Team NP. I also took advantage of the online education courses offered by ONS [Oncology Nursing Society]. In September 2012, I embarked on a big trip that started in Phoenix, where I attended the Academy of Oncology Nurse Navigators Annual Conference. From there I flew to Atlanta for the EduCare, Inc. 4-day Breast Health Navigator training program, which was valuable and extremely worthwhile. The last leg of my journey brought me to Chicago, where I sat for and passed the National Consortium of Breast Centers’ certification exam for Breast Patient Navigator in both Imaging and Cancer. I would like to add that the trip would not have been possible for

“Communication between the highly specialized Nurse Coordinators is essential for keeping patients on track during each phase of cancer care.” Beth High, RN, BSN, OCN, CBCN, CBPN-IC

clinical trials. It takes the whole team to ensure that our patients have the best possible outcome!

What was the path that led to your present career? BH: After I graduated from nursing school, I joined the Air Force because I was offered a 6-month internship in obstetric nursing, which was the field I was interested in pursuing. Everything was great until, 6 years later, when my pilot husband and I were stationed in Germany and the first Gulf War was declared. I was pregnant at the time, so I opted to leave military service. I did not return to my nursing career until 16 years later when my kids decidedly no longer needed their mama. This is one of the really great things about nursing: you can always go back! My goal after taking the Nursing Refresher course was to work in women’s health. Eventually, I found a job at the University of Arizona Women’s Cancer Center in a position that did not involve much patient care. About a year later, I was recruited by Dr Alison Stopeck, Director of the Clinical Breast Cancer Program, to work in her clinic as a Nurse Coordinator. The prospect of working with patients again appealed to me; however, knowing very little about breast cancer, it required that I hit the books. It’s been 2 years since I started, and I have learned a great

me financially without help from the ONS Foundation. I am very grateful to have been the recipient of a Pearl Moore education grant, and I would encourage my fellow oncology nurses to explore all the resources that ONS has to offer. And then finally, a few months ago, I became an ONS Certified Breast Care Nurse.

What are you excited about right now in the field of oncology? BH: I am excited to be the captain of our team for the American Cancer Society “Making Strides” event in Tucson on October 27. National Breast Cancer Awareness Month is the perfect opportunity for those of us who care for breast cancer patients to get together outside of work and show our support for the strong women facing this disease. What are some of the challenges of your job? BH: While it’s great that so much progress is being made in breast cancer treatments, like TDM-1 and pertuzumab, it is a challenge to keep up with all the new developments. Plus, there is so much about breast cancer in the general news. Angelina Jolie stirred up a lot of business for our genetic counselors! I try to read something every day in order to keep up with my patients. For the most part, breast cancer

patients are a savvy bunch. Recently, a patient read about long-term use of calcium channel blockers being related to increased risk of breast cancer. She wanted to know if she should stop taking her blood pressure medication. Much to my surprise, when I looked it up, I found out she was referring to a legitimate study reported in JAMA [Journal of the American Medical Association]. The author recommended confirmation of the results by other studies before anyone changed clinical practice, so I encouraged the patient to stay on her antihypertensive therapy and let her primary care provider know about the study. Another patient read about iodine deficiency leading to breast cancer. I learned that researchers are looking at iodine to see if it can be used for prevention. Patients teach me something every day and keep me on my toes!

What advice would you give to a nurse or nurse practitioner entering the field? BH: I would say join ONS! You can learn only so much on the job. The ONS online course, “Site-Specific Cancer Series: Breast Cancer,” is about the best way I can think of to get detailed information about the entire spectrum of breast care (CEUs too!). As an added benefit to your ONS membership, you can sign up for the ONS Special Interest Group for breast care. Read the breast cancer information on the NCI, ACS [American Cancer Society], and NCCN [National Comprehensive Cancer Network] websites. Another great site aimed at patients is Breastcancer.org. I go there again and again for information. I especially recommend the downloadable pamphlet “Your Pathology Report” from that site. What would you be doing if you were not a breast cancer nurse? BH: I would definitely stay in oncology: so many cancers, so much to learn, so many patients to help. l

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