APRIL 2012, VOL 5, NO 2 by The Oncology Nurse

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APRIL 2012

www.TheOncologyNurse.com

VOL 5, NO 3

THE FUTURE OF NURSING

CANCER CENTER PROFILE

Ohio State University Wexner Medical Center Oncology Research and Personalized Healthcare

A New Look at Nursing Education and Practice By Catherine Bishop, DNP, NP, AOCNP Hematology/Oncology Nurse Practitioner, Lansdowne, Virginia

he future of nursing education and practice was outlined in a landmark report published in October 2010 by the Institute of Medicine (IOM). The report was a 2-year joint effort between the Robert Wood Johnson Foundation and the IOM entitled The Future of Nursing: Leading Change, Advancing Health.1 The committee mem-

bers who proposed future recommendations were distinguished leaders in nursing, medicine, healthcare administration, and business. In the final report there were 4 key issues (Table 1) and 8 recommendations (Table 2) that reflected the need for nurses to continue their formal education and expand current Continued on page 32

PERSONALIZED MEDICINE IN ONCOLOGY Carli Greenfield, ACNP; Lisa Merritt, RN; Gisele Rieser, RN; Megan Sell, CNP; and Courtney Bakan, research assistant (left to right) at a fundraiser for the Multiple Myeloma Opportunities for Research & Education organization.

he Ohio State University (OSU) Wexner Medical Center, located in Columbus, Ohio, is one of the largest medical centers in the country. As the only academic medical center in central Ohio, it includes the College of Medicine, more than a dozen research centers, and 20 core laboratories, as well as 6 hospitals. The OSU Wexner Medical Center identifies 6 signature programs— Cancer, Critical Care, Heart, Imaging, Neurosciences, and Transplantation—as key elements in its provision of science-based and individually tailored patient care. Since the 2006 opening of the Biomedical Research Tower, the OSU Wexner Medical Center has become a national leader in the developing field of personalized healthcare, focusing on each individual’s unique biology, behavior, and environment.

Continued on page 12

Precision Medicine: Applying Predictive and Prognostic Indices to Risk-Adapted Treatment Selection By Sandra Kurtin, RN, MS, AOCN, ANP-C The University of Arizona Cancer Center, Tucson, Arizona

he shift from dose-intense standard chemotherapy to therapies targeting specific signaling pathways, molecular targets, or elements of the tumor microenvironment presents a number of challenges to the oncology professional and the patient. Cancer diagnosis and treatment requires precision in the diagnostic evaluation (asking

all the critical diagnostic questions at the time of diagnosis), comprehensive assessment of the individual patient (personal attributes that place a patient at risk), and consideration of a life-span approach (the concept of a marathon as opposed to a sprint). Precision medicine allows for the best evidence-based approach to treatment for each individual patient, Continued on page 38

NEWS BRIEFS

CYP2D6 Genotyping Fails to Predict Effectiveness of Tamoxifen By Alice Goodman

ccording to 2 large breast cancer trials, CYP2D6 genotyping was not predictive of the effectiveness of tamoxifen in postmenopausal women. Thus, the results of these studies are not generalizable to premenopausal women. CYP2D6 genotyping has been a focus

INSIDE Your FAQs…Answered!

ComplimentArY Ce

of research interest, but studies have been inconclusive as to the value of testing. In theory, certain CYP2D6 genotypes and phenotypes would be associated with breast cancer outcomes on treatment with tamoxifen; that is, tamoxifen would be less effective in

.....

nutrition with KAren

the

Is it safe for women at risk for breast cancer–related lymphedema to lift weights? ..........

Considerations in Multiple Myeloma Ask the Experts: Newly Diagnosed Patients GenetiC CounselinG

.......

How Old Is Too Old for Genetic Testing?

Spring Into Cruciferous Vegetables

.....

ONE Award

Vote Now for Your Choice

www.TheOncology Nurse.com/award See Our 4 Finalists on Page 14

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NOW APPROVED FOR SUBCUTANEOUS ADMINISTRATION

Subcutaneous VELCADE Demonstrated Efficacy Consistent With IV for the Primary Endpoint RESPONSE RATES† IN RELAPSED MULTIPLE MYELOMA (MM): SUBCUTANEOUS AND IV AT 24 WEEKS (AFTER 8 CYCLES) VELCADE±dexamethasone

AT 12 WEEKS (AFTER 4 CYCLES) Single-agent VELCADE® (bortezomib)

53% 51%

43% 42%

11% 12%

7% 8% ORR Primary Endpoint

SC (n=148) IV (n=74)

ORR

▼ The study met its primary non-inferiority objective that single-agent subcutaneous VELCADE retained at least 60% of the overall response rate after 4 cycles relative to single-agent IV VELCADE SUBCUTANEOUS VS IV TRIAL: a non-inferiority, phase 3, randomized (2:1), open-label trial compared the efficacy and safety of VELCADE administered subcutaneously (n=148) with VELCADE administered intravenously (n=74) in patients with relapsed MM. The primary endpoint was overall response rate at 4 cycles. Secondary endpoints included response rate at 8 cycles, median TTP and PFS (months), 1-year overall survival (OS), and safety. *INDICATIONS: VELCADE is indicated for the treatment of patients with multiple myeloma. VELCADE is indicated for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy. †

Responses were based on criteria established by the European Group for Blood and Marrow Transplantation.1

VELCADE IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. VELCADE is contraindicated for intrathecal administration.

WARNINGS, PRECAUTIONS AND DRUG INTERACTIONS ▼ Peripheral neuropathy, including severe cases, may occur – manage with dose modification or discontinuation. Patients with preexisting severe neuropathy should be treated with VELCADE only after careful risk-benefit assessment ▼ Hypotension can occur. Use caution when treating patients receiving antihypertensives, those with a history of syncope, and those who are dehydrated ▼ Closely monitor patients with risk factors for, or existing heart disease ▼ Acute diffuse infiltrative pulmonary disease has been reported ▼ Nausea, diarrhea, constipation, and vomiting have occurred and may require use of antiemetic and antidiarrheal medications or fluid replacement ▼ Thrombocytopenia or neutropenia can occur; complete blood counts should be regularly monitored throughout treatment ▼ Tumor Lysis Syndrome, Reversible Posterior Leukoencephalopathy Syndrome, and Acute Hepatic Failure have been reported

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IN ALL INDICATIONS*

Difference in Incidence of Peripheral Neuropathy With Subcutaneous VELCADE PERIPHERAL NEUROPATHY (PN) IN RELAPSED MM: SUBCUTANEOUS AND IV GRADE ≥3

SC (n=147) IV (n=74)

16% ALL GRADES

38% 53% ▼ Starting VELCADE® (bortezomib) subcutaneously may be considered for patients with preexisting PN or patients at high risk for PN. Patients with preexisting severe neuropathy should be treated with VELCADE only after careful risk-benefit assessment ▼ Treatment with VELCADE may cause PN that is predominantly sensory. However, cases of severe sensory and motor PN have been reported. Patients should be monitored for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain, or weakness ▼ Patients experiencing new or worsening PN during therapy with VELCADE may require a decrease in the dose, a less-dose-intense schedule, or discontinuation. Please see full Prescribing Information for dose modification guidelines for PN

WARNINGS, PRECAUTIONS AND DRUG INTERACTIONS CONTINUED ▼ Women should avoid becoming pregnant while being treated with VELCADE. Pregnant women should be apprised of the potential harm to the fetus ▼ Closely monitor patients receiving VELCADE in combination with strong CYP3A4 inhibitors. Concomitant use of strong CYP3A4 inducers is not recommended

ADVERSE REACTIONS Most commonly reported adverse reactions (incidence ≥30%) in clinical studies include asthenic conditions, diarrhea, nausea, constipation, peripheral neuropathy, vomiting, pyrexia, thrombocytopenia, psychiatric disorders, anorexia and decreased appetite, neutropenia, neuralgia, leukopenia, and anemia. Other adverse reactions, including serious adverse reactions, have been reported Please see Brief Summary for VELCADE on next page. For Patient Assistance Information or Reimbursement Assistance, call 1-866-VELCADE (835-2233), Option 2, or visit VELCADEHCP.com Reference: 1. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011;12(5):431-440.

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Brief Summary INDICATIONS: VELCADE® (bortezomib) for Injection is indicated for the treatment of patients with multiple myeloma. VELCADE® (bortezomib) for Injection is indicated for the treatment of patients with mantle cell lymphoma who have received at least 1 prior therapy. CONTRAINDICATIONS: VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. VELCADE is contraindicated for intrathecal administration. WARNINGS AND PRECAUTIONS: VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. Complete blood counts (CBC) should be monitored frequently during treatment with VELCADE. Peripheral Neuropathy: VELCADE treatment causes a peripheral neuropathy that is predominantly sensory. However, cases of severe sensory and motor peripheral neuropathy have been reported. Patients with pre-existing symptoms (numbness, pain or a burning feeling in the feet or hands) and/or signs of peripheral neuropathy may experience worsening peripheral neuropathy (including ≥ Grade 3) during treatment with VELCADE. Patients should be monitored for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain or weakness. In the Phase 3 relapsed multiple myeloma trial comparing VELCADE subcutaneous vs. intravenous the incidence of Grade ≥ 2 peripheral neuropathy events was 24% for subcutaneous and 41% for intravenous. Grade ≥ 3 peripheral neuropathy occurred in 6% of patients in the subcutaneous treatment group, compared with 16% in the intravenous treatment group. Starting VELCADE subcutaneously may be considered for patients with pre-existing or at high risk of peripheral neuropathy. Patients experiencing new or worsening peripheral neuropathy during VELCADE therapy may benefit from a decrease in the dose and/or a less dose-intense schedule. In the single agent phase 3 relapsed multiple myeloma study of VELCADE vs. Dexamethasone following dose adjustments, improvement in or resolution of peripheral neuropathy was reported in 51% of patients with ≥ Grade 2 peripheral neuropathy in the relapsed multiple myeloma study. Improvement in or resolution of peripheral neuropathy was reported in 73% of patients who discontinued due to Grade 2 neuropathy or who had ≥ Grade 3 peripheral neuropathy in the phase 2 multiple myeloma studies. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma. Hypotension: The incidence of hypotension (postural, orthostatic, and hypotension NOS) was 13%. These events are observed throughout therapy. Caution should be used when treating patients with a history of syncope, patients receiving medications known to be associated with hypotension, and patients who are dehydrated. Management of orthostatic/postural hypotension may include adjustment of antihypertensive medications, hydration, and administration of mineralocorticoids and/or sympathomimetics. Cardiac Disorders: Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have been reported, including reports in patients with no risk factors for decreased left ventricular ejection fraction. Patients with risk factors for, or existing heart disease should be closely monitored. In the relapsed multiple myeloma study of VELCADE vs. dexamethasone, the incidence of any treatment-emergent cardiac disorder was 15% and 13% in the VELCADE and dexamethasone groups, respectively. The incidence of heart failure events (acute pulmonary edema, cardiac failure, congestive cardiac failure, cardiogenic shock, pulmonary edema) was similar in the VELCADE and dexamethasone groups, 5% and 4%, respectively. There have been isolated cases of QT-interval prolongation in clinical studies; causality has not been established. Pulmonary Disorders: There have been reports of acute diffuse infiltrative pulmonary disease of unknown etiology such as pneumonitis, interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome (ARDS) in patients receiving VELCADE. Some of these events have been fatal. In a clinical trial, the first two patients given high-dose cytarabine (2 g/m2 per day) by continuous infusion with daunorubicin and VELCADE for relapsed acute myelogenous leukemia died of ARDS early in the course of therapy. There have been reports of pulmonary hypertension associated with VELCADE administration in the absence of left heart failure or significant pulmonary disease. In the event of new or worsening cardiopulmonary symptoms, a prompt comprehensive diagnostic evaluation should be conducted. Reversible Posterior Leukoencephalopathy Syndrome (RPLS): There have been reports of RPLS in patients receiving VELCADE. RPLS is a rare, reversible, neurological disorder which can present with seizure, hypertension, headache, lethargy, confusion, blindness, and other visual and neurological disturbances. Brain imaging, preferably MRI (Magnetic Resonance Imaging), is used to confirm the diagnosis. In patients developing RPLS, discontinue VELCADE. The safety of reinitiating VELCADE therapy in patients previously experiencing RPLS is not known. Gastrointestinal Adverse Events: VELCADE treatment can cause nausea, diarrhea, constipation, and vomiting sometimes requiring use of antiemetic and antidiarrheal medications. Ileus can occur. Fluid and electrolyte replacement should be administered to prevent dehydration. Thrombocytopenia/Neutropenia: VELCADE is associated with thrombocytopenia and neutropenia that follow a cyclical pattern with nadirs occurring following the last dose of each cycle and typically recovering prior to initiation of the subsequent cycle. The cyclical pattern of platelet and neutrophil decreases and recovery remained consistent over the 8 cycles of twice weekly dosing, and there was no evidence of cumulative thrombocytopenia or neutropenia. The mean platelet count nadir measured was approximately 40% of baseline. The severity of thrombocytopenia was related to pretreatment platelet count. In the relapsed multiple myeloma study of VELCADE vs. dexamethasone, the incidence of significant bleeding events (≥Grade 3) was similar on both the VELCADE (4%) and dexamethasone (5%) arms. Platelet counts should be monitored prior to each dose of VELCADE. Patients experiencing thrombocytopenia may require change in the dose and schedule of VELCADE. There have been reports of gastrointestinal and intracerebral hemorrhage in association with VELCADE. Transfusions may be considered. The incidence of febrile neutropenia was <1%. Tumor Lysis Syndrome: Because VELCADE is a cytotoxic agent and can rapidly kill malignant cells, the complications of tumor lysis syndrome may occur. Patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken. Hepatic Events: Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Other reported hepatic events include increases in liver enzymes, hyperbilirubinemia, and hepatitis. Such changes may be reversible upon discontinuation of VELCADE. There is limited re-challenge information in these patients. Hepatic Impairment: Bortezomib is metabolized by liver enzymes. Bortezomib exposure is increased in patients with moderate or severe hepatic impairment; these patients should be treated with VELCADE at reduced starting doses and closely monitored for toxicities.

ADVERSE EVENT DATA: Safety data from phase 2 and 3 studies of single-agent VELCADE 1.3 mg/m2/dose administered intravenously twice weekly for 2 weeks followed by a 10-day rest period in 1163 patients with previously treated multiple myeloma (N=1008, not including the phase 3, VELCADE plus DOXIL® [doxorubicin HCI liposome injection] study) and previously treated mantle cell lymphoma (N=155) were integrated and tabulated. In these studies, the safety profile of VELCADE was similar in patients with multiple myeloma and mantle cell lymphoma. In the integrated analysis, the most commonly reported adverse events were asthenic conditions (including fatigue, malaise, and weakness); (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheral neuropathy NEC (including peripheral sensory neuropathy and peripheral neuropathy aggravated); (39%), thrombocytopenia and appetite decreased (including anorexia); (each 36%), pyrexia (34%), vomiting (33%), anemia (29%), edema (23%), headache, paresthesia and dysesthesia (each 22%), dyspnea (21%), cough and insomnia (each 20%), rash (18%), arthralgia (17%), neutropenia and dizziness (excluding vertigo); (each 17%), pain in limb and abdominal pain (each 15%), bone pain (14%), back pain and hypotension (each 13%), herpes zoster, nasopharyngitis, upper respiratory tract infection, myalgia and pneumonia (each 12%), muscle cramps (11%), and dehydration and anxiety (each 10%). Twenty percent (20%) of patients experienced at least 1 episode of ≥Grade 4 toxicity, most commonly thrombocytopenia (5%) and neutropenia (3%). A total of 50% of patients experienced serious adverse events (SAEs) during the studies. The most commonly reported SAEs included pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia (each 3%). In the phase 3 VELCADE + melphalan and prednisone study in previously untreated multiple myeloma, the safety profile of VELCADE administered intravenously in combination with melphalan/prednisone is consistent with the known safety profiles of both VELCADE and melphalan/prednisone. The most commonly reported adverse events in this study (VELCADE+melphalan/prednisone vs melphalan/prednisone) were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%), nausea (48% vs 28%), peripheral neuropathy (47% vs 5%), diarrhea (46% vs 17%), anemia (43% vs 55%), constipation (37% vs 16%), neuralgia (36% vs 1%), leukopenia (33% vs 30%), vomiting (33% vs 16%), pyrexia (29% vs 19%), fatigue (29% vs 26%), lymphopenia (24% vs 17%), anorexia (23% vs 10%), asthenia (21% vs 18%), cough (21% vs 13%), insomnia (20% vs 13%), edema peripheral (20% vs 10%), rash (19% vs 7%), back pain (17% vs 18%), pneumonia (16% vs 11%), dizziness (16% vs 11%), dyspnea (15% vs 13%), headache (14% vs 10%), pain in extremity (14% vs 9%), abdominal pain (14% vs 7%), paresthesia (13% vs 4%), herpes zoster (13% vs 4%), bronchitis (13% vs 8%), hypokalemia (13% vs 7%), hypertension (13% vs 7%), abdominal pain upper (12% vs 9%), hypotension (12% vs 3%), dyspepsia (11% vs 7%), nasopharyngitis (11% vs 8%), bone pain (11% vs 10%), arthralgia (11% vs 15%) and pruritus (10% vs 5%). In the phase 3 VELCADE subcutaneous vs. intravenous study in relapsed multiple myeloma, safety data were similar between the two treatment groups. The most commonly reported adverse events in this study were peripheral neuropathy NEC (38% vs 53%), anemia (36% vs 35%), thrombocytopenia (35% vs 36%), neutropenia (29% vs 27%), diarrhea (24% vs 36%), neuralgia (24% vs 23%), leukopenia (20% vs 22%), pyrexia (19% vs 16%), nausea (18% vs 19%), asthenia (16% vs 19%), weight decreased (15% vs 3%), constipation (14% vs 15%), back pain (14% vs 11%), fatigue (12% vs 20%), vomiting (12% vs 16%), insomnia (12% vs 11%), herpes zoster (11% vs 9%), decreased appetite (10% vs 9%), hypertension (10% vs 4%), dyspnea (7% vs 12%), pain in extremities (5% vs 11%), abdominal pain and headache (each 3% vs 11%), abdominal pain upper (2% vs 11%). The incidence of serious adverse events was similar for the subcutaneous treatment group (36%) and the intravenous treatment group (35%). The most commonly reported SAEs were pneumonia (6%) and pyrexia (3%) in the subcutaneous treatment group and pneumonia (7%), diarrhea (4%), peripheral sensory neuropathy (3%) and renal failure (3%) in the intravenous treatment group. DRUG INTERACTIONS: Bortezomib is a substrate of cytochrome P450 enzyme 3A4, 2C19 and 1A2. Co-administration of ketoconazole, a strong CYP3A4 inhibitor, increased the exposure of bortezomib by 35% in 12 patients. Therefore, patients should be closely monitored when given bortezomib in combination with strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir). Co-administration of omeprazole, a strong inhibitor of CYP2C19, had no effect on the exposure of bortezomib in 17 patients. Co-administration of rifampin, a strong CYP3A4 inducer, is expected to decrease the exposure of bortezomib by at least 45%. Because the drug interaction study (n=6) was not designed to exert the maximum effect of rifampin on bortezomib PK, decreases greater than 45% may occur. Efficacy may be reduced when VELCADE (bortezomib) is used in combination with strong CYP3A4 inducers; therefore, concomitant use of strong CYP3A4 inducers is not recommended in patients receiving VELCADE. St. John’s Wort (Hypericum perforatum) may decrease bortezomib exposure unpredictably and should be avoided. Co-administration of dexamethasone, a weak CYP3A4 inducer, had no effect on the exposure of bortezomib in 7 patients. Co-administration of melphalan-prednisone increased the exposure of bortezomib by 17% in 21 patients. However, this increase is unlikely to be clinically relevant. USE IN SPECIFIC POPULATIONS: Nursing Mothers: It is not known whether bortezomib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from VELCADE, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use: The safety and effectiveness of VELCADE in children has not been established. Geriatric Use: No overall differences in safety or effectiveness were observed between patients ≥ age 65 and younger patients receiving VELCADE; but greater sensitivity of some older individuals cannot be ruled out. Patients with Renal Impairment: The pharmacokinetics of VELCADE are not influenced by the degree of renal impairment. Therefore, dosing adjustments of VELCADE are not necessary for patients with renal insufficiency. Since dialysis may reduce VELCADE concentrations, VELCADE should be administered after the dialysis procedure. For information concerning dosing of melphalan in patients with renal impairment, see manufacturer’s prescribing information. Patients with Hepatic Impairment: The exposure of bortezomib is increased in patients with moderate and severe hepatic impairment. Starting dose should be reduced in those patients. Patients with Diabetes: During clinical trials, hypoglycemia and hyperglycemia were reported in diabetic patients receiving oral hypoglycemics. Patients on oral antidiabetic agents receiving VELCADE treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetic medication. Please see full Prescribing Information for VELCADE at VELCADEHCP.com.

Use in Pregnancy: Pregnancy Category D. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE (bortezomib). Bortezomib administered to rabbits during organogenesis at a dose approximately 0.5 times the clinical dose of 1.3 mg/m2 based on body surface area caused post-implantation loss and a decreased number of live fetuses. VELCADE, MILLENNIUM and are registered trademarks of Millennium Pharmaceuticals, Inc. Other trademarks are property of their respective owners. Millennium Pharmaceuticals, Inc., Cambridge, MA 02139 Copyright © 2012, Millennium Pharmaceuticals, Inc. All rights reserved. Printed in USA V-12-0017a 03/12

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Editorial Board EDITOR-IN-CHIEF

Cassandra J. Hammond, RN,

Melinda Oberleitner, RN,

Karla Wilson, RN,

MSN, CRNP

DNS, APRN, CNS

Avid Education Partners, LLC Sharpsburg, MD

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

City of Hope National Medical Center Duarte, CA

Elizabeth Bilotti,

Shannon Hazen,

Jayshree Shah, NP

RN, MSN, APRN, BC, OCN

RN, BSN, OCN

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

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

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Novant Health Presbyterian Cancer Center Charlotte, NC

DNP, NP, AOCNP

Patricia Irouer Hughes, RN, MSN,

Lansdowne, VA

BSN, OCN

Catherine Bishop,

Piedmont Healthcare Rex, GA

MSN, FNP-C, CPON

Pharmacy John F. Aforismo, BSc Pharm, RPh, FASCP

Gary Shelton,

RJ Health Systems International, LLC Wethersfield, CT

MSN, NP, ANP-BC, AOCNP NYU Clinical Cancer Center New York, NY

Nutrition Karen Connelly, RD, CSO

Deena Damsky Dell, MSN, RN-BC,

Taline Khoukaz,

Lori Stover, RN,

NP, MSN, ACNP-C

BSN

AOCN, LNC

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

Western Pennsylvania Cancer Institute Pittsburgh, PA

Wendy DiSalvo,

Sandra E. Kurtin,

DNP, APRN, AOCN

RN, MS, AOCN, ANP-C

Joseph D. Tariman, PhD,

Fox Chase Cancer Center Philadelphia, PA

Genentech New London, NH

Denice Economou, RN, MN, CNS, AOCN

APRN, BC

Arizona Cancer Center Tucson, AZ

Northwestern University Myeloma Program Chicago, IL

Ann McNeill,

Jacqueline Marie Toia, RN, MS, DNP

MSN, RN, NP-C, OCN

Northwestern University Myeloma Program Chicago, IL

Somerset Medical Center Somerville, NJ

Patient Advocate Peg Ford Ovarian Cancer Advocacy Alliance Coronado, CA

Social Work Carolyn Messner,

City of Hope National Medical Center Duarte, CA

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Constance Engelking, RN,

Kena C. Miller,

MS, CNS, OCN

Roswell Park Cancer Institute Buffalo, NY

Saratoga, CA

Managed Care and Pharmaceutical Management Burt Zweigenhaft,

Amy Ford, RN,

Patricia Molinelli,

Connie Visovsky,

BSN, OCN

MS, RN, APN-C, AOCNS

RN, PhD, APRN

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

Innovex Dallas, TX

RN, MSN, FNP

Somerset Medical Center Somerville, NJ

DSW, MSW, LCSW-R, BCD CancerCare New York, NY

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

University of South Florida College of Nursing Tampa, FL

BioPharma Partners LLC New York, NY

Isabell Castellano, RN Sharon S. Gentry, RN, MSN, AOCN Derrick L. Davis Forsyth Regional Cancer Center Winston-Salem, NC

www.TheOncologyNurse.com

Dolores “Jeff” Nordquist, RN, MS,

Rita Wickham,

CS, FNP

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

Mayo Clinic Rochester, MN

PhD, RN, AOCN

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

Jeanne Westphal, RN Meeker County Memorial Hospital Litchfield, MN

April 2012 I VOl 5, NO 3

TON_April2012_v5_TON 4/13/12 3:15 PM Page 6

From the Editor

ith this issue, we introduce the 4 finalists for the second annual Oncology Nurse Excellence award. The 4 finalists—Darcie Deaver, MSN, NP-C; Wendy Miano, RN, MSN, DNP, DN; Patricia (Patti) Palmer, RN, MS, AOCN; and Deborah Thompson, BSN, ONC—were selected from among the many nominations we received. Given Beth Faiman, PhD(c), MSN, APRN-BC, AOCN the caliber of all the nominees, it Editor-in-Chief was very difficult to narrow it down to just 4 finalists. By recognizing their outstanding contributions, we acknowledge not only their accomplishments but also the endeavors of all those who are part of the oncology nursing profession. And now it’s your turn. Go to www.The OncologyNurse.com/award to vote for your choice as the recipient of the Oncology Nurse Excellence award. The winner will be announced in the June issue of The Oncology Nurse-APN/PA. This issue covers a range of topics—everything from the future of nursing education and practice to the importance of making sure we all include cruciferous vegetables in our diet. Catherine Bishop sums up the recommendations laid out in the Institute of Medicine report regarding the need

PUBLISHING STAFF Senior Vice President, Sales & Marketing Philip Pawelko phil@greenhillhc.com Publisher John W. Hennessy john@greenhillhc.com Director, Client Services Joe Chanley joe@greenhillhc.com Editorial Director Kristin Siyahian kristin@greenhillhc.com Managing Editor Kristen Olafson kristen@greenhillhc.com Quality Control Director Barbara Marino Production Manager Stephanie Laudien Business Manager Blanche Marchitto blanche@greenhillhc.com Executive Administrator Jackie Luma Circulation Department circulation@greenhillhc.com Editorial Contact: Telephone: 732.992.1891 Fax: 732.656.7938

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for nurses to continue their formal education and to expand their roles within the entire spectrum of healthcare. Sandra Kurtin tells us about the key elements of precision medicine and how we must all educate ourselves and our patients about these complex concepts. In the Your FAQs…Answered column, Deena Damsky Dell addresses the issue of whether it is safe for women at risk for breast cancer–related lymphedema to lift weights.

Visit our Web site to vote for the recipient of the second annual Oncology Nurse Excellence award. She informs us about the evidence-based literature on the subject and provides a list of resources for both healthcare providers and patients. And once again, Karen Connelly makes us pull out our grocery shopping lists so we can prepare one of her delicious and healthy recipes. This time, we’ll be in the veggie section, stocking up on bok choy and collard greens. Don’t forget to visit our Web site to vote for the recipient of the second annual Oncology Nurse Excellence award. ●

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241 Forsgate Drive, Suite 205C Monroe Twp, NJ 08831 The Oncology Nurse-APN/PA®, ISSN 1944-9798 (print); ISSN 1944-9801 (online) is published 11 times a year by Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. Telephone: 732.656.7935. Fax: 732.656.7938. Copyright ©2012 by Green Hill Healthcare Communications, LLC. All rights reserved. The Oncology Nurse-APN/PA® logo is a registered trademark of Green Hill Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America. EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, The Oncology Nurse-APN/PA®, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. E-mail: kristin@greenhillhc. com. YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $105.00; institutions, $135.00; single issues, $17.00. Orders will be billed at individual rate until proof of status is confirmed. Prices are subject to change without notice. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed to REPRINT PERMISSIONS DEPARTMENT, Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. The ideas and opinions expressed in The Oncology Nurse-APN/PA® do not necessarily reflect those of the Editorial Board, the Editorial Director, or the Publisher. Publication of an advertisement or other product mention in The Oncology Nurse-APN/PA® should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturer with questions about the features or limitations of the products mentioned. Neither the Editorial Board nor the Publisher assumes any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other healthcare professional, relying on independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Every effort has been made to check generic and trade names, and to verify dosages. The ultimate responsibility, however, lies with the prescribing physician. Please convey any errors to the Editorial Director. BPA Worldwide membership applied for April 2011.

April 2012 I VOl 5, NO 3

Noteworthy Numbers Because skin is the largest organ in the body, is it not surprising that skin cancer is the most common of all cancers. Melanoma, the most deadly skin cancer, is caused by overexposure to ultraviolet radiation. So with spring in the air and summer right around the corner, let us dig deeper into the statistics surrounding this fatal disease.

Melanoma accounts for about 4% of all skin cancer cases but 79% of all skin cancer deaths. It is currently the seventh most common cancer in American women and the sixth most common cancer in American men. Incidence rates have been on the rise for the past 30 years. It is estimated there will be 76,250 new cases of melanoma in the US this year. Melanoma has a wide age distribution. There is an increase in occurrence with age, and rates are highest among those in their 80s. Melanoma is not uncommon among those younger than age 30. In fact, it is the

second most common cancer in women between the ages of 20 and 35 and the leading cause of cancer death in women aged 25 to 30. The primary risk factor for developing melanoma is race, with rates 10 times higher for whites than blacks. The lifetime risk of a melanoma diagnosis is about 2% (1 in 50) for whites, 0.5% (1 in 200) for Hispanics, and 0.1% (1 in 1000) for blacks. From 2004 to 2008, 68 years of age was the median age at death for patients with melanoma. The disease is expected to cause approximately 9180

deaths during 2012 (6060 men and 3120 women). If melanoma is discovered early enough, the chance of survival is high. Fiveyear survival rates range from 97% for stage IA down to 15% for stage IV melanoma. In order to prevent this deadly disease, the American Cancer Society encourages everyone to “Slip! Slop! Slap!...and Wrap!” • Slip on a shirt • Slop on sunscreen • Slap on a hat • Wrap on sunglasses Sources: w w w. m e l a n o m a c e n t e r. o rg / b a s i c s / index.html; www.cancer.org/Cancer/Skin C a n c e r- M e l a n o m a / D e t a i l e d G u i d e / melanoma-skin-cancer-key-statistics; seer.cancer.gov/statfacts/html/melan.html.

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TON_April2012_v5_TON 4/13/12 9:59 AM Page 8

News Briefs CYP2D6 Genotyping Fails to Predict Effectiveness... Continued from cover poor and intermediate metabolizers of endoxifen (a metabolite of tamoxifen) and more effective in extensive metabolizers of endoxifen. The 2 studies—ATAC and BIG 1-98—were published in the Journal of the National Cancer Institute (JNCI) online on March 6, 2012. ATAC was a prospective clinical trial that compared effectiveness and safety of the aromatase inhibitor anastrozole versus tamoxifen in postmenopausal women with hormone receptor–positive early-stage breast cancer. Tumor samples from 1203 women were genotyped for CYP2D6. At a median follow-up of 10 years, no significant associations were found in the tamoxifen-treated group between the CYP2D6 genotype for poor metabolizers versus extensive metabolizers for distant recurrence or for any recurrence. As might be expected, no associations were found between the CYP2D6 genotype and recurrence in the patients who received anastrozole.

to postmenopausal women, nor to withhold treatment with an aromatase inhibitor. The presence or absence of hot

flushes should not be used in the clinical setting to estimate tamoxifen efficacy.” In an accompanying editorial in the

same issue of JNCI, Catherine M. Kelly, MD, and Kathleen I. Pritchard, MD, wrote: “The fact that these two studies

TREANDA® is her chemo.

This is her therapy.

Results of ATAC and BIG 1-98 illustrate that laboratory observations that raise hypotheses must be independently validated in order to guide clinical practice.

BIG 1-98 randomized postmenopausal women with hormone-sensitive, operable, invasive breast cancer to 5 years of treatment with tamoxifen monotherapy versus letrozole monotherapy. The findings were similar to those of ATAC, with no significant association found between CYP2D6 metabolism phenotypes and breast cancer–free interval in women treated with tamoxifen. The authors of BIG 1-98 also studied new-onset or worsening hot flushes during the first 2 years of tamoxifen therapy. They wrote, the results “suggest that CYP2D6 testing is not justified to determine whether tamoxifen should be given

April 2012 I VOl 5, NO 3

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News Briefs confirm each other suggests that this matter has likely been laid to rest.â&#x20AC;? They noted that the findings suggest that the vast industry of CYP2D genotype testing was premature, that

patients underwent additional and unnecessary tests and charges related to genotyping, and that therapy was adjusted according to genotyping test results without firm evidence.

Both editorial writers wrote that the lessons learned from these 2 large trials include the need for large confirmatory studies of therapeutic agents and biomarkers. Results of

ATAC and BIG 1-98 illustrate that laboratory observations that raise hypotheses must be independently validated in order to guide clinical practice. â&#x2014;?

Single-agent TREANDA tripled median PFS in patients with CLL* 42%!.$! IS INDICATED FOR THE TREATMENT OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA #,, %FlCACY RELATIVE TO lRST LINE THERAPIES OTHER THAN CHLORAMBUCIL HAS NOT BEEN ESTABLISHED

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

TREANDA (n=153)

1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1

Chlorambucil (n=148)

18 months median PFS

s 42%!.$! HAS AN ESTABLISHED SAFETY PROlLE

6 months

s )N THE PIVOTAL PHASE TRIAL OF PATIENTS WITH #,, THE MOST common non-hematologic adverse reactions (frequency â&#x2030;Ľ WERE PYREXIA NAUSEA AND VOMITING N 4HE MOST COMMON HEMATOLOGIC abnormalities (frequency â&#x2030;Ľ WERE ANEMIA THROMBOCYTOPENIA NEUTROPENIA

LYMPHOPENIA AND LEUKOPENIA N

median PFS

P<.0001 HRâ&#x20AC; =0.27 (95% CIâ&#x20AC;Ą: 0.17, 0.43)

s 42%!.$! WAS COMPARED WITH CHLORAMBUCIL IN A randomized, open-label, phase 3 trial in treatment-naĂŻve PATIENTS WITH "INET STAGE " OR # 2AI STAGES ) )6 #,, WHO REQUIRED TREATMENT . 0ATIENTS WERE SCHEDULED TO RECEIVE EITHER 42%!.$! MG M2 intravenously on $AYS AND N OR CHLORAMBUCIL MG KG ORALLY ON $AYS AND N OF A DAY TREATMENT CYCLE

up to 6 cycles

20 25 Months

*TREANDA (95% CI: 11.7, 23.5) vs chlorambucil (95% CI: 5.6, 8.6). â&#x20AC; HR=hazard ratio. â&#x20AC;Ą CI=confidence interval.

Single-agent TREANDA produced a 74% ORRÂ§ in patients with indolent B-cell NHL that had progressed 42%!.$! IS INDICATED FOR THE TREATMENT OF PATIENTS WITH INDOLENT " CELL NON (ODGKIN S LYMPHOMA .(, THAT HAS PROGRESSED DURING OR WITHIN MONTHS OF TREATMENT WITH RITUXIMAB OR A RITUXIMAB CONTAINING REGIMEN s 42%!.$! WAS EVALUATED IN A SINGLE ARM PIVOTAL STUDY OF PATIENTS WITH INDOLENT " CELL .(, THAT HAD PROGRESSED during or within 6 months of treatment with rituximab or a rituximab-containing regimen. Patients were scheduled TO RECEIVE 42%!.$! MG M2 ON $AYS AND OF A 21-day treatment cycle, up to 8 cycles

ORRÂ§: INDOLENT B-CELL NHL THAT HAS PROGRESSED

57%

PR (n=57)

74%

Total ORR (95% CI: 64.3, 82.3)

17%

CR/CRu (n=17)

s 42%!.$! HAS AN ESTABLISHED SAFETY PROlLE

s )N SINGLE ARM STUDIES OF PATIENTS WITH INDOLENT " CELL .(, THAT HAD PROGRESSED . THE MOST COMMON non-hematologic adverse reactions (frequency â&#x2030;Ľ30%) WERE NAUSEA FATIGUE VOMITING

DIARRHEA AND PYREXIA . 4HE MOST common hematologic abnormalities (frequency â&#x2030;Ľ WERE LYMPHOPENIA LEUKOPENIA ANEMIA (88%), neutropenia (86%), and thrombocytopenia (86%)

100

Patients responding (%) Â§

Independent Review Committee assessment was based on modified International Working Group response criteria (IWG-RC). Modifications to IWG-RC specified that persistently positive bone marrow in patients who met all other criteria for complete response (CR) would be scored as partial response (PR). Bone marrow sample lengths were not required to be â&#x2030;Ľ20 mm.

Important Safety Information s 3ERIOUS ADVERSE REACTIONS INCLUDING MYELOSUPPRESSION INFECTIONS INFUSION REACTIONS AND ANAPHYLAXIS TUMOR LYSIS SYNDROME SKIN REACTIONS INCLUDING 3*3 4%.

OTHER MALIGNANCIES AND EXTRAVASATION HAVE BEEN ASSOCIATED WITH 42%!.$! 3OME REACTIONS SUCH AS MYELOSUPPRESSION INFECTIONS AND 3*3 4%. WHEN 42%!.$! WAS ADMINISTERED CONCOMITANTLY WITH ALLOPURINOL AND OTHER MEDICATIONS KNOWN TO CAUSE 3*3 4%. HAVE BEEN FATAL 0ATIENTS SHOULD BE MONITORED CLOSELY FOR THESE REACTIONS AND TREATED PROMPTLY IF ANY OCCUR s !DVERSE REACTIONS MAY REQUIRE INTERVENTIONS SUCH AS DECREASING THE DOSE OF 42%!.$! OR WITHHOLDING OR DELAYING TREATMENT s 42%!.$! IS CONTRAINDICATED IN PATIENTS WITH A KNOWN HYPERSENSITIVITY TO BENDAMUSTINE OR MANNITOL 7OMEN SHOULD BE ADVISED TO AVOID BECOMING PREGNANT WHILE USING 42%!.$! l

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

Oncology

Built for ActionÂŽ

ÂĽ #EPHALON )NC IS A WHOLLY OWNED SUBSIDIARY OF 4EVA 0HARMACEUTICAL )NDUSTRIES ,TD !LL RIGHTS RESERVED 42% .OVEMBER

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News Briefs

“Chemo Brain” Can Persist for 2 Decades

he term “chemo brain” was coined to describe mild cognitive problems in cancer patients attributed to chemotherapy. Although

minor chemotherapy-induced memory and cognitive impairments have been described previously, a case-cohort study suggests that these effects can

persist more than 20 years posttherapy. The authors state that chemo brain effects are subtle compared with women who never had chemotherapy, but it’s

Brief Summary of Prescribing Information INDICATIONS AND USAGE: TREANDA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). Efficacy relative to first line therapies other than chlorambucil has not been established. TREANDA for Injection is indicated for the treatment of patients with indolent B-cell non-Hodgkin’s lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. CONTRAINDICATIONS: TREANDA is contraindicated in patients with a known hypersensitivity (eg, anaphylactic and anaphylactoid reactions) to bendamustine or mannitol. [See Warnings and Precautions] WARNINGS AND PRECAUTIONS: Myelosuppression. Patients treated with TREANDA are likely to experience myelosuppression. In the two NHL studies, 98% of patients had Grade 3-4 myelosuppression. Three patients (2%) died from myelosuppression-related adverse reactions; one each from neutropenic sepsis, diffuse alveolar hemorrhage with Grade 3 thrombocytopenia, and pneumonia from an opportunistic infection (CMV). In the event of treatment-related myelosuppression, monitor leukocytes, platelets, hemoglobin (Hgb), and neutrophils closely. In the clinical trials, blood counts were monitored every week initially. Hematologic nadirs were observed predominantly in the third week of therapy. Hematologic nadirs may require dose delays if recovery to the recommended values have not occurred by the first day of the next scheduled cycle. Prior to the initiation of the next cycle of therapy, the ANC should be ≥ 1 x 109/L and the platelet count should be ≥ 75 x 109/L. [See Dosage and Administration]. Infections. Infection, including pneumonia and sepsis, has been reported in patients in clinical trials and in post-marketing reports. Infection has been associated with hospitalization, septic shock and death. Patients with myelosuppression following treatment with TREANDA are more susceptible to infections. Patients with myelosuppression following TREANDA treatment should be advised to contact a physician if they have symptoms or signs of infection. Infusion Reactions and Anaphylaxis. Infusion reactions to TREANDA have occurred commonly in clinical trials. Symptoms include fever, chills, pruritus and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe reactions. Patients should be asked about symptoms suggestive of infusion reactions after their first cycle of therapy. Patients who experienced Grade 3 or worse allergic-type reactions were not typically rechallenged. Measures to prevent severe reactions, including antihistamines, antipyretics and corticosteroids should be considered in subsequent cycles in patients who have previously experienced Grade 1 or 2 infusion reactions. Discontinuation should be considered in patients with Grade 3 or 4 infusion reactions. Tumor Lysis Syndrome. Tumor lysis syndrome associated with TREANDA treatment has been reported in patients in clinical trials and in post-marketing reports. The onset tends to be within the first treatment cycle of TREANDA and, without intervention, may lead to acute renal failure and death. Preventive measures include maintaining adequate volume status, and close monitoring of blood chemistry, particularly potassium and uric acid levels. Allopurinol has also been used during the beginning of TREANDA therapy. However, there may be an increased risk of severe skin toxicity when TREANDA and allopurinol are administered concomitantly. Skin Reactions. A number of skin reactions have been reported in clinical trials and post-marketing safety reports. These events have included rash, toxic skin reactions and bullous exanthema. Some events occurred when TREANDA was given in combination with other anticancer agents, so the precise relationship to TREANDA is uncertain. In a study of TREANDA (90 mg/m2) in combination with rituximab, one case of toxic epidermal necrolysis (TEN) occurred. TEN has been reported for rituximab (see rituximab package insert). Cases of Stevens-Johnson syndrome (SJS) and TEN, some fatal, have been reported when TREANDA was administered concomitantly with allopurinol and other medications known to cause these syndromes. The relationship to TREANDA cannot be determined. Where skin reactions occur, they may be progressive and increase in severity with further treatment. Therefore, patients with skin reactions should be monitored closely. If skin reactions are severe or progressive, TREANDA should be withheld or discontinued. Other Malignancies. There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with TREANDA, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia and bronchial carcinoma. The association with TREANDA therapy has not been determined. Extravasation. There are postmarketing reports of bendamustine extravasations resulting in hospitalizations from erythema, marked swelling, and pain. Precautions should be taken to avoid extravasations, including monitoring of the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of TREANDA. Use in Pregnancy. TREANDA can cause fetal harm when administered to a pregnant woman. Single intraperitoneal doses of bendamustine in mice and rats administered during organogenesis caused an increase in resorptions, skeletal and visceral malformations, and decreased fetal body weights. ADVERSE REACTIONS: The data described below reflect exposure to TREANDA in 349 patients who participated in an actively-controlled trial (N=153) for the treatment of CLL and two single-arm studies (N=176) for the treatment of indolent B-cell NHL. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following serious adverse reactions have been associated with TREANDA in clinical trials and are discussed in greater detail in other sections [See Warnings and Precautions] of the label: Myelosuppression; Infections; Infusion Reactions and Anaphylaxis; Tumor Lysis Syndrome; Skin Reactions; Other Malignancies. Clinical Trials Experience in CLL. The data described below reflect exposure to TREANDA in 153 patients. TREANDA was studied in an active-controlled trial. The population was 45-77 years of age, 63% male, 100% white, and had treatment naïve CLL. All patients started the study at a dose of 100 mg/m2 intravenously over 30 minutes on days 1 and 2 every 28 days. Adverse reactions were reported according to NCI CTC v.2.0. In the randomized CLL clinical study, non-hematologic adverse reactions (any grade) in the TREANDA group that occurred with a frequency greater than 15% were pyrexia (24%), nausea (20%), and vomiting (16%). Other adverse reactions seen frequently in one or more studies included asthenia, fatigue, malaise, and weakness; dry mouth; somnolence; cough; constipation; headache; mucosal inflammation; and stomatitis. Worsening hypertension was reported in 4 patients treated with TREANDA in the randomized CLL clinical study and none treated with chlorambucil. Three of these 4 adverse reactions were described as a hypertensive crisis and were managed with oral medications and resolved. The most frequent adverse reactions leading to study withdrawal for patients receiving TREANDA were hypersensitivity (2%) and pyrexia (1%). Table 1 contains the treatment emergent adverse reactions, regardless of attribution, that were reported in ≥ 5% of patients in either treatment group in the randomized CLL clinical study. Table 1: Non-Hematologic Adverse Reactions Occurring in Randomized CLL Clinical Study in at Least 5% of Patients Number (%) of patients TREANDA Chlorambucil (N=153) (N=143) System organ class Preferred term All Grades Grade 3/4 All Grades Grade 3/4 Total number of patients with at least 1 adverse reaction 121 (79) 52 (34) 96 (67) 25 (17) Gastrointestinal disorders Nausea 31 (20) 1 (<1) 21 (15) 1 (<1) Vomiting 24 (16) 1 (<1) 9 (6) 0 Diarrhea 14 (9) 2 (1) 5 (3) 0

April 2012 I VOl 5, NO 3

possible that these effects place people at greater risk for cognitive decline associated with aging. A partial explanation for chemo

Table 1: Non-Hematologic Adverse Reactions Occurring in Randomized CLL Clinical Study in at Least 5% of Patients (continued) Number (%) of patients TREANDA Chlorambucil (N=153) (N=143) System organ class Preferred term All Grades Grade 3/4 All Grades Grade 3/4 General disorders and administration site conditions Pyrexia 36 (24) 6 (4) 8 (6) 2 (1) Fatigue 14 (9) 2 (1) 8 (6) 0 Asthenia 13 (8) 0 6 (4) 0 Chills 9 (6) 0 1 (<1) 0 Immune system disorders Hypersensitivity 7 (5) 2 (1) 3 (2) 0 Infections and infestations Nasopharyngitis 10 (7) 0 12 (8) 0 Infection 9 (6) 3 (2) 1 (<1) 1 (<1) Herpes simplex 5 (3) 0 7 (5) 0 Investigations Weight decreased 11 (7) 0 5 (3) 0 Metabolism and nutrition disorders Hyperuricemia 11 (7) 3 (2) 2 (1) 0 Respiratory, thoracic and mediastinal disorders Cough 6 (4) 1 (<1) 7 (5) 1 (<1) Skin and subcutaneous tissue disorders Rash 12 (8) 4 (3) 7 (5) 3 (2) Pruritus 8 (5) 0 2 (1) 0 The Grade 3 and 4 hematology laboratory test values by treatment group in the randomized CLL clinical study are described in Table 2. These findings confirm the myelosuppressive effects seen in patients treated with TREANDA. Red blood cell transfusions were administered to 20% of patients receiving TREANDA compared with 6% of patients receiving chlorambucil. Table 2: Incidence of Hematology Laboratory Abnormalities in Patients Who Received TREANDA or Chlorambucil in the Randomized CLL Clinical Study

Laboratory Abnormality Hemoglobin Decreased Platelets Decreased Leukocytes Decreased Lymphocytes Decreased Neutrophils Decreased

TREANDA (N=150) All Grades Grade 3/4 n (%) n (%) 134 (89) 20 (13) 116 (77) 16 (11) 92 (61) 42 (28) 102 (68) 70 (47) 113 (75) 65 (43)

Chlorambucil (N=141) All Grades Grade 3/4 n (%) n (%) 115 (82) 12 (9) 110 (78) 14 (10) 26 (18) 4 (3) 27 (19) 6 (4) 86 (61) 30 (21)

In the randomized CLL clinical study, 34% of patients had bilirubin elevations, some without associated significant elevations in AST and ALT. Grade 3 or 4 increased bilirubin occurred in 3% of patients. Increases in AST and ALT of Grade 3 or 4 were limited to 1% and 3% of patients, respectively. Patients treated with TREANDA may also have changes in their creatinine levels. If abnormalities are detected, monitoring of these parameters should be continued to ensure that significant deterioration does not occur. Clinical Trials Experience in NHL. The data described below reflect exposure to TREANDA in 176 patients with indolent B-cell NHL treated in two singlearm studies. The population was 31-84 years of age, 60% male, and 40% female. The race distribution was 89% White, 7% Black, 3% Hispanic, 1% other, and <1% Asian. These patients received TREANDA at a dose of 120 mg/m2 intravenously on Days 1 and 2 for up to 8 21-day cycles. The adverse reactions occurring in at least 5% of the NHL patients, regardless of severity, are shown in Table 3. The most common non-hematologic adverse reactions (≥30%) were nausea (75%), fatigue (57%), vomiting (40%), diarrhea (37%) and pyrexia (34%). The most common non-hematologic Grade 3 or 4 adverse reactions (≥5%) were fatigue (11%), febrile neutropenia (6%), and pneumonia, hypokalemia and dehydration, each reported in 5% of patients. Table 3: Non-Hematologic Adverse Reactions Occurring in at Least 5% of NHL Patients Treated With TREANDA by System Organ Class and Preferred Term (N=176) System organ class Preferred term Total number of patients with at least 1 adverse reaction Cardiac disorders Tachycardia Gastrointestinal disorders Nausea Vomiting Diarrhea Constipation Stomatitis Abdominal pain Dyspepsia Gastroesophageal reflux disease Dry mouth Abdominal pain upper Abdominal distension General disorders and administration site conditions Fatigue Pyrexia Chills Edema peripheral Asthenia Chest pain Infusion site pain Pain Catheter site pain

Number (%) of patients* All Grades Grade 3/4 176 (100) 94 (53)

13 (7)

132 (75) 71 (40) 65 (37) 51 (29) 27 (15) 22 (13) 20 (11) 18 (10) 15 (9) 8 (5) 8 (5)

7 (4) 5 (3) 6 (3) 1 (<1) 1 (<1) 2 (1) 0 0 1 (<1) 0 0

101 (57) 59 (34) 24 (14) 23 (13) 19 (11) 11 (6) 11 (6) 10 (6) 8 (5)

19 (11) 3 (2) 0 1 (<1) 4 (2) 1 (<1) 0 0 0

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News Briefs brain may be that chemotherapy penetrates the blood-brain barrier, killing healthy brain cells, or that chemotherapy affects the immune system or is proinflammatory. The study, published online in

February in the Journal of Clinical Oncology (Koppelmans V, Breteler MM, Boogerd W, et al) included 196 breast cancer survivors treated with adjuvant CMF (cyclophosphamide, methotrexate, and fluorouracil) who were tested with a

Table 3: Non-Hematologic Adverse Reactions Occurring in at Least 5% of NHL Patients Treated With TREANDA by System Organ Class and Preferred Term (N=176) (continued) System organ class Number (%) of patients* Preferred term All Grades Grade 3/4 Infections and infestations Herpes zoster 18 (10) 5 (3) Upper respiratory tract infection 18 (10) 0 Urinary tract infection 17 (10) 4 (2) Sinusitis 15 (9) 0 Pneumonia 14 (8) 9 (5) Febrile Neutropenia 11 (6) 11 (6) Oral Candidiasis 11 (6) 2 (1) Nasopharyngitis 11 (6) 0 Investigations Weight decreased 31 (18) 3 (2) Metabolism and nutrition disorders Anorexia 40 (23) 3 (2) Dehydration 24 (14) 8 (5) Decreased appetite 22 (13) 1 (<1) Hypokalemia 15 (9) 9 (5) Musculoskeletal and connective tissue disorders Back pain 25 (14) 5 (3) Arthralgia 11 (6) 0 Pain in extremity 8 (5) 2 (1) Bone pain 8 (5) 0 Nervous system disorders Headache 36 (21) 0 Dizziness 25 (14) 0 Dysgeusia 13 (7) 0 Psychiatric disorders Insomnia 23 (13) 0 Anxiety 14 (8) 1 (<1) Depression 10 (6) 0 Respiratory, thoracic and mediastinal disorders Cough 38 (22) 1 (<1) Dyspnea 28 (16) 3 (2) Pharyngolaryngeal pain 14 (8) 1 (<1) Wheezing 8 (5) 0 Nasal congestion 8 (5) 0 Skin and subcutaneous tissue disorders Rash 28 (16) 1 (<1) Pruritus 11 (6) 0 Dry skin 9 (5) 0 Night sweats 9 (5) 0 Hyperhidrosis 8 (5) 0 Vascular disorders Hypotension 10 (6) 2 (1) *Patients may have reported more than 1 adverse reaction. NOTE: Patients counted only once in each preferred term category and once in each system organ class category. Hematologic toxicities, based on laboratory values and CTC grade, in NHL patients treated in both single arm studies combined are described in Table 4. Clinically important chemistry laboratory values that were new or worsened from baseline and occurred in >1% of patients at grade 3 or 4, in NHL patients treated in both single arm studies combined were hyperglycemia (3%), elevated creatinine (2%), hyponatremia (2%), and hypocalcemia (2%). Table 4: Incidence of Hematology Laboratory Abnormalities in Patients Who Received TREANDA in the NHL Studies Percent of patients All Grades Grade 3/4 99 94 94 56 88 11 86 60 86 25

Hematology Variable Lymphocytes Decreased Leukocytes Decreased Hemoglobin Decreased Neutrophils Decreased Platelets Decreased

series of cognitive and memory tests. Ages were from 50 to 80 years, the mean number of chemotherapy cycles was 6, and the mean interval since chemotherapy was 21 years. Scores on speed processing, word, memory, and general cog-

TREANDA administration should be delayed in the event of Grade 4 hematologic toxicity or clinically significant ≥ Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to ≤ Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) ≥ 1 x 109/L, platelets ≥ 75 x 109/L], TREANDA can be reinitiated at the discretion of the treating physician. In addition, dose reduction may be warranted. [See Warnings and Precautions] Dose modifications for hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 25 mg/m2 on Days 1 and 2 of each cycle. Dose modifications for non-hematologic toxicity: for clinically significant Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on Days 1 and 2 of each cycle. Dose re-escalation in subsequent cycles may be considered at the discretion of the treating physician. Dosing Instructions for NHL. Recommended Dosage: The recommended dose is 120 mg/m2 administered intravenously over 60 minutes on Days 1 and 2 of a 21-day cycle, up to 8 cycles. Dose Delays, Dose Modifications and Reinitiation of Therapy for NHL: TREANDA administration should be delayed in the event of a Grade 4 hematologic toxicity or clinically significant ≥ Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to ≤ Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) ≥ 1 x 109/L, platelets ≥ 75 x 109/L], TREANDA can be reinitiated at the discretion of the treating physician. In addition, dose reduction may be warranted. [See Warnings and Precautions] Dose modifications for hematologic toxicity: for Grade 4 toxicity, reduce the dose to 90 mg/m2 on Days 1 and 2 of each cycle; if Grade 4 toxicity recurs, reduce the dose to 60 mg/m2 on Days 1 and 2 of each cycle. Dose modifications for non-hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 90 mg/m2 on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 60 mg/m2 on Days 1 and 2 of each cycle. Reconstitution/Preparation for Intravenous Administration. M D6AE:42==J C64@?DE:EFE6 6249 ,* & G:2= 2D 7@==@HD M >8 ,* & G:2= 55 >$ @7 @?=J Sterile Water for Injection, USP M >8 ,* & G:2= 55 >$ @7 @?=J Sterile Water for Injection, USP. Shake well to yield a clear, colorless to a pale yellow solution with a bendamustine HCl concentration of 5 mg/mL. The lyophilized powder should completely dissolve in 5 minutes. If particulate matter is observed, the reconstituted product should not be used. M D6AE:42==J H:E95C2H E96 G@=F>6 ?66565 7@C E96 C6BF:C65 5@D6 32D65 @? >8 >$ 4@?46?EC2E:@? and immediately transfer to a 500 mL infusion bag of 0.9% Sodium Chloride Injection, USP (normal saline). As an alternative to 0.9% Sodium Chloride Injection, USP (normal saline), a 500 mL infusion bag of 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, may be considered. The resulting final concentration of bendamustine HCl in the infusion bag should be within 0.2–0.6 mg/ mL. The reconstituted solution must be transferred to the infusion bag within 30 minutes of reconstitution. After transferring, thoroughly mix the contents of the infusion bag. The admixture D9@F=5 36 2 4=62C 2?5 4@=@C=6DD E@ D=:89E=J J6==@H D@=FE:@? M -D6 +E6C:=6 /2E6C 7@C "?;64E:@? -+( for reconstitution and then either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, for dilution, as outlined above. No other diluents have been shown E@ 36 4@>A2E:3=6 M (2C6?E6C2= 5CF8 AC@5F4ED D9@F=5 36 :?DA64E65 G:DF2==J 7@C A2CE:4F=2E6 >2EE6C 2?5 discoloration prior to administration whenever solution and container permit. Any unused solution should be discarded according to institutional procedures for antineoplastics. Admixture Stability. TREANDA contains no antimicrobial preservative. The admixture should be prepared as close as possible to the time of patient administration. Once diluted with either 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, the final admixture is stable for 24 hours when stored refrigerated (2-8°C or 36-47°F) or for 3 hours when stored at room temperature (15-30°C or 59-86°F) and room light. Administration of TREANDA must be completed within this period. DOSAGE FORMS AND STRENGTHS: TREANDA for Injection single-use vial containing either 25 mg or 100 mg of bendamustine HCl as white to off-white lyophilized powder. HOW SUPPLIED/STORAGE AND HANDLING: Safe Handling and Disposal. As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of solutions prepared from TREANDA. The use of gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. If a solution of TREANDA contacts the skin, wash the skin immediately and thoroughly with soap and water. If TREANDA contacts the mucous membranes, flush thoroughly with water. Procedures for the proper handling and disposal of anticancer drugs should be considered. Several guidelines on the subject have been published. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate. How Supplied. TREANDA (bendamustine hydrochloride) for Injection is supplied in individual cartons as follows: NDC 63459-390-08 TREANDA (bendamustine hydrochloride) for Injection, 25 mg in 8 mL amber single-use vial and NDC 63459-391-20 TREANDA (bendamustine hydrochloride) for Injection, 100 mg in 20 mL amber single-use vial. Storage. TREANDA may be stored up to 25°C (77°F) with excursions permitted up to 30°C (86°F) (see USP Controlled Room Temperature). Retain in original package until time of use to protect from light.

In both studies, serious adverse reactions, regardless of causality, were reported in 37% of patients receiving TREANDA. The most common serious adverse reactions occurring in ≥ 5% of patients were febrile neutropenia and pneumonia. Other important serious adverse reactions reported in clinical trials and/or post-marketing experience were acute renal failure, cardiac failure, hypersensitivity, skin reactions, pulmonary fibrosis, and myelodysplastic syndrome. Serious drug-related adverse reactions reported in clinical trials included myelosuppression, infection, pneumonia, tumor lysis syndrome, and infusion reactions. [See Warnings and Precautions] Adverse reactions occurring less frequently but possibly related to TREANDA treatment were hemolysis, dysgeusia/taste disorder, atypical pneumonia, sepsis, herpes zoster, erythema, dermatitis, and skin necrosis. PostMarketing Experience. The following adverse reactions have been identified during post-approval use of TREANDA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: anaphylaxis; and injection or infusion site reactions including pruritus, irritation, pain, and swelling. Skin reactions including SJS and TEN have occurred when TREANDA was administered concomitantly with allopurinol and other medications known to cause these syndromes. [See Warnings and Precautions] OVERDOSAGE: The intravenous LD of bendamustine HCl is 240 mg/m2 in the mouse and rat. Toxicities included sedation, tremor, ataxia, convulsions and respiratory distress. Across all clinical experience, the reported maximum single dose received was 280 mg/m2. Three of four patients treated at this dose showed ECG changes considered dose-limiting at 7 and 21 days post-dosing. These changes included QT prolongation (one patient), sinus tachycardia (one patient), ST and T wave deviations (two patients), and left anterior fascicular block (one patient). Cardiac enzymes and ejection fractions remained normal in all patients. No specific antidote for TREANDA overdose is known. Management of overdosage should include general supportive measures, including monitoring of hematologic parameters and ECGs. 50

DOSAGE AND ADMINISTRATION: Dosing Instructions for CLL. Recommended Dosage: The recommended dose is 100 mg/m2 administered intravenously over 30 minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles. Dose Delays, Dose Modifications and Reinitiation of Therapy for CLL:

www.TheOncologyNurse.com

Manufactured by: Pharmachemie B.V. The Netherlands

Manufactured for: Cephalon, Inc. Frazer, PA 19355

TREANDA is a trademark of Cephalon, Inc., or its affiliates. ©2008-2011 Cephalon, Inc., or its affiliates. TRE-2263 (Label Code: 00016287.03) This brief summary is based on TREANDA full Prescribing Information.

nitive functioning tests were compared with scores of a population-based sample of 1509 women who did not undergo cancer treatment and were participants in a larger long-term study. Women treated with chemotherapy scored significantly lower on tests of immediate and delayed verbal memory, processing speed, executive function, and psychomotor speed than the reference group and similarly on the other 10 tests included in the study. The intergroup differences were small. On word learning tests, women who had chemotherapy had an average score of 24.3 of 45 compared with a score of 25.5 in the control group.

Someone in a demanding job might notice these changes in cognition, but someone who is not working and has a more relaxed lifestyle may not.

Senior author Sanne Schagen, MD, Netherlands Cancer Institute, Amsterdam, the Netherlands, said that these differences might or might not be apparent, depending on the specific tasks involved in people’s daily lives. Someone in a demanding job might notice these changes in cognition, but someone who is not working and has a more relaxed lifestyle may not. One limitation of this study is that CMF is an older chemotherapy regimen no longer considered a standard of care. However, Dr Schagen noted that more modern drugs would probably cause the same effects. Other limitations include the inability to prove cause and effect between chemotherapy and cognitive changes, which may be an effect of breast cancer itself. Also, baseline mental function was not assessed prior to chemotherapy. The study does not imply that women with breast cancer should not undergo chemotherapy. Rather, the implication is that patients and physicians should be aware of the potential cognitive effects of chemotherapy and seek help if these problems interfere with daily function. The effects documented in this study do not appear to be serious cognitive impairment or even mild cognitive impairment, but patients are scoring slightly lower on tests of memory and thinking, explained neuropsychologist Barbara Collins, PhD, Ottawa Hospital, Ontario, Canada, who was not involved in this study. ● —AG

April 2012 I VOl 5, NO 3

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News Briefs

GIST Outside GI Tract Has Poor Prognosis

rimary gastrointestinal stromal tumor (GIST) sited outside the gastrointestinal (GI) tract carries a poorer prognosis than primary GIST within the GI tract, according to a study presented at the recent ASCO GI Symposium in January 2012. Lead investigator of the study, Mary L. Guye, MD, surgical oncologist at the City of Hope Medical Center in Duarte, California, noted that these results suggest that GIST location should be factored into risk stratification. The reasons are unknown for the poorer prognosis in

GIST sited outside the GI tract, she said, noting that molecular analysis is needed to investigate the biology of

Extra-GI tumors were still associated with almost a 30% increase in mortality. these less common GISTs to help determine why they carry a worse prognosis.

The study included 2591 patients from a SEER (Surveillance, Epidemiology, and End Results) database from 1996-2008 who underwent primary surgery for GIST. Primary tumors were located outside the GI tract (omentum, mesentery, retroperitoneum, or another location) in 10% of cases. Patients with intra-GI and extra-GI primary tumors were of similar ages and racial distribution. For the group with extra-GI primary tumors, 5-year survival was 62% versus 70% for those with tumors located within the GI tract. Median overall sur-

vival was 105 months for extra-GI tumors versus 120 months for those with tumors in the GI tract (P = .002). Tumors sited outside the GI tract tended to be larger than 10 cm, have more advanced regional or distant disease, and were more likely to be treated with radiation therapy. In a multivariate analysis adjusting for these confounding factors, the findings remained the same. Extra-GI tumors were still associated with almost a 30% increase in mortality (P = .03). One limitation of the study is that the SEER registry does not include data on mitotic rate or on systemic medical therapies patients were taking. ● —AG

Cancer Center Profile Ohio State University Wexner Medical Center Carli Greenfield, ACNP, is part of the oncology program at the OSU Wexner Medical Center. She answered our questions about research and patient care.

of clinical trials and working with investigative pharmacological agents that could potentially change the face of medicine. Proudly, up to 10% of the patient population that we manage on a daily basis is actively taking part in a phase 1 or 2 clinical trial at any given time.

What are you excited about right now in the cancer field? Carli Greenfield (CG): One of the best aspects of Carli Greenfield, ACNP What approach does your working at a research institution such as the Ohio State University institution take in treating people Medical Center is being on the forefront with cancer?

Continued from cover

CG: We believe that mental health is just as important as a patient’s physical health, and an accessible support system plays a vital part in this. We encourage patients to include family members and/or friends in all appointments and decision making in order to improve the overall comfort level with their plan of care.

How does that translate to better outcomes for your patients? CG: This allows patients to have a better understanding of their treatment plan as well as to develop real-

ONCOLOGY ONCOLOGY NP NP

IMMEDIATE IMMEDIATE O OPPORTUNITY PPORTUNITY for an experienced Oncology NP at Marshall Hematology and Oncology, an independent, nonprofit community healthcare provider located in the heart of the Sierra Foothills between Sacramento and South Lake Tahoe. RESPONSIBILITIES RESPONSIBILITIES FOR FOR ONCOLOGY ONCOLOGY NP NP INCLUDE: INCLUDE: Work collaboratively with oncologist to provide direct patient care to outpatient population and oversee chemotherapy administration. Management experience required to facilitate staff ff,, physician, infusion center, clinic operations and oversight. Requires current CA RN license, BLS certification, Masters of Science degree in nursing with 12-24 xperimental learning as a nurse months of specialized classroom and ex practitioner,, minimum 2 years related clinical experience. Oncology certification strongly preferred. Certification by the American Nurse Credentialing Center to be obtained within 12 months of employment and must apply for, be awarded, and maintain privileges as an Allied Health Professional in accordance with the bylaws, rules & regulations of the medical staff of Marshall Medical Center.

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

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

www.marshallmedical.org www .marshallmedical.org

April 2012 I VOl 5, NO 3

How has the role of the oncology nurse changed over the past 5 years? CG: As medicine evolves, so does the disease itself. Patients are being diagnosed with cancer earlier and living longer than they were 5 years ago. I’m fortunate enough to work with physicians who are passionate about understanding the latest treatments that allow us to stay up-to-date with how we approach our patients’ care. What inspired you to enter the field of oncology nursing? CG: To be honest, I kind of fell into this specialty by accident, but I am thankful I did. Everyone knows someone who has been affected by cancer. And every day when I leave work, I am thankful to be working alongside some of the best healthcare providers in the country toward one goal: a cure.

Outstanding Outstanding O Opportunity pportunity ffor or

istic expectations and goals regarding their care.

Any advice for nurses just entering the field? CG: There is an extremely high rate of turnover in the world of oncology, and anyone who has worked in the field can understand why. At times you feel that no matter what you do, it’s not enough. But you have to remember that you are playing an active part in prolonging your patients’ lives another day, week, month, or year to spend time with their loved ones. If you weren’t working in this field, what would you be doing? CG: Orthopedic surgery. There’s always been something about the “glorified carpentry” that gets my adrenaline going. ●

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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 second 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 in the June issue of The Oncology Nurse-APN/PA.

Darcie Deaver, MSN, NP-C Moffitt Cancer Center Tampa, Florida

arcie Deaver has been an oncology nurse since 2003, when she began her career as a staff nurse in the inpatient bone marrow transplant unit. She completed a master of science degree in nursing at the University of South Florida (USF) in 2006 and is currently a nurse practitioner in the malignant hematology program at Moffitt Cancer Center in Tampa, Florida. According to her colleagues, she “has been a rock of support for our patients, our physicians, and our nurses. She consistently communicates with and includes the primary care team in the patient care plan.” The most important information she gives patients is the truth, explaining the disease in a way that makes sense to them, focusing on the facts, research, and reality. Her col-

Wendy Miano, RN, MSN, DNP, DN University Hospitals Case Medical Center Cleveland, Ohio

April 2012 I VOl 5, NO 3

inalist Wendy Miano became interested in nursing as an undergraduate student when she had the opportunity to volunteer at a hospice and was “struck by the notion of the patient and family as a unit of care, focusing on quality of life and empowerment.” This focus has continued through her career as an oncology nurse at University Hospitals, Case Medical Center (UH/CMC), beginning in 1984. Wendy has practiced in adult and pediatric acute care oncology and adult and pediatric hospice, in addition to contributing to the development of new nurses as an instructor of medical/surgical nursing. Her career path turned to nursing leadership in 1996 when she became Administrative Director of the Ireland Cancer Center Ambulatory Services and, in 2008, Chief Nursing Officer for Cancer Services at UH/CMC. Wendy believes the most important qualities in an oncology

leagues say Darcie’s delivery of this information is what makes her unique. She loves her job of caring for patients, and they experience her confidence and compassion. If she weren’t a nurse, Darcie would probably go to medical school.

Valuing a quest for knowledge and exhibiting a never quitting spirit, Darcie

is also a doctoral candidate at USF. She now spends most of her day seeing patients for her research. She has extensive knowledge about cutaneous T-cell lymphoma, peripheral T-cell lymphoma, mycosis fungoides, and Sézary syndrome and has given many presentations on these topics. Darcie has received a number of awards, including an Oncology Nursing Society commendation for outstanding achievement for her article “The Development of Pericarditis Following Peripheral Blood Stem Cell Transplantation: A Case Report” and Moffitt’s 2010 Advance Practice Professional. In nominating her for the ONE award, Darcie’s colleagues emphasize she “is always professional in her demeanor, gets along well with her peers, and always gives her best to patient care.”

nurse are critical thinking skills and emotional maturity that accompany a focus on holistic communication with patients to help them successfully navigate the complex multimodality nature of cancer treatment. Wendy’s colleagues view her as a key member of the team that collaborated to design, construct, and open the Seidman Cancer Center in 2011. This freestanding cancer hospital contains 144 inpatient beds, ambulatory clinics, and support services. In writing their nomination, they emphasized that Wendy was “truly a leader and role model who effectively utilized clinical knowledge in cancer patient care to create a new physical and programmatic model of oncology patient care, a unique achievement accomplished rarely in this field.” Staying true to her early impressions as an undergraduate student, Wendy attributes the success of the new facility to the input of 15 to

20 patient and family volunteers who were involved in all facets of the design process, “sitting as partners with organizational leaders.” Based on this input, the new facility has comfortable rooms outside each patient room where family and friends can be close to the patient, while also being able to have personal time meeting their own needs and attending to other responsibilities. Even a small detail such as including a small safe in each room allows what Wendy characterizes as a “monumental shift in how patients and families move within the space.” When asked to reflect on what she would be if not a nurse, Wendy would see herself as an oceanographer, caring for the earth through the interaction of water and animals. It is unmistakable that Wendy Miano considers the big picture, while emphasizing the importance of the individual, no matter what the situation.

The most important information Darcie gives patients is the truth, explaining the disease in a way that makes sense to them.

www.TheOncologyNurse.com

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the

hen nominating Patti Palmer for the ONE award, her colleagues described her as an exceptional oncology nurse educator who, during the past 2 years, guided the inpatient oncology team at the University of California Davis Medical Center through Putting Evidence Into Practice initiatives that improved satisfaction scores for communication

cell transplant multidisciplinary teams, for whom she identifies patients who may need to be seen for education or emotional support. She participates in institutional committees for the online chemotherapy order project, the shared governance research committee, the scientific review committee for the Cancer Center, and the clinical nurse specialist group.

ONE Award

from 40% to 92%, teamwork from 57% to 81%, cohesiveness from 30% to 81%, and overall excellent quality of care from 40% to 92%. Patti is involved with many aspects of oncology care at the Medical Center, including daily huddles with the medical oncology, surgical oncology, and stem

Patti has been an oncology nurse for 38 years. When she was preparing to go to college, she thought nursing was a good fit for someone like herself who likes science and math. Over the years she has found that “empathy, compassion, caring, and a mind with a neversatisfied thirst for learning” are impor-

tant qualities for an oncology nurse to possess. She strives to get to know her patients as individuals so she can make a plan of care that is uniquely suited to them. In the future, Patti believes that the patient’s treatment experience can be changed for the better by improving teamwork from outpatient to inpatient and back again. Patti enjoys oncology as an ever-changing specialty and has noticed that in the beginning she spent “a lot of time helping people die (and not doing it very well), and now we really focus on living full lives until and if you die.” She sees 2012 as a very exciting time for oncology and a great time to be an oncology nurse. If she weren’t a nurse, Patti enthusiastically proclaimed that she would see herself as a small and large animal veterinarian. This would be in addition to keeping her current hobby as a fiber artist. Combining science and softness, calculations and caring are characteristics that make Patti Palmer a worthy nominee for the ONE award.

Deborah and her coworkers administer chemotherapy, immunotherapy, and blood products to 35 to 45 patients per day. In almost 3 decades of practice, she has seen many improvements in medications available to the oncology patient. She relates that when she first started practicing, patients became deathly ill with nausea and vomiting after chemotherapy, and that is rare now. She has seen a significant shift in chemotherapy administration from the

The importance of education is also manifest by Deborah’s other possible career choice if not a nurse, that of a health reporter. She feels that increased knowledge in the community about diseases, and the importance of regular check-ups and early reporting of problems, is very important. Deborah believes in the importance of providing patients with hope and encourages them to keep a positive attitude during their journey toward an

Patti believes that the patient’s treatment experience can be changed for the better by improving teamwork from outpatient to inpatient and back again.

hen Deborah Thompson describes the connections she hopes to form with her patients, she calls them “her family members.” She explains that her first priority is to help the patient develop trust in her and comfort within the environment, because when they first come to the infusion center where she works, they are afraid. To create this, Deborah talks about “taking part in the journey together” with the patients, their family, and their friends, and she has found that when she refers to her patients as family members, they view her differently. Other important qualities for an oncology nurse, according to Deborah, are compassion, honesty, integrity, dedication, and dependability. As evidence that Deborah practices what she preaches, one of her patients wrote a letter of appreciation to Eric Shinseki, Secretary of Veterans Affairs, commending the care she rendered to him. For the past 29 years, Deborah has been an oncology staff nurse at the Atlanta Veterans Administration Medical Center. In the infusion center,

www.TheOncologyNurse.com

Deborah believes in the importance of providing patients with hope and encourages them to keep a positive attitude during their journey toward an end goal. inpatient to the outpatient setting, and most importantly, patients are living much longer after treatment. Ac cording to her colleagues, Deborah is a dedicated nurse who is “enthusiastic about educating her peers, the veterans, and the community, as evidenced by her consistent educational offerings.”

Patricia (Patti) Palmer, RN, MS, AOCN University of California Davis Medical Center Sacramento, California

Deborah Thompson, BSN, ONC Veterans Administration Medical Center Atlanta Decatur, Georgia

end goal. In fact, each day she writes a positive affirmation on the wall. Two of our ONE award nominee’s favorites are “A word of encouragement can mean the difference between giving up and going on” and “When life knocks you down, try to land on your back, because if you can look up, you can get up.”

April 2012 I VOl 5, NO 3

TON_April2012_v5_TON 4/13/12 3:18 PM Page 16

Thank you to all for Participating in the 2012

Oncology Nurse Excellence Award Joann Ackler, RN, OCN

Susan Epting, MSN, AOCN

Rita M. Levy, RN, OCN

Kimberly Rohan, MS, APN, AOCN, BSN, MSN, NP

Albert Einstein Cancer Center

Genentech

Doylestown Hospital

Edward Cancer Center

Khaled Alqawasmeh, MSN

Sylvia S. Estrada, RNC, WHCNP, CBCN, CCRP, MSN, MSHCM, BSN

Robin Lewis, RN, BSN, CBCN

Julie Ross, NP

Wake Forest Baptist Medical Center

Roswell Park Cancer Institute

Jennifer Lindeman, MS

Kim Ryan, APRN, OCN

Roswell Park Cancer Institute

Saul and Joyce Brandman Breast Center, Cedars-Sinai Medical Center

Roswell Park

CT Oncology Group

Toni Armstrong, BSN, ACLS

Sharon Etris, MSN, NP

Vera Luzietti, RN, ONS

Julie Sanner, RN, ONS, CBCN

UC Health

Coborn Cancer Center

Suzanne “Windy” Lyle, MS, FNP, AOCNP, MS, NP

Susan Schneider, PhD, RN, AOCN, ACNS-BC, FAAN

Portland VA Medical Center

Duke University School of Nursing

Denise Margiotta, Acute Nurse Practitioner

Marie Christine Seitz, RN, MSN, ANP-BC, AOCN

New York University Memorial Sloan-Kettering Cancer Center

Mount St. Mary’s College

David Lee Cancer Center, affiliated with Charleston Area Medical Center

Evangeline Masalta, BSN, APN

Moffitt Cancer Center and Research Institute

University of Texas MD Anderson Cancer Center

Kathy Shine, BSN, RN

Sara Flickner, RN, BSN, OCN

Toni McCoy, RN, BSN

Ironwood Cancer & Research Centers

Northwestern Memorial Hospital

Longview Regional Medical Center

Michelle Shriner, BSN, OCN

Jana Floershiem, RN, ADN, OCN

Susan McDonald, BSN, OCN

Adams County Cancer Center

Miners Colfax Medical Center

Brigham and Women’s Hospital

Anne Skwira-Brown, RN, CNP

Sandy Forrester, RN, OCN

Melissa McEwen, ADN, OCN

Essentia Duluth Clinic Cancer Center

Auerbach Hematology-Oncology

Texas Oncology

Elisabeth Smith, BSN

Diashea Foster

Myra Mcgrath, RN

Winship Cancer Institute, Emory University

Methodist Infusion Center

Halifax Health Center for Oncology

Maria Solaun, BSN

Lana Fournier, BS

Holly Meyerowich, RN, OCN

City Of Hope

Minnesota Oncology

Jupiter Medical Center

Karen Sommers, NP

Susan Foy, RN, OCN

Amy Miller, OCN

University of California Irvine

Reston Hospital Center

Paynesville Area Health Care System

Pauline Soucy, RN, AD, OCN

Jennifer Goldschmitt, NP

MaryKay Moore, BSN

Southern New Hampshire Medical Center

North Shore University Hospital/ Monter Cancer Center

Cleveland Clinic

Maria Stir, RN

Andrea Moran, APRN

Bayhealth Medical Center, Kent General Hospital

Cassie Gossett, RN, BSN, OCN

Cristina Suarez, CPN

University Medical Center Brackenridge

Neag Comprehensive Cancer Center University of Connecticut Health Center

Deborah Hancock, RN

Sabrina Mosseau, BS, RN, OCN

Maggie Syta, RN/NP

Grady Memorial Hospital

Samaritan Hospital Cancer Treatment Center

Shannon Hazen, RN, BSN, OCN

Mary P. Murphy, RN, OCN, CBCN

Bone Marrow Clinic at Roswell Park Cancer Institute

Presbyterian Hospital

Albert Einstein Cancer Center

Rosemary Taormina, BSN, OCN

Kimberly Hess, ANP, OCN

Massey Nematollahi, BScN, MScN, RN

Coastal Carolina Health Care, New Bern Cancer Care

Stronack Cancer Center at Southlake

Nancy N. & J. C. Lewis Cancer and Research Pavilion

Iris Nieves, BSN, OCN

Kimberly Elizabeth Thorn, RN, BSN, OCN

Sarah Holmes, RN, OCN

Nassau University Medical Center

Texas Oncology-Tyler

Auerbach Hematology-Oncology

Bridget E. O’Brien, DNP, APN, FNP-BC, AOCNP

Rose Tiabbi, RN, BS, OCN

Christine Hull, MSN, AOCNS

Northwestern Faculty Foundation, Robert H. Lurie Comprehensive Cancer Center of Northwestern University

North Shore Long Island Jewish Health System at Glen Cove Sara M. Tinsley, MS, ARNP, AOCN

Marsha Opalach, RN, OCN, MeD, CHPN

Moffitt Cancer Center

CentraState Medical Center

Jennifer Tripp, BSN, OCN

Lisa Pittman, RN

Parkland Medical Center

Adventist Hinsdale Hospital

Julie Vaday, MSN

Tina Pryor, RN

Kaiser Permanente Santa Clara Medical Center

Virginia Oncology Associates

Nancy Warner, RN

Meghan C. Punda, CRNP

Minnesota Oncology

Center for Cancer and Blood Disorders

Wendy Waters, RN, OCN

Anna Quincy, BSN, OCN

South Carolina Oncology Associates

Providence Sacred Heart Medical Center

Marigo Werner, RN, BSN, OCN

Annette Quinn, RN, MSN

Pikeville Medical Center Megan Wholey, NP/OCN

Tawam Hospital Rebecca Amirian, BSN

Terrebonne General Medical Center

Winship Cancer Institute of Emory University

Monica Averia, MSN, ACNP, NP

Trudie Eubanks, RN

USC Kenneth Norris Cancer Hospital

Forrest General Hospital

Gayle Balmaceda, RN, BSN, ANP-BC, GNP-BC

Helen Evers, BSN, RN

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UCDMC, Adult Infusion Center Patricia Bluml, MSN, ARNP, OCN

Via Christi Hospitals, Wichita-Blood and Marrow Transplant Center of Kansas Carolyn Bowers, RN, OCN

Ochsner Baptist Radiation Oncology Megan Brown

Methodist Infusion Center Michele Brown, NP

St. Luke’s Mountain State Tumor Institute Tess Buckles, RN, OCN

South Carolina Oncology Associates Dyane Bunnell, MSN, RN-BC, CPON, AOCNS

Nemours/Alfred I. duPont Hospital for Children Matthew Burke, MBA, RN, MSN, APRN-BC

Smilow Cancer Hospital at Yale Joan Burnham, RN

Methodist Willobrook Dorothy Cafran, RN, BSN, OCNS, CHPN

Northern Westchester Hospital Kim Calabro, BSN, RN, OCN

OSF Saint Anthony Medical Center-Center for Cancer Care Pamela Calarese, MS, RN, CS, OCN

Dana Farber Cancer Institute Mahnaz Capps, BSN

Walter Reed National Military Medical Center Sherry Cesati, RN

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Abramson Cancer Center, Hospital of the University of PA Freda Clark, RN, OCN

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Maimonides Cancer Center Stephany Jacques, RN, OCN

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Answered!

Your FAQs... Q:

Is it safe for women at risk for breast cancer–related lymphedema to lift weights?

The short answer is yes, with caveats. Exercise for patients In the past it was believed that exercise increased the flow of blood to tissues with breast cancer with, or at risk for, lymphedema is one set of and thus increased the workload of the already overloaded system. Women were recommendations for which there is actually evidence-based littold not to lift children, heavy bags, or other items with the affected arm. erature support. Many are not aware that most of the recommenHowever, this claim has not been supported in the evidence-based literature. In dations health professionals make regarding precautions to fact, more current literature speaks of the benefits and safety of exercise. Exercise decrease the risk of lymphedema are based on knowledge of the increases muscle mass, which increases the capabilities of the muscular pump pathophysiology and years of clinical expertise, but not on responsible for the movement of the lymph fluid. evidence. Additionally, it increases flexibility and strength and comThe fact that physical activity affects one’s energy supply, bats obesity (a risk factor for lymphedema).3 Swenson and The possibility colleagues found that strength training was a predictor of decreases fatigue and depression, maintains function, increasless lymphedema.4 Avoidance of exercise may recondition es bone mass, and even lowers the risk of breast cancer has that upper the arm and increase the chance of overuse, resulting in been accepted for awhile. However, previous to the late extremity exercise injury and potentially lymphedema. (See Table 1 for other 1990s, it was felt that strenuous exercise needed to be avoidfactors that have been identified to increase the risk of lymed to prevent lymphedema. The possibility that upper extremcould improve phedema after breast cancer treatment.) ity exercise could improve range of motion, prevent muscle Courneya and colleagues studied the effects of both aeratrophy, improve the pumping action of the muscle, and stimrange of motion, obic and resistance exercise in breast cancer patients initiulate the immune system was largely ignored. prevent muscle ating chemotherapy. This was a multicenter randomized Then Donald McKenzie, MD, PhD, at the University of controlled trial involving 243 patients. Patients were British Columbia, decided to test his theory that exercise was atrophy, improve assigned to usual care, supervised aerobic exercise, or superbeneficial. In February 1996, he formed a dragon boat team of the pumping action vised resistance exercise for the duration of their breast cancer survivors. This diagnosis of breast cancer was The primary end point was quality of life; the only criterion to join the team. McKenzie chose dragon of the muscle, and chemotherapy. occurrence of lymphedema was one of the secondary end boat rowing because it was a strenuous, repetitive upper body points. The authors’ conclusions were that neither type of exercise that he felt sent a visible message to people with stimulate the exercise significantly improved cancer-specific quality of breast cancer. Being a non–weight-bearing activity, it was immune system life, but they significantly improved self-esteem, physical associated with lower risk of physical injury than weight-bearing activities. Reasonable amounts of muscle mass are recruit- was largely ignored. fitness, body composition, and chemotherapy completion rate without causing lymphedema.5 ed. Frequency, duration, type of exercise, as well as intensity, Two more recent randomized controlled trials focused was prescribed in a progressive manner. Prescriptions started specifically on weight lifting in women at risk for or with with strengthening and stretching exercises and included sugbreast cancer–associated lymphedema. gestions for aerobic fitness. The 24 paddlers who signed up ranged in age from 31 In a pilot study, Schmitz and colleagues, at the University of Pennsylvania, to 62 years. They chose the team name “Abreast in a Boat.” No new cases of lymrecruited 141 women with a history of breast cancer and current lymphedema. phedema arose in these women. Several women reported an increase in shoulder Inclusion criteria included a unilateral nonmetastatic breast cancer, diagnosis 1 range of motion, and one even reported resolution of a reflex sympathetic dysto 15 years prior, body mass index (BMI) ≤50, not actively trying to lose weight, trophy. Anecdotally, all paddlers had an improvement in both physical and mental health.1 Continued on page 20 So what is lymphedema and why might exercise, including weight lifting, be beneficial for patients with breast cancer? Lymphedema of the skin and subcutaneous tissues is the most common clinical manifestation of the lymphatic fluid (load) exceeding the transport capacity for lymphatic fluid, ie, the body is unable to drain lymph fluid from the tissues. Lymph fluid is composed mainly of water and protein but also contains fatty acids, salts, white blood cells, microorganisms, and foreign debris. In breast cancer patients, a functional or anatomic abnormality due to surgery and/or radiation causes a reduction in the transport capacity of the lymphatic system. Lymphatic insufficiency or failure occurs, and interFox Chase Cancer Center stitial edema results. The edema worsens because of osmosis: trying for a state of balance, the protein in the lymphedematous fluid draws more water into the lymPhiladelphia, Pennsylvania phatic system to dilute the lymph fluid. Additionally, the white blood cells are unable to work properly in lymphedematous fluid, so the risk for infection Do you have a question you’d like answered? increases. Lymphedema is a chronic condition. If not treated very early, it E-mail us at editorial@greenhillhc.com can cause progressive swelling, fibrosis of soft tissues, infections, pain, and/or 2 paresthesias.

This Month’s FAQ

Answered by:

Deena Damsky Dell, MSN, RN-BC, AOCN, LNC

April 2012 I VOl 5, NO 3

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Your FAQs...

Answered!

Is it safe for women at risk for breast cancer–related... Continued from page 18 no evidence of cancer at the present, no medical conditions that limit exercise, and no history of weight lifting during the previous year. Women were assigned by computer to 1 of 2 groups. The computer program balanced the groups by age (<54 vs ≥54); difference in volume between affected and unaffected limbs (<10% vs 10%-20% vs >20%); number of nodes removed (<6 vs ≥6); BMI (<30 vs ≥30); months since diagnosis (<60 vs ≥60); and whether they had received radiation treatment.6 Based on the hypothesis that a program of controlled weight lifting exercises may increase the work capacity of affected limbs and protect them from injury sustained during common activities, participants were assigned to either a control group (no exercise) or a supervised progressive weight lifting group. The latter group received a 1-year membership at a community fitness center. For the first 13 weeks, women received two 90-minute instructional sessions a week. They continued unsupervised exercise twice a week for another 39 weeks. There was no upper limit placed on the resistance level to which the women could progress.6 After a year, there was no significant difference between the groups in the number of women who had an increase in arm swelling of ≥5% as assessed by certified lymphedema therapists. In fact, weight lifting reduced the number and severity of arm and hand symptoms and reduced the number of lymphedema exacerbations. Additionally, muscle strength was increased. The program developed in this study is available to breast cancer survivors at YMCAs across the country through the LIVESTRONG at the YMCA program.6 Schmitz and colleagues then recruited a group of women who did not have lymphedema but were at risk. Most breast cancer survivors do not have lymphedema; nevertheless, they alter the use of their upper limbs out of fear of developing it. Therefore, the Physical Activity and Lymphedema study was conducted to assess if exercise is safe for this group. The goal was to evaluate the incidence of lymphedema that could be attributed to weight lifting.7 Inclusion criteria in this study included nonmetastatic breast cancer diagnosis 1 to 5 years before; BMI of ≤50; no evidence of cancer; no medical conditions that would limit participation; no plans for surgery or to be away for 1 month during the study; stable weight, and not trying to lose weight; at least 2 lymph nodes

April 2012 I VOl 5, NO 3

Table 1 Predictors of Lymphedema After Breast Cancer Surgery4 Significant Predictor P Value Overweight (body mass index >25) .009 Axillary radiation .011 Mastectomy .008 Chemotherapy .033 More positive nodes .009 Fluid aspiration after surgery .005 Active cancer .008 Routine activity that causes aching .019 of arm on side of surgery Nonsignificant Factors-Significant Factors Usually lift more than 10 pounds .144 Whirlpool, hot tub, or sauna use .258 Ever wear compression sleeve .638 Wear breast prosthesis .371 Medical procedure on arm or hand on .862 side of surgery Injury on hand or arm on side of .28 surgery Prior medical condition limiting .292 hand or shoulder movement Predictors of Less Lymphedema Strength training .014 Air travel since surgery .0005

Odds Ratio 2.29 3.6 2.18 2.33 1.14 1.88 5.33 2.25

0.64 0.5 0.8 1.38 0.94 0.61 1.8

0.36 0.23

Table 2 Lymphedema Resources National Lymphedema Network American Cancer Society National Cancer Institute Living Beyond Breast Cancer Circle of Hope Lymphedema Foundation Lymphedema Research Foundation Lymphology Association of North America

www.lymphnet.org www.cancer.org www.cancer.gov www.lbbc.org www.lymphedemacircleofhope.org

LIVESTRONG at the YMCA

www.livestrong.org

removed; and no prior or current lymphedema diagnosis. Of the 3200 women recruited, 154 were found to meet the criteria and were randomized to 1 of 2 groups, again using a computer program to balance potential baseline confounders. Women assigned to the exercise group received a fitness center membership and supervised instruction for progressive weight resistance increments for 13 weeks, similar to the intervention in Schmitz’s first study, and then exercised without supervision for the next 39 weeks. Women in the control group were asked not to change their baseline activity level but were offered a 1-year fitness center membership as well as 13 weeks of instruction after the study was completed.7

www.lymphaticresearch.org www.clt-lana.org

Women in the weight lifting group gained strength, had a lower percentage of body fat, and had <5% increases in volume between their 2 arms. The control group had a 17% (13 of 75 patients) occurrence rate of those having ≥5% volume increase, while the weight lifting group only had an 11% (8 of 72 patients) occurrence rate. There were 3 cases of clinician-defined lymphedema in the control group and only 1 in the weight lifting group. A secondary analysis looked at women who had ≥5 nodes removed. In the control group, 22% experienced an increase in interlimb volume of ≥5%, compared with only 7% in the weight lifting group. This was a reduction of 70%.7 The authors concluded that there was

no increase in the risk of developing lymphedema with a program composed of slowly progressive weight lifting compared with no exercise and that there was the chance of a decrease in the onset of swelling in women who were deemed to be at higher risk due to the removal of ≥5 nodes. They recommended that all breast cancer survivors start participating in weight lifting in order to experience the health benefits it provides.7 Based on these results, recommendations for preventing and treating lymphedema in breast cancer survivors have been updated. The National Lymphedema Network (NLN) has issued a position statement on exercise. NLN states that exercise is an important component to maintaining health and that the majority of patients at risk for lymphedema can safely perform aerobic and resistance exercise if the exercises are initiated at a low intensity and increased gradually. There is no clear evidence that wearing a compression garment is helpful for those at risk. For those with lymphedema, aerobic and resistive exercise are still considered safe as long as compression garments are worn on the affected body part(s); the affected body part(s) are not exercised to fatigue; and appropriate modifications are utilized to prevent trauma and overuse injury.8 The American Cancer Society states “It’s important to use your affected arm for normal everyday activities to help you to heal properly and regain strength. This includes doing things like brushing your hair and bathing. Using your muscles also helps drain lymph fluid from the limbs. If you’ve had surgery or radiation treatment, ask your doctor or nurse when you can start to exercise and what type of exercises you can do. But keep in mind that overuse, which can result in injury, has been linked with the start of lymphedema in some women. It’s a good idea to follow these tips: • Use your affected arm as normally as you can. Once you are fully healed, about 4 to 6 weeks after surgery or radiation treatment, you can begin to go back to the activities you did before your surgery • Exercise regularly but try not to overtire your shoulder and arm. Before doing any strenuous exercise, such as lifting weights or playing tennis, talk with your doctor, nurse, or physical therapist. They can help you set goals and limits so that you can work at the level of activity that is right for you. Ask your doctor or physical therapist if you should be fitted for a

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Your FAQs... sleeve to wear during strenuous activities â&#x20AC;˘ If your arm starts to ache, lie down and raise it above the level of your heart â&#x20AC;˘ Avoid vigorous, repeated activities, heavy lifting, or pulling â&#x20AC;˘ Use your unaffected arm or both arms as much as possible to carry heavy packages, groceries, handbags, or childrenâ&#x20AC;?9

Lymphedema remains of great concern to breast cancer survivors because it has such a significant impact on their quality of life.

Lymphedema remains of great concern to breast cancer survivors because it has such a significant impact on their quality of life. It is important for healthcare professionals to know what factors actually influence the development of lymphedema. Many of the risk factors are not modifiable, but the addition of exercise, including a prescribed, progressive program of weight resistance, is one way to modify risk in a positive manner. Patients need education. A retrospective study of breast cancer patients revealed that those who developed lymphedema consistently stated that they received little or no education about this condition. Pretreatment and posttreatment education need to take place and be reinforced throughout the continuum of survivorship.2 Remember, survivors should be medically cleared before starting an exercise program, and exercise needs to be started slowly and increased gradually. Exercise should be stopped for signs of injury such as pain or increased swelling. Refer to Table 2 for information resources available for both healthcare providers and patients. â&#x2014;? References 1. McKenzie DC. Abreast in a Boatâ&#x20AC;&#x201D;a race against breast cancer. CMAJ. 1998;159:376-378. 2. Lawenda BD, Mondry TE, Johnstone PA. Lymphedema: a primer on the identification and

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management of a chronic condition in oncologic treatment. CA Cancer J Clin. 2009;59:8-24. 3. Poage E, Singer M, Armer J, et al. Demystifying lymphedema: development of the lymphedema putting evidence into practice card. Clin J Oncol Nurs. 2008;12:951-964. 4. Swenson KK, Nissen MJ, Leach JW, et al. Casecontrol study to evaluate predictors of lymphedema after breast cancer surgery. Oncol Nurs Forum. 2009;36:185-193. 5. Courneya KS, Segal RJ, Mackey JR, et al. Effects of aerobic and resistance exercise in breast

Answered!

cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol. 2007;25:4396-4404. 6. Schmitz KH, Ahmed RL, Troxel A, et al. Weight lifting in women with breast-cancer-related lymphedema. N Engl J Med. 2009;361:664-673. 7. Schmitz KH, Ahmed RL, Troxel AB, et al. Weight lifting for women at risk for breast cancerâ&#x20AC;&#x201C;related lymphedema. JAMA. 2010;304:26992705. 8. NLN Medical Advisory Committee. Position

Statement of the National Lymphedema Network. Topic: exercise. www.lymphnet.org/pdfDocs/nln exercise.pdf. Accessed October, 12, 2011. 9. American Cancer Society. Lymphedema: what every woman with breast cancer should know. www.cancer.org/Treatment/TreatmentsandSideEff ects/PhysicalSideEffects/Lymphedema/WhatEvery WomanwithBreastCancerShouldKnow/lymphede ma-with-breast-cancer-to-prevent-lymphedema. Updated October 25, 2010. Accessed October 12, 2011.

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CONTINUING EDUCATION APRIL 2012 • VOLUME 5 • NUMBER 1

5th Annual

CONSIDERATIONS in

Multiple Myeloma

™

ASK THE EXPERTS: Newly Diagnosed Patients LETTER PUBLISHING STAFF President & CEO Brian F. Tyburski

Chief Operating Officer Pam Rattananont Ferris

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

Editorial Director Susan Berry susan@coexm.com

Project Manager Elizabeth S. Cohen liz@coexm.com

Copyeditor Dana Delibovi

FROM THE

EDITOR-IN-CHIEF

Over the past several years, significant progress has been made in the management of multiple myeloma (MM). This is due, in large part, to an accumulating knowledge of the biology of the disease, along with the development and clinical investigation of highly effective therapies. The shift in the paradigm of care for MM has resulted in revised criteria for diagnosing, staging, and risk-stratifying patients; new standards of care; and updated guidelines for the management of comorbidities and treatment-related toxicities. However, more progress is needed and many questions remain regarding the application and interpretation of recent clinical advances. In this fifth annual “Considerations in Multiple Myeloma” newsletter series, we continue to address frequently asked questions related to the diagnosis and treatment of the disease. To provide an interprofessional perspective, questions are answered by physicians, nurses, and pharmacists from leading cancer institutions, who share their insight, knowledge, and professional experience regarding evidence-based care. In this first issue, experts from Winship Cancer Institute of Emory University answer questions pertaining to the management of newly diagnosed patients.

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

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FACULTY Leonard T. Heffner, Jr., MD Associate Professor of Hematology and Oncology and Internal Medicine Emory University Clinical Director of the Myeloma Program at Winship Cancer Institute of Emory University, Atlanta, GA

Melanie Watson, RN, OCN Oncology Certified Registered Nurse Myeloma Team/BMT Winship Cancer Institute Emory University Atlanta, GA

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Supported by educational grants from Celgene Corporation and Millennium: The Takeda Oncology Company.

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

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CONSIDERATIONS IN MULTIPLE MYELOMA Sponsor This activity is jointly sponsored by Medical Learning Institute, Inc., and Center of Excellence Media, LLC. Target Audience The activity was developed for physicians, nurses, and pharmacists involved in the treatment of patients with multiple myeloma (MM). Educational Objectives Upon completion of this activity, the participant will be able to: • Use diagnostic and staging criteria to distinguish active multiple myeloma (MM) from smoldering MM and monoclonal gammopathy of undetermined significance • Determine appropriate treatment for newly diagnosed MM based on patient- and disease-related characteristics and the riskbenefit profile of available agents and combinations • Apply evidence-based strategies to prevent and/or manage common comorbidities in patients with MM Commercial Support Acknowledgment This activity is supported by educational grants from Celgene Corporation and Millennium: The Takeda Oncology Company. Instructions for Credit There is no fee for this activity. To receive credit after reading this CME/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/P12025.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 MLI at 609-333-1693 or cgusack@mlicme.org. Physician Credit Designation The Medical Learning Institute, Inc. (MLI) designates this enduring material for a maximum of 1.25 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 (ACCME) through the joint sponsorship of the Medical Learning Institute, Inc. and the Center of Excellence Media, LLC. The Medical Learning Institute, Inc. is accredited by the ACCME to provide continuing medical education for physicians. Registered Nurse Designation Medical Learning Institute, Inc. (MLI). Provider approved by the California Board of Registered Nursing, Provider Number 15106, for 1.25 contact hours. Registered Pharmacy Designation Medical Learning Institute, Inc. (MLI) is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. Completion of this activity provides for 1.25 contact hours (0.125 CEUs) of continuing education credit. The universal activity number for this activity is 04689999-12-012-H01-P. 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 MLI for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations. Planners’ and Managers’ Disclosures Dana Delibovi, Medical Writer, has nothing to disclose. William J. Wong, MD, MLI Reviewer, has nothing to disclose. Patricia A. Ensor, RPh, MBA, MLI Reviewer, has nothing to disclose. Judith A. Bonomi, RN, MS, MSN, OCN, has disclosed that her spouse is investigator on a study for Agenix and Lilly; on the data monitoring committee for Infinity; and on the data monitoring committee and PI on a study for Pfizer.

Faculty Disclosures *Sagar Lonial, MD, is Consultant to Bristol-Myers Squibb, Celgene Corporation, Merck, Millennium: The Takeda Oncology Company, Novartis, and Onyx. Leonard T. Heffner, Jr., MD, has nothing to disclose. Melanie Watson, RN, OCN, has nothing to disclose. *Minal Surati, PharmD, has nothing to disclose. 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/CE activity for any amount during the past 12 months. Disclaimer The information provided in this CME/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 towards or promotion for any agent discussed in this program should be inferred. Agenda: 1.25 hours Articles/Commentaries: 60 minutes Evaluation/Posttest: 15 minutes Date of original release: April 16, 2012 Valid for CME/CE credit through: April 16, 2013

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

Evolving Concepts in the Management of Newly Diagnosed Multiple Myeloma Leonard T. Heffner, Jr., MD Associate Professor of Hematology and Oncology and Internal Medicine, Emory University Clinical Director of the Myeloma Program at Winship Cancer Institute of Emory University, Atlanta, GA

Introduction The management of multiple myeloma (MM) is rapidly changing. New prognostic systems based on clinical and biologic features, such as cytogenetic abnormalities, continue to be developed and refined. Novel agents designed to interrupt myeloma growth and survival pathways have also entered the clinical arena, leading to improved response rates, survival, and quality of life. A major challenge is to define the optimal use of these new tools and therapies in order to significantly impact the natural history of disease. In this article, Leonard T. Heffner, Jr., MD, answers questions related to the diagnosis, staging, and initial management of patients with MM, and offers insights on his institution’s approach to aligning patient- and disease-characteristics with the most appropriate treatments to optimize care.

monoclonal (M) protein in serum and <10% of bone marrow plasma cells (BMPCs), but they do not have end-organ damage. In SMM, the clinical and laboratory findings are the same as MGUS except that the serum Mprotein is 3 g/dL and/or the BMPCs are 10%. Symptomatic MM is determined by the presence of 10% BMPCs, serum or urinary M-protein, and evidence of end-organ damage; specifically, hypercalcemia, renal insufficiency, anemia, or bone lesions (Table 1).1-4 Overall, the risk of MGUS progressing to MM is about 1% per year.2 However, the risk of progression for SMM is considerably higher; approximately 10% per year in the first 5 years.2 Risk factors for progression in SMM include: plasma cell mass including M-protein size and the percentage of BMPCs, abnormal free light chain (FLC) ratio, proportion of phenotypically abnormal BMPC, and presence of magnetic resonance imaging (MRI) abnormalities2 (Table 2). Patients with SMM who have an FLC ratio of either <0.125 or >8 have an increased risk for progression to symptomatic myeloma, and this risk is independent of the risk defined by the percentage of BMPCs or size of the M-protein spike.2,5 Should patients with high-risk SMM be observed or treated?

What criteria are used to distinguish smoldering multiple myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) from active myeloma?

MGUS and SMM are asymptomatic, and each carries a considerably different potential for progression to MM. Patients with MGUS have <3 g/dL

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The current standard of care for asymptomatic SMM is observation.6 However, we do know that a large majority of high-risk patients will evolve into symptomatic myeloma that requires treatment. Clinical trials are ongoing to assess whether the progression of SMM can be delayed or halted with early treatment. One such study is the Eastern Cooperative Oncology Group

April 2012 I VOl 5, NO 3

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CONTINUING EDUCATION

Table 1. Diagnostic Criteria for Specific Plasma Cell Disorders1-4

Table 2. Risk Factors for Progression in Smoldering Multiple Myeloma5

Monoclonal gammopathy of undetermined significance (MGUS) All 3 criteria must be met: • Serum monoclonal protein <3 g/dL • Clonal bone marrow plasma cells <10% • Absence of end-organ damage (such as CRAB criteria) that can be attributed to the plasma cell proliferative disorder

Higher plasma cell mass (including monoclonal-protein size and percentage of BMPCs) Abnormal free light chain ratio Abnormal immunophenotype and immunoparesis (95% of BMPCs with abnormal phenotype; decrease in 1-2 uninvolved immunoglobulins)

Smoldering multiple myeloma (SMM) (also referred to as asymptomatic multiple myeloma)

Evolving pattern (progressive increase in the serum monoclonal-protein value, eg, increase in monclonal-protein level in each of the first 2 follow-up visits)

Both criteria must be met: • Serum monoclonal protein (IgG or IgA) 3 g/dL and/or clonal bone marrow plasma cells 10% • Absence of end-organ damage (such as CRAB criteria) that can be attributed to the plasma cell proliferative disorder

Presence of MRI abnormalities (especially a focal pattern on spinal MRI) BMPCs indicates bone marrow plasma cells; MRI, magnetic resonance imaging.

Multiple myeloma (MM) All 3 criteria must be met, except as noted: • Clonal bone marrow plasma cells 10% • Presence of serum and/or urinary monoclonal protein (except in patients with true nonsecretory MM) • Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder (specifically CRAB): Calcium elevation: serum calcium 11.5 mg/dL or Renal insufficiency: serum creatinine >2 mg/dL Anemia: hemoglobin >2 g/dL below lower limit of normal or value <10 g/dL Bone lesions: lytic lesions, severe osteopenia, or pathologic fractures

(ECOG) E3A06 phase 2/3 trial, which is comparing the progression-free survival of patients with high-risk SMM treated with lenalidomide or observation.7 Lenalidomide was chosen because of its clinical activity in MM, as well as the fact that it can be administered orally and is generally well tolerated. Thirty-four patients were enrolled in the phase 2 portion of the trial and were treated with lenalidomide 25 mg/day on days 1 to 21 of a 28-day cycle for 6 cycles in the absence of disease progression or unacceptable toxicity. Following a 6-month hold for safety analysis of the phase 2 data, the phase 3 portion of the trial, in which 370 patients will be randomized to either lenalidomide or observation, will begin enrollment. I think this is an exciting trial because we are trying to move back the clock a little rather than wait until a patient with SMM has become symptomatic. It will be interesting to see whether the natural history of the disease can be influenced with early treatment, especially in a population that has a fairly high risk of eventually requiring therapy. How have staging criteria for MM evolved over time?

First published in 1975, the Durie-Salmon (DS) staging system was the method clinicians commonly relied on for staging MM for more than 25 years. This system assessed myeloma tumor burden, and based stages I, II, and III on serum M-spike, hemoglobin, calcium level, and number of bone lesions. Subclassifications A and B reflected the degree of kidney involvement, as measured by creatinine level.8 The DS staging system provided a framework by which clinicians could communicate clearly with each other regarding the extent of the disease. Unfortunately, there were drawbacks to this system. Many found it to be too complex, and there were problems in terms of evaluating lytic bone lesions accurately. To address these issues, investigators proposed a new method of staging called the International Staging System (ISS). This system includes an assessment of beta-2-microglobulin (ß2M) and serum

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albumin levels, which were shown in a multi-variant analysis to be the 2 important prognostic factors in myeloma.9 Patients with stage I disease have a ß2M level <3.5 mg/L and albumin level 3.5 g/dL (median survival 62 months) compared with stage III with ß2M 5.5 mg/L (median survival 29 months) and stage II (not meeting criteria for either stage I or III) (median survival 44 months).9 Because ß2M and serum albumin are easily obtainable parameters, the ISS has superseded the DS staging system and is now widely accepted as the standard of care for staging MM. What role does cytogenetic testing play in the prognosis and treatment of newly diagnosed patients with MM?

The use of cytogenetic testing to help identify myeloma patients with highrisk disease continues to evolve as we learn more about the biology of the disease. Conventional metaphase karyotyping is one modality for assessing risk, but it is not as informative as we would like because myeloma cells proliferate poorly in vitro.10 This method of analysis is useful, however, for the screening of hyper- and hypodiploidy and cytogenetic abnormalities such as deletion of chromosome 13 [del(13q)].4,11 Fluorescence in situ hybridization (FISH), on the other hand, analyzes cells in mitotic interphase, which allows better identification of certain chromosomal abnormalities.11 In particular, it is instrumental in screening for del(13q), deletion of the short arm of chromosome 17 [del(17p)], translocations involving chromosomes 4, 11, 14, and 16 [t(4;14), t(11;14), and t(14;16)], and 1q21 amplification.4,11 Abnormalities indicative of poorer prognosis in myeloma include del(17p), t(4;14), and t(14;16).10,12,13 Interestingly, del(13q), once considered a high-risk characteristic, is no longer thought to indicate a poor prognosis if it occurs independently of other cytogenetic abnormalities.10,14 At diagnosis, metaphase karyotyping and FISH results are certainly very important to obtain and use in treatment planning, but they must be considered in the context of other features of a patient’s condition, such as age, stage of disease, extent of bone disease and renal function, and comorbidities. In addition, there is still a question as to how best to incorporate results into a patient’s course of therapy because cytogenetic abnormalities continue to evolve over time.14,15 At our institution, we retest cytogenetics prior to transplantation to determine whether a patient’s risk status has changed in any way. Clinical evidence suggests that bortezomib and lenalidomide may have particular value in the context of certain high-risk cytogenetics.13,16-19 Whenever possible, we treat newly diagnosed myeloma patients with regimens that contain one or both of these agents. In addition to cytogenetic abnormalities, gene expression profiling (GEP) signatures are now being identified, including a 70-gene profile from the

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University of Arkansas20 and a 15-gene profile by the Intergroupe Francophone du Myélome.21 Although these 2 profiles do not share any common genes, GEP has the potential to be a useful tool for risk-stratifying patients and determining optimal therapy, and investigation in this area continues. For example, GEP signatures are being utilized in the ECOG E3A06 trial for SMM,7 to help identify patients who are going to have higher or lower risk of progression.

Figure. Best responses to RVD for the treated population and the phase 2 population.19

100

100%

How do you determine the appropriate treatment for newly diagnosed MM?

What advances have been made to help clinicians assess bone disease in MM?

74% 67%

Patients (%)

For transplant-eligible patients, the approach we typically use is frontline treatment with a combination of lenalidomide, bortezomib, and dexamethasone (RVD). In a phase 1/2 study in newly diagnosed patients, this combination was shown to have favorable tolerability, and resulted in a partial response or better rate of 100%, with a 74% rate of very good partial response or better in the phase 2 population (Figure).19 The study included subgroup analyses of patients with high-risk cytogenetics, which showed that response to RVD was unaffected by cytogenetic abnormalities. This finding suggested that RVD may overcome high-risk cytogenetics, but was not definitive because of the small sample size of patients with these abnormalities. We almost always use this combination, whether the risk is standard or high, unless the patient has plasma cell leukemia or another medical condition that would require a different approach to treatment. RVD is also being used more frequently in the nontransplant setting, as long as patients can tolerate these agents. If RVD is too aggressive, we consider regimens using melphalan and prednisone combined one of the novel agents bortezomib, lenalidomide, or thalidomide. If we can find a clinical trial that would suit the needs of transplant-ineligible patients better, we may offer that to them.

PR VGPR CR/nCR

57%

39%

Best Responses in All Patients (n=66)

Best Responses in Phase 2 Patients (n=35)

CR/nCR indicates complete response/near-complete response; PR, partial response; VGPR, very good partial response; RVD, lenalidomide/bortezomib/dexamethasone.

sion. We also repeat bone assessments by PET or MRI after a course of therapy. For transplant-eligible patients, this is done prior to transplant to document the degree of response to treatment. For transplant-ineligible patients, this practice helps us to determine whether we should continue with the current approach to therapy. Conclusion

In the most recent consensus guidelines from the International Myeloma Working Group, the bone survey is still the gold standard for assessing myeloma bone disease.22 However, there is a movement among many cancer centers to make more frequent use of MRI and positron emission tomography/computed tomography (PET/CT) scans.4,23 Fortunately, Medicare now allows coverage of PET/CT scans for myeloma. At our institution, we consider each patient’s case on an individual basis. In general, we still conduct a bone survey. If results are negative, we will typically do an MRI of the spine and pelvis, as this procedure can pick up abnormalities even if a plain film is negative in symptomatic patients.22 The use of PET scans is clearly important, because they can detect not only bone-based disease, but also extramedullary disease.22,24

The use of PET scans is clearly important, because they can detect not only bone-based disease, but also extramedullary disease.

For patients with oligosecretory or nonsecretory disease who do not have laboratory parameters to monitor outside of a bone marrow examination, and particularly for patients with extramedullary plasmacytomas, we use PET scans to monitor them and to document whether they are in remis-

Progress in the diagnosis and treatment of MM has been tremendous over the past 10 to 15 years and continues to move forward. We are going to continue to see new drugs come along that will no doubt result in even more progress. In this last decade alone, we have been able to take the novel agents thalidomide, lenalidomide, and bortezomib, and utilize them in numerous combinations and schedules. In addition to the continued research to find an approach to cure, I think the future of myeloma may be in going back to the precursor diseases. I believe MGUS and SMM are where we are ultimately going to learn why these plasma cell dyscrasias progress to myeloma. ◆ References 1. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009;23:3-9. 2. Kyle RA, Durie BG, Rajkumar SV, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010:24:11211127. 3. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haem. 2003;121:749-757. 4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Multiple myeloma. Version 1.2012. www.nccn.org/professionals/physician_gls/pdf/ myeloma.pdf. Accessed March 18, 2012. 5. Blade J, Dimopoulos M, Rosinol L, et al. Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations. J Clin Oncol. 2010;28:690-697. 6. Dispenzieri A, Kyle RA, Katzmann JA, et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood. 2008;111:785-789. 7. Lenalidomide or observation in treating patients with asymptomatic high-risk smoldering multiple

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Improving Patient Outcomes in Newly Diagnosed Multiple Myeloma Oncology Certified Registered Nurse/Myeloma Team/BMT Winship Cancer Institute, Emory University Atlanta, GA

Introduction At the time of diagnosis, patients with multiple myeloma (MM) may present with numerous disease-related symptoms. Each of these complications requires supportive care, and providing that care demands a high degree of individualization. In many cases, one symptom can influence the management of another. For example, renal insufficiency may impact the administration of bisphosphonates used to protect bone health. In addition, specific agents used to treat myeloma may produce confounding symptoms, such as neurotoxicity in a patient already experiencing disease-related bone pain. In this article, Melanie Watson, RN, OCN, discusses her center’s evidence-based approach to providing symptom relief for patients with newly diagnosed myeloma.

What is the nurse’s role in the assessment and management of patients with MM who present with hypercalcemia?

Elevated calcium is a relatively common laboratory finding in patients newly diagnosed with MM (Figure).1 The incidence of hypercalcemia— defined as a very high serum calcium ( 11 mg/dL)—is approximately 13%; however, an additional 15% of patients present with calcium levels of 10.2 mg/dL to 10.9 mg/dL.1 When we conduct an initial work-up on a patient, a finding of hypercalcemia prompts us to take necessary steps to minimize this complication. Intervention becomes especially urgent if the patient reports potential symptoms of hypercalcemia, such as emesis, weakness, and confusion. Immediate hydration is essential, and many patients will also require bisphosphonate therapy. In some instances, it is necessary to prescribe antiemetic agents for patients who are experiencing hypercalcemia-related nausea and vomiting. At our center, we treat hypercalcemia if the serum calcium level is 10.5 mg/dL. We also initiate treatment if serum calcium is only borderline high, but serum albumin is low, as the serum calcium should be corrected based on the serum albumin. Some patients present with very mild hypercalcemia (10.5 mg/dL with a low albumin); our approach with these patients is to treat with intravenous (IV) hydration only, and then routinely check their calcium levels. For all other patients, we control hypercalcemia with hydration plus bisphosphonate therapy (zoledronic acid or pamidronate). If zoledronic acid is used, it is given as a single IV dose of 4 mg infused over 15 to 30 minutes. This is followed by a second 4-mg dose given at a minimum of 7 days, if necessary.2 Pamidronate dosing of 60 mg to 90 mg, infused over 2 to 4 hours, is dependent on the level of albumin-corrected serum calcium as well as a patient’s renal function.3 Treatment with bisphosphonate therapy generally results in rapid resolution of hypercalcemia.

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Renal insufficiency is also prevalent in newly diagnosed patients with MM. What role do nurses play in the evaluation, monitoring, and supportive care of this complication?

Approximately 19% of patients with MM present with a serum creatinine 2 mg/dL at the time of diagnosis (Figure). Renal dysfunction may be exacerbated by hypercalcemia, but even after serum calcium levels have stabilized, we still have to contend with myeloma-related renal tubular pathology.4 The presence of renal insufficiency sometimes signals that the patient has light-chain myeloma, which has been correlated with elevated creatinine.1 Circulating monoclonal immunoglobulin free light chains can clog up renal tubules; myeloma kidney is characterized by light-chain cast nephropathy.4 Laboratory testing for serum creatinine, creatinine clearance, and serum and urine protein electrophoresis are critical in the initial work-up of patients with MM. Nurses are primarily responsible for the evaluation of any symptom patterns related to impaired renal function, such as elevated blood pressure, changes in urination, and fatigue. It is important to remember, however, that a patient may have renal insufficiency in the absence of any physical signs or symptoms. Following initial assessment, we keep a close watch on renal function and check laboratory results at every visit, which during frontline treatment may be several times a week. We also encourage patients to drink between 2 and 3 L of fluid a day to stay hydrated. It is imperative to obtain a list of every drug the patient is taking, to ensure that none of them are renally toxic—this includes over-the-counter (OTC) medications. We strongly advise patients to avoid the use of OTC or prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), which can have adverse renal effects. We also remind them to report any changes in their urine (eg, output, frequency, appearance, presence of blood).

Figure. Incidence of anemia, renal dysfunction, and hypercalcemia in newly diagnosed patients with MM (N=1027).1

50 40

Patients (%)

Melanie Watson, RN, OCN

35%

30 19%

13% 10 0 Hemoglobin 10 g/dL

Creatinine 2 mg/dL

Calcium 11 mg/dL

MM indicates multiple myeloma.

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Table 1. Suggested Lenalidomide Dose Reductions for Renal Impairment7 Degree of Renal Dysfunction Moderate

Renal Function (Cockcroft-Gault CrCl) 30-60 mL/min

Dose for MM 10 mg orally every 24 hours

Severe (not requiring dialysis)

<30 mL/min

15 mg orally every 48 hours

End-stage renal disease (requiring dialysis)

<30 mL/min

5 mg orally once dailya

CrCl indicates creatinine clearance; MM, multiple myeloma. a Doses that fall on dialysis days should be given after dialysis.

Table 2. Bortezomib Dose Modifications Based on Severity of Peripheral Neuropathy10 Severity of Peripheral Neuropathy

Modification of Dose and Regimen

Grade 1 (paresthesia or loss of reflex) without pain or loss of function

No action

Grade 1 with pain or grade 2 (interferes with function but not with activities of daily living)

Reduce bortezomib dose from 1.3 to 1.0 mg/m2

Grade 2 with pain or grade 3 (interferes with activities of daily living)

Withhold bortezomib until toxicity resolves, then reinitiate at a dose of 0.7 mg/m2 once weekly

Grade 4 (permanent sensory loss that interferes with function)

Discontinue bortezomib

Grading based on NCI Common Toxicity Criteria CTCAE V 3.0.

A small subset of patients with myeloma-related renal insufficiency will require dialysis. In many cases, this need for dialysis is reversible with effective antimyeloma treatment. Reducing the myeloma burden as quickly as possible is the key to getting patients off dialysis. Our induction therapy for newly diagnosed patients with significant renal dysfunction—certainly in the transplant-eligible group but also in many nontransplant candidates— is the combination of bortezomib, thalidomide, and dexamethasone (VTD).5 The inclusion of novel agents in this regimen offers a benefit to patients with renal insufficiency.6 Current consensus suggests that treatment with bortezomib plus dexamethasone provides optimal therapy to reverse renal dysfunction in myeloma. Lenalidomide is also effective in reversing renal insufficiency if given at doses appropriately reduced on the basis of renal function (Table 1).6,7

The severity of renal impairment affects our selection of bisphosphonate therapy to protect against skeletal-related events.

The severity of renal impairment affects our selection of bisphosphonate therapy to protect against skeletal-related events (SREs), since this class of drugs is excreted via the kidney and can therefore produce renal toxicity. At our institution, we use zoledronic acid for patients with a baseline crea-

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Table 3. Selected Outcomes in Cancer Patientsa with Vertebral Compression Fractures Treated with Balloon Kyphoplasty vs Nonsurgical Management12 Outcome Variable at 1 Month of Follow-Up

Kyphoplasty (n=70)

Nonsurgical Management (n=64)b

P Value

Mean change from baseline in RDQc score (primary endpoint; improvement = decline in score)

-8.3 points

+0.1 points

<.0001

Change in medication utilization (% change in the incidence of use)

-44.7

-2.3

<.001

Overall incidence of adverse events (% of patients)

37.1

29.7

Not reported

32% of patients in the kyphoplasty group and 44% of patients in the nonsurgical management group had a diagnosis of MM. Analgesics, bed rest, bracing, physiotherapy, rehabilitation programs, walking aids, radiation treatment, and other antitumor therapy at the discretion of treating physicians. Patients receiving kyphoplasty were allowed to receive these treatments as well, in addition to their surgery, if needed. c RDQ indicates back-specific functional status measured by the Roland-Morris disability questionnaire. b

tinine clearance of 30 mL/min, dose-adjusted as creatinine clearances from >60 mL/min to 30 mL/min.2 This is given as a 30-minute infusion, which, in our experience, tends to be gentler on the kidney than the standard 15-minute infusion. If creatinine clearance is below 30 mL/min we use pamidronate, although the pharmacokinetic data on its use in such instances is limited.3 In addition to initiating bisphosphonate therapy, what other supportive care strategies are necessary for patients with myelomarelated bone disease?

Approximately 80% of patients with MM present with SREs, which typically manifest as osteolytic lesions or fractures.1 Therefore, bisphosphonate therapy is a mainstay of bone support in MM. From a nursing perspective, ongoing patient education about bisphosphonate use is critical to help patients remain on this effective therapy. The most important educational intervention is in the area of dental hygiene, since osteonecrosis of the jaw (ONJ) is a rare but very serious adverse effect of bisphosphonate therapy, for which there is no satisfactory intervention.8 For example, zoledronic acid was shown in the Medical Research Council Myeloma IX study to reduce SREs and improve overall survival compared with clodronic acid, but it also produced a higher rate of ONJ than clodronic acid.9 We require a dental exam before we start a bisphosphonate for SRE prevention. We repeatedly inform patients that they should have no invasive dental procedures that disturb the bone while being treated with bisphosphonates. We tell patients, “If it’s above the gum line, it’s fine. If it’s below the gum line, it’s not.” If an invasive procedure becomes necessary, we need to know in advance. We hold the bisphosphonate therapy for 2 months before and 2 months after any invasive dental procedure. Treatment of bone pain is another critical aspect of supportive care. Nurses have always held a leadership role in the management of pain, and it takes all of our skill and insight to effectively treat the complexities of

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pain associated with MM. The first step is always an assessment based on the patient’s self-reported level of pain, using both qualitative inventories and a quantitative scale such as the 1-10 visual analog scale. Pain assessment should be frequent and routine, not only to determine severity, but also to help distinguish between bone pain and neurotoxicity that may be associated with the use of specific novel agents.7,10 We recently switched from IV to subcutaneous (SC) bortezomib in certain regimens, because SC dosing appears to significantly reduce the risk of bortezomib-induced peripheral neuropathy (BIPN).11 For patients who receive bortezomib as an IV infusion, dose reductions can be implemented to prevent irreversible nerve damage and ensure optimal benefits of treatment (Table 2).10 BIPN typically improves following implementation of these recommendations or resolves following treatment discontinuation.

As a nurse, I feel I have done my job well when a patient demonstrates an understanding of their disease and feels comfortable calling me to report a new symptom or potential complication.

Opioid treatment is often necessary for myeloma-associated bone pain, which was reported by 58% of patients at the time of diagnosis in one study.1 Since we cannot prescribe NSAIDs to myeloma patients, we rely on opioid analgesics to control pain. When we give these medications, we always put patients on a bowel regimen that includes dietary and hydration support and a stool softener, as opioids can cause significant constipation. We try not to use radiation therapy for pain; we only radiate for severe pain that has not responded to other interventions, including analgesic medication, physical therapy (PT), and surgery. Patients sometimes do not understand why PT can help with bone pain, so we explain that improving muscle strength around a bone may improve pain control and function. Compression fracture of the spine is one of the more common SREs in myeloma patients.1 In our weekly clinic, a spine specialist is available to evaluate individuals with back pain. If necessary, patients may undergo kyphoplasty, which has been shown to be effective in treating vertebral compression fractures in patients with MM or bone metastasis from solid tumors (Table 3).12 The specialist may also recommend a steroid injection into the back to relieve the pain. Finally, we advise patients to take the necessary steps to protect themselves from trauma. The last thing they need is an injury to bone. We urge them to avoid risky sports and counsel them to evaluate their homes for hazards such as slippery rugs and broken steps. What supportive care strategies are necessary for managing anemia in patients with MM?

Anemia is a common finding among newly diagnosed MM patients (Figure).1 This condition may also occur at later points in the clinical course of the disease and can be an adverse effect of specific agents. We take a dual approach to combat anemia, using effective antimyeloma therapy and transfusions. Controlling a patient’s disease is the best way to manage anemia over the long term. We order blood transfusions whenever a patient’s hematocrit drops to about 25% to 27%. Hematocrit 25% signals that a transfusion is appropriate; 26% to 27%, in the presence of anemia symptoms, also indicates a need for transfusion.6

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We rarely use erythropoietins to treat anemia, as most of our patients are receiving therapies that may elevate risk of thrombosis, such as thalidomide or lenalidomide, combined with dexamethasone.13 In addition, erythropoietins can increase thromboembolic risk.13,14 We therefore do not want to augment risk of thrombosis by adding an erythropoietin to the mix. In rare instances, we may opt for erythropoietin support of anemia in heavily treated patients who are far into the clinical course and have already received multiple transfusions and anticoagulant therapy. It is important to provide ongoing education to patients regarding the signs and symptoms of anemia, which can include shortness of breath or extreme fatigue. We describe how hemoglobin in red blood cells carries oxygen throughout the body, so that they understand why we must frequently check their counts and recommend transfusions. Patients often call us and say, “I’ve been extremely tired over the past couple of days. I wonder if I need a transfusion.” When this occurs, we have them come in to the clinic so that we can assess their blood cell counts, and we often find that these patients are correct and do need to be transfused. To be effective in providing prompt and appropriate supportive care, nurses must listen attentively to their patients’ concerns. Most patients can sense subtle changes in their bodies, and our education is designed to contribute to that knowledge. As a nurse, I feel I have done my job well when a patient demonstrates an understanding of their disease and feels comfortable calling me to report a new symptom or potential complication. Good communication between nurses and patients is the cornerstone for providing the best possible supportive care. Conclusion

MM is an incurable hematologic malignancy that attacks the body in many ways, resulting in renal dysfunction, hypercalcemia, SREs, and anemia. It is imperative that patients are carefully screened for these complications at the time of diagnosis and throughout the course of the disease. Proactive nursing measures are the key to reducing the impact and severity of these symptoms, which in turn will help patients remain on therapy and achieve the best possible outcomes. ◆ References 1. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78:21-33. 2. Zometa® [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation. February 2011. 3. Aredia® [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation. November 2008. 4. Hutchison CA, Batuman V, Behrens J, et al. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma. Nat Rev Nephrol. 2011;8:43-51. 5. Kaufman JL, Nooka A, Vrana M, et al. Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma: a retrospective study. Cancer. 2010;116:3143-3151. 6. Dimopoulos MA, Terpos E, Chanan-Khan A, et al. Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group. J Clin Oncol. 2010;28:4976-4984. 7. Revlimid® [package insert]. Summit, NJ: Celegene Corporation. October 2010. 8. Badros A, Weikel D, Salama A, et al. Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol. 2006;24:945-952. 9. Morgan GJ, Davies FE, Gregory WM, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010;376:1989-1999. 10. Velcade® [package insert]. Cambridge, MA: Millennium Pharmaceuticals, Inc. December 2010. 11. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011;12:431-440. 12. Berenson J, Pflugmacher R, Jarzem P, et al. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial. Lancet Oncol. 2011;12:225-235. 13. Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22:414-423. 14. Rizzo JD, Somerfield MR, Hagerty KL, et al. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update. Blood. 2008;111:25-41.

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Pharmacologic Considerations in Newly Diagnosed Multiple Myeloma Minal Surati, PharmD Clinical Pharmacy Specialist Department of Hematology and Medical Oncology Emory University Hospital/Winship Cancer Institute Atlanta, GA

Introduction Symptom patterns in patients with newly diagnosed multiple myeloma (MM) can influence the approach to both antimyeloma therapy and supportive care. The core “CRAB” symptoms (hypercalcemia, renal insufficiency, anemia, or bone lesions) may require interventions, such as transfusions for anemia or bisphosphonates for hypercalcemia; renal dysfunction may influence drug selection and dosing. Complicating the clinical picture are several additional factors: drug-drug interactions; medical comorbidities; the adverse events associated with treatments for MM; and the inherent, myeloma-related risks of fracture and venous thromboembolism (VTE). In this article, Minal Surati, PharmD, describes the key role of pharmacy in identifying and clarifying the needs of each patient, to personalize drug choices and dosing strategies.

Symptomatic MM is defined by the presence of CRAB symptoms, which identify end-organ involvement. As a pharmacy professional, what is your role in minimizing these symptoms in newly diagnosed patients?

Our priority as pharmacists is to counsel patients regarding their treatment regimen and assess the interaction of agents, whether it be with other drugs or with a patient’s comorbid conditions.1 When a patient newly diagnosed with MM presents with CRAB symptoms, we evaluate the drugs he or she takes for preexisting conditions in the context of the proposed treatment regimen, in an effort to discover and manage any problematic interactions. For example, a newly diagnosed, elderly woman may present with renal insufficiency and bone lesions attributable to MM, but may also have a history of diabetes, controlled with oral metformin, and osteoporosis treated with the oral bisphosphonate, ibandronate. Oral ibandronate and metformin do not interact.2 However, the risk of lactic acidosis, a rare but serious complication of metformin, is elevated in patients with renal insufficiency and older age.3 Antimyeloma regimens that include steroids such as dexamethasone or prednisone may interfere with glycemic control.3 Intravenous (IV) bisphosphonate therapy for MM should replace oral ibandronate; if the patient’s creatinine clearance is <30 mL/min, IV pamidronate rather than IV zoledronic acid would be the recommended agent.4,5 It is important to stress that medication therapy management provided by a pharmacist is not a one-time event. Patients are assessed prior to each cycle of chemotherapy or IV bisphosphonate treatment, to ensure medications are adjusted appropriately based on changes in renal function, anemia, calcium levels, etc, that may have occurred since their last visit.

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We have found that patients often research their disease state and therapies through various means such as the internet or discussions with other patients, family, and friends. This is encouraged to promote knowledge and support throughout their treatment. However, with the increasing trend of holistic and alternative health movements, patients may begin taking overthe-counter (OTC) supplements or herbal medications without discussing it with their providers. For example, I recently consulted with a myeloma patient who was taking 21 different supplements. Pharmacists must check for herbal and synthetic supplements—especially high-dose vitamins, which can affect the efficacy of chemotherapy treatment or exacerbate a patient’s disease. For example, if a newly diagnosed patient with hypercalcemia is taking excess calcium OTC, we need to address this issue. After discussing the situation with the team, we inform the patient of the appropriate calcium supplementation strategy. This may include discontinuation of the supplement, decreasing the dose, or replacing it with a simple multivitamin. Our fundamental approach to the symptom of anemia in MM is to provide effective antimyeloma treatment, which should elevate and stabilize red blood cell counts.6 We do provide transfusions if necessary,6 when the hemoglobin is <10 g/dL or hematocrit is <25%. Given the fact that many of our patients’ treatments include thalidomide or lenalidomide, we seldom use erythropoietins to treat chronic anemia. Both thalidomide and lenalidomide can put patients at an increased risk of developing a VTE. The addition of erythropoietins would further increase this risk,7,8 therefore, we do not use these agents concurrently. This is a cautious interpretation of guidance from the American Society of Hematology/American Society of Clinical Oncology (ASH/ASCO), which also warns against the use of an erythropoietin in combination with lenalidomide or thalidomide plus corticosteroids.7

It is important to stress that medication therapy management provided by a pharmacist is not a one-time event.

Myeloma-related bone disease tends to be very painful, as is peripheral neuropathy (PN) that may result from bortezomib or immunomodulators used in the treatment of MM.9-11 Since we increasingly use the RVD regimen (lenalidomide, bortezomib, and dexamethasone) in newly diagnosed patients (Figure),12 we monitor closely for PN. Working with pain assessments provided by the nursing staff, the pharmacist plays a key role in developing a rational plan for pharmacologic management of nociceptive and neuropathic pain in the myeloma patient. We rely on opioid medication, typically oxycodone or morphine, for bone pain, which requires us to be very cautious about opioid adverse effects. One must distinguish between opioid tolerance, a natural physiological response to these drugs, and opioid addiction, which has psychological ramifications.13 In our practice, we avoid the use of both acetaminophen and nonsteroidal antiinflammatory drugs since these agents may affect liver and/or kidney func-

April 2012 I VOl 5, NO 3

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CONTINUING EDUCATION

Figure. Common adverse events with RVD in newly diagnosed patients with MM (N=66).12

Table. Disease-Related and Comorbid Thromboembolic Risk Factors in Patients with Myeloma8 Risk Factors

Specific Examples

Related to the disease and treatment

Myeloma itself Hyperviscosity Therapies: erythropoietins, immunomodulators, high-dose dexamethasone, doxorubicin, multiagent chemotherapy

Related to comorbidities

History of venous thromboembolism Obesity Heart disease/atrial fibrillation Chronic renal disease Diabetes Infection Immobilization Surgery/anesthesia Trauma Central venous catheter or pacemaker Clotting disorders

100

Overall Grade 3

90 80

80%

Patients (%)

64% 61%

60 50

45%

44%

36%

35% 32%

32%

30 20 10 3%

0 y

sor Sen

thy pa uro ne

e igu

Fat

n n ain ma tio tio de ep ipa ma scl be ua nst Mu Lim Co esq d / sh Ra

3% 0%

ea rrh Dia

a use Na

thy pa uro Ne

MM indicates multiple myeloma; RVD, lenalidomide, bortezomib, and dexamethasone.

tion, as well as mask fevers, which can deprive us of a warning sign for infection in our frequently neutropenic patients. To a large extent, opioid therapy is very helpful with neuropathic pain.14 However, additional agents such as gabapentin or pregabalin can be useful as well. Other therapies that may also be used are alpha lipoic acid, L-carnitine, folic acid, and B complex vitamins. What strategies can be used for the prevention of infection in patients with MM?

Many newly diagnosed MM patients experience a disease-related increase in infection risk; extensive disease, poor renal function, and compromise to plasma cells can produce poor health status. Add to that the risks of therapy, such as viral reactivation and neutropenia, and the result is a significant potential for infection. At our center, we ensure that every individual receives basic preventive care. Patients receive vaccines, including seasonal flu vaccine and, if not up-to-date, pneumococcal vaccine. Bortezomib use can increase the risk of herpes zoster reactivation,15 therefore, if a patient receives this agent as part of the treatment regimen, we always include antiviral prophylaxis with acyclovir or another drug in its class. Pneumocystis carinii pneumonia (PCP) is always a concern in patients receiving high-dose steroids. If a steroid is part of the patientâ&#x20AC;&#x2122;s treatment regimen, we will begin prophylaxis for PCP. With regard to the use of prophylactic antibiotics and antifungals, we are selective and commensurate with recommendations from the National Comprehensive Cancer Network.16 We simply do not want to add the adverse events of antimicrobial agents if not necessary. From my perspective, education is an extremely important aspect regarding infection control. When counseling patients for the first time, I typically ask if they have a history of herpes viral infections, cold sores, or zoster. If they report recurrent zoster infections, this would prompt me to consider the use of valacyclovir, if acyclovir has previously not been effective. Bisphosphonates are a mainstay of therapy for myeloma-related bone disease, but their use can be complicated by certain CRAB symptoms. What is your approach to bisphosphonate use in patients with renal dysfunction or hypercalcemia?

April 2012 I VOl 5, NO 3

The bisphosphonate we use the majority of the time is IV zoledronic acid, administered monthly for 2 years, then every 2 to 6 months, depending on the patientâ&#x20AC;&#x2122;s status at that time. An advantage of zoledronic acid is a relatively short IV infusion time of at least 15 minutes.4,17 Zoledronic acid also produced favorable outcomes in the recent Medical Research Council Myeloma IX study.18 However, this bisphosphonate must be dose-adjusted downward in increments, ranging from 4 mg to 3 mg, as patientsâ&#x20AC;&#x2122; baseline creatinine clearance falls from a normal value (>60 mL/min) to 30 mL/min; zoledronic acid is not recommended in patients with severe renal insufficiency (creatinine clearance <30 mL/min).4,17 Although the prescribing information for zoledronic acid suggests that the criterion for dose adjustment is the baseline creatinine clearance, we assess serum creatinine and calculate clearance at each visit and adjust the dose accordingly. We will also infuse zoledronic acid over 30 minutes rather than 15 minutes. For patients with significant renal impairment, we often elect to use pamidronate infused over 2 to 4 hours.5,17

When counseling patients for the first time, I typically ask if they have a history of herpes viral infections, cold sores, or zoster. The approach is different, however, when hypercalcemia complicates the clinical picture. A newly diagnosed MM patient presenting with hypercalcemia will receive aggressive, acute treatment with zoledronic acid, which is the preferred bisphosphonate for this condition.19 Per our institutional guidelines, zoledronic acid dosing for hypercalcemia is 4 mg as a single-dose IV infusion over 30 minutes, followed by close monitoring to assess if further treatment is needed. No specific dose adjustment is suggested for patients with renal impairment. Similarly, if a patient with renal impairment is receiving zoledronic acid monthly, and we detect the emergence of hypercalcemia, we will administer a 1-time, full 4-mg dose, rather than adjusting the dose for renal dysfunction. There are situations in which a switch from zoledronic acid to pamidronate may be necessary. We look for trends in serum creatinine and

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CONSIDERATIONS IN MULTIPLE MYELOMA

creatinine clearance with our patients, and if we notice a trend toward worsening renal insufficiency, with serum creatinine rising, we may discontinue the zoledronic acid and begin pamidronate, with the infusion rate at the slower end of the recommended time.17 How do you reduce the risk of disease- or treatment-related VTE in newly diagnosed patients?

We ensure that all patients with thromboembolic risk factors, specifically those receiving thalidomide- or lenalidomide-containing regimens, receive VTE prophylaxis.8 Clinicians should be aware of the increased risk of VTE in the MM population—typically older patients with a disease that exacerbates thrombosis8—regardless of therapy (Table). Many patients present with a history of VTE, or with comorbidities that can increase the risk of thrombus formation. Numerous patients may already be taking warfarin or low-molecularweight heparin, which we continue as their VTE prophylaxis. Conclusion

It is vitally important for all members of the interdisciplinary cancer care team to understand the complexity of MM. Symptoms of the disease, including hypercalcemia, renal insufficiency, anemia, and bone disease, will influence not only which therapies can be used, but the dose and duration of treatment. Myeloma-related complications may change over time, as the disease responds to treatment or progresses. In addition, drug-drug interactions have the potential to cause clinical emergencies, which require immediate interventions. The pharmacist plays a key role in identifying these complex relationships, counseling patients, and monitoring responses to various therapies to ensure optimal clinical outcomes. ◆

References 1. Tam-McDevitt J. Polypharmacy, aging, and cancer. Oncology (Williston Park). 2008;22:10521055. 2. Boniva® [package insert]. South San Francisco, CA: Genentech USA, Inc. January 2011. 3. Glucophage® [package insert]. Princeton, NJ: Bristol-Myers Squibb Company. January 2009. 4. Zometa® [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation. February 2011. 5. Aredia® [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation. November 2008. 6. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Cancer- and chemotherapy-induced anemia. Version 2.2012. www.nccn.org/professionals/physician_gls/pdf/anemia.pdf. Accessed March 26, 2012. 7. Rizzo JD, Somerfield MR, Hagerty KL, et al. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update. Blood. 2008;111:25-41. 8. Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22:414-423. 9. Velcade® [package insert]. Cambridge, MA: Millennium Pharmaceuticals, Inc. December 2010. 10. Thalomid® [package insert]. Summit, NJ: Celegene Corporation. August 2010. 11. Revlimid® [package insert]. Summit, NJ: Celegene Corporation. October 2010. 12. Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116:679686. 13. Jan SA. Introduction: landscape of opioid dependence. J Manag Care Pharm. 2010;16(suppl 1b):S4-S8. 14. Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007;132:237-251. 15. San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359:906-917. 16. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Prevention and treatment of cancer-related infections. Version 2.2011. www.nccn.org/professionals/physician_gls/pdf/infections.pdf. Accessed March 26, 2012. 17. Kyle RA, Yee GC, Somerfield MR, et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol. 2007;25:2464-2472. 18. Morgan GJ, Child JA, Gregory WM, et al. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol. 2011;12:743-752. 19. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Multiple myeloma. Version 1.2012. www.nccn.org/professionals/physician_ gls/pdf/myeloma.pdf. Accessed March 15, 2012.

Evolving Concepts in the Management of Newly Diagnosed Multiple Myeloma Continued from page 25 myeloma. NCT01169337. http://clinicaltrials.gov/ct2/show/NCT01169337?term= E3A06&rank=1. Accessed March 27, 2012. 8. Durie BGM, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975;36:842-854. 9. Griepp PR, San Miguel J, Durie BGM, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412-3420. 10. Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007;109:3489-3495. 11. Fonseca R, Barlogie B, Bataille R, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004;64:1546-1558. 12. Fonseca R, Blood E, Rue M, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood. 2003;101:4569-4575. 13. mSMART. Mayo Stratification for Myeloma and Risk-adapted Therapy. Newly diagnosed myeloma. http://msmart.org/newly%20diagnosed%20myeloma.pdf. Accessed March 28, 2012. 14. Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23:2210-2221. 15. Munshi NC, Anderson KC, Bergsagel L, et al. Consensus recommendations for risk stratification in multiple myeloma: report of the international Myeloma Workshop Consensus Panel 2. Blood. 2011;117:4696-4700. 16. Cavo M, Tacchetti P, Patriarca F, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction 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.

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17. 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. 18. Klein U, Jauch A, Hielscher T, et al. Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone. Cancer. 2011;117:2136-2144. 19. 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. 20. Shaughnessy JF Jr, Zhan F, Burington B, et al. A validated gene expression signature of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007;109:2276-2284. 21. Decaux O, Lode L, Magrangeas F, et al. Intergoupe Francophone du Myelome. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myelome. J Clin Oncol. 2008;26:4798-4805. 22. Dimopoulos M, Terpos E, Comenzo RL, et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple myeloma. Leukemia. 2009;23:1545-1556. 23. Durie BGM. The role of anatomic and functional staging in myeloma: description of Durie/Salmon plus staging system. Eur J Cancer. 2006;42:1539-1543. 24. Zamagni E, Patriarca F, Nanni C, et al. Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation. Blood. 2011;118:5989-5995.

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The Future of Nursing A New Look at Nursing Education and Practice Continued from cover roles.1 This pivotal undertaking will place nurses in strategic positions to transform our nation’s healthcare. The business of healthcare is more complex than in years past. Nurses need to have a broader education in order to successfully care for the patient in a complete and comprehensive manner. The

IOM report highlighted nursing competencies to include leadership, health policy, system improvement, research, and evidence-based practice.1 Additionally, teamwork and collaboration across the entire spectrum of healthcare are critical elements in caring for patients today in any setting. Gone are the days when a

Table 1 Key Issues1 • Nurses should practice to the full extent of their education and training • Nurses should achieve higher levels of education and training through an improved education system that promotes seamless academic progression • Nurses should be full partners with physicians and other healthcare professionals in redesigning healthcare in the United States • Effective workforce planning and policy making require better data collection and information infrastructure Adapted from The Future of Nursing: Leading Change, Advancing Health. Report rcommendations. Institute of Medicine of the National Academies; October 2010.

patient is discharged from the hospital to go directly home. Coordination of care and transition to interim care facilities are common and necessary in order for a patient to achieve normal activities of daily life. However, this coordination and skill in teamwork and collaboration are typically not part of nursing school curricula, even though they are an essential part of caring for patients today. As a result of the IOM report, schools of nursing will likely take a careful look at curricula and may realize that some of what is being taught today could perhaps be replaced with lessons in these important elements of care.

The IOM report is the result of thousands of hours of deep discussion

Table 2 Recommendations

between highly

• Increasing the number of nurses with baccalaureate degrees from 50% to 80% by 2020 and encouraging nurses with associate degrees and diplomas to enter baccalaureate programs within 5 years of graduation

respected individuals in many professional fields.

• Doubling the number of nurses with a doctorate by 2020 • Addressing the faculty shortage by creating salary and benefits packages that are market competitive • Moving to have at least 10% of baccalaureate program graduates enter master’s or doctoral degree programs within 5 years of graduation • Removing scope of practice barriers that inhibit advanced practice registered nurses from practicing to the full extent of their education and training and serving in primary care roles • Enhancing new nurse retention by implementing transition-into-practice nurse residency programs • Embedding leadership development into nursing education programs and increasing the emphasis on interdisciplinary education • Ensuring that nurses engage in lifelong learning to gain the competencies needed to provide care for diverse populations across the life span Adapted from The Future of Nursing: Focus on Education. Institute of Medicine of the National Academies; January 2011.

Communication with other members of the healthcare team is vital in the proper care of patients, whether it be in the hospital or in an outpatient setting. Polishing this useful skill and creating an environment where positive interactions take place in the context of patient care is essential. The hierarchical system that once existed is less apparent today and not relevant in 21st century patientcentered healthcare. Therefore, it is imperative that members understand how to communicate and effectively interact with each other in the most efficient way possible to achieve excellence in patient caring.

APRN Specialties Focus on practice beyond role and population foci linked to healthcare needs

Population Foci

Family/Individual

AdultGerontology

Neonatal

Pediatrics

Women’s Health

PsychiatricMental Health

APRN Roles Nurse Anesthetist

Figure. APRN Regulatory Model

NurseMidwife

Clinical Nurse Specialist

Nurse Practitioner

Specialties such as oncology nursing demand a great deal of unique knowledge and a special skill set. There are few schools of nursing that offer electives in oncology nursing at the baccalaureate level. Providing opportunities for nursing students to complete a preceptorship with an oncology nurse in either the hospital or outpatient setting would stimulate a larger pool of new oncology nurses who would have a basic understanding of the unique knowledge and expertise necessary for caring for the oncology population. Providing education in survivorship and end-oflife care would go a long way in helping new nurses understand how to interact with both of these special populations. Additionally, nurse residency programs are few and far between. The IOM report elaborates on this need and the advantages of such residency programs. The allotted time for a residency allows nursing graduates to acquire special knowledge and skills necessary to providing safe quality care within an evidence-based framework. This likely would promote confidence in new graduates and better functioning once they are employed. Moreover, these types of programs may provide the impetus for the baccalaureate-prepared nurse to continue to the graduate level, keeping in line with one of the IOM recommendations. According to Aiken and colleagues, hospitals with higher proportions of nurses educated at the baccalaureate level or higher experience lower mortality and failure-to-rescue rates.2 The IOM report is the result of thousands of hours of deep discussion between highly respected individuals in many professional fields. The report concluded that nurses need to be part of the global discussion regarding the health of our nation. Specifically, advanced practice nurses (APNs) need to be able to practice fully, as compatible with their graduate education and training. APNs, particularly nurse practitioners and clinical nurse specialists in oncology, are one solution in caring for the many survivors that will make up an enormous population in the years to come. These advanced practitioners should be able to practice in a collaborative manner with (not under the supervision of) an oncologist. According to Peter Yu, MD (oral communication, November 2011), an oncologist with the Palo Alto Medical Foundation in Mountain View, California, “we are directing our NPs to genetic counseling and survivorship programs where they can develop new models [of care] that are not constrained by the past.” Continued on page 34

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SARCOMA: THE ONLY THING PROGRESSING IS THE DISEASE T H E 5 - Y EAR S UR V IVAL RATE I S 17 % F OR PATIENTS WITH M E TAS TATIC S OF T TISSUE SA RC OMA , Y E T SIG NIF ICANT THERA PEUTIC A D VA NCEM ENTS AR E LA GGING. 1

NEW TREATMENTS ARE URGENTLY NEEDED.

Reference: 1. National Cancer Institute. Surveillance Epidemiology and End Results. seer.cancer.gov/statfacts/html/soft.html. Accessed March 19, 2010.

Merck Oncology

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The Future of Nursing A New Look at Nursing Education and Practice Continued from page 32 Additionally, he commented on the education specifically of the oncology nurse practitioner, “Perhaps ASCO should create a training module [for the oncology nurse practitioner] from the physician perspective that could be adopted by ONS as part of the ONS certification process.” These ideas may create a more solid foundation for the collaborative practice for APNs and oncologists going forward.

practitioner. Advanced practitioners may specialize, but they cannot be licensed solely within a specialty area. For example, a

CNP working as an advanced oncology certified nurse practitioner (AOCNP) must be certified by either the American

Academy of Nurse Practitioners (AANP) or the American Nurses Credentialing Center (ANCC), first with-

TREANDA® is her chemo. There are 4 essential elements—licensure,

This is her therapy.

accreditation, certification, and education—that create the framework for the model.

Advanced Practice In addition to the IOM recommendation that advanced practice registered nurses (APRNs) be able to practice to the full extent of their education and training, the APRN Advisory Panel met with the APRN Consensus Work Group in April 2006 to discuss APRN issues. For some time they worked in parallel, but they eventually joined forces in January 2007 to begin a dialogue for the purpose of developing a document that would become a new model for advanced practice nurses—APRN Model of Regulation (Figure).3 Advanced practice nurses are defined as certified registered nurse anesthetist (CRNA), certified nurse-midwife (CNM), clinical nurse specialist (CNS), and certified nurse practitioner (CNP). There are 4 essential elements— licensure, accreditation, certification, and education—that create the framework for the model. Individuals are licensed as independent practitioners for practice at the level of 1 of the 4 APRN roles within at least 1 of the 6 identified population foci (Figure). Education, certification, and licensure of an individual must be congruent in terms of role and population. An example of this would be that an individual graduating from a Family Nurse Practitioner program could not practice as a psychiatric/mental health nurse

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The Future of Nursing in the specific population foci in which she/he was educated and trained, and then by the Oncology Nursing Certification Corporation. Special certification, such as AOCNP or advanced

oncology clinical nurse specialist (AOCNS), is an option but is often recommended because it may be a requirement for employment in a particular state. According to the APRN

Consensus Model Frequently Asked Questions,4 an APRN must legally represent herself/himself as APRN plus the specific role (CRNA, CNM, CNS, CNP). An example of this would be as

follows: APRN, CNP, adult oncology. Many in nursing believe we currently have too many initials after our names that the patient population doesnâ&#x20AC;&#x2122;t Continued on page 36

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

TREANDA (n=153)

1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1

Chlorambucil (n=148)

18 months median PFS

s 42%!.$! HAS AN ESTABLISHED SAFETY PROlLE

6 months

LYMPHOPENIA AND LEUKOPENIA N

median PFS

P<.0001 HRâ&#x20AC; =0.27 (95% CIâ&#x20AC;Ą: 0.17, 0.43)

up to 6 cycles

20 25 Months

*TREANDA (95% CI: 11.7, 23.5) vs chlorambucil (95% CI: 5.6, 8.6). â&#x20AC; HR=hazard ratio. â&#x20AC;Ą CI=confidence interval.

ORRÂ§: INDOLENT B-CELL NHL THAT HAS PROGRESSED

57%

PR (n=57)

74%

Total ORR (95% CI: 64.3, 82.3)

17%

CR/CRu (n=17)

s 42%!.$! HAS AN ESTABLISHED SAFETY PROlLE

s )N SINGLE ARM STUDIES OF PATIENTS WITH INDOLENT " CELL .(, THAT HAD PROGRESSED . THE MOST COMMON non-hematologic adverse reactions (frequency â&#x2030;Ľ30%) WERE NAUSEA FATIGUE VOMITING

DIARRHEA AND PYREXIA . 4HE MOST common hematologic abnormalities (frequency â&#x2030;Ľ WERE LYMPHOPENIA LEUKOPENIA ANEMIA (88%), neutropenia (86%), and thrombocytopenia (86%)

100

Patients responding (%) Â§

Important Safety Information s 3ERIOUS ADVERSE REACTIONS INCLUDING MYELOSUPPRESSION INFECTIONS INFUSION REACTIONS AND ANAPHYLAXIS TUMOR LYSIS SYNDROME SKIN REACTIONS INCLUDING 3*3 4%.

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

Oncology

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ÂĽ #EPHALON )NC IS A WHOLLY OWNED SUBSIDIARY OF 4EVA 0HARMACEUTICAL )NDUSTRIES ,TD !LL RIGHTS RESERVED 42% .OVEMBER

www.TheOncologyNurse.com

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The Future of Nursing A New Look at Nursing Education and Practice Continued from page 35 understand. One may argue that APRNs did not have much input into this signature regulation and that having to sign both APRN and the role is redundant.

Additionally, many in advanced practice roles believe that once you have been educated beyond the basic RN role, the designation of RN should not be used,

but rather the new role, such as CNP. After all, an advanced practice nurse practices under a different license and different scope of practice than an RN.

April 2012 I VOl 5, NO 3

However, if every state adopts the Consensus Model, nursing may finally have, in part, some standardization of how we sign our names.

Laboratory Abnormality Hemoglobin Decreased Platelets Decreased Leukocytes Decreased Lymphocytes Decreased Neutrophils Decreased

TREANDA (N=150) All Grades Grade 3/4 n (%) n (%) 134 (89) 20 (13) 116 (77) 16 (11) 92 (61) 42 (28) 102 (68) 70 (47) 113 (75) 65 (43)

Chlorambucil (N=141) All Grades Grade 3/4 n (%) n (%) 115 (82) 12 (9) 110 (78) 14 (10) 26 (18) 4 (3) 27 (19) 6 (4) 86 (61) 30 (21)

Number (%) of patients* All Grades Grade 3/4 176 (100) 94 (53)

13 (7)

132 (75) 71 (40) 65 (37) 51 (29) 27 (15) 22 (13) 20 (11) 18 (10) 15 (9) 8 (5) 8 (5)

7 (4) 5 (3) 6 (3) 1 (<1) 1 (<1) 2 (1) 0 0 1 (<1) 0 0

101 (57) 59 (34) 24 (14) 23 (13) 19 (11) 11 (6) 11 (6) 10 (6) 8 (5)

19 (11) 3 (2) 0 1 (<1) 4 (2) 1 (<1) 0 0 0

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The Future of Nursing As it stands now, states have different practice acts with specific restrictions on practice for the advanced practice nurse. This creates a cumbersome process when an APRN wishes to move from state to state, as there may

be different educational, licensure, or prescriptive requirements. Goals of the APRN Consensus Model include improved mobility for APRNs, standardization in educational programs, and homogeneity in independent prac-

Hematology Variable Lymphocytes Decreased Leukocytes Decreased Hemoglobin Decreased Neutrophils Decreased Platelets Decreased

tice, assuring the public that the APRN is highly prepared and certified to provide safe quality care and better access to the APRN for all patients. The target date for implementation is 2015. Implementation will likely be stag-

gered, and full implementation may go beyond the target date. Healthcare systems and the manner in which we deliver care are changing and becoming increasingly more important to the consumer, healthcare provider, and institution. Nursing has always played a critical role in the implementation and delivery of care. Now, more than ever, nursing has the opportunity to be front and center in the sharing of ideas to improve the trajectory of care for patients. The IOM report and the APRN Consensus Model both serve as roadmaps for now and the future in guiding the profession of nursing in its quest to make valuable contributions to the overall health and well-being of all those we serve. ● References 1. Institute of Medicine of the National Academies (IOM). The Future of Nursing: Leading Change, Advancing Health. www.iom.edu/nursing. Published October 5, 2010. Accessed November 11, 2011. 2. Aiken L, Clarke SP, Cheung RB, Sloane DM, Silber JH. Educational levels of hospital nurses and surgical patient mortality. JAMA. 2003;290:1617-1623. 3. APRN Consensus Work Group, National Council of State Boards of Nursing APRN Advisory Committee. Consensus Model for APRN Regulation: Licensure, Accreditation, Certification & Education. www.aacn. nche.edu/education-resources/APRNReport.pdf. Published July 7, 2008. Accessed November 13, 2011. 4. APRN Consensus Frequently Asked Questions. American Nurses Association Web site. www.nursingworld.org/ConsensusModelFAQ. Updated August 19, 2010. Accessed November 27, 2011.

Reader Poll Give us your opinion about the issues Catherine Bishop presented in her article, “A New Look at Nursing Education and Practice.” Do you agree that the IOM report and the APRN Consensus Model should serve as guidelines for the future of the nursing profession? r Yes r No

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Personalized Medicine in Oncology Precision Medicine: Applying Predictive and Prognostic... while limiting unnecessary exposure to potentially toxic and costly therapies in order to preserve future treatment options for patients unlikely to respond. Implementing the principles of precision medicine requires ongoing integration of advances in molecular biology, diagnostic imaging, and risk-adapted treatment selection. Scientific practicality (knowing how to adapt these key elements and clinical trials data for the individual patient based on the goals of therapy) is essential to the best possible outcome. This article describes the key elements of precision medicine with clinical insights gained over 27 years of oncology practice, including 22 years as an advanced practitioner in oncology. Advances in Molecular Biology: The Foundation for Effective Treatment Precision medicine is the application of predictive biomarkers, together with consideration of prognostic biomarkers and patient attributes, in the selection of therapy using a personalized life-span approach (Table 1).1,2 Prognostic biomarkers reflect the likely natural history of a given disease in untreated patients3 and may influence the approach to treatment based on high-risk or low-risk disease. For example, a patient with multiple myeloma with the 17p cytogenetic abnormality is known to have an inferior disease trajectory independent of other disease attributes and will be considered for autologous stem cell transplant earlier in the phase of treatment.4 Similarly, a patient with triplenegative breast cancer (negative estrogen, progesterone, and HER2) is felt to have high-risk disease, which with no option for hormonal therapy will require combination therapy with drugs thought to be effective in this setting.5 Predictive biomarkers, on the other hand, are attributes of the tumor thought to identify patients who may benefit from a given therapy.3 These biomarkers are used to guide treatment selection. For example, a patient with metastatic colorectal cancer who is found to have wild-type KRAS is more likely to benefit from epidermal growth factor receptor inhibitor (EGFR-I) therapy, whereas a patient who has mutated KRAS is not likely to benefit.6 A single biomarker can have both predictive and prognostic value, but each has different clinical utility. For example, HER2 testing in patients with breast cancer serves as a negative prognostic indicator (considered higher risk) but also has positive predictive value (patients are likely to respond to HER2-directed therapies).5,7 Thus, biomarker-driven treatment selection may limit exposure of potentially toxic treatments in patients not likely to

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Continued from cover

Table 1 Key Elements of Precision Medicine1 Definition • Application of predictive biomarkers together with consideration of prognostic biomarkers and patient attributes in the selection of therapy, using a personalized life-span approach • Effective diagnostics • Characteristics of the individual patient • Comorbidities • Performance status • Lifestyle • Finances • Quality of life Risk-adapted treatment selection • Characteristics of the disease • Prognostic biomarkers • Predictive biomarkers • Tissue type • Staging • Currently available treatment options • Shift from safety and efficacy alone to biomarker-driven therapy • Optimal sequencing and duration of therapy • Understanding and application of response criteria Partnership with the patient and family • Selection based on risk analysis and patient choice Adapted from Kurtin S. J Adv Pract Oncol. 2010;1:19-29.

benefit and is therefore more cost-effective and offers the best option for therapy in patients with positive predictive biomarkers. Optimally, all subpopulations of patients with predictive and prognostic biomarkers enrolled in clinical trials will be enrolled in tandem trials for tissue banking and longitudinal analysis to further characterize these attributes and clinical outcomes. Selected predictive and prognostic indices for common solid tumors are included in Table 2.5-12 Examples of highrisk features for common hematologic malignancies are provided in Table 3.1

Sandra Kurtin, RN, MS, AOCN, ANP-C

The growing trend in risk-adapted treatment selection—based on specific attributes of the tumor, extent of disease, and the individual patient—challenges the oncology professional to maintain a working knowledge of tissue diagnoses and specific pathology tech-

niques. This is necessary to facilitate accurate diagnoses and consider all necessary testing at the time of the original biopsy or resection. Selecting treatment based on the global diagnosis for both solid and liquid tumors is no longer adequate, and several technologies are now available for obtaining molecular biomarkers, including interphase cytogenetics, fluorescence in situ hybridization, polymerase chain reaction, and gene expression profiling. Individual testing may be performed on tissue or blood, and diagnostic packages such as the Oncotype DX, a 21-gene assay estimating a recurrence score in breast cancer with both prognostic and predictive value, have become more common. Risk-Adapted Treatment Selection: What You See Is What You Get Applying the concepts of predictive and prognostic indices in risk-adapted treatment selection is expected, based on recent scientific discoveries. However, selecting therapies based on the diagnostic evaluation adds an element of complexity to the treatment of each patient. The selection of primary therapies in some tumors, the sequencing of therapies, and the choice of therapies in metastatic disease or in the instance of disease progression are driven by these principles. For effective treatment planning, a comprehensive disease-specific diagnostic evaluation is essential, as each disease requires specific testing. Asking key questions at the time of the initial tissue diagnosis is perhaps the most critical step in the diagnostic

process. For example, it is well established that a fine-needle aspirate is inadequate for the diagnosis of lymphoma, that obtaining fewer than 12 regional lymph nodes with primary colorectal surgery is suboptimal, and that an adequate bone marrow analysis requires an aspirate with spicules, a core biopsy, and analysis of cytogenetics to provide adequate diagnostic and prognostic information. In all cases, a complete diagnostic evaluation prior to implementing any antineoplastic therapy is essential, since once treatment has been administered, the tissue will be altered and testing will not provide similar prognostic or predictive information. Most tumor types require baseline diagnostic imaging. Because appropriate baseline imaging for each tumor type will vary, however, it is critical to understand the best approach to diagnosing each tumor type in order to adequately plan the diagnostic process and prepare the patient and family. For example, bone involvement is common in a patient with multiple myeloma; however, a bone scan is of limited diagnostic value. Similarly, whereas obtaining a positron emission tomography/computed tomography (PET/CT) scan for staging a patient with follicular nonHodgkin lymphoma (NHL) is not useful, it may provide diagnostic benefit in a patient with more aggressive diffuse large B-cell NHL. Appropriate diagnostic imaging at baseline and at defined intervals can also provide the most accurate analysis of response to treatment, but the timing for evaluation varies for each tumor type. For example, a patient with Hodgkin lymphoma will typically have undergone a PET/CT scan after 2 months of treatment, and negative results from the scan in this setting are considered a positive predictor of longterm survival. A patient with follicular lymphoma, on the other hand, generally receives 3 to 4 months of treatment prior to undergoing repeat imaging, unless a physical exam and analysis of laboratory measures such as serum lactate dehydrogenase show no evidence of improvement. It should be noted that PET/CT evaluation is only recommended in selected cases of follicular lymphoma. Common approaches to diagnostic imaging are reviewed in Table 4.10-18 Scientific practicality is perhaps the most important component of precision medicine. This is a term I use to describe the application of clinical trials data to the population at large in a way that allows effective control of the disease for as long as possible with an acceptable level of toxicity. This concept is of particular importance in patients with metastatic or incurable disease. Many tumor types have limited treatment options. Perhaps the best

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Personalized Medicine in Oncology Table 2 Application of Predictive and Prognostic Indices in Selected Solid Tumors5-12 Biomarker

Technique for Evaluation

Clinical Significance

Hormone receptors (ER, PR)

Tissue analysis (IHC)

Recommended for all patients with newly diagnosed invasive or recurrent BC ER status has significant predictive value for tumor response to HT in metastatic disease Significance of PR status less clear ER+, PR+ tumors may respond better to HT ER/PR status may change over the course of disease

HER2

Tissue analysis (IHC, FISH, HERmark)

Recommended for all newly diagnosed BC patients TK that is overexpressed in 15%-30% of BC 3+ HER2 expression associated with poor prognosis HER2+ patients may benefit from trastuzumab and anthracyclines Measurement of activated form of HER2 may be useful in evaluating disease progression

BRCA1 BRCA2

Tissue analysis (IHC, serum)

Tumor suppressor genes Mutation linked to increased lifetime risk of breast, ovarian, and pancreatic cancer Patients with presence of mutations may benefit from increased surveillance

uPA PAI-1

Tissue analysis (IHC)

Plays a role in degradation of the extracellular matrix, tissue remodeling, cell adhesion, and migration Elevated levels associated with negative outcomes in node-negative BC Recommended in risk assessment for N0 BC

CTC

Serum

High CTC count at diagnosis is associated with poor prognosis (≥5 CTC at baseline) If the number of CTC does not decrease during therapy, patient is likely to progress on current therapy

Breast Cancer (BC)

Colorectal Cancer (CC) CEA

Serum

Used as a measure of tumor activity Not elevated in all patients, even with bulky disease Not specific to CC; elevated in smokers

UGT1A1

Serum

DPD deficiency

Serum

Enzyme critical to inactivation of SN-38 (irinotecan metabolism) Polymorphism associated with hyperbilirubinemia UGT1A1*28 allele may have increased toxicity to irinotecan DPD deficiency is important for 5-FU metabolism Deficiency associated with severe toxicity to 5-FU

MSI

Tissue (IHC)

Mutations (microsatellites) in the mismatch repair gene Testing recommended for all patients <50 years Stage II patients with MSI high-frequency tumors have a good prognosis and may not benefit from adjuvant chemotherapy using 5-FU

KRAS

Tissue

KRAS mutations are a biomarker predictive of negative response to anti-EGFR monoclonal antibodies (EGFR-I) Mutations in codon 12 and 13 of exon 2 most common KRAS13 p.G13D mutation may have response to EGFR-I; being investigated in clinical trials WT-KRAS with low-level expression of amphiregulin and epiregulin (ligands for EGFR) also have inferior response to EGFR

BRAF

Tissue (PCR)

BRAF mutation is an indicator of poor prognosis BRAF V600E mutations predictive of negative response to EGFR-I May have limited benefit in the first-line metastatic setting with chemo

PI3KCA

Tissue

Mutated PI3KCA stimulates the AKT pathways, increasing tumor cell growth in CC

PTEN

Tissue

Negative regulator of PI3KCA PTEN+ tumors may have more favorable outcomes PTEN− tumors may not respond to EGFR-I

example is the patient with metastatic colorectal cancer, with FDA-approved therapies limited to 6 agents; patients with mutated KRAS are limited to 4 FDA-approved therapies. Thus, each agent must be used to its fullest potential over the longest period of time. The goals of therapy and the degree of flexibility with treatment must be adapted to the individual patient. For example, in the setting of metastatic disease, achieving stable disease is an acceptable outcome. In patients with potentially curable disease, however, a more aggressive approach to treatment

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For effective treatment planning, a comprehensive disease-specific diagnostic evaluation is essential, as each disease requires specific testing.

is preferred, with application of the principles of precision medicine and an attempt to emulate the clinical trial protocol associated with the most favorable outcomes. Nevertheless, the patient’s tolerance of therapy must also

be considered, including reversible versus potentially irreversible adverse events, and the severity of symptoms despite optimal management. Risk-adapted treatment selection for non–small cell lung cancer is illustrat-

ed in the Figure. This algorithm illustrates the variability in approach to treatment based on the application of principles of precision medicine. Similar algorithms and guidelines are available online through the National Cancer Institute, the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the American Society of Hematology. To remain effective as members of the oncology team, advanced practice clinicians in oncology and oncology nurses must maintain a Continued on page 40

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Personalized Medicine in Oncology Precision Medicine: Applying Predictive and Prognostic... Continued from page 39 Table 2 Application of Predictive and Prognostic Indices in Selected Solid Tumors5-12 (Continued) Biomarker

Technique for Evaluation

Clinical Significance

Non –Small Cell Lung Cancer (NSCLC) EGFR

Tissue (IHC, FISH, or PCR)

EGFR (HER1) commonly overexpressed in NSCLC; indicates proliferative advantage and ↑ metastatic potential More common in adenocarcinoma, never-smokers, Asian descent EGFR mutation predictive of response to EGFR-I Most common EGFR mutation: exon 19 (60%), associated with ↑ OS Rare EGFR mutation: exon 20 insertion, associated with resistance to EGFR-I

KRAS

Tissue (IHC)

One of the most common mutations associated with NSCLC (20%-30%) Regulates activation of ≥10 downstream effector pathways Clinical utility not yet established for NSCLC KRAS-mutant patients may have higher risk of recurrence postoperatively

ERCC1 RRM1 EML4-ALK

Tissue Tissue Tissue

Low ERCC1 predictive of response to platinum compounds Low RRM1 predictive of response to gemcitabine EML4-ALK+ predictive of response to crizotinib

BRCA indicates breast cancer susceptibility protein; CEA, carcinoembryonic antigen; CTC, circulating tumor cell; DPD, dihydropyrimidine dehydrogenase; EGFR, epidermal growth factor receptor; EML4-ALK, echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase; ER, estrogen receptor; ERCC1, excision repair cross-complementation group; FISH, fluorescence in situ hybridization; HT, hormone therapy; IHC, immunohistochemistry; MSI, microsatellite instability; OS, overall survival; PAI-1, plasminogen activator inhibitor type-1; PCR, polymerase chain reaction; PR, progesterone receptor; PTEN, phosphatase and tensin homolog; RRM1, ribonucleotide reductase 1; TK, tyrosine kinase; uPA, urokinase plasminogen activator.

Table 3 High-Risk Features of Common Hematologic Malignancies1 Disease

High-Risk Features

ALL

BCR-ABL+ disease Undifferentiated leukemia Age >35 WBC >30 x 109/L at diagnosis

Null ALL CD10+ (CALLA) mature B-cell ALL >4-5 weeks to achieve a CR (>0.1% residual disease by PCR)

AML

High-risk cytogenetics: Complex cytogenetics (>5 abnormalities) Abnormalities of chromosome 5 or 7 17p abnormality, t(6;9), t(3;21), 11q23 deletion (common in MDR AML)

Intermediate cytogenetic risk: +8, +6, +21, −Y, 12p− NPM1 mutation with FLT3-ITD CEBPα mutation Increasing blasts Antecedent hematologic malignancies

CLL

High-risk cytogenetics: del(11q) and del(17p) Intermediate-risk cytogenetics: 14q, 12+ Unmutated (germline) IgVH gene CD38 expression in >30% of lymphocytes ZAP-70 expression in >20% of lymphocytes

Elevated serum thymidine kinase Presence of large-cell transformation Elevated b2-microglobulin Doubling time of lymphocyte count <12 months Rai stage III or IV, Binet stage C

MDS

High-risk cytogenetics: Complex (>3 abnormalities) Chromosome 7 abnormalities: 7q, −7, del(7p); t(5q) Inv16, t(8;12)—implies diagnosis of AML

Thrombocytopenia at presentation High transfusion burden IPSS intermediate 2-high risk disease

High-risk cytogenetics: t(4;14), t(14;16), −17p13 Intermediate-risk cytogenetics: −13q Serum albumin <3 g/dL Plasma cell labeling index >3% Hypodiploidy ISS stage III-IV

Bone marrow plasma cells >50% b2-microglobulin >4 mg/L Creatinine >2 mg/dL Platelet count <150,000/mm3 Relapse <12 months from HCT or first-line therapy

NHL

Elevated lactate dehydrogenase IPI stage III-IV disease High Ki-67 rate Elevated b2-microglobulin

Elevated HLA-DR Elevated c-Myc (>80%) Bcl-2 overexpression

Adapted from Kurtin S. J Adv Pract Oncol. 2010;1:19-29. Reprinted with permission. ALL indicates acute lymphoblastic leukemia; AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; CR, complete response; IPI, International Prognostic Index; IPSS, International Prognostic Scoring System; MDR, multidrug resistance; MDS, myelodysplastic syndromes; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; PCR, polymerase chain reaction; WBC, white blood cell.

April 2012 I VOl 5, NO 3

current working knowledge of all these concepts. Made-to-Order Clinical Trials: The Way Forward Predictive and prognostic indices and the notion of precision medicine have evolved as a result of ongoing clinical trials in oncology. The integration of functional imaging, sequential tissue analysis, and use of biomarker assays has developed as a result of these trials. The shift from a one-size-fits-all model of drug development, where a new agent is tested in a wide variety of tumor types to determine the maximum tolerated dose and sensitivity to individual diseases, is now being replaced by trials with a specific patient prototype in mind. These made-to-order clinical trials are designed based on a predetermined biomarker profile generated by laboratory disease models, with inclusion criteria specific to the biomarker and disease prototype.2 This approach will require a shift in the definition of clinical efficacy and clinical trial end points as well as development of new technologies to obtain these measures. Because these trials will be costly, with the potential benefit focused on only a small population of patients, it will be necessary to address hard questions, such as who will spend the time and money discovering, designing, and developing novel drugs for newly discovered targets. The current environment of skepticism toward pharmaceutical corporations, despite their significant contributions to clinical research in oncology and limited funding sources outside of these corporate entities, will make this new drug development process more difficult, particularly for orphan diseases.

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Personalized Medicine in Oncology Cancer Happens in Humans— Most Often the Older Adult We must always remember that beyond the tissue diagnosis, diagnostic imaging results, and laboratory values, there is a patient with all of the unique characteristics of age, comorbidities, lifestyle, treatment goals, and available resources. These are what I consider the personalized aspects of oncology care. The goal of personalized medicine is to apply the principles of precision medicine in a way that provides the greatest benefit with the least amount of risk to the individual patient. Consideration of the effect of comorbidities, the cost of treatment, self-care capabilities, available caregiver support, proximity to the clinical setting, and quality of life must be central to the treatment plan. The patients and their primary caregivers should be provided with adequate information to make an informed choice. As clinicians, we must find ways to educate ourselves and our patients about these complex concepts. Continued enrollment of patients in clinical trials that include tissue banking and biomarker assays will promote refinement of riskadapted treatment selection based on predictive and prognostic indices. ● References 1. Kurtin S. Risk analysis in the treatment of hematologic malignancies in the elderly. J Adv Pract Oncol. 2010;1:19-29. 2. Yap A, Sandhu SK, Workman P, et al. Envisioning the future of early anticancer drug development. Nat Rev Cancer. 2010;10:514-523. 3. Chu E. An update on the current and emerging targeted agents in metastatic colorectal cancer. Clin Colorectal Cancer. 2011;11:1-13. 4. Richardson PG, Lauback J, Mitsiades C, et al. Tailoring treatment for multiple myeloma patients with relapsed and refractory disease. Oncology (Williston Park). 2010;24(suppl 2):22-29. 5. Bishop C. Biomarkers in breast cancer. J Adv Pract Oncol. 2011;2:101-111. 6. Grande C, Viale PH, Yamamoto D. Biomarkers in colorectal cancer: implications for nursing practice. J Adv Pract Oncol. 2010;1:245-255. 7. Aggarwal C, Somiah N, Simon GR. Biomarkers with predictive and prognostic function in non-small cell lung cancer: ready for prime time? J Natl Compr Canc Netw. 2010;8:822-832. 8. National Cancer Institute. Breast cancer treatment (PDQ®): triple-negative breast cancer. NCI Web site. www.cancer.gov/cancertopics/pdq/treatment/breast/healt hprofessional/page8. Updated November 21, 2011. Accessed March 14, 2012. 9. National Cancer Institute. General information about non-small cell lung cancer (NSCLC). NCI Web site. www.cancer.gov/cancertopics/pdq/treatment/non-smallcell-lung/healthprofessional#Section_48499. Updated February 10, 2012. Accessed March 14, 2012. 10. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Breast Cancer. V.1.2012. www.nccn.org. Published January 20, 2012. Accessed March 16, 2012. 11. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Non-Small Cell Lung Cancer. V.2.2012. www.nccn.org. Published October 4, 2011. Accessed March 16, 2012. 12. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Colon Cancer. V.3.2012. www.nccn.org. Published January 17, 2012. Accessed March 16, 2012. 13. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Multiple Myeloma. V.1.2012. www.nccn.org. Published July 26, 2011. Accessed March 16, 2012. 14. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Acute Myeloid Leukemia. V.2.2011. www.nccn.org. Published December 21, 2010. Accessed March 16, 2012. 15. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Acute Lymphoblastic Leukemia. V.1.2012. www.nccn.org. Published March 12, 2012. Accessed March 16, 2012.

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Table 4 Disease-Specific Diagnostic Imaging10-18 Cancer Type Recommended Baseline Imaging ALL

• CXR • Other imaging based on symptoms or clinical findings only

AML

• CXR • Other imaging based on symptoms or clinical findings only

Breast

• Diagnostic bilateral mammography, ultrasound, or MRI as indicated • Additional testing determined by stage of disease and symptoms – Stage III—bone scan, CT of abdomen and pelvis, chest imaging – Bone scan for localized bone pain or elevated alkaline phosphatase – CT of abdomen and pelvis for elevated LFTs, abnormal PE – FDG PET/CT only in selected instances of locally advanced or metastatic disease

CML

• CXR PA & lateral • Abdominal ultrasound or CT of abdomen with clinical evidence of splenomegaly

Colorectal

• Contrast-enhanced diagnostic CT of chest, abdomen, and pelvis • PET/CT not routinely indicated

MDS

• CXR • Other imaging based on symptoms of clinical findings only

Myeloma

• Skeletal survey (plain films) • CXR PA & lateral • MRI of spine if findings on plain films or clinical signs/symptoms

NHL— DLBCL, FL, MCL, CLL/SLL

• CT of chest, abdomen, and pelvis • MUGA scan or echocardiogram • PET/CT only indicated for initial diagnosis of mantle cell or DLBCL—recommended only in selected cases for diagnosis or treatment evaluation for indolent lymphomas (FL, CLL/SLL) • MRI or CT of brain for selected high-risk cases or with symptoms

Non–small cell lung

• CT of chest to adrenals • PET/CT—findings require pathological confirmation • MRI of brain • Endoscopic ultrasound and biopsy

ALL indicates acute lymphoblastic leukemia; AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; CT, computed tomography; CXR, chest x-ray; DLBCL, diffuse large B-cell lymphoma; FDG, fluorodeoxyglucose; FL, follicular lymphoma; LFT, liver function test; MCL, mantle cell lymphoma; MDS, myelodysplastic syndromes; MUGA, multigated acquisition; NHL, non-Hodgkin lymphoma; PA, posteroanterior; PE, physical examination; PET, positron emission tomography; SLL, small lymphocytic leukemia.

NSCLC Stage III or IV

EML4-ALK+

Crizotinib

EML4-ALK– EGFR– Nonsquamous histology

EGFR+

Erlotinib or gefitinib

EML4-ALK– EGFR– Squamous histology

VEGF-I eligible

VEGF-I ineligible

Carboplatin-paclitaxel + bevacizumab OR cisplatin-pemetrexed

Cisplatin-pemetrexed OR cisplatin-vinorelbine ± cetuximab OR cisplatin OR carboplatin with docetaxel OR gemcitabine OR paclitaxel

NSCLC indicates non –small cell lung cancer.

Cisplatin-vinorelbine ± cetuximab OR cisplatin OR carboplatin with docetaxel OR gemcitabine OR paclitaxel

Figure. Application of Biomarkers in NSCLC11 16. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Myelodysplastic Syndromes. V.1.2012. www.nccn.org. Published December 6, 2011. Accessed March 16, 2012.

17. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™: Non-Hodgkin’s Lymphomas. V.2.2012. www.nccn.org. Published February 23, 2012. Accessed March 16, 2012.

18. Kurtin S. Leukemia and myelodysplastic syndromes. In: Yarbro CH, Wujcik D, Gobel BH, eds. Cancer Nursing: Principles and Practice. 7th ed. Sudbury, MA: Jones & Bartlett LLC; 2010:1369-1398.

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Third Annual Navigation and S September 14-16, 2012 • Phoenix, Arizona • PRELIMINARY AGENDA* Friday, September 14 1:00 – 3:00 pm

Pre-Conference Workshops • Core Principles of Navigation • Grant Writing, Research, and Getting Published • Providing Optimal Community Outreach • Implementing a Survivorship Program/Clinic 3:15 – 5:15 pm Pre-Conference Workshops • Core Principles of Navigation • Grant Writing, Research, and Getting Published • Providing Optimal Community Outreach • Implementing a Survivorship Program/Clinic 5:15 – 7:00 pm FREE TIME 7:00 – 9:00 pm Welcome Reception/Posters in the Exhibit Hall

Saturday, September 15 7:30 – 8:30 am 8:30 – 8:45 am 8:45 – 9:45 am 10:00 – 11:30 am

Breakfast Symposium/Product Theater Welcome & Introductions Conference Co-Chairs General Session 1: Navigation Update: 2012 Disease-Site–Specific Breakouts A) Breast Cancer Navigation B) Lung Cancer Navigation C) GI Cancer Navigation D) Prostate Cancer Navigation E) Head & Neck Cancer Navigation F) Hematologic Malignancies Navigation G) Gynecologic Cancers Navigation H) Navigation Program Administration 11:45 am – 1:00 pm Lunch in the Exhibit Hall 1:15 – 2:15 pm Advocacy Keynote 2:15 – 3:15 pm General Session 2: Best Practices in Survivorship Care Planning 3:15 – 4:15 pm General Session 3: Plenary Session Moderator: Research Committee Member 4:15 – 5:00pm Poster Reception in the Exhibit Hall 5:00 – 7:00 pm FREE TIME 7:00 – 10:00 pm Awards Dinner

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

TARGET AUDIENCE AONN’s Third Annual Conference is the only meeting that gives you access to decision-makers and key practitioners involved in oncology navigation and survivorship. If your company provides any of the following services/products for the oncology healthcare community, this is the meeting for you. This educational initiative is directed toward oncology nurse navigators, patient navigators, and social workers. • • • • •

Pharmaceutical/Biotech Genetic Laboratory Services Navigation Software Patient Advocacy Training

• • • • •

Patient Access Reimbursement Publishers Education Certification

CONTINUING EDUCATION INFORMATION Goal AONN’s Third Annual Navigation and Survivorship Conference will advance the role of navigation and survivorship in cancer care to ultimately improve the quality of patient care. Objectives • Discuss the evolution of the role of navigation in healthcare • Assess strategies for navigating diverse patient populations by cancer type and environmental factors • Define methods for providing patient support and guidance in the age of personalized cancer care • Evaluate best practices regarding survivorship and psychosocial care

CALL FOR ABSTRACTS

Sunday, September 16 7:30 – 8:30 am Breakfast Symposium/Product Theater 8:30 – 9:30 am General Session 4: Navigation in the Age of Personalized Cancer Care 9:30 – 10:30 am General Session 5: Best Practices in Psychosocial Care 10:45 am – 12:15 pm Practice-Setting–Specific Breakouts • Urban • Suburban • Rural 12:15 – 1:15 pm Lunch in the Exhibit Hall 1:30 – 2:30 pm Survivor Keynote 2:30 – 2:45 pm Conclusion of the Conference

This is an opportunity to share research, programs, and results with your colleagues. Submit your abstract via e-mail to Liz@aonnonline.org. Abstract Deadline: August 1, 2012

SPONSORS This activity is jointly sponsored by AONN Foundation for Learning, Inc., and Medical Learning Institute, Inc.

*Preliminary agenda, subject to change.

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Survivorship Conference â&#x20AC;˘

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

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

CONFERENCE REGISTRATION Register online: www.regonline.com/aonn2012

Current Members New Members Nonmembers

$295 $345 $425*

*Register by July 15 and save $100 off full registration of $525.

CONFERENCE CO-CHAIRS Sharon Gentry, RN, MSN, AOCN, CBCN Breast Health Navigator Derrick L. Davis Forsyth Regional Cancer Center Winston-Salem, NC Lillie Shockney, RN, BS, MAS University Distinguished Service Associate Professor of Breast Cancer Depts of Surgery and Oncology Administrative Director, Johns Hopkins Breast Clinical Programs Administrative Director, Johns Hopkins Cancer Survivorship Programs Associate Professor, JHU School of Medicine, Depts of Surgery & Gynecology and Obstetrics Associate Professor, JHU School of Nursing Baltimore, MD

INVITED FACULTY* Juli Aistars, RN, APN Prostate Nurse Navigator Northwest Community Hospital Arlington Heights, IL

Kristin Holmberg, MN, RN Lung Cancer Nurse Navigator Overlake Hospital Medical Center Bellevue, WA

Robin Atkinson, RN, BSN, OCN GYN Nurse Navigator Forsyth Medical Center Winston-Salem, NC

Kimberly F. Leake, RN, MSN Nurse Navigator Hematologic Malignancies Program University of Virginia Health System Hematologic Malignancies Program and Cancer Center Charlottesville, VA

Karyl Blaseg, RN, MSN, OCN Manager of Cancer Programs Billings Clinic Cancer Center Billings, MT Linda Fleisher, PhD, MPH Assistant Vice President, Health Communications and Health Disparities Fox Chase Cancer Center Cheltenham, PA

Coralyn Martinez, MSN, RN, OCN GI Nurse Navigator The Lacks Cancer Center Saint Maryâ&#x20AC;&#x2122;s Health Care Grand Rapids, MI

Pamela Matten, RN, BSN, OCN Nurse Navigator Thoracic Oncology Program The Center for Cancer Prevention and Treatment St. Joseph Hospital Orange, CA Nicole Messier, BSN, RN Upper GI and GU Nurse Navigator/ Clinical Program Coordinator Vermont Cancer Center Fletcher Allen Health Care Burlington, VT Roxanne Parker, MSN Clinical Nurse Navigator Arizona Oncology Associates Phoenix, AZ Mandi Pratt Chapman, MA Associate Director GW Cancer Institute Community Programs Co-Director, GWCI Center for the Advancement of Cancer Survivorship, Navigation and Policy Project Director, National Cancer Survivorship Resource Center Washington, DC Elaine Sein, RN, BSN, OCN, CBCN Senior Project Manager, Fox Chase Cancer Center Fox Chase Cancer Center Partners Rockledge, PA

Jean B. Sellers, RN, MSN, OCN Administrative Clinical Director UNC Cancer Outreach Chapel Hill, NC Julie Silver, MD Assistant Professor Department of Physical Medicine and Rehabilitation Harvard Medical School Boston, MA Jay R. Swanson, RN, BSN, OCN Oncology Nurse Navigator Saint Elizabeth Cancer Institute Lincoln, NE Pamela Vlahakis, RN, CEN, CRN, CBCN Nurse Coordinator Hunterdon Regional Breast Care Program Hunterdon Regional Cancer Center Flemington, NJ Cindy Waddington, RN, MSN, AOCN Clinical Nurse Specialist Cancer Care Management Certified Health and Wellness Coach Mind, Body and Spirit Wellness Program Helen F. Graham Cancer Center Christiana Care Health System Newark, DE

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*Subject to change

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Genetic Counseling

How Old Is Too Old for Genetic Testing? The Importance of Testing the Most Appropriate Family Member By Cristi Radford, MS, CGC Sarasota Memorial Health Care System, Sarasota, Florida Cristi Radford, MS, CGC

Kristin Kalla, MS, CGC

arah is a 59-year-old female referred by her OB/GYN provider for genetic counseling and cancer risk assessment. She has never had a diagnosis of cancer, colonic polyps, or benign tumors. Additionally, she has never undergone any risk-reducing surgeries, and no family members have undergone genetic testing. When making her appointment, she expresses concern about her risk of pancreatic cancer because 2 of her brothers died of it (per medical records adenocarcinoma of the pancreas). What else would you want to know?

Kristin Kalla, MS, CGC Scripps Cancer Center, San Diego, California

affected first-degree relatives resulted in a 32-fold increased risk.2 Pancreatic cancer is associated with germline mutations in multiple genes, including PRSS1, SPINK1, CTRC, CFTR, CDKN2A, BRCA1, BRCA2, PALB2, STK11, MLH1, MSH2, MSH6, PMS2, APC, P53, MEN1, and VHL.3-7 Each gene has its own associated cancer risks. Thus, identifying the gene harboring the mutation is not only important for determining an individual’s risk of developing pancreatic cancer but also to provide tailored medical management for other associated cancers. Additionally, depending on the gene mutation and/or family history, an asymptomatic individual may be able to enroll in a research study investigating pancreatic cancer surveillance modalities.

Family History Sarah’s family history is imperative in developing a genetic testing strategy. In taking the family history, the genetic counselor learns: Sarah has 2 children, a daughter aged 29 and a son aged 27 years. She has 6 living siblings who all have children. Additionally, she has 3 siblings who are deceased: a sister who died of breast cancer at age 63 and 2 brothers who died of pancreatic cancer, one at age 47 and the other at age 57. Her father died at age 82 of heart disease. His family history is negative for malignancy. Maternal family history includes her mother, who was diagnosed with breast cancer at age 69 and died at age 73 of metastatic disease. Sarah has 2 living maternal aunts; one aunt aged 96 who was diagnosed with breast cancer at age

One key component is developing a genetic testing strategy that includes prioritizing the order of tests and identifying the best individual in the family to test.

Background At least 10% of pancreatic cancer cases are estimated to be hereditary. In the absence of a gene mutation, a family with 2 or more first-degree relatives with pancreatic cancer is typically considered hereditary. For families where a germline mutation cannot be identified, the lifetime risk of pancreatic cancer depends on family history and has an increased relative risk of 1.5 to 3.4.1 The risk of pancreatic cancer increases as the number of affected family members increases. In a prospective registry-based study, members of familial pancreatic cancer kindreds with 1 affected first-degree relative had a 4.5fold increased risk of developing pancreatic cancer, while individuals with 2 affected first-degree relatives had a 6.4fold increased risk, and 3 or more

April 2012 I VOl 5, NO 3

Multiple professional organizations have guidelines outlining standards for the practice of cancer risk assessment. One key component is developing a genetic testing strategy that includes prioritizing the order of tests and identifying the best individual in the family to test.8,9 As pancreatic cancer is associated with numerous hereditary cancer syndromes, the clinician must develop a strategy that assesses all likely syndromes. Additionally, to provide the most accurate risk information to Sarah, the clinician should attempt, if possible, to begin testing on the most informative family member.

40. Her other living aunt, who is now in her 80s, was diagnosed with breast cancer at approximately age 60. She has 2 deceased maternal aunts. One of these aunts was diagnosed with breast cancer at age 70 and died in her 70s, and the second aunt was diagnosed with breast cancer at approximately age 70 and also died in her 70s. She also has 1 maternal uncle who is deceased, and she does not have information about his history. Her maternal grandmother died of pancreatic cancer at age 80, and she has a great aunt who died of breast cancer in her 40s. There are at least 30 relatives, including

Sarah’s multiple nieces and nephews and her maternal first cousins and their children, who are potentially at an increased risk for cancer. Sarah’s maternal family is of Irish and other non-Jewish Caucasian ancestry. Her paternal family is of English and Irish ancestry. Knowledge Applied to Sarah According to the genetic counselor’s assessment, Sarah’s family is highly suggestive of a hereditary cancer syndrome and appears most consistent with a mutation in the BRCA1 or BRCA2 genes. She has multiple generations affected with cancer, early onset of cancer, and multiple cancers associated with the BRCA genes. The genetic counselor now has the option of proceeding with testing for Sarah or encouraging her to contact her maternal aunt, aged 96, who lives in Florida and is a 56-year breast cancer survivor, regarding the option of genetic testing. Testing the maternal aunt is important for 2 reasons: she is the most informative family member, and testing her is the most cost-effective method. In Sarah’s case, there is not currently a known familial alteration in the family. Therefore, if she tests negative for alterations in the BRCA1/2 genes, she would be considered an “uninformative negative.” Thus, she would still need to be managed as at-risk for a hereditary pancreatic syndrome, particularly BRCA1/2. Without an identified mutation in the BRCA1/2 genes in the family, it cannot be assumed that Sarah is a true negative. Additionally, the other 30+ at-risk family members would need to undergo full gene analysis of BRCA1/2 until a mutation is identified—if one is present. A true negative result would mean a mutation has been identified in the family, and Sarah does not carry it. Thus, she would be managed as general population risk. The genetic counselor discusses genetic testing options with Sarah. Sarah opts to speak with her aunt about genetic testing. The genetic

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Genetic Counseling counselor assists Sarah by locating professionals in Sarah’s geographical area familiar with cancer risk assessment. Sarah signs medical releases allowing family history information to be shared with her aunt’s genetic professional. Ultimately, Sarah’s aunt undergoes testing for the BRCA1/2 genes and is found to have a mutation in BRCA2. Sarah’s aunt is provided with multiple copies of her family history and test results for distribution to at-risk family members, including signing releases for this information to be released directly to Sarah’s genetic provider. Armed with a positive genetic test result, the 30+ at-risk family members can now undergo single-site gene analysis for the familial BRCA2 mutation. For Sarah and other family members, this drastically changes the cost of their genetic test. Additionally, for individuals who test negative for the BRCA2 mutation, they are considered “true negatives” and most likely managed as general population risk for developing cancer.

Testing the individual in the

References 1. Haddad A, Kowdley GC, Pawlik TM, et al. Hereditary pancreatic and hepatobiliary cancers. Int J Surg Oncol. 2011. Article ID 154673. 2. Klein AP, Brune KA, Petersen GM, et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 2004;64:2634-2638. 3. Brand RE, Lerch MM, Rubinstein WS, et al. Advances in counseling and surveillance of patients at risk for pancreatic cancer. Gut. 2007;56:1460-1469. 4. Hruban RH, Canto MI, Goggins M, et al. Update on familial pancreatic cancer. Adv Surg. 2010;44:293-311. 5. Jensen RT, Berna MJ, Bingham DB, et al. Inherited pancreatic tumor syndromes: advances in molecular

pathogenesis, diagnosis, management, and controversies. Cancer. 2008;113(7 suppl):1807-1843. 6. Shi C, Hruban RH, Klein AP. Familial pancreatic cancer. Arch Pathol Lab Med. 2009;133:365-374. 7. Trepanier A, Ahrens M, McKinnon W, et al. Cancer risk assessment and counseling: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2004;13:83-114. 8. Weitzel JN, Blazer KR, Macdonald DJ, et al. Genetics, genomics, and cancer risk assessment: state of the art and future directions in the era of personalized medicine. CA Cancer J Clin. 2011;61:327-359. 9. Weitzel JN. Genetic cancer risk assessment. Putting it all together. Cancer. 1999;86(11 suppl):2483-2492.

Did You Know?

An estimated 2.5 million Americans travel outside the United States to receive medical treatment. —Aesthet Surg J. 2011;31:694-697.

“Quality care is everyone’s business.”

family most likely to have a gene mutation typically provides the most informative Beth Faiman, PhD(c), MSN, APRN-BC, AOCN

results... Take-Home Messages Testing the individual in the family most likely to have a gene mutation typically provides the most informative results and is the most cost-effective method for the family. An individual cannot be too old for genetic testing. Remember, genetic testing is relatively new. Thus, cancer survivors may not have had the option of genetic testing at the time of their diagnosis. Sometimes the most informative family member for genetic testing lives far away, such as on the opposite coast. You can assist patients in finding professionals for cancer risk assessment by encouraging them to ask for a referral from their healthcare team. Additionally, the following Web sites may be useful: GeneTests/Clinic Directory: www.ncbi. nlm.nih.gov/sites/GeneTests/; National Society of Genetic Counselors Find a Genetic Counselor, www.nsgc.org/; NCIPDQ/Cancer Genetics Services Directory, www.cancer.gov/cancertopics/ genetics/directory/. ●

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Nurse Practitioner, Multiple Myeloma Program Cleveland Clinic Taussig Cancer Institute Cleveland, OH

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Spring Into Cruciferous Vegetables By Karen Connelly, RD, CSO pring is upon us, and with it comes the prospect thiocyanates.3 Because of the presence of these comof new beginnings with flowers blooming and pounds, detoxification enzymes are stimulated and begin trees, plants, and bushes budding with the fruits the process of eliminating carcinogens in the body before and vegetables of the season. The warm breeze of spring they can damage DNA.3,4 These compounds have been brings motivation to start the “spring cleaning” of our the focus of many types of research studies evaluating diets. There is no better way to shape up a diet than to their impact on cancer prevention as well as the prevenstart incorporating more cruciferous vegetables into the tion of other chronic conditions. Breast cancer has been the focus of many studies diet. Cruciferous vegetables include such nutrition superstars as broccoli, cauliflower, kale, arugula, watercress, investigating the impact of the phytochemicals found in cruciferous vegetables on its prevention as well as on bok choy, cabbage, collard greens, and brussels sprouts. Cruciferous vegetables belong to the Brassicaceae fam- reducing the risk of breast cancer recurrence. The isoily, and all of these vegetables share the same 4-petal con- thiocyanates and indoles found in cruciferous vegetastruction resembling its namesake the “cross” or “cru- bles have been shown to alter estrogen metabolism, cifer.” Some cruciferous vegetables have a “head” like shifting the estrogen from a stronger, active form to a broccoli and cauliflower, and others are “headless” like weaker, less active form.5 This may help reduce the risk of hormone-based cancers kale and collard greens. The such as breast as well as impressive vitamin, mineral, Eating your vegetables endometrial and cervical canand phytochemical content of cer.5 According to the cruciferous vegetables is undehas never held as much American Institute for Cancer niable, and their impact on disResearch (AICR), more ease prevention, especially meaning as it does now, recent, well-designed studies cancer prevention, has been do not strongly or consistently the focus of many research with emerging research support a link between crucifstudies. The unique phytonurevealing their strength erous vegetable intake and trient content of these vegetareduced cancer risk.6 The lack bles has been shown in epiand power on our health. of evidence to support the posdemiologic studies to help itive impact of cruciferous prevent the onset and halt the progression of colon, breast, prostate, bladder, cervical, vegetables on cancer reduction may be due to genetic differences from person to person. The AICR reports and other cancers.1,2 Every day, we are exposed to pollutants that our bod- that scientists have discovered that some individuals are ies must fight. Exposure to these pollutants can be a unable to “retain” or “utilize” the protective phytochemresult of choices we make in our lives such as the foods icals present in cruciferous vegetables, which ultimately we eat or a result of factors outside of our control such as inhibits their ability to initiate the detoxification elements in the environment that adversely affect our process.6 At this time, it is still beneficial to encourage health. Cruciferous vegetables have been shown to help breast, endometrial, and cervical cancer patients to eliminate these toxins from our body and reduce their include 3 to 5 servings of cruciferous vegetables a week in negative impact, thereby reducing the risk of certain their diet. In addition to the phytochemicals present in chronic diseases. The ability of cruciferous vegetables to cruciferous vegetables, they are also rich in fiber, help protect our bodies from chronic disease is due to carotenoids, vitamin C, and folate. Researchers continue to investigate the effect and their sulfur-containing compounds called glucosinolates. Once one of these vegetables is altered by chewing, cut- impact of cruciferous vegetable intake on various ting, or chopping, specific plant enzymes are activated cancer sites. Based on recent research, bladder cancer and initiate the breakdown of the glucosinolates into survival may be improved with the intake of cruciferbiologically active compounds called indoles and iso- ous vegetables. In an in vivo study, researchers found that isothiocyanates in broccoli sprout extracts were able to inhibit bladder tumor formation in rats by 61%.7 These studies show the potential impact of Ms Connelly is a Registered Dietitian and Certified Specialist phytochemicals on a specific organ site. This is valuin Oncology Nutrition at the able information to utilize when developing an indiSteeplechase Cancer Center in vidualized dietary plan that can actually make a sigSomerville, New Jersey. As nificant impact on the patient’s health. Additional part of her responsibilities, she support for the intake of cruciferous vegetables to provides nutrition counseling, reduce cancer risk comes from a review of case-congroup classes, and monthly trol studies from Italy and Switzerland. This review cooking classes for patients concluded that the studies examined suggested there and families. is a “favorable effect” of cruciferous vegetables on

April 2012 I VOl 5, NO 3

cancers of the oral cavity/pharynx, esophagus, colorectum, breast, and kidney.8 Increased fruit and vegetable intake is protective against many different chronic diseases, including cancer. As health professionals, we constantly encourage patients to increase their intake of these health-promoting, disease-fighting foods. This is a health message that has been touted for years, and the wisdom of those words is now becoming clearer. Science is evolving and diving deeper into the human body’s metabolism of plant phytochemicals and how well our bodies are able to utilize their biologically active compounds. Research may even be able to tell us exactly which cruciferous vegetable is most protective against a particular type of cancer and if an individual is genetically capable of utilizing those compounds effectively. Eating your vegetables has never held as much meaning as it does now, with emerging research revealing their strength and power on our health. At times it may seem too simplistic to tell patients to consume more vegetables to improve their health. However, a simple truth may be all they need to make significant changes to their overall well-being. Three to 5 servings per week of broccoli, cauliflower, kale, collard greens, brussels sprouts, cabbage, or bok choy can help reap the benefits of these nutrientpacked vegetables. Enjoy them prepared in a variety of ways such as steamed or sautéed, or eat them raw. Because of their high fiber content, patients who are having issues with abdominal bloating, diarrhea, or nausea may have difficulty tolerating these vegetables. Once symptoms resolve, these vegetables can be slowly reincorporated into the diet. If patients are currently under treatment, it may not be feasible for them to consume as many of these vegetables as recommended due to a variety of side effects caused by treatment. It is still important to share these dietary recommendations with patients as it empowers them, provides them with options and a means to improve their well-being, and even augments the treatment prescribed by their doctors. Bottom line: eat your veggies! ● References 1. Bosetti C, Filomeno M, Riso P, et al [published online ahead of print February 10, 2012]. Cruciferous vegetables and cancer risk in a network of case-control studies. Ann Oncol. 2. Liu B, Mao Q, Lin Y, et al [published online ahead of print March 6, 2012]. The association of cruciferous vegetables intake and risk of bladder cancer: a meta-analysis. World J Urol. 3. Holst B, Williamson G. A critical review of the bioavailability of glucosinolates and related compounds. Nat Prod Rep. 2004;21:425-447. 4. Talalay P, Fahey JW. Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. J Nutr. 2001;131(11 suppl):3027S-3033S. 5. Auborn KJ, Fan S, Rosen EM, et al. Indole-3-carbinol is a negative regulator of estrogen. J Nutr. 2003;133(7 suppl):2470S-2475S. 6. American Institute for Cancer Research. Foods that fight cancer: broccoli & cruciferous vegetables. www.aicr.org/foods-that-fight-cancer/broccoli-cru ciferous.html. Accessed March 30, 2012. 7. Munday R, Mhawech-Fauceglia P, Munday CM, et al. Inhibition of urinary bladder carcinogenesis by broccoli sprouts. Cancer Res. 2008;68:1593-1600. 8. Tang L, Zirpoli GR, Guru K, et al. Intake of cruciferous vegetables modifies bladder cancer survival. Cancer Epidemiol Biomarkers Prev. 2010;19:18061811.

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Recipes ■ Spring Asian Salad Ingredients 2 heads of mizuna, cut from stem 2 heads of tatsoi, cut from stem 1 cup baby arugula ½ lb daikon, julienne ¼ cup mandarin oranges ¼ cup cucumber, sliced 6 cherry tomatoes, quartered

Dressing 2 tablespoons ginger, chopped 2 cloves garlic, chopped 1 bunch scallion, sliced thin 1 tablespoon sesame oil ¼ cup lite soy sauce

1. Toss together first 7 ingredients. 2. Whisk remaining ingredients. 3. Toss salad with dressing. Nutritional Information Yield: 4 servings 110 calories, 6 g fat, 0.5 g saturated fat, 0 mg cholesterol, 520 mg sodium, 11 g carbohydrate, 2 g dietary fiber, 6 g sugar, 5 g protein

■ Collard Greens Ingredients 2 bunches collard greens, about 4 cups 4 garlic cloves, chopped 2 onions, diced 4 tablespoons salt-free herb seasoning 1 teaspoon hot sauce Cooking spray

1. Cut collard leaves from stem. Cut leaves to small dice. 2. Wash leaves by soaking in a bowl of cold water. Remove greens from water and transfer to new bowl. Repeat this process until the bottom of the wash bowl comes out clean. 3. Simmer in water for 20 minutes until tender. 4. Chill in ice water. 5. Heat sauté pan and add cooking spray. Sauté onions for 5 minutes until soft. 6. Add garlic and sauté an additional minute. 7. Add collard greens and heat through. 8. Add seasoning and hot sauce. Nutritional Information Serving size: 1/2 cup 40 calories, 0 g total fat, 0 g saturated fat, 0 mg cholesterol, 50 mg sodium, 9 g total carbohydrate, 2 g dietary fiber, 2 g sugar, 2 g protein

■ Napa/Bok Choy Slaw Ingredients 1 head napa cabbage, chiffonade 1 head bok choy, chiffonade 2 carrots, julienne 1 bunch scallions, sliced thin 2 garlic cloves, chopped ½ cup rice wine vinegar

¼ cup canola oil 2 tablespoons sugar ¼ teaspoon salt

Toss all the ingredients together. Mixture can be used immediately, or it can sit overnight and be served the next day.

BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE SANCUSO® (Granisetron Transdermal System) is indicated for the prevention of nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy regimens of up to 5 consecutive days duration. DOSAGE AND ADMINISTRATION The transdermal system (patch) should be applied to clean, dry, intact healthy skin on the upper outer arm. SANCUSO should not be placed on skin that is red, irritated or damaged. Each patch is packed in a pouch and should be applied directly after the pouch has been opened. The patch should not be cut into pieces. Adults Apply a single patch to the upper outer arm a minimum of 24 hours before chemotherapy. The patch may be applied up to a maximum of 48 hours before chemotherapy as appropriate. Remove the patch a minimum of 24 hours after completion of chemotherapy. The patch can be worn for up to 7 days depending on the duration of the chemotherapy regimen. DOSAGE FORMS AND STRENGTHS SANCUSO is a 52 cm2 patch containing 34.3 mg of granisetron. The patch releases 3.1 mg of granisetron per 24 hours for up to 7 days. CONTRAINDICATIONS SANCUSO is contraindicated in patients with known hypersensitivity to granisetron or to any of the components of the patch. WARNINGS AND PRECAUTIONS Gastrointestinal The use of granisetron in patients may mask a progressive ileus and/or gastric distention caused by the underlying condition. Skin Reactions In clinical trials with SANCUSO, application site reactions were reported which were generally mild in intensity and did not lead to discontinuation of use. The incidence of reactions was comparable with placebo. If severe reactions, or a generalized skin reaction occur (e.g. allergic rash, including erythematous, macular, papular rash or pruritus), the patch must be removed. Exposure to Sunlight Granisetron may be affected by direct natural or artiﬁcial sunlight. Patients must be advised to cover the patch application site, e.g. with clothing, if there is a risk of exposure to sunlight throughout the period of wear and for 10 days following its removal because of a potential skin reaction. ADVERSE REACTIONS Clinical Trials Experience The safety of SANCUSO was evaluated in a total of 404 patients undergoing chemotherapy who participated in two doubleblind, comparator studies with patch treatment durations of up to 7 days. The control groups included a total of 406 patients who received a daily dose of 2 mg oral granisetron, for 1 to 5 days. Adverse reactions considered by the investigators as drug-related occurred in 8.7% (35/404) of patients receiving SANCUSO and 7.1% (29/406) of patients receiving oral granisetron. The most common adverse reaction was constipation that occurred in 5.4% of patients in the SANCUSO group and 3.0% of patients in the oral granisetron group. Table 1 lists the treatment emergent adverse reactions that occurred in at least 3% of patients treated with SANCUSO or oral granisetron. Table 1: Incidence of Adverse Reactions in Double-Blind, Active Comparator Controlled Studies in Cancer Patients Receiving Chemotherapy (Events ≥ 3% in either group) Body System Preferred Term

SANCUSO TDS N=404 (%)

Oral granisetron N=406 (%)

5.4

3.0

0.7

3.0

Gastrointestinal disorders Constipation Nervous system disorders Headache

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

Nutritional Information Serving size: 1/2 cup 70 calories, 4.5 g total fat, 0 g saturated fat, 0 mg cholesterol, 95 mg sodium, 5 g total carbohydrate, 1 g dietary fiber, 3 g sugar, 1 g protein

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category B Reproduction studies with granisetron hydrochloride have been performed in pregnant rats at intravenous doses up to 9 mg/kg/day (54 mg/m2/day, about 24 times the recommended human dose delivered by the SANCUSO patch, based on body surface area) and oral doses up to 125 mg/m2/day (750 mg/m2/day, about 326 times the recommended human dose with SANCUSO based on body surface area). Reproduction studies have been performed in pregnant rabbits at intravenous doses up to 3 mg/kg/day (36 mg/m2/day, about 16 times the human dose with SANCUSO based on body surface area) and at oral doses up to 32 mg/kg/day (384 mg/m2/day, about 167 times the human dose with SANCUSO based on body surface area). These studies did not reveal any evidence of impaired fertility or harm to the fetus due to granisetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, SANCUSO should be used during pregnancy only if clearly needed. Nursing Mothers It is not known whether granisetron is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when SANCUSO is administered to a nursing woman. Pediatric Use Safety and effectiveness of SANCUSO in pediatric patients under 18 years of age have not been established. Geriatric Use Clinical studies of SANCUSO did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, cautious treatment selection for an elderly patient is prudent because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Renal Failure or Hepatically-Impaired Patients Although no studies have been performed to investigate the pharmacokinetics of SANCUSO in patients with renal or hepatic impairment, pharmacokinetic information is available for intravenous granisetron. OVERDOSAGE There is no specific antidote for granisetron overdosage. In the case of overdosage, symptomatic treatment should be given. Overdosage of up to 38.5 mg of granisetron hydrochloride, as a single intravenous injection, has been reported without symptoms or only the occurrence of a slight headache. In clinical trials there were no reported cases of overdosage with SANCUSO. HOW SUPPLIED/STORAGE AND HANDLING SANCUSO (Granisetron Transdermal System) is supplied as a 52 cm2 patch containing 34.3 mg of granisetron. Each patch is printed on one side with the words “Granisetron 3.1 mg/24 hours”. Each patch is packaged in a separate sealed foil-lined plastic pouch. SANCUSO is available in packages of 1 (NDC 42747-726-01) patch. Store at 20˚-25˚C (68˚-77˚F); excursions permitted between 15˚-30˚C (59˚-86˚F). [see USP Controlled Room Temperature]. SANCUSO should be stored in the original packaging. PATIENT COUNSELING INFORMATION See FDA-approved patient labeling. Gastrointestinal Because the use of granisetron may mask a progressive ileus and/or gastric distention caused by the underlying condition, patients should be instructed to tell their physician if they have pain or swelling in their abdomen. Skin Reactions Patients should be instructed to remove the patch if they have a severe skin reaction, or a generalized skin reaction (e.g. allergic rash, including erythematous, macular, papular rash or pruritus). When patients remove the patch, they should be instructed to peel it off gently. Exposure to Sunlight Granisetron may be degraded by direct sunlight or exposure to sunlamps. In addition, an in vitro study using Chinese hamster ovary cells suggests that granisetron has the potential for photogenotoxicity. Patients must be advised to cover the patch application site, e.g. with clothing, if there is a risk of exposure to sunlight or sunlamps throughout the period of wear and for 10 days following its removal. FDA-Approved Patient Labeling Rx Only Manufactured by: Aveva Drug Delivery Systems Inc., Miramar FL 33025

Manufactured for: ProStrakan Inc., Bedminster NJ 07921 Copyright ©2008, ProStrakan Inc. All rights reserved. SANCUSO and ProStrakan are trademarks owned by the ProStrakan group of companies Revised: 08/2008

5:28 PM

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

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

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

References: 1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Antiemesis. V.1.2012. http://www.nccn.org/professionals/ physician_gls/pdf/antiemesis.pdf. Accessed December 13, 2011. 2. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2011;29(31):4189-4198. 3. Boccia RV, Gordan LN, Clark G, Howell JD, Grunberg SM; on behalf of the Sancuso Study Group. Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study. Support Care Cancer. 2011;19(10):1609-1617. 4. SANCUSO [package insert]. Bedminster, NJ: ProStrakan, Inc; 2008.

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Please see brief summary of Prescribing Information on adjacent page.

Keeps them covered

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