September 2010, Vol 3, No 6

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SEPTEMBER 2010

www.TheOncologyPharmacist.com

VOL 3, NO 6

The Official Newspaper for the Hem/Onc Pharmacist

Special Issue: A Collaborative Focus on Survivorship Care SURVIVORSHIP ISSUES

SURVIVORSHIP PROGRAM

Cancer Rehabilitation and Survivorship: Cedars-Sinai Medical Center Experience Arash Asher, MD Director, Cancer Rehabilitation and Survivorship, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles

The Cancer Survivorship Movement: From Idealism to Reality Susan Leigh, BSN, RN Founding Member and Past President, National Coalition for Cancer Survivorship

O

ver the past three decades, there has been a gradual yet steady increase in survivorship awareness, resources, and services. Although none of this has happened easily or rapidly, there is no doubt that the concept of cancer survivorship is here to stay. If this concept or social movement could be superimposed onto Erikson’s Stages of Development,1 it could be said that survivorship has grown from the stage of infancy (drive and hopefulness), through

adolescence (idealism and search for identity), and into middle adulthood (meaningful work and stability). The challenge now is to continue the cycle of growth.

This continued growth will happen by recognizing the multiple dimensions of survivorship and adapting to its complexities.

Concepts and definitions Although numerous reports have been published about different aspects of survivorship, inconsistencies remain around Continued on page 11

CLINICAL CONCERNS

Late and Long-term Physical Effects in Cancer Survivors Positive affirmation project from Cedars-Sinai’s Hope & Healing workshop.

mericans afflicted with cancer are living longer, and the outlook for them continues to improve. On the strength of public awareness, early detection, and improved multimodal cancer treatment, cancer has evolved for many patients from an often fatal disease to a chronic, treatable condition. Cancer survivors have increased in number by more than threefold over the past 30 years.

Today, there are more than 11 million survivors in the United States, with the expectation that this number will double over the next 30 years.1 Among patients diagnosed today, nearly two thirds are expected to survive at least 5 years.2 Many of these survivors will live 10, 15, 20, or more years after a cancer diagnosis.

A

Continued on page 18

Denice Economou, RN, MN, CNS, AOCN1; Marcia Grant, RN, DNSc, FAAN2 1 Project Director, Survivorship Education for Quality Cancer Care, Division of Nursing Research and Education; 2Director, Division of Nursing Research and Education, and Professor, Department of Population Sciences, City of Hope National Medical Center, Duarte, California

C

ancer survivorship can mean different things to different survivors. The consequences of cancer and its treatments can affect individuals in many ways. When patients survive their cancer, the residual effects may severely impact their future health.

With survivor issues increasingly studied, evidence is accumulating to help identify consequences associated with particular

treatments, such as surgery, chemotherapy, radiation therapy, and immunotherapy. Although the goal of treatment is to extend the life of cancer patients, providers must be equally cognizant of their patients’ quality of life.1,2 This article provides a brief overview of physical side effects patients may experience, based on the type of treatment they receive and the system affected (Table).

Continued on page 12

Inside Survivorship Programs e MSKCC Approach

Clinical Concerns Help Your Patients with Intimacy and Sexuality

Survivorship News Putting the Family Back into Family Practice

Page 13

Page 40

Fostering a Dialogue to Improve Patient Care & Outcomes

Page 14

Bridging the Gaps in Cancer Care Page 22

Developing a Psychosocial-focused Survivorship Program Page 30

Survivorship News Physical Activity and Survivors Page 36

Survivorship Resource Guide

Models of Care Resolving the Impending SupplyDemand Imbalance Page 26

Page 34 ©2010 Green Hill Healthcare Communications, LLC

Submit your cases online today at www.myelomacases.com

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When treating patients with HER2+ breast cancer

No one touches their HER2-positive status is associated with more aggressive disease and poorer outcomes than HER2-negative breast cancer. Women who received 1 year of Herceptin had a lower risk of HER2+ breast cancer returning.

We applaud you for playing such a critical role in helping patients with HER2+ breast cancer complete the full course of treatment with Herceptin.

Adjuvant indications Herceptin is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature*) breast cancer: s As part of a treatment regimen containing doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel s With docetaxel and carboplatin s As a single agent following multi-modality anthracyclinebased therapy *High-risk features for patients with ER/PR+ breast cancer include: tumor size >2 cm, age <35 years, and histologic and/or nuclear grade 2/3.

Metastatic indications Herceptin is indicated: s In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer s As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease Š2009 Genentech USA

Boxed WARNINGS and Additional Important Safety Information Herceptin administration can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure (CHF) and decreased left ventricular ejection fraction (LVEF). The incidence and severity of left ventricular cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracyclinecontaining chemotherapy regimens. Discontinue Herceptin treatment in patients receiving adjuvant therapy and strongly consider discontinuation of Herceptin in patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function.

Patients should undergo monitoring for decreased left ventricular function before Herceptin treatment, and frequently during and after Herceptin treatment. More frequent monitoring should be employed if Herceptin is

So. San Francisco, CA

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lives like you

withheld in patients who develop significant left ventricular cardiac dysfunction. In one adjuvant clinical trial, cardiac ischemia or infarction occurred in the Herceptin-containing regimens.

Serious infusion reactions and pulmonary toxicity have occurred; fatal infusion reactions have been reported. In most cases, symptoms occurred during or within 24 hours of administration of Herceptin. Herceptin infusion should be interrupted for patients experiencing dyspnea or clinically significant hypotension. Patients should be monitored until signs and symptoms completely resolve. Discontinue Herceptin for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.

Exacerbation of chemotherapy-induced neutropenia has also occurred. Herceptin can cause oligohydramnios and fetal harm

9568900

01/09

when administered to a pregnant woman.

The most common adverse reactions associated with Herceptin use were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia.

Please see brief summary of full Prescribing Information, including Boxed WARNINGS and additional important safety information, on the following pages.

www.herceptin.com

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HERCEPTIN® (trastuzumab) Brief Summary For full Prescribing Information, see package insert.

WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, and PULMONARY TOXICITY Cardiomyopathy Herceptin can result in sub-clinical and clinical cardiac failure manifesting as CHF and decreased LVEF. The incidence and severity of left ventricular cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracycline-containing chemotherapy regimens.

Evaluate left ventricular function in all patients prior to and during treatment with Herceptin. Discontinue Herceptin treatment in patients receiving adjuvant therapy and strongly consider discontinuation of Herceptin treatment in patients with metastatic breast cancer for clinically significant decrease in left ventricular function. [see Warnings and Precautions and Dosage and Administration] Infusion Reactions; Pulmonary Toxicity Herceptin administration can result in serious infusion reactions and pulmonary toxicity. Fatal infusion reactions have been reported. In most cases, symptoms occurred during or within 24 hours of administration of Herceptin.

Herceptin infusion should be interrupted for patients experiencing dyspnea or clinically significant hypotension.

Patients should be monitored until signs and symptoms completely resolve. Discontinue Herceptin for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. [see Warnings and Precautions] INDICATIONS AND USAGE Adjuvant Breast Cancer Herceptin is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature [see Clinical Studies]) breast cancer • as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel • with docetaxel and carboplatin • as a single agent following multimodality anthracycline based therapy. Metastatic Breast Cancer Herceptin is indicated: • In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer • As a single agent for treatment of HER2overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease.

CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS Cardiomyopathy Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death [see Boxed Warning: Cardiomyopathy ]. Herceptin can also cause asymptomatic decline in left ventricular ejection fraction (LVEF). There is a 4–6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving Herceptin as a single agent or in combination therapy compared with those not receiving Herceptin. The highest absolute incidence occurs when Herceptin is administered with an anthracycline. Withhold Herceptin for 16% absolute decrease in LVEF from pre-treatment values or an LVEF value below institutional limits of normal and 10% absolute decrease in LVEF from pretreatment values. [see Dosage and Administration] The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied. Cardiac Monitoring Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended: • Baseline LVEF measurement immediately prior to initiation of Herceptin • LVEF measurements every 3 months during and upon completion of Herceptin • Repeat LVEF measurement at 4 week intervals if Herceptin is withheld for significant left ventricular cardiac dysfunction [see Dosage and Administration] • LVEF measurements every 6 months for at least 2 years following completion of Herceptin as a component of adjuvant therapy. In Study 1, 16% (136/844) of patients discontinued Herceptin due to clinical evidence of myocardial dysfunction or significant decline in LVEF. In Study 3, the number of patients who discontinued Herceptin due to cardiac toxicity was 2.6% (44/1678). In Study 4, a total of 2.9% (31/1056) patients in the TCH arm (1.5% during the chemotherapy phase and 1.4% during the monotherapy phase) and 5.7% (61/1068) patients in the AC-TH arm (1.5% during the chemotherapy phase and 4.2% during the monotherapy phase) discontinued Herceptin due to cardiac toxicity. Among 32 patients receiving adjuvant chemotherapy (Studies 1 and 2) who developed congestive heart failure, one patient died of cardiomyopathy and all other patients were receiving cardiac medication at last follow-up. Approximately half of the surviving patients had recovery to a normal LVEF (defined as 50%) on continuing medical management at the time of last follow-up. Incidence of congestive heart failure is presented in Table 1. The safety of continuation or resumption of Herceptin in patients with Herceptin-induced left ventricular cardiac dysfunction has not been studied.

Table 1 Incidence of Congestive Heart Failure in Adjuvant Breast Cancer Studies Study 1 & 2a 3 4 4 a

Regimen ACb Paclitaxel+ Herceptin Chemo Herceptin ACb Docetaxel+ Herceptin Docetaxel+Carbo+ Herceptin

Incidence of CHF Herceptin Control 2% (32/1677) 2% (30/1678)

0.4% (7/1600) 0.3% (5/1708)

2% (20/1068)

0.3% (3/1050)

0.4% (4/1056)

0.3% (3/1050)

Includes 1 patient with fatal cardiomyopathy. b Anthracycline (doxorubicin) and cyclophosphamide

Table 2 Incidence of Cardiac Dysfunctiona in Metastatic Breast Cancer Studies

Study 5 (AC)b 5 (paclitaxel)

Incidence NYHA I-IV NYHA III-IV Herceptin Control Herceptin Control

Event Cardiac 28% 7% 19% 3% Dysfunction Cardiac 11% 1% 4% 1% Dysfunction Cardiac 6 7% N/A 5% N/A Dysfunctionc a Congestive heart failure or significant asymptomatic decrease in LVEF. b Anthracycline (doxorubicin or epirubicin) and cyclophosphamide c Includes 1 patient with fatal cardiomyopathy.

Infusion Reactions Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion included nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia. [see Adverse Reactions]. In postmarketing reports, serious and fatal infusion reactions have been reported. Severe reactions which include bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension, were usually reported during or immediately following the initial infusion. However, the onset and clinical course were variable including progressive worsening, initial improvement followed by clinical deterioration, or delayed post-infusion events with rapid clinical deterioration.

For fatal events, death occurred within hours to days following a serious infusion reaction. Interrupt Herceptin infusion in all patients experiencing dyspnea, clinically significant hypotension, and intervention of medical therapy administered, which may include: epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen. Patients should be evaluated and carefully monitored until complete resolution of signs and symptoms. Permanent discontinuation should be strongly considered in all patients with severe infusion reactions.

There are no data regarding the most appropriate method of identification of patients who may safely be retreated with Herceptin after experiencing a severe infusion reaction. Prior to resumption of Herceptin infusion, the majority of patients who experienced a severe infusion reaction were pre-medicated with antihistamines and/or corticosteroids. While some patients tolerated Herceptin infusions, others had recurrent severe infusion reactions despite pre-medications. Exacerbation of Chemotherapy-Induced Neutropenia In randomized, controlled clinical trials in women with metastatic breast cancer, the perpatient incidences of NCI CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was not significantly increased. [see Adverse Reactions]. Pulmonary Toxicity Herceptin use can result in serious and fatal pulmonary toxicity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions [see Warnings and Precautions (5.2)].

Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity. HER2 Testing Detection of HER2 protein overexpression is necessary for selection of patients appropriate for Herceptin therapy because these are the only patients studied and for whom benefit has been shown. Assessment for HER2 overexpression and of HER2 gene amplification should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results. Several FDA-approved commercial assays are available to aid in the selection of patients for Herceptin therapy. These include HercepTestTM and Pathway® HER-2/neu (IHC assays) and PathVysion® and HER2 FISH pharmDxTM (FISH assays).

Users should refer to the package inserts of specific assay kits for information on the validation and performance of each assay.

Limitations in assay precision (particularly for the IHC method) and in the direct linkage between assay result and overexpression of the Herceptin target (for the FISH method) make it inadvisable to rely on a single method to rule out potential Herceptin benefit. A negative FISH result does not rule out HER2 overexpression and potential benefit from Herceptin.

Treatment outcomes for metastatic breast cancer (Study 5) as a function of IHC and FISH testing are provided in Table 9.

Treatment outcomes for adjuvant breast cancer (Studies 2 and 3) as a function of IHC and FISH testing are provided in Table 7.

HER2 Protein Overexpression Detection Methods HER2 protein overexpression can be established by measuring HER2 protein using an IHC method. HercepTest®, one test approved for this use, was assessed for concordance with the Clinical Trial Assay (CTA), using tumor specimens collected and stored independently from those obtained in Herceptin clinical studies in women with metastatic breast cancer. Data are provided in the package insert for HercepTest®. HER2 Gene Amplification Detection Method The presence of HER2 protein overexpression and gene amplification are highly correlated, therefore the use of FISH to detect gene amplification may be employed for selection of patients appropriate for Herceptin therapy.

PathVysion®, one test approved for this use, was evaluated in an exploratory, retrospective assessment of available CTA 2+ or 3+ tumor specimens collected as part of patient screening for clinical studies in metastatic breast cancer (Studies 5 and 6).

Data are provided in the package insert for PathVysion®.

Embryo-Fetal Toxicity (Pregnancy Category D) Herceptin can cause fetal harm when administered to a pregnant woman. Postmarketing case reports suggest that Herceptin use during pregnancy increases the risk of oligohydramnios during the second and third trimesters. If Herceptin is used during pregnancy or if a woman becomes pregnant while taking Herceptin, she should be apprised of the potential hazard to a

fetus. [see Use in Specific Populations]. ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: • Cardiomyopathy [see Warnings and Precautions] • Infusion reactions [see Warnings and Precautions] • Exacerbation of chemotherapy-induced neutropenia [see Warnings and Precautions] • Pulmonary toxicity [see Warnings and Precautions] The most common adverse reactions in patients receiving Herceptin are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia. Adverse reactions requiring interruption or discontinuation of Herceptin treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity [see Dosage and Administration]. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adjuvant Breast Cancer Studies The data below reflect exposure to Herceptin across three randomized, open-label studies, Studies 1, 2, and 3, with (n= 3355) or without (n= 3308) trastuzumab in the adjuvant treatment of breast cancer. The data summarized in Table 3 below, from Study 3, reflect exposure to Herceptin in 1678 patients; the median treatment duration was 51 weeks and median number of infusions was 18. Among the 3386 patients enrolled in Study 3, the median age was 49 years (range: 21 to 80 years), 83% of patients were Caucasian, and 13% were Asian.

Table 3 Adverse Reactions for Study 3, All Gradesa: MedDRA (v. 7.1) 1 Year Herceptin Adverse Event Preferred Term (n= 1678) Cardiac Hypertension 64 (4%) Dizziness 60 (4%) Ejection Fraction Decreased 58 (3.5%) Palpitations 48 (3%) Cardiac Arrhythmiasb 40 (3%) Cardiac Failure Congestive 30 (2%) Cardiac Failure 9 (0.5%) Cardiac Disorder 5 (0.3%) Ventricular Dysfunction 4 (0.2%) Respiratory Thoracic Mediastinal Disorders Nasopharyngitis 135 (8%) Cough 81 (5%) Influenza 70 (4%) Dyspnea 57 (3%) URI 46 (3%) Rhinitis 36 (2%) Pharyngolaryngeal Pain 32 (2%) Sinusitis 26 (2%) Epistaxis 25 (2%) Pulmonary Hypertension 4 (0.2%) Interstitial Pneumonitis 4 (0.2%) Gastrointestinal Disorders Diarrhea 123 (7%) Nausea 108 (6%) Vomiting 58 (3.5%) Constipation 33 (2%) Dyspepsia 30 (2%) Upper Abdominal Pain 29 (2%) Musculoskeletal & Connective Tissue Disorders Arthralgia 137 (8%) Back Pain 91 (5%) Myalgia 63 (4%) Bone Pain 49 (3%) Muscle Spasm 46 (3%) Nervous System Disorders Headache 162 (10%) Paraesthesia 29 (2%) Skin & Subcutaneous Tissue Disorders Rash 70 (4%) Nail Disorders 43 (2%) Pruritis 40 (2%) General Disorders Pyrexia 100 (6%) Edema Peripheral 79 (5%) Chills 85 (5%) Aesthenia 75 (4.5%) Influenza-like Illness 40 (2%) Sudden Death 1 (.06%) Infections Nasopharyngitis 135 (8%) UTI 39 (3%) Immune System Disorders Hypersensitivity 10 (0.6%) Autoimmune Thyroiditis 4 (0.3%)

Observation (n= 1708) 35 (2%) 29 (2%) 11 (0.6%) 12 (0.7%) 17 (1%) 5 (0.3%) 4 (0.2%) 0 (0%) 0 (0%) 43 (3%) 34 (2%) 9 (0.5%) 26 (2%) 20 (1%) 6 (0.4%) 8 (0.5%) 5 (0.3%) 1 (0.06%) 0 (0%) 0 (0%) 16 (1%) 19 (1%) 10 (0.6%) 17 (1%) 9 (0.5%) 15 (1%) 98 (6%) 58 (3%) 17 (1%) 26 (2%) 3 (0.2%) 49 (3%) 11 (0.6%) 10 (.6%) 0 (0%) 10 (0.6%) 6 (0.4%) 37 (2%) 0 (0%) 30 (2%) 3 (0.2%) 0 (0%) 43 (3%) 13 (0.8%) 1 (0.06%) 0 (0%)

a The incidence of Grade 3/4 adverse reactions was <1% in both arms for each listed term. b Higher level grouping term.

The data from Studies 1 and 2 were obtained from 3206 patients enrolled, of which 1635 patients received Herceptin; the median treatment duration was 50 weeks. The median age was 49.0 years (range: 24-80); 84% of patients were White, and 7% were Black, 4% were Hispanic, and 4% were Asian. In Study 1, only Grade 3-5 adverse events, treatment-related Grade 2 events, and Grade 2-5 dyspnea were collected during and for up to 3 months following protocol-specified treatment. The following noncardiac adverse reactions of Grade 2-5 occurred at an incidence of at least 2% greater among patients randomized to Herceptin plus chemotherapy as compared to chemotherapy alone: arthralgia (31% vs. 28%), fatigue (28% vs. 22%), infection (22% vs. 14%), hot flashes (17% vs. 15%), anemia (13% vs. 7%), dyspnea (12% vs. 4%), rash/desquamation (11% vs. 7%), neutropenia (7% vs. 5%), headache (6% vs. 4%), and insomnia (3.7% vs. 1.5%). The majority of these events were Grade 2 in severity. In Study 2, data collection was limited to the following investigator-attributed treatment-related adverse reactions NCICTC Grade 4 and 5 hematologic toxicities, Grade 3–5 nonhematologic toxicities, selected Grade 2–5 toxicities associated with taxanes (myalgia, arthralgias, nail changes, motor neuropathy, sensory neuropathy) and Grade 1–5 cardiac toxicities occurring during chemotherapy and/or Herceptin treatment. The following non-cardiac adverse reactions of

Grade 2–5 occurred at an incidence of at least 2% greater among patients randomized to Herceptin plus chemotherapy as compared to chemotherapy alone: arthralgia (11% vs. 8.4%), myalgia (10% vs. 8%), nail changes (9% vs. 7%), and dyspnea (2.5% vs. 0.1%). The majority of these events were Grade 2 in severity. Safety data from Study 4 reflect exposure to Herceptin as part of an adjuvant treatment regimen from 2124 patients receiving at least one dose of study treatment [AC-TH: n = 1068; TCH: n = 1056]. The overall median treatment duration was 54 weeks in both the AC-TH and TCH arms. The median number of infusions was 26 in the AC-TH arm and 30 in the TCH arm, including weekly infusions during the chemotherapy phase and every three week dosing in the monotherapy period. Among these patients, the median age was 49 years (range 22 to 74 years). In Study 4, the toxicity profile was similar to that reported in Studies 1, 2, and 3 with the exception of a low incidence of CHF in the TCH arm. Metastatic Breast Cancer Studies The data below reflect exposure to Herceptin in one randomized, openlabel study, Study 5, of chemotherapy with (n=235) or without (n=234) trastuzumab in patients with metastatic breast cancer, and one single-arm study (Study 6; n=222) in patients with metastatic breast cancer. Data in Table 5 are based on Studies 5 and 6. Among the 464 patients treated in Study 5, the median age was 52 years (range: 25–77 years). Eighty-nine percent were White, 5% Black, 1% Asian and 5% other racial/ethnic groups.

All patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for 6 months and 12 months were 58% and 9%, respectively. Among the 352 patients treated in single agent studies (213 patients from Study 6), the median age was 50 years (range 28–86 years), 100% had breast cancer, 86% were White, 3% were Black, 3% were Asian, and 8% in other racial/ ethnic groups. Most of the patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for 6 months and 12 months were 31% and 16%, respectively.

Table 4 Per-Patient Incidence of Adverse Reactions Occurring in 5% of Patients in Uncontrolled Studies or at Increased Incidence in the Herceptin Arm (Studies 5 and 6) (Percent of Patients) Herceptin Single + Paclitaxel Herceptin ACb a Agent Paclitaxel Alone + ACb Alone n = 352 n = 91 n = 95 n = 143 n = 135 Body as a Whole Pain 47 61 62 57 42 Asthenia 42 62 57 54 55 Fever 36 49 23 56 34 Chills 32 41 4 35 11 Headache 26 36 28 44 31 Abdominal pain 22 34 22 23 18 Back pain 22 34 30 27 15 Infection 20 47 27 47 31 Flu syndrome 10 12 5 12 6 Accidental injury 6 13 3 9 4 Allergic reaction 3 8 2 4 2 Cardiovascular Tachycardia 5 12 4 10 5 Congestive 7 11 1 28 7 heart failure Digestive Nausea 33 51 9 76 77 Diarrhea 25 45 29 45 26 Vomiting 23 37 28 53 49 Nausea and 8 14 11 18 9 vomiting Anorexia 14 24 16 31 26 Heme & Lymphatic Anemia 4 14 9 36 26 Leukopenia 3 24 17 52 34 Metabolic Peripheral edema 10 22 20 20 17 Edema 8 10 8 11 5 Musculoskeletal Bone pain 7 24 18 7 7 Arthralgia 6 37 21 8 9 Nervous Insomnia 14 25 13 29 15 Dizziness 13 22 24 24 18 Paresthesia 9 48 39 17 11 Depression 6 12 13 20 12 Peripheral neuritis 2 23 16 2 2 Neuropathy 1 13 5 4 4 Respiratory Cough increased 26 41 22 43 29 Dyspnea 22 27 26 42 25 Rhinitis 14 22 5 22 16 Pharyngitis 12 22 14 30 18 Sinusitis 9 21 7 13 6 Skin Rash 18 38 18 27 17 Herpes simplex 2 12 3 7 9 Acne 2 11 3 3 <1 Urogenital Urinary tract 5 18 14 13 7 infection a Data for Herceptin single agent were from 4 studies, including 213 patients from Study 6. b Anthracycline (doxorubicin or epirubicin) and cyclophosphamide The following subsections provide additional detail regarding adverse reactions observed in clinical trials of adjuvant breast, metastatic breast cancer, or post-marketing experience.

Cardiomyopathy Serial measurement of cardiac function (LVEF) was obtained in clinical trials in the adjuvant treatment of breast cancer. In Study 3, the median duration of follow-up was 12.6 months (12.4 months in the observation arm; 12.6 months in the 1-year Herceptin arm); and in Studies 1 and 2, 23 months in

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the AC-T arm, 24 months in the AC-TH arm. In Studies 1 and 2, 6% of patients were not permitted to initiate Herceptin following completion of AC chemotherapy due to cardiac dysfunction (LVEF <50% or 15 point decline in LVEF from baseline to end of AC). Following initiation of Herceptin therapy, the incidence of new-onset dose-limiting myocardial dysfunction was higher among patients receiving Herceptin and paclitaxel as compared to those receiving paclitaxel alone in Studies 1 and 2, and in patients receiving Herceptin monotherapy compared to observation in Study 3 (see Table 5, Figures 1 and 2).

Table 5a Per-patient Incidence of New Onset Myocardial Dysfunction (by LVEF) Studies 1, 2, 3 and 4 LVEF <50% and Absolute Decrease from Baseline

Studies 1 & 2b AC TH (n=1606) AC T (n=1488) Study 3 Herceptin (n=1678) Observation (n=1708) Study 4c TCH (n=1056) AC TH (n=1068) AC T (n=1050)

LVEF ≥10% ≥16% <50% decrease decrease

Absolute LVEF Decrease <20% and ≥10% ≥20%

22.8% 18.3% (366) (294) 9.1% 5.4% (136) (81)

11.7% (188) 2.2% (33)

33.4% (536) 18.3% (272)

9.2% (148) 2.4% (36)

8.6% (144) 2.7% (46)

7.0% (118) 2.0% (35)

3.8% (64) 1.2% (20)

22.4% (376) 11.9% (204)

3.5% (59) 1.2% (21)

8.5% (90) 17% (182) 9.5% (100)

5.9% (62) 13.3% (142) 6.6% (69)

3.3% (35) 9.8% (105) 3.3% (35)

34.5% (364) 44.3% (473) 34% (357)

6.3% (67) 13.2% (141) 5.5% (58)

a For Studies 1, 2 and 3, events are counted from the beginning of Herceptin treatment. For Study 4, events are counted from the date of randomization. b Studies 1 and 2 regimens: doxorubicin and cyclophosphamide followed by paclitaxel (AC T) or paclitaxel plus Herceptin (AC TH) c Study 4 regimens: doxorubicin and cyclophosphamide followed by docetaxel (AC T) or docetaxel plus Herceptin (AC TH); docetaxel and carboplatin plus Herceptin (TCH)

Figure 1 Studies 1 and 2: Cumulative Incidence of Time to First LVEF Decline of 10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event

Time 0 is initiation of paclitaxel or Herceptin + paclitaxel therapy.

Figure 2 Study 3: Cumulative Incidence of Time to First LVEF Decline of 10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event

Time 0 is the date of randomization.

Figure 3 Study 4: Cumulative Incidence of Time to First LVEF Decline of 10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event

Time 0 is the date of randomization.

The incidence of treatment emergent congestive heart failure among patients in the metastatic breast cancer trials was classified for severity using the New York Heart Association classification system (I–IV, where IV is the most severe level of cardiac failure) (see Table 2). In the metastatic breast cancer trials the probability of cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracyclines. Infusion Reactions During the first infusion with Herceptin, the symptoms most commonly reported were chills and fever, occurring in approximately 40% of patients in clinical trials. Symptoms were treated with acetaminophen, diphenhydramine, and meperidine (with or without reduction in the rate of Herceptin infusion); permanent discontinuation of Herceptin for infusional toxicity was required in <1% of patients. Other signs and/or symptoms may include nausea, vomiting, pain (in some cases at tumor sites), rigors, headache, dizziness, dyspnea, hypotension, elevated blood pressure, rash, and asthenia.

Infusional toxicity occurred in 21% and 35% of patients, and was severe in 1.4% and 9% of patients, on second or

subsequent Herceptin infusions administered as monotherapy or in combination with chemotherapy, respectively. In the post-marketing setting, severe infusion reactions, including hypersensitivity, anaphylaxis, and angioedema have been reported. Anemia In randomized controlled clinical trials, the overall incidence of anemia (30% vs. 21% [Study 5]), of selected NCI-CTC Grade 2–5 anemia (12.5% vs. 6.6% [Study 1]), and of anemia requiring transfusions (0.1% vs. 0 patients [Study 2]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone.

Following the administration of Herceptin as a single agent (Study 6), the incidence of NCI-CTC Grade 3 anemia was < 1%. Neutropenia In randomized controlled clinical trials in the adjuvant setting, the incidence of selected NCI-CTC Grade 4–5 neutropenia (2% vs. 0.7% [Study 2]) and of selected Grade 2–5 neutropenia (7.1% vs. 4.5 % [Study 1]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. In a randomized, controlled trial in patients with metastatic breast cancer, the incidences of NCI-CTC Grade 3/4 neutropenia (32% vs. 22%) and of febrile neutropenia (23% vs. 17%) were also increased in patients randomized to Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone. Infection The overall incidences of infection (46% vs. 30% [Study 5]), of selected NCI-CTC Grade 2–5 infection/febrile neutropenia (22% vs. 14% [Study 1]) and of selected Grade 3–5 infection/febrile neutropenia (3.3% vs. 1.4%) [Study 2]), were higher in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. The most common site of infections in the adjuvant setting involved the upper respiratory tract, skin, and urinary tract. In study 4, the overall incidence of infection was higher with the addition of Herceptin to AC-T but not to TCH [44% (AC-TH), 37% (TCH), 38% (AC-T)]. The incidences of NCI-CTC grade 3-4 infection were similar [25% (AC-TH), 21% (TCH), 23% (AC-T)] across the three arms. In a randomized, controlled trial in treatment of metastatic breast cancer, the reported incidence of febrile neutropenia was higher (23% vs. 17%) in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone. Pulmonary Toxicity Adjuvant Breast Cancer Among women receiving adjuvant therapy for breast cancer, the incidence of selected NCICTC Grade 2–5 pulmonary toxicity (14% vs. 5% [Study 1]) and of selected NCI-CTC Grade 3–5 pulmonary toxicity and spontaneous reported Grade 2 dyspnea (3.4 % vs. 1% [Study 2]) was higher in patients receiving Herceptin and chemotherapy compared with chemotherapy alone. The most common pulmonary toxicity was dyspnea (NCI-CTC Grade 2–5: 12% vs. 4% [Study 1]; NCI-CTC Grade 2–5: 2.5% vs. 0.1% [Study 2]). Pneumonitis/pulmonary infiltrates occurred in 0.7% of patients receiving Herceptin compared with 0.3% of those receiving chemotherapy alone. Fatal respiratory failure occurred in 3 patients receiving Herceptin, one as a component of multi-organ system failure, as compared to 1 patient receiving chemotherapy alone. In Study 3, there were 4 cases of interstitial pneumonitis in Herceptin-treated patients compared to none in the control arm. Metastatic Breast Cancer Among women receiving Herceptin for treatment of metastatic breast cancer, the incidence of pulmonary toxicity was also increased. Pulmonary adverse events have been reported in the post-marketing experience as part of the symptom complex of infusion reactions. Pulmonary events include bronchospasm, hypoxia, dyspnea, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, and acute respiratory distress syndrome. For a detailed description, see Warnings and Precautions. Thrombosis/Embolism In 4 randomized, controlled clinical trials, the incidence of thrombotic adverse events was higher in patients receiving Herceptin and chemotherapy compared to chemotherapy alone in three studies (3.0% vs. 1.3% [Study 1], 2.5% and 3.7% vs.

2.2% [Study 4] and 2.1% vs. 0% [Study 5]). Diarrhea Among women receiving adjuvant therapy for breast cancer, the incidence of NCI-CTC Grade 2–5 diarrhea (6.2% vs. 4.8% [Study 1]) and of NCI-CTC Grade 3–5 diarrhea (1.6% vs. 0% [Study 2]), and of grade 1-4 diarrhea (7% vs. 1% [Study 3]) were higher in patients receiving Herceptin as compared to controls. In Study 4, the incidence of Grade 3–4 diarrhea was higher [5.7% AC-TH, 5.5% TCH vs. 3.0% AC-T] and of Grade 1–4 was higher [51% AC-TH, 63% TCH vs. 43% AC-T] among women receiving Herceptin. Of patients receiving Herceptin as a single agent for the treatment of metastatic breast cancer, 25% experienced diarrhea.

An increased incidence of diarrhea was observed in patients receiving Herceptin in combination with chemotherapy for treatment of metastatic breast cancer.

Glomerulopathy In the postmarketing setting, rare cases of nephrotic syndrome with pathologic evidence of glomerulopathy have been reported. The time to onset ranged from 4 months to approximately 18 months from initiation of Herceptin therapy. Pathologic findings included membranous glomerulonephritis, focal glomerulosclerosis, and fibrillary glomerulonephritis.

Complications included volume overload and congestive heart failure. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. Among 903 women with metastatic breast cancer, human anti-human antibody (HAHA) to Herceptin was detected in one patient using an enzyme-linked immunosorbent assay (ELISA). This patient did not experience an allergic reaction. Samples for assessment of HAHA were not collected in studies of adjuvant breast cancer. The incidence of antibody formation is highly dependent on the sensitivity and the specificity of the assay.

Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample

GREEN HILL HEALTHCARE COMMUNICATIONS

collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Herceptin with the incidence of antibodies to other products may be misleading. USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects: Category D [see Warnings and Precautions] Herceptin can cause fetal harm when administered to a pregnant woman. Postmarketing case reports suggest that Herceptin use during pregnancy increases the risk for oligohydramnios during the second and third trimester. If Herceptin is used during pregnancy or if a woman becomes pregnant while taking Herceptin, she should be apprised of the potential hazard to a fetus. In the postmarketing setting, oligohydramnios was reported in women who received Herceptin during pregnancy, either alone or in combination with chemotherapy. In half of these women, amniotic fluid index increased after Herceptin was stopped. In one case, Herceptin was resumed after the amniotic fluid index improved, and oligohydramnios recurred. Women using Herceptin during pregnancy should be monitored for oligohydramnios. If oligohydramnios occurs, fetal testing should be done that is appropriate for gestational age and consistent with community standards of care. Additional intravenous (IV) hydration has been helpful when oligohydramnios has occurred following administration of other chemotherapy agents, however the effects of additional IV hydration with Herceptin treatment are not known. Reproduction studies in cynomolgus monkeys at doses up to 25 times the recommended weekly human dose of 2 mg/kg trastuzumab have revealed no evidence of harm to the fetus. However, HER2 protein expression is high in many embryonic tissues including cardiac and neural tissues; in mutant mice lacking HER2, embryos died in early gestation. Placental transfer of trastuzumab during the early (Days 20-50 of gestation) and late (Days 120-150 of gestation) fetal development period was observed in monkeys. [See Nonclinical Toxicology] Because animal reproduction studies are not always predictive of human response, Herceptin should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Registry Pregnant women with breast cancer who are using Herceptin are encouraged to enroll in MotHER- the Herceptin Pregnancy Registry: phone 1-800-690-6720. Nursing Mothers It is not known whether Herceptin is excreted in human milk, but human IgG is excreted in human milk. Published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Trastuzumab was present in the breast milk of lactating cynomolgus monkeys given 12.5 times the recommended weekly human dose of 2 mg/kg of Herceptin. Infant monkeys with detectable serum levels of trastuzumab did not have any adverse effects on growth or development from birth to 3 months of age; however, trastuzumab levels in animal breast milk may not accurately reflect human breast milk levels.

Because many drugs are secreted in human milk and because of the potential for serious adverse reactions in nursing infants from Herceptin, a decision should be made whether to discontinue nursing, or discontinue drug, taking into account the elimination half-life of trastuzumab and the importance of the drug to the mother. Pediatric Use The safety and effectiveness of Herceptin in pediatric patients has not been established. Geriatric Use Herceptin has been administered to 386 patients who were 65 years of age or over (253 in the adjuvant treatment and 133 in metastatic breast cancer treatment settings). The risk of cardiac dysfunction was increased in geriatric patients as compared to younger patients in both those receiving treatment for metastatic disease in Studies 5 and 6, or adjuvant therapy in Studies 1 and 2. Limitations in data collection and differences in study design of the 4 studies of Herceptin in adjuvant treatment of breast cancer preclude a determination of whether the toxicity profile of Herceptin in older patients is different from younger patients. The reported clinical experience is not adequate to determine whether the efficacy improvements (ORR, TTP, OS, DFS) of Herceptin treatment in older patients is different from that observed in patients <65 years of age for metastatic disease and adjuvant treatment.

OVERDOSAGE There is no experience with overdosage in human clinical trials. Single doses higher than 8 mg/kg have not been tested. PATIENT COUNSELING INFORMATION • Advise patients to contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness [see Boxed Warning: Cardiomyopathy]. • Advise women with reproductive potential to use effective contraceptive methods during treatment and for a minimum of six months following Herceptin [see Pregnancy]. • Encourage pregnant women who are using Herceptin to enroll in MotHER- the Herceptin Pregnancy Registry [see Pregnancy].

HERCEPTIN® [trastuzumab] Manufactured by: 4839803 Genentech, Inc. Initial US Approval: Sept. 1998 1 DNA Way Revision Date: March 2009 South San Francisco, CA LK0726 7172911 94080-4990 7172713 ©2009 Genentech, Inc.

News Notes Most Read Oncology Pharmacy Newspaper The Oncology Pharmacist was recently recognized as the most widely read newspaper of the oncology pharmacy community. In a survey by Kantar Media Professional Health, oncology pharmacists read The Oncology Pharmacist 1.5 times more than its closest competitor in the pharmacy market. In addition, almost half of readers read every issue. Of the 433 oncology pharmacists who participated in the survey, 58% are members of the Hematology/Oncology Pharmacy Association and 31% are board-certified Oncology Pharmacists. Thirty-one percent of respondents have established a collaborative practice agreement allowing them to prescribe supportive care therapies, and 53% said they are always or sometimes involved in patient recommendations/referrals to clinical trials.

Tool Estimates Local Recurrence after Breast-conserving Surgery Researchers have developed a tool for predicting individualized risk of local recurrence after breast-conserving surgery (BCS) in women with ductal carcinoma in situ (DCIS). The tool integrates 10 clinicopathologic variables to assist patients and their healthcare professionals decide among various treatment options with the goal of reducing over- and undertreatment.

Rudloff and colleagues at Memorial SloanKettering Cancer Center in New York identified 1868 consecutive women treated for DCIS with BCS between 1991 and 2006. They created a nomogram that estimated the probability of ipsilateral breast tumor recurrence at 5 and 10 years after BCS. Bootstrap resampling showed the nomogram to have good calibration and discrimination. Of the 10 clinicopathologic variables, adjuvant radiotherapy, age, margin status, number of excisions, and treatment time period were of the greatest influence on risk (J Clin Oncol.

2010;28:762-769).

Multivitamin Use Does Not Improve Outcomes in Colon Cancer Multivitamin use during and after adjuvant chemotherapy did not reduce the risk of cancer recurrence or mortality in patients with stage III colon cancer, according to recently released findings of Cancer and Leukemia Group B (CALGB) 89803. Multivitamin use, however, also did not impact patients’ health negatively.

To determine the association between use of multivitamins and cancer recurrence and death, the CALGB researchers conducted a prospective, observational study of 1038 patients with stage III colon cancer enrolled in a separate adjuvant chemotherapy trial. Patients self-reported use of multivitamins during and 6 months after adjuvant chemotherapy. Fifty percent (518) of patients reported use during adjuvant chemotherapy.

Compared with nonusers, the multivariate hazard ratio for disease-free survival was 0.94 (95% confidence interval [CI], 0.77-1.15), for recurrencefree survival was 0.93 (95% CI, 0.75-1.15), and for overall survival was 0.92 (95% CI, 0.74-1.16).

Use at 6 months after completion of adjuvant chemotherapy was also not associated with improved outcome (J Clin Oncol. Aug 30, 2010.

Epub ahead of print). ● SEpTEMbER 2010 I VOL 3, NO 6

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Editorial Board EDITOR-INCHIEF Patrick Medina, PharmD, BCOP Oklahoma University College of Pharmacy Tulsa, OK

Beth Faiman, RN, MSN, APRN, BC, AOCN Cleveland Clinic Taussig Cancer Institute Cleveland, OH

Jim Koeller, MS University of Texas at Austin San Antonio, TX

Timothy G. Tyler, PharmD, FCSHP Desert Regional Medical Center Palm Springs, CA

Christopher Fausel, PharmD

Christopher J. Lowe, PharmD

John M. Valgus, PharmD, BCOP

Indiana University Simon Cancer Center Indianapolis, IN

Novant Health Winston-Salem, NC

University of North Carolina Hospitals and Clinics Chapel Hill, NC

David Baribeault, RPh, BCOP

Rebecca S. Finley, PharmD, MS

Emily Mackler, PharmD, BCOP

Boston Medical Center Boston, MA

Jefferson School of Pharmacy Philadelphia, PA

University of Michigan Health System & College of Pharmacy Ann Arbor, MI

Gary C. Yee, PharmD, FCCP, BCOP

Betty M. Chan, PharmD, BCOP

David C. Gammon, BS Pharm

Laura Boehnke Michaud, PharmD, BCOP, FASHP

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

USC/Norris Cancer Hospital Los Angeles, CA

University of Massachusetts Memorial Hospital Worcester, MA

University of Nebraska College of Pharmacy Omaha, NE

Burt Zweigenhaft, BS BioPharma Partners LLC New York, NY

The University of Texas M. D. Anderson Cancer Center Houston, TX

Marlo Blazer, RPh, PharmD Steven L. Dâ&#x20AC;&#x2122;Amato, RPh, BCOP

Lew Iacovelli, BS, PharmD, BCOP, CPP

LeAnn Best Norris, PharmD, BCPS, BCOP

Maine Center for Cancer Medicine Scarborough, ME

Moses H. Cone Health System Greensboro, NC

South Carolina College of Pharmacy Columbia, SC

James Cancer Hospital & Solove Research Institute Columbus, OH

Heidi D. Gunderson, PharmD, BCOP Mayo Clinic Cancer Center Rochester, MN

4

Anjana Elefante, PharmD, BSc, BSc Pharm, RPh

Dwight Kloth, PharmD, FCCP, BCOP

Steve Stricker, PharmD, MS, BCOP

Roswell Park Cancer Institute Buffalo, NY

Fox Chase Cancer Center Philadelphia, PA

Samford University McWhorter School of Pharmacy Birmingham, AL

September 2010 I VOL 3, NO 6

Kamakshi V. Rao, PharmD, BCOP University of North Carolina Hospitals and Clinics Chapel Hill, NC

GreeN HILL HeALtHCAre COmmUNICAtIONS

TOP_Sept 2010_TOP 9/15/10 1:25 PM Page 5

THANK YOU FOR MAKING US $( &

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The Official Newspaper for the Hem/Onc Pharmacist

FROM THE EDITOR

PUBLISHING STAFF Publisher Philip Pawelko phil@greenhillhc.com

W

e’re number 1 and we try harder, to borrow from familiar advertising campaigns. In an independent survey of more than 400 oncology pharmacists, The On cology Pharmacist scored highest in average readership and page exposure scores compared with seven competitive oncology and pharmacy journals. We thank Patrick Medina, our loyal readers and outstanding PharmD, BCOP editorial board members and Editor-in-Chief contributors who have helped us achieve this distinction.

We’re proud but we’re not resting on our laurels. We are constantly seeking ways to improve our publication.

Reader surveys are just one way we use to determine our readers’ interests, and the feedback we get is used to develop new stories and features for our print and digital editions. Survivorship care is one topic of interest that has

Editorial Director Karen Rosenberg karen@greenhillhc.com Associate Editor Dawn Lagrosa dawn@greenhillhc.com Directors, Client Services John W. Hennessy john@greenhillhc.com Jimmy Palko jimmy@greenhillhc.com Production Manager Stephanie Laudien Business Manager Blanche Marchitto blanche@greenhillhc.com Executive Administrator Andrea Boylston Circulation Department circulation@greenhillhc.com Editorial Contact: Telephone: 732-992-1891 Fax: 732-656-7938

been identified by readers. This special issue focuses on this important topic, with articles on long-term issues in survivorship care and different models developed by cancer centers throughout the country to provide survivorship care. Denice Economou, RN, MN, CNS, AOCN, director of a survivorship education program at City of Hope National Medical Center, served as guest editor of this special issue. She has brought together a distinguished group of contributors, who share their experience, thoughts, and suggestions for providing survivorship care in diverse settings.

As discussed in the article by Drs Bunnell and Shulman, physicians will not be able to provide all the healthcare services that the growing population of cancer survivors will need. Pharmacists and other healthcare professionals will have to assume new responsibilities for survivorship care to ensure that demand does not exceed the supply of those trained to care for survivors’ multiple medical and psychological needs.

We thank all the contributors to this issue, which we hope you will find informative and share with your colleagues. l

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The Oncology Pharmacist®, ISSN 1944-9607 (print); ISSN 1944-9593 (online) is published 8 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 ©2010 by Green Hill Healthcare Communications LLC. All rights reserved. The Oncology Pharmacist® 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.

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Publication of an advertisement or other product mention in The Oncology Pharmacist® 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.

6

SEpTEMbER 2010 I VOL 3, NO 6

CONTENTS

SEpTEMbER 2010 • VOL 3, NO 6

INTRODUCTION

8 Making survivorship care a priority CLINICAL CONCERNS

13 Why intimacy and sexuality matter and what you can do to help your patients 13

SURVIVORSHIP PROGRAM

14 A model of survivorship care: the Memorial Sloan-Kettering approach 22 Bridging the gaps in cancer care: the development of a survivorship program in an academic medical center

30 Developing a psychosocial-focused survivorship program in a community cancer center

MODELS OF CARE

26 Resolving the impending supply-demand imbalance in cancer

36

survivorship care: a need for new models

SURVIVORSHIP NEWS

36 Physical activity to the fore 40 Putting the family back into family practice DEPARTMENTS

3 News Notes 34 Survivorship Resources

40

GREEN HILL HEALTHCARE COMMUNICATIONS

TON_Sept 2010_steph_v4_TON 9/14/10 4:28 PM Page 7

“After my balloon kyphoplasty, I’m walking pain-free again.”

Tom Callaghan experienced debilitating pain due to spinal fractures caused by multiple myeloma. He underwent a minimally invasive procedure, Balloon Kyphoplasty, to treat the spinal fractures.

KYPHON® Balloon Kyphoplasty

To learn more about Balloon Kyphoplasty, visit our website at www.kyphon.com.

The complication rate with KYPHON® Balloon Kyphoplasty has been demonstrated to be low. As with all surgical procedures, there are risks associated with the procedure, including serious complications, and though rare, some of which can be fatal. For complete information regarding indications for use, contraindications, warnings, precautions, adverse events, and methods of use, please reference the devices’ Instructions for Use included with the product. © 2009 Medtronic Spine LLC. All Rights Reserved. 16003611_001 rev 1

TON_Sept 2010_steph_v4_TON 9/14/10 4:28 PM Page 8

Introduction

Making Survivorship Care a Priority

By Denice Economou, RN, MN, CNS, AOCN Guest Editor Project Director, Survivorship Education for Quality Cancer Care, Division of Nursing Research and Education City of Hope National Medical Center, Duarte, California

A

recent editorial in the Annals of Internal Medicine states, “If survivorship is a priority, we can improve the lives of survivors.”1 Increasing recognition of the importance of making survivorship care a priority was the motivating factor for this issue dedicated to cancer survivorship.

Cancer survivorship may be defined in general from the day of diagnosis and beyond and includes the family and caregivers as they are all impacted by the diagnosis and treatment of cancer. This definition is broad because the population is so large.

Health settings need to define which survivorship services their institution is able to provide. Large academic settings, especially LIVESTRONG Centers of Excellence, are able to provide multidisciplinary options to meet multiple needs for patients, families, and caregivers.

Their outreach programs also extend to smaller community healthcare settings.

This collaborative care is essential and allows the many issues that survivors and their families may experience to be addressed. This collaborative focus also allows settings with specific expertise to focus on what they are good at and share the burden of care with others in the community as well as access national survivor-focused programs.

Collaborative care models in which oncologists work closely with advanced practice nurses, physician assistants, and other “extenders” and primary care physicians take increasing responsibility for the long-term care of survivors are discussed in the article by Craig A. Bunnell, MD, MPH, MBA, and Lawrence N. Shulman, MD, of Dana-Farber Cancer Institute, a leader in survivorship care.

Marcia Grant and I provide a brief overview of the physical symptoms associated with cancer and its treatments.

The goal is to describe these treatment effects to establish the basis of survivorship care and identify the core changes patients may experience. These symptoms have been recognized by many and have been the motivating stimulus to the survivorship movement.

Susan Leigh, BSN, RN, an expert in survivorship care, who is herself a survivor, provides an overview of survivorship and its history. As she explains, various models of survivorship care have been developed, and this issue provides examples of several of these.

Nancy G. Houlihan, MA, AOCN, and Zana Correa, MSN, NP-BC, describe the model of survivorship care provided at Memorial Sloan-Kettering Cancer Center. Their mission is to provide nurse practitioner–led survivorship follow-up in an effort to assist the patient with “optimal recovery and transition to wellness.”

Collaborative care is essential and allows the many issues that survivors and their families may experience to be addressed.

Susan Daubman, RN, BSN, Theresa Franco, RN, MSN, and Katherine Gross, RN, MSN, of the Nebraska Medical Center describe the development of a survivorship program in an academic medical center. Beginning with their institutional assessment of the components of survivorship care available at their medical center and the needs of

©iStockphoto.com/zhang bo

their population, they review their program-building process and the model of survivorship care they follow.

Scott D. Siegel, PhD, and Cindy Waddington, RN, MSN, AOCN, share their experience with building a psychosocial-focused survivorship program at the Helen F. Graham Cancer Center, Christiana Care Health System in Newark, Delaware. Their focus is to provide psychosocial care to patients as they transition to life after cancer, a critical time for a cancer survivor.

Rehabilitation is becoming a major focus for the future. Arash Asher, MD, and his colleagues have begun a rehabilitation program for cancer survivors at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles. His article helps define the many components of rehabilitation and how psychosocial and supportive care work together to create a program that will include rehabilitation services, psychosocial care, and palliative/symptom management.

WHO ARE CANCER SURVIVORS?

Cancer survivors are people who have been diagnosed with cancer and those people in their lives who are affected by the diagnosis, including family members, friends, and caregivers.

—US Centers for Disease Control and Prevention

8

September 2010 I VOL 3, NO 6

Other articles in this issue provide insights into other aspects of cancer survivorship. The article by Rosemary Frei discusses the importance of including families as part of the patient care we provide. A family assessment is as important as a patient assessment to understand the capability the family has to care for the needs of the patient. As the article notes, the FOCUS model (family involvement, optimistic attitude, coping effectiveness, uncertainty reduction, and symptom management) can help promote optimal care for cancer patients.

Recognition and attention to sexual and intimacy issues are also essential components of cancer survivorship care, as discussed in the article by Darja Brandenburg, DClinPsych, DipPST, CPsychol, AFBPS. She reviews sexual issues commonly experienced by cancer patients and provides suggestions for how healthcare providers can help patients and their partners cope with these concerns.

We hope the information and insights provided in this issue will be helpful for those who have established survivorship programs and those planning to do so. For further information on the medical, psychological, legal, and financial issues involved in survivorship care, we have included a guide to resources for cancer survivors and their healthcare providers. ● Reference 1. Iwashyna TJ. Survivorship will be the defining challenge of critical care in the 21st century. Ann Intern Med. 2010;153:204-205.

GreeN HILL HeALtHCAre COmmUNICAtIONS

TOP_Sept 2010_TOP 9/14/10 4:33 PM Page 9

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Demonstrates 98% overall efficacy based on two biopsy-confirmed clinical trials1,2 in reducing or avoiding surgical intervention (i.e., surgical debridement, plastic surgery and their related costs), thereby reducing postponement of a patient’s chemotherapy treatments and the avoidance of long-term consequences.

Cited in nursing guidelines.3,4 Extravasation management is now a chemotherapy administration safety standard.5

For more information, call 866-478-8274 or visit our website at www.totect.com To order Totect®, contact one of our authorized distributors.

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Mouridsen HT et al. Treatment of anthracycline extravasation with savene (dexrazoxane).

Results from two prospective clinical multicentre studies. Ann Oncol 2007; 18:546-550.

2 Totect® package insert.

3 Polovich M, White JM, Olsen, M (eds.). Chemotherapy and Biotherapy Guidelines and Recommendations for Practice (ed 3). Pittsburgh, PA, Oncology Nursing Society, 2009.

4 Alexander M, Corrigan A, Gorski L, Hankins J, Perucca R. (eds). Infusion Nurses Society Infusion Nursing an Evidence-Based Approach (ed 3). Boston, MA, Infusion Nurses Society, 2009.

5 Jacobsen J., et al. American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards. Oncology Nursing Forum, 2009; 36:651-658. © 2010 Topotarget USA. All rights reserved. TOT0111/7-10 Totect and its logo mark are registered trademarks of Topotarget A/S Image is copyright © Photo Researchers, Inc.

TOP_Sept 2010_TOP 9/14/10 4:33 PM Page 10

Totect® – Brief prescribing information Please refer to the package insert for full prescribing information. Each Totect carton contains 10 vials of Totect® (dexrazoxane for injection) 500 mg and 10 vials of 50 mL diluent. Indication: Treatment of extravasation resulting from IV anthracycline chemotherapy. Dosage and administration: Totect is a cytotoxic drug. Vial contents must be mixed and diluted before use. Totect should not be mixed or administered with any other drug during the infusion. Administration of Totect should begin as soon as possible and within 6 hours following the anthracycline extravasation. Totect should be given as an intravenous (IV) infusion once daily for 3 consecutive days. The dose of Totect is based on the patient’s body surface area: day one, 1000 mg/m2; day two, 1000 mg/m2; day three, 500 mg/m2. For patients with a body surface area of > 2 m2, a dose of 2000 mg should be given on days 1 and 2, and a dose of 1000 mg should be given on day 3. Treatment on Day 2 and Day 3 should start at the same hour (+/- 3 hours) as on the first day. The Totect dose should be reduced 50% for patients with creatinine clearance values of <40 mL/minute. Cooling procedures such as ice packs should be removed from the affected area at least 15 minutes prior to Totect administration. Totect (dexrazoxane for injection) must be reconstituted with diluent supplied in the carton. The patient’s Totect dose is diluted in 0.9% 1000 mL NaCl prior to administration. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.3-5 Direct contact of Totect® with the skin or mucous membranes prior to and following reconstitution should be avoided. If contact occurs, wash immediately and thoroughly with water. Contraindications: None.

Warnings and Precautions: Myelosuppression: treatment with Totect is associated with leukopenia, neutropenia, and thrombocytopenia. Hematological monitoring should be performed. Use in Pregnancy: Pregnancy Category D. Totect can cause fetal harm when administered to a pregnant woman. There is no adequate information about the use of Totect in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Adverse reactions: The most common adverse reactions (≥ 16%) are nausea, pyrexia, injection site pain and vomiting.

www.totect.com

Rx only

Totect® is a registered trademark of Topotarget A/S US Patent No. 6,727,253B2 NDC 38423-110-01

TOT0111/7-10 © 2010 Topotarget USA

Drug Interactions: No drug interactions have been identified. Based on anecdotal reports concurrent use of topical dimethyl sulfoxide (DMSO) at the site of tissue injury may reduce the benefit of Totect. Additionally, nonclinical studies using a mouse model that simulates extravasation of anthracyclines has shown that concomitant treatment with topical DMSO decreases the efficacy of systemic dexrazoxane. Use in Specific Populations: Nursing Mothers: Discontinue drug or nursing, taking into consideration the importance of drug to the mother. Renal Impairment: Reduce the Totect dose by 50% In patients with creatinine clearance values <40 mL/min. Pediatric Use: The safety and effectiveness of Totect in pediatric patients have not been established.

Geriatric Use: This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Overdosage: There are no data on overdosage. There is no known antidote for dexrazoxane.

Carcinogenesis, Mutagenesis, Impairment of Fertility: The carcinogenic potential of dexrazoxane has not been investigated. Nevertheless, a study by the National Cancer Institute has reported that long term dosing with razoxane (the racemic mixture of dexrazoxane, ICRF-187, and its enantiomer ICRF-186) is associated with the development of malignancies in rats and possibly in mice. Dexrazoxane was not mutagenic to bacteria in vitro (Ames assay), but caused significant chromosomal aberrations in mammalian cells in vitro. It also increased the formation of micronucleated polychromatic erythrocytes in mice. Thus, dexrazoxane is mutagenic and clastogenic. The possible adverse effects of Totect on the fertility of humans and experimental animals, male or female, have not been adequately studied. Testicular atrophy was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (about 1/5 the human dose on a mg/m2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs (about half the human dose on a mg/m2 basis).

Manufactured by: Ben Venue Laboratories, Inc. Bedford, OH 44146 Hameln Pharmaceuticals GmbH 31789 Hameln Germany

Manufactured for: Topotarget A/S Fruebjergvej 3 DK-2100 Copenhagen Denmark

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Survivorship Issues The Cancer Survivorship Movement... Continued from cover semantics, time frames, and issues. Who is or who is not a cancer survivor? What is and what is not survivorship? When does survivorship begin, and when does it end? Who is responsible for survivorship care, and who pays for it? And does any of this really matter? The questions go on and on. Maybe these arguments surrounding the semantics and issues of survivorship could actually be viewed as progress. Rowland writes: “Arguably, without substantial numbers of survivors, issues of survivorship would never have become of interest; the focus of research would have remained, as it had in the past, largely on trying simply to enable an individual to become a survivor, not what the future of that person’s life might be like.”2 Thus, as the numbers of survivors increase, so does the need for different models of care.

Attention to survivorship is no longer a luxury but a responsibility, and this certainly could be perceived as progress.

Progress can be seen among survivors, as they struggle with new identities.

Individuals diagnosed and treated for cancer tend to adopt labels that have specific meaning to themselves as individuals. Take the term survivor. Those who like the term survivor really love it.

Those who dislike this label really hate it.

So other labels are used, such as advocate, thriver, veteran, exceptional cancer patient, sufferer, warrior, cancer conqueror, or cancer killer. Many of these descriptions illustrate a philosophic and qualitative approach to survival and are defined within the context of a continuum: According to the National Coalition for Cancer Survivorship (NCCS), “From the time of its discovery and for the balance of life, an individual with cancer is a survivor.”3 Other definitions of survivor, for example, a cured patient or one who has completed treatment, are more often used by researchers and clinicians who are defining a specific population for specialized care.

Rather than defining the person, one can also describe the experience.

Survivors, advocates, researchers, and clinicians regularly focus on the concept of survivorship in their work. Survivorship is often more about how one survives rather than if one is considered cured.

The original definition created by the NCCS, “living with, through, and beyond cancer,”4 is seen more as an individual, dynamic progression of events rather than a static clinical stage. In addition, it encompasses physical, psychological, social, and spiritual domains, and includes “secondary survivors,” that is, personal and professional caregivers.2,6,7 For many healthcare providers, these definitions seem too nebulous and allencompassing to be useful when directing research or delivering clinical care. Thus,

from a more pragmatic and quantitative perspective, survivorship can also be defined in more concrete terms, such as5: • A time frame (eg, 2, 5, or 10 years after diagnosis) • A stage or phase that usually begins after initial treatment ends • An outcome of treatment (ie, no evidence of disease).

Practical applications Although opinions differ surrounding semantics and priorities, there are still many opportunities to introduce survivorship care into clinical practice. The important factor is to get started and do something. Whether you are in an academic setting, community hospital, freestanding cancer center, or rural clinic, a survivorship program is possible.

Grant and Economou provided helpful hints to get started in their article, “Cancer Survivorship: Current Issues in

Table Professional Overviews of Survivorship Cancer Survivorship: Today and Tomorrow Ganz PA, ed. New York, NY: Springer; 2007.

Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs Institute of Medicine. Washington, DC: National Academies Press; 2007.

Implementing Cancer Survivorship Care Planning: Workshop Summary Institute of Medicine. Washington, DC: National Academies Press; 2006.

From Cancer Patient to Cancer Survivor: Lost in Transition Institute of Medicine. Washington, DC: National Academies Press; 2005.

Cancer Rehabilitation: Principles and Practice Stubblefield MD, O’Dell MW. New York, NY: Demos Medical Publishing; 2009.

clinic. Those involved in care of pediatric oncology patients were the first to identify the need for continual followup of their young population and developed the idea of survivor clinics. Their areas of concern included long-term or lingering effects of treatment, such as fatigue, neuropathies, and pain, along with late or delayed effects, including

“Each model has advantages and disadvantages for successful implementation. The challenge is to select the right model for the specific type of institution or program.”

—Susan Leigh, BSN, RN

Providing Survivorship Care.”7 They suggested starting small, doing a needs assessment, defining simple goals, and re-evaluating existing programs. An additional suggestion would be finding champions in your practice setting who will support your goals and are in positions of power to help make them happen.

Whether you are in an academic setting, community hospital, free-standing cancer center, or rural clinic, a survivorship program is possible.

Because survivorship is a relatively new concept with few guidelines, a good place to begin is with existing resources.

Just looking at the physiologic fallout from cancer treatment is a huge area by itself, taking up entire articles and textbooks. Resources for healthcare professionals and cancer patients and survivors are listed in the Resource Guide (page 34). In addition, several professional publications provide further information (Table).

The newest model of delivering survivorship care is to establish a follow-up

GREEN HILL HEALTHCARE COMMUNICATIONS

recurrence, second cancers, and premature onset of organ or system failures.

Those in adult oncology are now recognizing the need for this type of care. The LIVESTRONG Survivorship Centers of Excellence Network is currently exploring methods to advance the field of survivorship care by supporting collaboration among comprehensive cancer centers and community partners. High priority is given to the development of models of care that will enhance posttreatment follow-up. Examples of these models include8: • Multidisciplinary clinics where the survivor is seen by many different providers during the same clinic visit • Disease- or treatment-specific clinics where all survivors with a single type of cancer (lymphoma) or a special type of treatment (transplant) are seen • Consultative services where survivors are seen during a one-time consultation to assess survivorship issues and develop a survivorship care plan • Integrated-care models where long-term care is an extension of the survivors’ care with their original oncology team • Shared-care models where any combination of providers—oncologists, surgeons, primary care providers, nurse practitioners, physician assistants— develop methods to share responsibilities for long-term follow-up.

Each model has advantages and dis-

advantages for successful implementation. The challenge is to select the right model for the specific type of institution or program.

Remaining questions Whether providers are counseling one-on-one, facilitating support groups, developing educational opportunities, creating survivorship care plans, or monitoring for long-term and late effects of treatment, all are contributing pieces to the overall care of cancer survivors and their loved ones. Yet, many questions remain: Who will care for survivors and who will pay? What models of care will work best in various clinical environments and with available resources? While we continue to wait for evidence-based guidelines and standards for survivorship care, we must remember that time is of the essence for our survivor population. We have come a long way over the past three decades, but we still have a long way to go. ● References 1. Harder AF. The developmental stages of Erik Erikson.

2009. www.learningplaceonline.com/stages/organize/ Erikson.htm. Accessed July 28, 2010.

2. Rowland JH. Survivorship research: past, present, and future. In: Ganz PA, ed. Cancer Survivorship: Today and Tomorrow. New York, NY: Springer; 2007.

3. NCCS Charter. Silver Spring, MD: National Coalition for Cancer Survivorship; 1986.

4. Leigh S. Myths, monsters, and magic: personal perspectives and professional challenges of survival. Oncol Nurs Forum. 1992;19:1475-1480.

5. Leigh S. Cancer survivorship: a nursing perspective.

In: Ganz PA, ed. Cancer Survivorship: Today and Tomorrow. New York, NY: Springer; 2007.

6. Grant M, Economou D, Ferrell B, Bhatia S. Preparing professional staff to care for cancer survivors. J Cancer Surviv. 2007;1:98-106.

7. Grant M, Economou D. Cancer survivorship: current issues in providing survivorship care. The Oncology Nurse. Sep/Oct 2009;2:1,14,16.

8. Baker S, Jacobs L, McCabe M. Models of cancer survivorship care. Presented at: Lance Armstrong Foundation Cancer Survivorship Training Institute: Excellence in Cancer Survivorship Care: Developing Sustainable Programs; December 2009; Austin, TX.

Did You Know?

According to a report in the Journal of the National Cancer Institute, 1402 of 14,359 5-year childhood cancer survivors had subsequent neoplasms.

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Clinical Concerns Late and Long-term Physical Effects... Continued from cover In general, different treatment approaches have specific sets of side effects.

Surgery Surgery, depending on the site, may cause alterations in function (ie, ostomy, malabsorption, incontinence, or neuropathic injury and pain). Nutritional deficits or chronic pain may occur secondary to surgical interventions.

Lymphedema is related to the surgical removal of lymph nodes or disruption of lymphatic circulation. Late-occurring lymphedema can develop within 1 year of treatment or more than 20 years after treatment. Evaluating patients for either upper or lower extremity edema, depending on the surgical site, is important to help identify lymphedema early and prevent further injury to the extremity and minimize the extent of swelling.

Chemotherapy Chemotherapy is associated with multiple acute side effects, but extended follow-up research has identified long-term and late effects related to specific classes of drugs.

The late effects of anthracyclines on cardiac function have been recognized since the 1970s.1 The long-term risk of developing congestive heart failure and conduction defects related to anthracycline and trastuzumab use are widely recognized. Age, combination therapy, radiation therapy to the chest, and preexisting cardiac disease are known to contribute to the risk.3,4 Bleomycin may cause an acute hypersensitivity reaction and, for some, this may develop into delayed pulmonary fibrosis. Contributing risk factors in-

Denice Economou, RN, MN, CNS, AOCN

Patients who have received chest radiation, such as those with breast cancer, lung cancer, or Hodgkin disease, may also experience radiation-related pneumonitis, which can manifest as early as 1 to 3 months posttreatment or as late as 24 months posttreatment. clude age, concomitant radiation therapy, and cumulative dosing.5 Nitrosoureas have also been associated with pulmonary fibrosis. Patients who have received conditioning regimens for allogeneic or autologous bone marrow transplants are at risk, and the presence of graft-versus-host disease further increases the risk for pulmonary fibrosis.

Methotrexate can lead to liver fibrosis and chronic hepatitis and, for those with baseline hepatitis B or C, methotrexate may reactivate viral hepatitis.6 Cisplatin can lead to nephrotoxicity by damaging the proximal tubules, and this can persist long term. Cisplatin toxicity is cumulative, commonly occurring

Table Major System Consequences of Cancer and Its Treatments System Cognitive/sensory

Consequences “Chemobrain” Slower responses Hearing loss Visual changes Neuropathy

Cardiovascular

Cardiomyopathy Effects on pericardium Myocardium Conduction Coronary arteries/valves Pulmonary fibrosis Interstitial lung disease Obstruction

Pulmonary

Gastrointestinal

Malabsorption Anatomic and functional changes Ischemia and fibrosis

Renal

Chronic kidney disease

Endocrine

Hypothyroidism Adrenal insufficiency Diabetes mellitus Hypothalamus Pituitary gland

Adapted from Reference 1.

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Marcia Grant, RN, DNSc, FAAN

when doses are greater than 1200 mg/m2.

This can lead to chronic kidney disease (CKD). Cyclophosphamide and ifosfamide, both alkylating agents, can also lead to CKD.7 Platinum agents as well as vinca alkaloids are associated with ototoxicity and hearing loss secondary to inner ear damage. Additional side effects secondary to chemotherapy include postchemotherapy rheumatism syndromes and chronic immunosuppression.8 Radiation therapy Radiation side effects correlate to the anatomic areas radiated. Chest radiation for Hodgkin disease or lung cancer, for instance, may lead to pericarditis, pericardial effusion, and interstitial fibrosis. In patients with lung cancer, chest radiation can reduce left ventricular volume and cause perfusion deficits that lead to dyspnea and coronary artery disease (CAD). Patients with other risk factors for CAD, such as hypertension, hyperlipidemia, and a history of smoking, are at higher risk.9 The risk for a fatal myocardial infarction in patients treated with mantel field radiation is 40 times higher than the baseline risk.10 This includes patients with Hodgkin disease as well as those with left breast, esophageal, and lung cancers. Patients who have received chest radiation, such as those with breast cancer, lung cancer, or Hodgkin disease, may also experience radiation-related pneumonitis, which can manifest as early as 1 to 3 months posttreatment or as late as 24 months posttreatment.11 Thoracic radiation may lead to fibrosis of the sinus node, muscular dysfunction, or complete heart block. Pulmonary complications may be short-lived, but as many as 50% of patients who have received thoracic radi-

ation will experience some late-effect pulmonary complications.12 The hope is that newer techniques that minimize radiation exposure of healthy tissues will reduce the risk for these posttreatment complications.

Radiation to the gastrointestinal tract causes significant physical side effects. As with surgical interventions, nutritional and functional changes can occur.

Because of the increased damage related to rapid cell turnover and the large surface area of mucosa, the gastrointestinal system is particularly vulnerable. Bowel dysfunction, pain, bloating, late complications of fibrosis, and vasculitis can severely affect quality of life.13 There is also the possibility of a second cancer occurring in the radiation field.

Head and neck radiation, depending on the site, may cause ototoxicity, balance issues, or chronic nausea.14,15 Conclusion Patients may experience multiple symptoms and side effects related to their cancer and its treatment. It is essential for healthcare providers to recognize the ramifications of the therapies our patients receive and to attempt to be proactive in educating them about side effects and minimizing them whenever possible. Providing the greatest quality of life for our patients, regardless of their quantity of life, is what matters most. ● References 1. Miller KD, Triano LR. Medical issues in cancer survivors—a review. Cancer J. 2008;14:375-387.

2. Rowland JH. What are cancer survivors telling us?

Cancer J. 2008;14:361-368.

3. Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1998;339:900-905.

4. Von Hoff DD, Layard MW, Basa P, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91:710-717.

5. Sleijfer S. Bleomycin-induced pneumonitis. Chest.

2001;120:617-624.

6. Rodriguez-Frias EA, Lee WM. Cancer chemotherapy I: hepatocellular injury. Clin Liver Dis. 2007;11:641-662.

7. Tarrass F, Benmensour M, Bayla A. End-stage renal disease following carboplatin chemotherapy for a nasopharyngeal carcinoma. Ren Fail. 2007;29:1049-1051.

8. Warner E, Keshavjee A, Shupak R, Bellini A. Rheumatic symptoms following adjuvant therapy for breast cancer. Am J Clin Oncol. 1997;20:322-326.

9. Hooning MJ, Botma A, Aleman BM, et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst. 2007;99:365-375.

10. Hancock SL, Donaldson SS, Hoppe RT. Cardiac disease following treatment of Hodgkin’s disease in children and adolescents. J Clin Oncol. 1993;11:1208-1215.

11. Carver JR, Shapiro CL, Ng A, et al; for the ASCO Cancer Survivorship Expert Panel. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J Clin Oncol. 2007;25:3991-4008.

12. Adams MJ, Lipshultz SE, Schwartz C, et al. Radiation-associated cardiovascular disease: manifestations and management. Semin Radiat Oncol. 2003;13:346-356.

13. Andreyev HJ. Gastrointestinal problems after pelvic radiotherapy: the past, the present and the future. Clin Oncol (R Coll Radiol). 2007;19:790-799.

14. Gabriele P, Orecchia R, Magnano M, et al. Vestibular apparatus disorders after external radiation therapy for head and neck cancers. Radiother Oncol. 1992;25:25-30.

15. Honore HB, Bentzen SM, Moller K, Grau C. Sensori-neural hearing loss after radiotherapy for nasopharyngeal carcinoma: individualized risk estimation. Radiother Oncol. 2002;65:9-16.

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Clinical Concerns

Why Intimacy and Sexuality Matter and What You Can Do to Help Your Patients Darja Brandenburg, DClinPsych, DipPST, CPsychol, AFBPS Consultant Clinical Psychologist and Sex Therapist, Sexual Rehabilitation Lead, Cancer Psychology Department Pan Birmingham Cancer Network, United Kingdom

D

ifficulties with intimacy and sexuality are among the most common and longest lasting side effects of cancer treatments and can be caused by any of the cancer treatments currently available.1 Fortunately, even simple recommendations can go a long way toward ameliorating distress for most patients and their partners.2,3 Yet until recently this aspect of care for cancer patients has remained one of the most neglected, even as cancer providers worldwide begin to address issues of survivorship.

The scale of the problem As many as 50% of all cancer patients will experience sexual difficulties after cancer treatments, significantly higher figures being reported for certain cancer types and treatments received. For example, as many as 70% of men undergoing localized treatment for prostate or bladder cancer will experience sexual difficulties.4-6 About 25% of other male cancer patients are similarly affected,6,7 with similar rates for survivors of leukemia and Hodgkin diseases.2 In terms of women’s cancers, approximately 50% of women who survive breast and gynecologic cancers also report sexual difficulties attributed to cancer and its treatment.8-11 Large numbers of colorectal cancer patients also report sexual dysfunction, with one recent survey reporting sexual difficulties in 39% of patients after treatment for colon cancer and in a staggering 86% of survivors of anal cancers.12 Less commonly thought about are survivors of head and neck cancers, 50% of whom also report dissatisfaction with their sexual functioning.1 The scope of this article does not allow a detailing of further figures, but it is worth noting that patients with advanced disease and those receiving palliative care report the highest overall levels of both sexual dysfunction and dissatisfaction of all patient groups.13 For a recent more detailed literature review about how different cancer types and cancer treatments affect sexual functioning, refer to Sadovsky and colleagues.14 Why intimacy and sexuality matter The ability to form and maintain intimate relationships represent a cornerstone for well-being and survival.

Among other things, intimate relationships have been found to validate personal worth and lead to better adapta-

tion to stress, faster recovery after potentially traumatic events, less physical illness and emotional distress such as anxiety or depression, and higher levels of well-being overall.15-23 Married individuals are generally happier and more satisfied with life, have fewer sick days, spend less time in hospital, and are less likely to suffer from chronic health conditions compared with their nonmarried counterparts.24,25 In fact, being married is associated not only with happier and healthier lives but also with living longer. This survival advantage is found in the population at large and also seems to apply more specifically to oncology. This effect has been reported for all of the most common cancers,26,27 and is also found in late-stage cancers.28 It has also been separately reported for breast cancer,29,30 bladder cancer,31,32 prostate cancer,33 and colorectal cancer.34,35 Although it is possible to share a truly intimate relationship without a sexual component, for most couples sexual intimacy is an important aspect of couple bonding, which continues to be relevant during periods of ill health and into old age and is associated with its own physi-

For some, sexual expression remains important throughout treatment as a way of holding onto normality.

cal and mental health benefits. A strong correlation has been found between the experience of sexual desire between partners and marital satisfaction.36 The experience of sexual dysfunction, in contrast, is associated with distress and poor marital adjustment,37 and can be a contributing factor to the ending of relationships.38 Improved sexual function often leads to improved quality of interactions and relationship satisfaction.39,40 Unfortunately, today public and professional discourse about sexuality is almost exclusively focused on risks and dangers, such as the prevention of sexually transmitted diseases, underage sex and teen pregnancies, abuse, and pedophilia. Much less attention has been paid to the demonstrated health benefits of sexual expression, which

GREEN HILL HEALTHCARE COMMUNICATIONS

©iStockphoto.com/Aldo Murillo

have led the World Association for Sexology to conclude that “Sexual pleasure, including autoeroticism, is a source of physical, psychological, intellectual, and spiritual well-being.”41 Specific health benefits associated with sexual expression include an overall sense of enhanced well-being, greater happiness and mental health, improved sexual and reproductive health, benefits to the immune system, relief from pain, physical and mental relaxation, and longevity to name but a few.

In terms of oncology-specific benefits, research suggests that regular sexual expression may offer some protection against certain types of cancer. For example, Le and colleagues and, separately, Gjorgov reported that infrequent or complete lack of sexual intercourse and use of barrier methods of contraception are associated with an increased risk of breast cancer.42,43 In terms of men’s cancers, several studies have found an association between reported frequency of ejaculation and lower prostate cancer risk.44,45 The reader is directed to three excellent summary and discussion papers on the field for a more detailed discussion of the evidence.46-48 Sexuality and the cancer journey A diagnosis of cancer brings with it a wide variety of difficult issues for the newly diagnosed person and his or her partner. There is perhaps, foremost, a close encounter with death and mortality, extended treatment periods with often difficult side effects, and long recovery periods. Then, there is the havoc cancer plays with a patient’s life:

work, finances, and relationships with family and friends. Indeed, some cancer patients describe cancer as a totally lifechanging event. They do not feel they are the same person they were before their diagnosis, and they often talk about the difficulties they have in adjusting to the many losses they have suffered as a result of their illness. Frequently, there is a re-evaluation of life priorities.

In this context, it is perhaps not surprising that for most couples affected by cancer, sexual concerns initially move into the background as they assess the degree of danger and upheaval a diagnosis presents. Even during longer periods of active treatment, people often focus on “just getting through.” Fatigue and other side effects of treatment mean that patients and their partners are often happy to put their love lives on hold under the circumstances. For some, however, sexual expression remains important throughout treatment as a way of holding onto normality, boosting selfesteem and a sense of still being an attractive sexual partner, sharing comfort and support, and reaffirming the couple bond. For others, sexual expression may even become more accentuated and important as a way of dealing with difficult emotions, getting reassurance and feeling sensations of well-being and relaxation. For most couples, however, concerns around sexuality come back into the foreground as the rest of life gradually returns to “normal,” and yet this aspect remains sadly missing or problematic. It is often only at this point in survivorship that couples contemplate seeking help for their Continued on page 16

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Survivorship Program

A Model of Survivorship Care: The Memorial Sloan-Kettering Approach Nancy G. Houlihan, MA, AOCN1; Zana Correa, MSN, NP-BC2 Clinical Program Manager, Survivorship Program; 2Survivorship Nurse Practitioner, Colorectal Service Memorial Sloan-Kettering Cancer Center, New York, New York

1

I

n 2005, the Institute of Medicine (IOM) published the report From Cancer Patient to Cancer Survivor: Lost in Transition that recognized survivorship as a distinct phase of the cancer care trajectory, beginning with diagnosis and extending beyond active cancer treatment through follow-up and longterm survival.1 The report defined optimal care after cancer treatment and offered models and strategies for meeting the long-term needs of survivors. With a growing number of cancer survivors and recognition of patients’ posttreatment needs, survivorship programs have flourished over the past 5 years in the United States and abroad. Programs vary depending on settings, resources, and needs of targeted populations.

Memorial Sloan-Kettering Cancer Center (MSKCC) implemented a comprehensive program for survivors of adult-onset cancers in 2005, in which nurse practitioners (NPs) provide disease- and treatment-specific care and counseling to survivors with a focus on assisting optimal recovery and transition to wellness. Aligned with the institutional quality-care initiatives, this program was designed to address an urgent organizational need for moving posttreatment patients to the most appropriate care providers, allowing for greater access for new patients needing acute cancer treatment. This article provides an overview of cancer survivorship care components and delivery models, using MSKCC’s experience in meeting patient and institutional needs.

Table Standard Set of Services by a Nurse Practitioner at the Independent Survivorship Visit • Monitor for recurrence of primary cancer • Evaluate and treat medical and psychosocial consequences of treatment • Screen for second cancers • Educate patient about survivorship issues and availability of community resources • Promote health, including smoking cessation, diet, and exercise • Provide patient with treatment summary and care plan • Communicate with community physician

Components of survivorship care The essential components of survivorship care include the prevention and early detection of new and recurrent cancer; surveillance of cancer spread, recurrence, or second cancers; interventions for physical and psychosocial sequelae of cancer and treatment; and coordination of ongoing healthcare between oncology and primary care providers.1 All patients need survivorship care with variations in need for services based on the complexity of cancer treatment, preexisting comorbidities, and the age at which treatment was delivered. For example, those receiving multimodality cancer treatment or intensive treatments, such as bone marrow transplantation, may require more long-term specialty services than adults treated with surgery alone.2 Survivorship care should begin at the end of active cancer treatment. A plan of care should be based on the treatment delivered and the presence of lingering effects and potential for late effects, with rec-

Follow-up Care of Cancer Survivors

DIAGNOSIS

TREATMENT

EARLY FOLLOW-UP

SURVIVORSHIP TX FOLLOW-UP

• Cancer recurrence • Screening new cancers • Sequelae of TX • Health promotion • Primary care provider communication • TX summary/care plan

Oncology specialist

Nurse practitioner

Community physician

Figure. Memorial Sloan-Kettering Cancer Center Model of Survivorship Care

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LONG-TERM POST-TX FOLLOW-UP

ommendations for reducing risk and promoting healthy behaviors.3 Surveillance for cancer recurrence includes careful review of interval history, physical examination, and appropriate diagnostic testing, which begin at treatment end and extend for a period of time that is dependent on the type of cancer, stage at diagnosis, tumor characteristics, and related risk of recurrence.

Follow-up visits and testing schedules tend to be frequent during the immediate posttreatment period and decrease in frequency over time as the risk of recurrence diminishes. The National Comprehensive Cancer Network and the American Society of Clinical Oncology (ASCO) as well as other organizations have developed consensus-based followup guidelines to assist with a standard approach. As with all survivorship care, surveillance for recurrence may be provided by the oncology specialist, primary care provider, or a combination of both.4 Monitoring for and management of disease and treatment effects, including second cancers, is essential for the longterm health and quality of life of survivors. Monitoring requires knowledge of particular treatment effects and related assessments and testing. There are few published guidelines for monitoring of late effects. Examples of monitoring include periodic cardiovascular evaluation for patients treated with anthracyclines, breast cancer screening with annual mammography for Hodgkin lymphoma survivors treated with mantle radiation, screening those treated with neck radiation for hypothyroidism, assessing restoration of ovulation after alkylating or hormonal agents, and screening for anxiety and depression.1 Interventions for managing long-term and late treatment effects are important for the recovery, adaptation, and enhanced quality of life of the survivor.

Examples include exploring causes for persistent fatigue after lymphoma, refer-

ral to specialists for patients with urinary incontinence and sexual dysfunction after radical prostatectomy, and initiating lymphedema therapy after lymph node dissection.

Routine screening for breast, colorectal, cervical, and endometrial cancers according to national guidelines should be included as part of ongoing healthcare recommendations. Promotion of positive health behaviors includes counseling survivors about lifestyle changes that can reduce comorbid conditions, which may be related to age, treatment, genetic susceptibility or behaviors. Recommendations should include known risk-reduction behaviors, such as smoking cessation, weight control, moderation of alcohol intake, control of sun exposure, regular physical activity, and vaccinations.1

A plan of care should be based on the treatment delivered and the presence of lingering effects and potential for late effects.

Summary of cancer treatment and plan for follow-up care According to Earle, quality survivor care is rooted in a plan for survivorship.5 The second recommendation of the IOM report calls for provision of a comprehensive care summary and a followup care plan that is clearly and effectively explained for all patients completing primary treatment.1 A survivorship care plan provides patients and their current and future care providers with a source of information about the treatment they received and the related risks and recommendations. It can serve as a tool for counseling survivors about the lifetime significance of cancer treatment and their health maintenance. There are barriers to providing these plans, such as time required and lack of reimbursement for completion, poor access to information over time because of multiple care providers and settings and lack of electronic records, and absence of evidence and consensus-based guidelines for follow-up care.3,6 In addition, no evaluation data support the usefulness of care plans. Although the IOM report concluded that as an element of care they “simply made sense” and that they had

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Survivorship Program strong face validity, the report acknowledged that research was needed to assess the impact and associated costs of care plans and their acceptance by patients and providers.1 ASCO has created sample templates for the prospective recording of treatment as well as a one-page summary care plan containing follow-up recommendations for breast and colorectal cancers; expansion to include other cancer types is under way. There is also a generic template for use with any type of cancer. All the templates are available on the ASCO website.3,6 Other groups have developed care plan templates and made them available as resources. The LIVESTRONG Care Plan was developed by the Lance Armstrong Foundation in a partnership with the OncoLink webpage of the University of Pennsylvania.

Journey Forward, created by a collaboration between the National Coalition for Cancer Survivorship, UCLA Cancer Survivorship Center, WellPoint, and Genentech, is a simple treatment summary format and guidelines for monitoring future care based on the ASCO treatment guidelines. Passport for Care, developed by a group from the Texas’ Children’s Cancer Center and Baylor College of Medicine, is an Internetbased care plan based on Children’s Oncology Group guidelines for the care of pediatric cancer survivors. Clinical application of Passport for Care is currently being evaluated.6

tems approach that incorporates a team of primary care, oncology, and other care providers who agree to communicate and develop streamlined transitions in care.1 Promising models of survivorship care have emerged, including a sharedcare model and various forms of specialized follow-up clinics.

Shared care is described as a sharing of responsibility for healthcare between

two or more clinicians of different specialties, where there is transfer of information about a patient and knowledge about the particular care requirements.1,4 Shared care has become the standard approach to managing chronic illnesses, such as diabetes, where care is coordinated between an endocrinologist and a primary care physician. Shared care in the oncology setting can be an effective

model for coordinating care during the transition from acute treatment to survivorship. As patients reach recovery from cancer treatment, it becomes vitally important that they resume their other healthcare maintenance and management of comorbidities.

Specialty survivorship programs are evolving in academic institutions. Initial Continued on page 20

Help reduce the risk of infection in patients receiving moderate-risk* chemotherapy regimens

Act before febrile neutropenia strikes Potential consequences of febrile neutropenia may be serious and can impact patient care First- and every-cycle Neulasta® achieved: ■ 94% reduction in febrile neutropenia (17% placebo vs 1% Neulasta®; P < 0.001).1,2 ■ 93% reduction in febrile neutropenia– related hospitalization (14% placebo vs 1% Neulasta®; P < 0.001).1,2 ■ 80% reduction in febrile neutropenia– related IV anti-infective use (10% placebo vs 2% Neulasta®; P < 0.001).1,2

Shared care in the oncology setting can be an effective model for coordinating care during the transition from acute treatment to survivorship.

Models of care The usual care of cancer survivors includes follow-up care with the treating oncologist who provides surveillance for cancer recurrence and assessment of persistent treatment effects.4 There is generally little time in a busy oncology practice to focus on a comprehensive plan of care, and communication with other providers is limited. At the same time, primary care physicians have a significant role with nearly half of cancerrelated ambulatory visits characterized as shared care with oncologists, although the role of each clinician during these visits is unclear.1 Barriers to providing optimal survivorship care include lack of professional education and training of primary care providers, limited standards or guidelines for care, and difficulties in communication. Overcoming these barriers requires building an integrated sys-

Neulasta® (pegfilgrastim) is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Neulasta® is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Important Safety Information Do not administer Neulasta® to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

Splenic rupture, including fatal cases, can occur following the administration of Neulasta®. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving Neulasta®.

Acute respiratory distress syndrome (ARDS) can occur in patients receiving Neulasta®. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving Neulasta® for ARDS. Discontinue Neulasta® in patients with ARDS. Serious allergic reactions, including anaphylaxis, can occur in patients receiving Neulasta®. The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue Neulasta® in patients with serious allergic reactions.

Severe sickle cell crises can occur in patients with sickle cell disorders receiving Neulasta®. Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim, the parent compound of pegfilgrastim.

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

Bone pain and pain in extremity occurred at a higher incidence in Neulasta®-treated patients as compared with placebo-treated patients.

Please see brief summary of Neulasta® Prescribing Information on the adjacent page. *Regimens associated with 17% risk of febrile neutropenia.

References: 1. Vogel C, et al. J Clin Oncol. 2005;23:1178-1184. 2. Neulasta® (pegfilgrastim) Prescribing Information. Thousand Oaks, Calif: Amgen. © 2010 Amgen. All rights reserved.

MC49047-A-1

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Clinical Concerns Why Intimacy and Sexuality Matter... Continued from page 13 difficulties, a process which will be much easier if appropriate early discussions have taken place during the acute phase of treatment.

It is essential to realize that the importance placed on sexuality does not usually change as a person approaches the end of their life, although the ways in which

sexuality is expressed may alter according to circumstances.

But what can I do?

One of the most important and also difficult things for health professionals to achieve is resisting the natural inclination to make assumptions about the

BRIEF SUMMARY OF PRESCRIBING INFORMATION Neulasta® (pegfilgrastim) injection, for subcutaneous use INDICATIONS AND USAGE Neulasta is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Neulasta is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

CONTRAINDICATIONS Do not administer Neulasta to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

WARNINGS AND PRECAUTIONS Splenic Rupture Splenic rupture, including fatal cases, can occur following the administration of Neulasta. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving Neulasta.

Acute Respiratory Distress Syndrome Acute respiratory distress syndrome (ARDS) can occur in patients receiving Neulasta. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving Neulasta, for ARDS. Discontinue Neulasta in patients with ARDS. Serious Allergic Reactions Serious allergic reactions, including anaphylaxis, can occur in patients receiving Neulasta. The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue Neulasta in patients with serious allergic reactions. Do not administer Neulasta to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

Use in Patients With Sickle Cell Disorders Severe sickle cell crises can occur in patients with sickle cell disorders receiving Neulasta. Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim, the parent compound of pegfilgrastim.

Potential for Tumor Growth Stimulatory Effects on Malignant Cells The granulocyte-colony stimulating factor (G-CSF) receptor through which pegfilgrastim and filgrastim act has been found on tumor cell lines. The possibility that pegfilgrastim acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim is not approved, cannot be excluded.

ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the Brief Summary: s 3PLENIC 2UPTURE ;3EE Warnings and Precautions] s !CUTE 2ESPIRATORY $ISTRESS 3YNDROME ;3EE Warnings and Precautions] s 3ERIOUS !LLERGIC 2EACTIONS ;3EE Warnings and Precautions] s 5SE IN 0ATIENTS WITH 3ICKLE #ELL $ISORDERS ;3EE Warnings and Precautions] s 0OTENTIAL FOR 4UMOR 'ROWTH 3TIMULATORY %FFECTS ON -ALIGNANT #ELLS ;3EE Warnings and Precautions] The most common adverse reactions occurring in r 5% of patients and with a between-group difference of r 5% higher in the pegfilgrastim arm in placebo controlled clinical trials are bone pain and pain in extremity.

Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Neulasta clinical trials safety data are based upon 932 patients receiving Neulasta in seven randomized clinical trials. The population was 21 to 88 years of age and 92% female. The ethnicity was 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian. Patients with breast (n = 823), lung and thoracic tumors (n = 53) and lymphoma (n = 56) received Neulasta after nonmyeloablative cytotoxic chemotherapy. Most patients received a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles.

The following adverse reaction data in Table 1 are from a randomized, double-blind, placebo-controlled study in patients with metastatic or non-metastatic breast cancer

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receiving docetaxel 100 mg/m2 every 21 days. (Study 3).

A total of 928 patients were randomized to receive either 6 mg Neulasta (n = 467) or placebo (n = 461). The patients were 21 to 88 years of age and 99% female. The ethnicity was 66% Caucasian, 31% Hispanic, 2% Black, and <1% Asian, Native American or other.

Bone pain and pain in extremity occurred at a higher incidence in Neulasta-treated patients as compared with placebo-treated patients.

Table 1. Adverse Reactions With ≥ 5% Higher Incidence in Neulasta Patients Compared to Placebo in Study 3 System Organ Class Preferred Term

Placebo (N = 461)

Neulasta 6 mg SC on Day 2 (N = 467)

Musculoskeletal and connective tissue disorders Bone pain

26%

31%

Pain in extremity

4%

9%

Leukocytosis In clinical studies, leukocytosis (WBC counts > 100 x 109/L) was observed in less than 1% of 932 patients with nonmyeloid malignancies receiving Neulasta. No complications attributable to leukocytosis were reported in clinical studies.

Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. Binding antibodies to pegfilgrastim were detected using a BIAcore assay. The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients with metastatic breast cancer. Four of 521 pegfilgrastim-treated subjects who were negative at baseline developed binding antibodies to pegfilgrastim following treatment. None of these 4 patients had evidence of neutralizing antibodies detected using a cell-based bioassay.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Neulasta with the incidence of antibodies to other products may be misleading.

Postmarketing Experience The following adverse reactions have been identified during post approval use of Neulasta. 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. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) reported frequency of the reaction, or (3) strength of causal relationship to Neulasta.

Gastro-intestinal disorders: 3PLENIC RUPTURE ;SEE Warnings and Precautions] Blood and lymphatic system disorder: Sickle cell crisis ;SEE Warnings and Precautions] Respiratory, thoracic, and mediastinal disorder: ARDS ;SEE Warnings and Precautions] General disorders and administration site conditions: Injection site reactions Skin and subcutaneous tissue disorders: Allergic reactions/ hypersensitivity, including anaphylaxis, skin rash, and urticaria, Sweet’s syndrome, generalized erythema and FLUSHING ;SEE Warnings and Precautions] DRUG INTERACTIONS No formal drug interaction studies between Neulasta and other drugs have been performed. Increased hematopoietic activity of the bone marrow in response to growth factor therapy may result in transiently positive bone-imaging changes. Consider these findings when interpreting boneimaging results.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Pegfilgrastim was embryotoxic and increased pregnancy loss in pregnant rabbits that received cumulative doses approximately 4 times the recommended human dose (based on body surface area). Signs of maternal toxicity occurred at these doses. Neulasta should be used during

patients in front of them: the importance of sexuality in their lives, the existence of any sexual difficulties and how concerned they might be about these, their willingness to discuss sexual matters with us, or their ability to raise the subject without encouragement. In fact, the vast majority of patients, irrespec-

pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

In animal reproduction studies, when pregnant rabbits received pegfilgrastim at cumulative doses approximately 4 times the recommended human dose (based on body surface area), increased embryolethality and spontaneous abortions occurred. Signs of maternal toxicity (reductions in body weight gain/food consumption) and decreased fetal weights occurred at maternal doses approximately equivalent to the recommended human dose (based on body surface area). There were no structural anomalies observed in rabbit offspring at any dose tested. No evidence of reproductive/ developmental toxicity occurred in the offspring of pregnant rats that received cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on body surface area).

Women who become pregnant during Neulasta treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program.

Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

Nursing Mothers It is not known whether pegfilgrastim is secreted in human milk.

Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. Caution should be exercised when administered to a nursing woman.

Pediatric Use Safety and effectiveness of Neulasta in pediatric patients have not been established. The adverse reaction profile and pharmacokinetics of pegfilgrastim were studied in 37 pediatric patients with sarcoma. The mean (± standard DEVIATION ;3$= SYSTEMIC EXPOSURE !5#0-inf) of pegfilgrastim after subcutaneous administration at 100 mcg/kg was 22.0 (± 13.1) mcg·hr/mL in the 6 to 11 years age group (n = 10), 29.3 (± 23.2) mcg·hr/mL in the 12 to 21 years age group (n = 13), and 47.9 (± 22.5) mcg·hr/mL in the youngest age group (0 to 5 years, n = 11). The terminal elimination half-lives of the corresponding age groups were 20.2 (± 11.3) hours, 21.2 (± 16.0) hours, and 30.1 (± 38.2) hours, respectively.

The most common adverse reaction was bone pain.

Geriatric Use Of the 932 patients with cancer who received Neulasta in clinical studies, 139 (15%) were age 65 and over, and 18 (2%) were age 75 and over. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients.

Renal Impairment In a study of 30 subjects with varying degrees of renal dysfunction, including end stage renal disease, renal dysfunction had no effect on the pharmacokinetics of pegfilgrastim. Therefore, pegfilgrastim dose adjustment in patients with renal dysfunction is not necessary.

DOSAGE AND ADMINISTRATION The recommended dosage of Neulasta is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle in adults. Do not administer Neulasta between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer Neulasta if discoloration or particulates are observed.

NOTE: The needle cover on the single-use prefilled syringe contains dry natural rubber (latex); persons with latex allergies should not administer this product.

This product, its production, and/or its use may be covered by one or more US Patents, including US Patent Nos. 5,824,784; 5,582,823; 5,580,755, as well as other patents or patents pending.

Neulasta® (pegfilgrastim) Manufactured by: Amgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-1799 © 2010 Amgen Inc. All rights reserved. www.neulasta.com 1-800-77-AMGEN (1-800-772-6436) v 11.0

tive of age, cancer type, or stage of the illness, are willing to talk about their sex lives and the impact of the disease on their sexual function.13 Unfortunately, most patients do not feel comfortable being the first to bring up the subject.

Patients are often unsure about the appropriateness of bringing up a sexual concern in a cancer setting and lack confidence about what words to use and how to express their concern. They also commonly express worries about being judged negatively for still being worried about sex at their age and when people might think they should be happy just to be alive. Moreover, patients do not wish to appear ungrateful in front of clinicians who helped save their lives.8,49,50 Patients, therefore, rely on their healthcare professionals to be the first to raise the subject or to find other ways of indicating it is acceptable to discuss the very sensitive topic of sexual problems after cancer. This can be done in a variety of ways; for example, it can be done by displaying written information or posters in waiting areas, by having it available as part of information packs, or by electronic means.

Early discussion of sexual issues is important, not only as a basic requirement to ensure the patient’s informed consent has been gained, but also because such early discussion may prevent some difficulties from developing in the first place1 and avoid an unnecessary aggravation of difficulties later on.13 What is equally important when raising the subject of sexual side effects routinely at this early stage is to be mentally prepared to hear most patients confirm that they are not currently concerned with this aspect of their lives and to cling to our professional rationale for nevertheless routinely including this sensitive topic in our discussions. Hearing that sexual difficulties are not uncommon and that further discussion and help will be available if necessary will encourage patients to come back and ask for support if difficulties are encountered later on.

Following an initial listing among other side effects when gaining patient consent, the subject of sexual issues can easily and unobtrusively be brought up again at regular intervals when treatment side effects are elicited or discussed or when an overall screening of psychosocial distress is conducted. Another helpful route to discussing intimacy can be to enquire about the partner’s coping or the impact the illness is having on the relationship, which can lead to more direct questioning of any impact on intimate aspects of the relationship without seeming out of context or inappropriate.

It is also important to acknowledge that as healthcare professionals we frequently share our patients’ hesitancy to begin a discussion about intimate topics.

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Clinical Concerns It is fundamentally important that each of us is aware of our personal comfort zone in this respect. We each have a role to play in ensuring that any side effects experienced, including the sexual consequences of cancer treatment, are identified and advice about management is given. Honest self-reflection, however, will help us decide how far our own involvement in the patient’s care will go and encourage us to map out the professional networks around us to be able to advise our patients about where else they can go to get the next level of support.

Annon provides a helpful model (the PLISSIT model) to conceptualize four different levels of psychosexual support, ranging from merely giving permission to raise sexual concerns, toward giving limited information about the potential side effects of treatment and provision of written information, then moving onto the making of specific suggestions tailored to an individual’s needs, often requiring some further training, and toward the final stage of intensive therapy required only by a few of the most complex cases.51 This model is helpful in allowing professionals to identify their own comfort and professional practice zone and encouraging them to identify colleagues capable of providing further input if required.

Similar stepped care approaches have been advocated in oncology settings, in which every cancer professional shares in the task of permission giving and the provision of some limited information, and patients are then stepped up a hierarchy of interventions according to need.2,7,10 Suggested interventions range from educational and practical to pharmacologic approaches at the lower levels, with access to psychological, psychosexual, and biomedical/ surgical approaches for more complex cases. Research increasingly points to the importance of partner involvement and the effectiveness of multidisciplinary approaches to treatment, even in traditionally fully medically managed areas such as erectile dysfunction.52-55 Unfortunately, the more intense levels of sexual rehabilitation are still not offered routinely in most oncology settings. More complex cases are, therefore, currently most appropriately referred to more generalist settings in sexual health, urology, gynecology, or psychology departments according to need.

Much lobbying and awareness raising still needs to be done before cancer patients will have access to the expertise they deserve in this frequently overlooked area. On a more positive note, it has been shown that more than 70% of cancer patients do not require access to such in-depth interventions. Instead, their difficulties can be significantly improved by nurse (or nonspecialist)-led

brief counseling involving some basic information about the impact of cancer treatment on sexual function combined with some practical tips and advice for how to resume intimacy and, if necessary, how to “find new ways of being intimate when old ways no longer work.”2,3 For those interested in studying these topics further, a number of relatively new resources are available that provide a helpful introduction to the field. Katz provides an excellent overview for professionals in her book Breaking the Silence on Cancer and Sexuality, in which she tackles questions, such as how to raise

“We each have a role to play in ensuring that any side effects experienced, including the sexual consequences of cancer treatment, are identified and advice about management is given.”

—Darja Brandenburg, DClinPsych, DipPST, CPsychol, AFBPS

the subject in clinical practice, and gives information about how different cancer types and treatments affect sexual functioning.56 The Cancer Council Victoria and Brandenburg and colleagues provide two examples of practically focused and relatively extensive patient information booklets on the subject of intimacy and sexuality after cancer that can both be downloaded free of charge.57,58 Further, quality information is provided by most national and site-specific cancer organizations. It also may be worthwhile to look for any introductory sexual communication skills workshops that can be both thought-provoking and great fun.

Workshops such as these can go a long way toward increasing confidence and skill levels and are usually well re ceived.59-64 The International Society for Sexuality and Cancer provides an excellent and cost-effective way of connecting professionals with an inter-

GREEN HILL HEALTHCARE COMMUNICATIONS

est in this area to each other within and across national boundaries. ● References 1. Monga U. Sexual functioning in cancer patients.

Sexuality Disability. 2002;20:277-295.

2. Schover LR. Counseling cancer patients about changes in sexual function. Oncology (Williston Park).

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3. Brandenburg U, Bitzer J. The challenge of talking about sex: the importance of patient-physician interaction. Maturitas. 2009;63:124-127.

4. Incrocci L, Madalinska JB, Essink-Bot ML, et al.

Sexual functioning in patients with localized cancer awaiting treatment. J Sex Marital Ther. 2001;27:353-363.

5. Incrocci L. Erectile dysfunction and radiation therapy for prostate cancer. Sexologies. 2006;15:116-120.

6. Incrocci L. Male cancer and sexual function. Sexologies.

2007;16:273-278.

7. Incrocci L. Changes in sexual function after treatment of male cancer. J Men’s Health & Gender. 2005;2:236-243.

8. Barni S, Mondin R. Sexual dysfunction in treated breast cancer patients. Ann Oncol. 1997;8:149-153.

9. Anllo LM. Sexual life after breast cancer. J Sex Marital Ther. 2000;26:241-248.

10. Thors CL, Broeckel JA, Jacobsen PB. Sexual functioning in breast cancer survivors. Cancer Control.

2001;8:442-448.

11. Langana L, Lloyd-McGarvey E, Classen C, Koopman C. Psychosexual dysfunction among gynecological cancer survivors. J Clin Psychol Med Settings. 2001;8:73-84.

12. Krouse R, Grant M, Ferrell B, et al. Quality of life outcomes in 599 cancer and non cancer patients with colostomies. J Surg Res. 2007;138:79-87.

13. Ananth H, Jones L, King M, Tookman A. The impact of cancer on sexual function: a controlled study.

Palliat Med. 2003;17:202-205.

14. Sadovsky R, Basson R, Krychman M, et al. Cancer and sexual problems. J Sex Med. 2010;7(1 pt 2):349-373.

15. Buhrmester D, Furman W. The development of companionship and intimacy. Child Dev. 1987;58:1101-1113.

16. Widows MR, Jacobsen PB, Fields KK. Relation of psychological vulnerability factors to posttraumatic stress disorder symptomatology in bone marrow transplant recipients. Psychosom Med. 2000;62:873-882.

17. Brady SS, Helgeson VS. Social support and adjustment to recurrence of breast cancer. J Psychosoc Oncol.

1999;17:37-55.

18. Moyer A, Salovey P. Predictors of social support and psychological distress in women with breast cancer. J Health Psychol. 1999;4:177-191.

19. Komproe IH, Rijken M, Ros WJG, et al. Available support and received support: different effects under stressful circumstances. J Soc Personal Relationships.

1997;14:59-77.

20. Weiss LJ. Intimacy and adaptation. In: Weg RB, ed.

Sexuality in the Later Years: Roles and Behavior. New York, NY: Academic Press; 1983:147-165.

21. Northouse LL. The impact of breast cancer on patients and husbands. Cancer Nurs. 1989;12:276-284.

22. Hinds C. Suffering: a relatively unexplored phenomenon among family caregivers of non-institutionalized patients with cancer. J Adv Nurs. 1992;17:918-925.

23. Roberts CS, Cox CE, Shannon VJ, Wells NL. A closer look at social support as a moderator of stress in breast cancer. Health Social Work. 1994;19:157-164.

24. Wood W, Rhodes N, Whelan M. Sex differences in positive well-being: a consideration of emotional style and marital status. Psychol Bull. 1989;106:249-264.

25. Stack S, Eshelman JR. Marital status and happiness: a 17-nation study. J Marriage Family. 1998;60:527-536.

26. Goodwin JS, Hunt WC, Key CR, Samet JM. The effect of marital status on stage, treatment and survival in cancer patients. JAMA. 1987;258:3125-3130.

27. Kravdal O. The impact of marital status on cancer survival. Soc Sci Med. 2001;52:357-368.

28. Lai H, Lai S, Krongrad A, et al. The effect of marital status on survival in late-stage cancer patients: an analysis based on surveillance, epidemiology, and end results (SEER) data, in the United States. Int J Behav Med. 1999;6:150-176.

29. Neale AV, Tilley BC, Vernon SW. Marital status, delay in seeking treatment and survival from breast cancer. Soc Sci Med. 1986;23:305-312.

30. Neale AV. Racial and marital status influences on 10 year survival from breast cancer. J Clin Epidemiol.

1994;47:475-483.

31. Nelles JL, Joseph SA, Konety BR. The impact of marriage on bladder cancer mortality. Urol Oncol. 2009; 27:263-267.

32. Datta GD, Neville BA, Kawachi I, et al. Marital status and survival following bladder cancer. J Epidemiol Community Health. 2009;63:807-813.

33. Denberg TD, Beaty BL, Kim FJ, Steiner JF. Marriage and ethnicity predict treatment in localized prostate carcinoma. Cancer. 2005;103:1819-1825.

34. Johansen C, Chow WH, Jørgensen T, et al. Risk of colorectal cancer and other cancers in patients with gall stones. Gut. 1996;39:439-443.

35. Villingshoj M, Ross L, Thomsen B, Johansen C. Does marital status and altered contact with the social network predict colorectal cancer survival? Eur J Cancer.

2006;42:3022-3027.

36. Brezsnyak M, Whisman MA. Sexual desire and relationship functioning: the effects of marital satisfaction and power. J Sex Marital Ther. 2004;30:199-217.

37. Badr H, Taylor CL. Sexual dysfunction and spousal communication in couples coping with prostate cancer.

Psychooncology. 2009;18:735-746.

38. Schover LR, von Eschenbach AC. Sexual and marital relationships after treatment for nonseminomatous testicular cancer. Urology. 1985;25:251-255.

39. Muller MJ, Ruof J, Graf-Morgenstern M, et al.

Quality of partnership in patients with erectile dysfunction after sildenafil treatment. Pharmacopsychiatry.

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40. Verheyden B, Roumeguere T, Bitton A, et al; for the DETECT study investigators. Effects of 12-month tadalafil therapy for erectile dysfunction on couple relationships: results from the DETECT Study. J Sex Med. 2009;6:3458-3468.

41. World Association for Sexology. Declaration of sexual rights. August 26, 1999. www.tc.umn.edu/~colem001/ was/wdeclara.htm. Accessed August 26, 2010.

42. Le MG, Bachelor A, Hill C. Characteristics of reproductive life and risk of breast cancer in a case-control study of nulliparous women. J Clin Epidemiol. 1989; 42:1227-1233.

43. Gjorgov AN. Breast cancer and barrier contraception. Postulated and corroborated potential for prevention. Folia Med (Plovdiv). 1998;40(3B suppl 3):17-23.

44. Giles GG, Severi G, English DR, et al. Sexual factors and prostate cancer. BJU Int. 2003;92:211-216.

45. Leitzmann MF, Platz EA, Stampfer MJ, et al.

Ejaculation frequency and subsequent risk of prostate cancer. JAMA. 2004;291:1578-1586.

46. Whipple B. The health benefits of sexual expression.

Sexologies. 2008;17(suppl 1):S45-S46.

47. Jannini EA, Fisher WA, Bitzer J, McMahon CG. Is sex just fun? How sexual activity improves health. J Sex Med. 2009;6:2640-2648.

48. Brody S. The relative health benefits of different sexual activities. J Sex Med. 2010;7(4 pt 1):1336-1361.

49. Ganz PA, Rowland JH, Desmond K, et al. Life after breast cancer: understanding women’s health-related quality of life and sexual functioning. J Clin Oncol.

1998;16:501-514.

50. Rosen R, Kountz D, Post-Zwicker T, et al. Sexual communication skills in residency training: the Robert Wood Johnson model. J Sex Med. 2006;3:37-46.

51. Annon JS. The PLISSIT model: a proposed conceptual scheme for behavioural treatment of sexual problems. J Sex Educ Ther. 1976;2:1-15.

52. Melnik T, Soares BG, Nasello AG. The effectiveness of psychological interventions for the treatment of erectile dysfunction: systematic review and meta-analysis, including comparisons of sildenafil treatment, intracavernosal injection, and vacuum devices. J Sex Med. 2008;5:2562-2574.

53. Abdo CH, Afif-Abdo J, Otani F, Machado AC. Sexual satisfaction among patients with erectile dysfunction treated with counseling, sildenafil or both. J Sex Med. 2008;5:1720-1726.

54. Hatzichristou D, Rosen RC, Derogatis LR, et al.

Recommendations for the clinical evaluation of men and women with sexual dysfunction. J Sex Med. 2010;7(1 pt 2):337-348.

55. Althof S. What’s new in sex therapy. J Sex Med. 2010;7(1 pt 1):5-13.

56. Katz A. Breaking the Silence on Cancer and Sexuality.

Pittsburgh, PA: Oncology Nursing Society; 2007.

57. Cancer Council Victoria. Sexuality & cancer.

January 31, 2008. www.cancervic.org.au/about-cancer/ living-with-cancer/sexuality_and_cancer. Accessed August 26, 2010.

58. Brandenburg D, Grover L, Quinn B, Malik S. Intimacy & Sexuality for Cancer Patients and Their Partners: A Booklet of Tips and Advice for your Journey of Recovery.

London, UK: Sexual Advice Association; 2010.

59. Gianotten WL. Training in sexology for medical and paramedical professionals: a model for the rehabilitation setting. Sexual Relat Ther. 2006;21:303-317.

60. Dodson L. Addressing intimacy and sexuality—on the development of a communication skills programme.

Presented at: 16th International Conference on Cancer Nursing; March 8, 2010; Atlanta, GA. 61. Bitzer J. How to talk to oncologists about sexual medicine and to sexologists about oncology. Presented at: 2nd Rotterdam Symposium on Cancer and Sexuality; June 4, 2010; the Netherlands.

62. Post MWM, Gianotten WL, Heinjnen L, et al.

Sexological competence of different rehabilitation disciplines and effects of a discipline-specific sexological training. Sexuality Disability. 2008;26:3-14.

63. Krebs LU. Sexual assessment: research and clinical.

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64. Park ER, Norris RL, Bober SL. Sexual health communication during cancer care: barriers and recommendations. Cancer J. 2009;15:74-77.

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Survivorship Program Cancer Rehabilitation and Survivorship... Continued from cover The central tenet of cancer rehabilitation is to help cancer patients and survivors regain and improve their physical, psychosocial, and vocational functioning within the limitations imposed by the disease and its treatment.3 Cancer survivors may be disease-free, but not “free of their disease.”

They may face a vast scope of issues, including, but not limited to, fatigue, pain, lymphedema, anxiety, and functional impairments as a result of their cancer or its treatment (Table 1).

Therefore, for many cancer patients, returning to “normal” life can be a very difficult transition.

In 2005, the Institute of Medicine published a report, From Cancer Patient to Cancer Survivor: Lost in Transition, which began to address the increasingly important role that rehabilitation plays in the lives of cancer survivors.4 The interdisciplinary survivorship committee at the Samuel Oschin Compre hensive Cancer Institute at CedarsSinai Medical Center has worked over the past year to develop a variety of programs to address some of the physical, cognitive, and psychosocial concerns experienced by our cancer survivors. This article highlights a few of these programs.

Arash Asher, MD

Expressions of Hope & Healing Cancer patients who have completed medical treatment often have unresolved psychological issues. Not only do people with cancer experience an increase in negative emotions, such as anxiety and depression, but they also experience a lack of positive emotions.5 Art programs have been shown to help integrate their difficult experience into their new identities.6 Whereas support groups can be extremely powerful and helpful for some cancer patients, we

I Am The Tree of Life. A project from Cedars-Sinai’s Hope & Healing workshop.

I am the Tree of Life I hold the Life Force of the Universe My veins are my branches.

My roots are strong & run deep into the earth; My limbs gain strength from the sky.

I hope to live a long life ahead.

I am the Tree of Life That brings comfort to all of your children I am going to live a long life with health and prosperity Life, Love, Positive Thinking; Live, Laugh, Love

I am a child of God. I am the Tree of Life I love the Redwood forest I am here to stay; to live, love, learn And leave a legacy Watch me Grow.

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September 2010 I VOL 3, NO 6

have found that many survivors are better able to express and find meaning in their experiences through art rather than through words. Expressions of Hope & Healing, an art healing workshop, was created to use art as an expressive tool to guide cancer patients through their healing process and help them find meaning in their experience.

In his seminal book published in 1949, The Hero with a Thousand Faces, Joseph Campbell identified the underlying pattern in virtually all myths, stories, and spiritual traditions—the Hero’s Journey.7 Campbell lays out a number of stages along every Hero’s Journey, including the “call to adventure,” “the ordeal,” “the road back,” and “return with the elixir.” Led by Flori Hendron, herself a cancer survivor, Expressions of Hope & Healing is an 8-week program that guides the cancer survivor through a journey that mirrors that of the prototypical hero. Based on primarily qualitative data that we have collected thus far, we have found that the program can increase self-esteem through engagement in the creative process, decrease a sense of isolation given the communal nature of the class, and improve coping skills by decreasing stress levels. More systematic and rigorous research is planned to better quantify the potential benefits and mechanisms of action that produce a benefit of art programs for patients with cancer.

Qigong program Cancer and its treatment are associated with considerable distress, impaired quality of life, poor mental health, and reduced physical function.8 It is important to integrate programs that may mitigate the wide scope of the treatmentrelated effects of cancer and improve quality of life. Moreover, given the demands of many multimodal treatment schedules, these programs work best when integrated into the cancer patient’s schedule and regimen.

Qigong (pronounced Chee-Gung) is a form of traditional Chinese mind-body exercise and meditation that uses slow and precise body movements with controlled breathing and mental focusing.

The goal is to improve balance, flexibility, muscle strength, and overall wellbeing. A recent randomized trial investigating the effects of qigong on quality of life, fatigue, and mood found significant improvements among cancer patients.9 Qigong has many practical advantages for program development at a cancer center. It is a viable practice for cancer patients with a wide spectrum of functional capacity and requires very little in the way of equipment or space. At Cedars-Sinai, the class is held outdoors on the plaza level of the hospital. The

program was put together as a collaborative effort with the local Wellness Community. The practice sessions take about 75 to 90 minutes, depending on how the participants wish to proceed on any given day. The break between the sets of exercises is referred to as “social oncology” in China; it is when the participants talk to each other, share stories, and relate experiences with each other.

The knitting together of classmates into a supportive group may be as therapeutic as any other part of the practice.

Table 1 Potential Issues Faced by Cancer Survivors • Endocrine and fertility effects in male cancer survivors • Cancer-related fatigue and sleep disturbances • Osteoporosis • Secondary malignancies • Existential and spiritual issues • Vocational and financial issues • Functional decline • Poor quality of life • Family and caregiver distress • Psychosocial distress and coping after cancer treatment • Sexuality and body image • Lymphedema • Pain and neuropathy • Cognitive changes • Cardiorespiratory effects • Reproductive and hormonal sequelae of chemotherapy in women • Dental changes

Emerging from the Haze Cancer treatments are aggressive and often include surgery, radiation, chemotherapy, and immunotherapy.

Improved survival rates are often attributed to these multimodal strategies; unfortunately, most are not highly specific and may place normal cells and organs at risk, including the central nervous system. Moreover, many of the adjunctive medications that cancer patients receive, such as corticosteroids, antiepileptic medications, immunosuppressive agents, opioids, hypnotics, and antiemetics, may also contribute to impaired cognition.

Therefore, cognitive dysfunction may be a consequence of the cancer, its treatment, or both.

The term chemobrain was coined after breast cancer patients started to notice mental fogginess around the same time they were being treated with chemotherapy. This term has its limitations because many other causes may contribute to cognitive dysfunction among cancer patients, such as depression, hormonal changes, insomnia, and Continued on page 21

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Survivorship Program A Model of Survivorship Care... Continued from page 15 models were developed for the care of pediatric cancer survivors, where there was early recognition of the need to monitor for late treatment effects. Most of these programs are directed by a pediatric oncologist and coordinated by an NP, and about half include other mental health providers and other specialties.4 Disease-specific models were the first example of adult survivorship care programs. Oeffinger and McCabe described three distinct adult care models.4 As in

the pediatric programs, NPs play a central role in care delivery. Their first care model is the most basic and is described as a one-time consultative visit to a survivorship care provider, often an NP. A summary of cancer treatment and a plan for monitoring late effects are developed, and needs-based counseling and health promotion recommendations are provided. Their second care model is an NP-led clinic that functions as an extension of the care continuum. The NP

Case study A 58-year-old woman who presented in May 2006 with a 6-month history of rectal bleeding was diagnosed with locally advanced rectal carcinoma. She was treated with neoadjuvant chemotherapy and radiation followed by abdominal perineal resection with pelvic sidewall dissection and posterior vaginectomy.

The pathology report revealed no residual carcinoma, and surgical margins were free of dysplasia; lymph nodes were negative; the vaginal mucosa was unremarkable. Adjuvant chemotherapy was given and tolerated well. She had not had a follow-up bone densitometry. The patient was followed by her colorectal surgeon for 2 years and transferred to the survivorship NP on the colorectal service. Her initial survivorship visit was in October 2009.

The patient’s medical history is significant for earlystage ovarian cancer treated with total abdominal hysterectomy with bilateral salpingo-oophorectomy and adjuvant chemotherapy (1999) and partial thyroidectomy for a goiter (2005). Comorbidities include hypertension, hypothyroidism, and osteopenia. Obstetrical history: G1 P1, vaginal delivery. She reports no gynecologic examination or mammogram in more than 3 years and has not seen her primary care doctor in 2 years. She has no family history of cancer. She is married with one adult daughter aged 33 years, works fulltime as a hair dresser, denies alcohol, drug, or tobacco use, and does not exercise regularly.

Assessment revealed the following findings.

• Review of systems: obesity secondary to high-fat diet and sedentary lifestyle; dyspareunia secondary to radiation, surgery; decreased libido; uncontrolled bowel movements through stoma; fatigue • Psychosocial assessment: anxiety related to fear of rectal cancer recurrence or a new cancer; relationship concerns related to absence of sexual activity; body image changes from stoma, weight gain • Physical examination: well-healed incision, no hernia on incision sites with stoma upright, and no peristomal hernia; body mass index, 30.1 (obese); blood pressure, 160/94 • Vaginal examination: negative except for tenderness during examination • Diagnostic testing: carcinoembryonic antigen (CEA), within normal limits: 1.6 ng/mL (range, 5 ng/mL); computed tomography scan chest, abdomen, and pelvis, no evidence of disease recurrence; colo noscopy overdue The possible physical late effects of rectal cancer treatment include bowel and bladder dysfunction, sexual

delivers ongoing care that includes a standard set of survivorship services and a follow-up care plan. Contact with the primary care provider is reestablished by the NP, with sharing of patient information and care guidelines. This facilitates shared care and a potential return to community follow-up care based on the patient’s risk for recurrence and late effects. Their most complex care model is a specialized multidisciplinary survivor program similar to the pediatric pro-

dysfunction, adhesions, hernia, dietary changes, and peripheral neuropathy due to chemotherapy. Psychosocial effects include body image changes and fears about recurrence and development of second cancer.

Our patient was found to have the following problems.

• Treatment effects: sexual dysfunction (dyspareunia); bowel dysfunction (uncontrolled bowel movements); hernia (hernia repair x 1) • Psychosocial: body image changes (stoma and weight gain); relationship changes (decreased libido); anxiety (fears of recurrence) The nurse practitioner summarized the visit findings with the patient and reviewed a survivorship care plan, which was sent to the primary care provider with a copy of the visit notes.

• Obesity: counseled on diet/exercise; educational materials provided on diet and exercise; patient was referred to a nutritionist • Dyspareunia: counseled about vaginal health strategies related to dryness and vaginal dilatation; referred to Women’s Sexual Health Program • Healthcare maintenance: annual mammogram, gynecological examination and Pap smear, also bone densitometry; encouraged to continue calcium and vitamin D supplements; referred to new gynecologist • Anxiety: referred to social worker • Comorbidities: instructed to follow up with primary care provider for management of hypertension and thyroid replacement medications • Counseling: screening colonoscopy for family especially her daughter; routine use of sun screen; annual influenza vaccination • Surveillance: patient was scheduled to return in 6 months with a CEA at the visit; colonoscopy scheduled prior to next visit The patient returned for her follow-up visit with the nurse practitioner 6 months later. Her colonoscopy was negative for recurrent or new disease. She had seen her primary care provider, who adjusted her thyroid replacement and antihypertensive medications.

Bone densitometry showed stable osteopenia. She had seen the gynecologist and had negative examination and cytology findings. She had multiple visits, along with her husband, in the Women’s Sexual Health Program for counseling and for vaginal dilatation management. She had seen the social worker and joined a regular support group for cancer survivors through her community center. She had also joined Weight Watchers and started a daily walking regimen; she had lost 6 pounds. The patient will return for regular visits with the survivorship nurse practitioner.

grams. This model includes physicians with training and experience in the care of cancer survivors, NPs, and other mental health and consulting specialists.

The team provides risk-based care. One example of this resource-intense model is the clinic that provides care for the adult survivors of pediatric cancers.

Survivorship model of care at MSKCC: adult-onset cancer clinics The clinical survivorship program for adult-onset cancers at MSKCC began in 2005. A pediatric long-term follow-up clinic had long been established and served as a resource for development of the adult program. Led by Mary McCabe, director of the Cancer Survivorship Initiative, a multidisciplinary steering committee developed a model of care to best meet the defined needs of adult patients and the institution. An institutional needs assessment and patient focus groups guided development and expansion of support programs and greater access to services for survivors and families. The overall goals of the clinical program are to extend the continuum of care by defining survivorship

NPs were selected as the survivorship care providers based on their educational preparation in holistic care and the hospital’s positive experience with NPs in acute care over many years. care for each disease specialty and to transition patients along the continuum from the oncology provider to the survivorship NP, who facilitates communication with the primary care provider (Figure, page 14). The program is designed to provide comprehensive follow-up care with a standard set of services that addresses survivors’ specific medical, psychosocial, functional, educational, and spiritual needs. Patient eligibility for transfer to survivorship care and standard follow-up guidelines are determined by the disease management team for that patient population.

NPs were selected as the survivorship care providers based on their educational preparation in holistic care and the hospital’s positive experience with NPs in acute care over many years. The survivorship NPs receive intensive training in survivorship care and the particular needs of the patient population. They practice in the clinical areas assigned to Continued on page 21

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Survivorship Program Cancer Rehabilitation and Survivorship... Continued from page 18 even the cancer itself.10 Nevertheless, the term chemobrain has increasingly become more publicized, particularly among the breast cancer community.11 Although chemobrain was first identified and named by breast cancer survivors, the same constellation of symptoms also affects other cancer patients.

A typical patient with chemobrain may report some or all of the concerns listed in Table 2.

Chemobrain has been reported to affect up to 75% of cancer patients and is often quite distressful.12 Symptoms persist in 17% to 34% of patients well after treatment has ended.13 Research on treatment options for cancer-related cognitive changes is still in its infancy.

Proposed interventions include various cognitive-behavioral strategies and pharmacologic options, with medications such as methylphenidate and modafinil. These interventions are still undergoing clinical testing and, therefore, should be considered on a case-bycase basis.

At Cedars-Sinai Medical Center, we have begun a 6-week psychoeducational series to provide strategies in coping with the symptoms of chemobrain.

After carefully screening participants

for potentially reversible medical contributors to cognitive dysfunction and neuropsychological testing to identify any objective cognitive impairment, patients may enroll in this program, called Emerging from the Haze. In collaboration with our neuropsychology service, the series provides tools to cope with the common issues that cancer survivors face that are believed to affect cognition. Topics addressed in the program include: • Relaxation techniques • Cognitive strategies for attention, memory, and executive function • Exercise • Sleep hygiene • Nutrition • Cognitive-behavioral therapy • Time management and balancing of life priorities.

We are gathering quality-of-life data to measure the benefit of this program.

Based on initial impressions, the program appears promising.

Conclusions As part of the cancer center’s commitment to treating the whole patient, not just the disease, the Samuel Oschin Comprehensive Cancer Institute at

Table 2 Typical Concerns Reported by Patients with “Chemobrain”

challenge and an opportunity for the oncology rehabilitation community. ●

• Memory lapses • Difficulty concentrating or staying focused on a task • Trouble remembering details such as names, dates, or phone numbers • Difficulty multitasking such as carrying a conversation and following a cooking recipe • Slower processing speeds • Difficulty with word retrieval

References

Cedars-Sinai Medical Center has worked to develop programs with the goal of helping cancer survivors live their lives to the fullest. Rehabilitation is an active process. Whereas chemotherapy, surgery, and radiation are often passive interventions from the perspective of the patient, exercise programs, psychoeducational series, and expressive arts programs are rehabilitation programs that require engagement and responsibility on the patient’s part.

Achieving the capacity to meet the complex rehabilitation needs of a growing population of cancer survivors and identifying the most cost-effective and beneficial programs represents a major

1. American Cancer Society. Cancer Facts & Figures 2010. Atlanta, GA: American Cancer Society; 2010.

2. National Cancer Institute. SEER Cancer Statistics Review, 1975-2006. seer.cancer.gov/csr/1975-2007/index. html. Accessed March 8, 2010.

3. Cole RP, Scialla SJ, Bednarz L. Functional recovery in cancer rehabilitation. Arch Phys Med Rehabil. 2000;81: 623-627.

4. Institute of Medicine. From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, DC: National Academies Press; 2005.

5. Jane H. Art therapy and cancer care. Alternative and Complementary Therapies. 2010;16:140-144.

6. Luzzatto P, Gabriel B. The creative journey: a model for short-term group art therapy with posttreatment cancer patients. Art Therapy: Journal of the American Art Therapy Association. 2000;17:265-269.

7. Campbell J. The Hero with a Thousand Faces. 2nd ed.

Princeton, NJ: Princeton University Press; 1968.

8. Trask PC. Quality of life and emotional distress in advanced prostate cancer survivors undergoing chemotherapy. Health Qual Life Outcomes. 2004;2:37.

9. Oh B, Butow P, Mullan B, et al. Impact of medical qigong on quality of life, fatigue, mood and inflammation in cancer patients: a randomized controlled trial.

Ann Oncol. 2010;21:608-614.

10. Ferguson RJ, Riggs R, Ahles T, Saykin AJ. Management of chemotherapy-related cognitive dysfunction. In: Feuerstein M, ed. Handbook of Cancer Survivorship. New York: Springer; 2006.

11. Hurria A, Somlo G, Ahles T. Renaming “chemobrain.” Cancer Invest. 2007;25:373-377.

12. Vardy J, Wong K, Yi QL, et al. Assessing cognitive function in cancer patients. Support Care Cancer.

2006;14:1111-1118.

13. Ahles TA, Saykin AJ. Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer. 2007;7:192-201.

A Model of Survivorship Care... Continued from page 20 the disease management teams, reinforcing the notion to both referring physicians and patients that the survivorship NP is an extension of overall cancer care. At the independent NP visit, the essential components of survivorship care, as outlined in the Table (page 14), are discussed. The NP prepares and reviews a survivorship care plan with the patient and provides the patient with a copy. A copy is also sent to the patient’s primary care provider along with the current visit note identifying any concerns and clarifying the NP’s role as a provider. Each time the patient is seen, a copy of the visit note is sent to the primary provider. Routine interdisciplinary referrals are made to both institutional and external resources, which may include nutritionists, wound and ostomy nurses, sexual health clinicians, fertility specialists, clinical geneticists, rehabilitation medicine services, dermatologists, integrative medicine programs, mental health workers, smoking cessation counselors, and cancer screening programs.

Each survivorship clinic began as a pilot program with simple metrics of feasibility, sustainability, and satisfaction identified for evaluation. Ongoing monitoring includes physician transfer of eligible patients, patient agreement to move to a new NP provider and

educational initiatives regarding survivorship care and late treatment effects have been expanded for patients and families, MSKCC clinicians, and community providers. A webpage, called Living Beyond Cancer (www.mskcc.org/ mskcc/html/58022.cfm) provides resources for patients and professionals.

reschedule follow-up appointments, and administrative support with space and other resources. Each pilot program was evaluated at the end of 1 year, and a determination made about its success prior to making it a permanent part of hospital operations. To date, there are eight NPs delivering disease-specific survivorship care to the following cancer populations: breast (three NPs), colorectal, thoracic, urology, bone marrow transplant, and radiation oncology (prostate).

In 2009, the NPs collectively saw more than 6000 survivors and had a greater than 90% average rescheduling rate, significant measures of referring physician and patient satisfaction.

A case study of a colorectal cancer survivor in the MSKCC program further demonstrates the role of the survivorship NP (sidebar, page 20).

In 2009, the NPs collectively saw more than 6000 survivors and had a greater than 90% average rescheduling rate, significant measures of referring physician and patient satisfaction.

Summary The survivorship program at MSKCC is committed to the expansion of survivorship research and education as well as clinical care. The survivorship clinics have served as platforms for clinical research as each patient visit creates data on posttreatment outcomes. A growth in the center’s survivorship research community, with increased funding and individual studies, has been an additional outcome of the program. In addition,

MSKCC has benefited from funding and collaboration with the Lance Armstrong Foundation and is designated as a LIVESTRONG Center of Excellence. This funding has, in particular, supported an investment in various New York City community cancer survivorship programs for the underserved.

Care of cancer survivors has advanced in recent years, largely in response to demands of patient advocates in pursuit of a better quality of life after cancer

treatment. The growing need to address patient concerns as well as the sheer number of survivors in the healthcare system has created an opportunity for development of creative care-delivery strategies. The MSKCC program has standardized follow-up care for populations of cancer survivors to address patient needs systematically. The use of specially trained advanced practice nurses as providers has maximized the institution’s dual goals of improving quality of care and providing more efficient, yet comprehensive services. The NP-led clinics have demonstrated that instituting a formal survivorship plan of care and using the unique skills of NPs can be an effective means of helping patients to achieve maximal recovery with the necessary tools for long-term survival. ● References

GREEN HILL HEALTHCARE COMMUNICATIONS

1. Institute of Medicine. From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, DC: National Academies Press; 2005.

2. Kattlove H, Winn RJ. Ongoing care of patients after primary treatment for their cancer. CA Cancer J Clin.

2003;53:172-196.

3. Ganz PA, Casillas J, Hahn EE. Ensuring quality care for cancer survivors: implementing the survivorship care plan. Semin Oncol Nurs. 2008;24:208-217.

4. Oeffinger KC, McCabe MS. Models for delivering survivorship care. J Clin Oncol. 2006;24:5117-5124.

5. Earle CC. Failing to plan is planning to fail: improving the quality of care with survivorship care plans. J Clin Oncol. 2006;24:5112-5116.

6. Houlihan NG. Transitioning to cancer survivorship: plans of care. Oncology (Williston Park). 2009;23(8 suppl):42-48.

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Survivorship Program

Bridging the Gaps in Cancer Care: The Development of a Survivorship Program in an Academic Medical Center

By Susan Daubman, RN, BSN1; Theresa Franco, RN, MSN2; and Katherine Gross, RN, MSN3 1 Case Manager, Oncology; 2Executive Director, Cancer Care Service Line; 3Manager, Oncology Clinics, The Nebraska Medical Center, Omaha

W

hen a cancer patient perseveres through the stressors of diagnosis and treatment, there are celebrations and relief. But the journey is far from over. Questions about what lies ahead surface. Moving beyond initial survival from treatment is the next phase of the cancer journey, which presents its own set of challenges. Late effects from chemotherapy and radiation, recurrence, secondary malignancies, and issues related to body image and quality of life are all part of the survivorship spectrum.1 Survivorship programs have emerged to help survivors move past diagnosis and acute treatment and on to the issues that may affect the rest of their life.

Until recently, accurate diagnosis and expertise in treatment were the hallmark of a successful cancer program.

Patients have expected a quality cadre of services that addresses their needs from initial disease presentation through treatment. It was common among cancer professionals to view the trajectory of cancer care through the acute phase of treatment and the requisite follow-up visits to ensure a sustaining cure or deal with ongoing disease-progression issues.

Only recently has the cancer communi-

From left: Theresa Franco, RN, MSN; Katherine Gross, RN, MSN; Susan Daubman, RN, BSN.

ty redefined the spectrum of cancer care to include the needs of the cancer survivor. Long-term and late effects of treatment, ongoing cancer surveillance, general medicine needs, and managing chronic conditions and comorbidities are finally receiving attention, and several models of care have evolved.

This article describes the development of a survivorship program at The Nebraska Medical Center (TNMC).

The initial steps, design components, and implementation process will be dis-

Name: Mary Doe Age: 57 years old Body mass index: 51.4 Diagnosis: Diffuse large B-cell non-Hodgkin lymphoma/stage IV Treatment regimens: R-CHOP ¥ 6 cycles/R-ICE ¥ 2 cycles/Autoperipheral stem-cell transplant Recommendations for future follow-up: Continue surveillance with oncologist Annual physical with primary care physician, eye exam, thyroid, diabetic and cholesterol screening, Pap smear, mammography, flu shot Bone density every 2 years Monthly breast self-exam Screening colonoscopy every 10 years 1-year posttransplant immunizations Nutrition: 1600-calorie diet for weight loss of 15 lb to 30 lb over next 6 months Total fat: 50 grams/Trans fat: 0 Saturated fat: <11 Fiber: 25 to 35 Calcium: 1200 mg Additional nutritional resources: Hy-Vee Dietician and Taste of Home Healthy Cooking website Physical therapy: Home program for improving strength and balance Increase activity using Wii Fit, elliptical machine at exercise center Social work: Arranged to see psychologist regarding grief counseling Figure 1. Sample Survivorship Summary Report and Plan of Care

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cussed in addition to evaluation elements and lessons learned.

The Nebraska Medical Center experience At TNMC the cancer care team embraced the importance of survivorship and mistakenly believed that patient needs were being addressed.

An assessment in 2006 of the components outlined in the Institute of Medicine report From Cancer Patient to Cancer Survivor: Lost in Transition2 revealed that our cancer program was not structured to adequately identify or address cancer patients’ survivorship needs. There was no established survivorship care structure, few assessment tools to assist with long-term effects, no consistent follow-up plan, and, at best, only fragmented education around the importance of survivorship. A medical oncologist and the cancer service line administrator viewed these findings as a call to action to improve our comprehensive approach to quality cancer care. Efforts to develop a survivorship program at TNMC were launched.

The first objective was to develop a greater knowledge base about all the facets of survivorship. A literature search was conducted to understand various models, key elements for inclusion, desired outcomes, and critical success factors. Feedback was solicited from a focus group of posttreatment cancer patients to understand their concerns about long-term care and level of preparation in dealing with survivorship issues. In addition, phone interviews were conducted with other cancer centers to gain understanding on how to build a successful survivorship program.

The examination of the different survivorship care delivery models, coupled

with an opportunity to address some current practice challenges, resulted in the decision to adopt a physician-led model with an internal medicine physician with previous oncology experience at the helm. This individual was hired by the Division of Oncology to lead a multidisciplinary team in a comprehensive assessment, to develop a survivorship plan of care, and spearhead implementation. In addition, the internist would be available to see cancer patients who have other general health needs during acute treatment. This model achieved two objectives: (1) development of a comprehensive survivorship initiative; and (2) dedication of the oncology specialists’ time and expertise to acute treatment issues and planning for newly diagnosed patients.

The components of TNMC survivorship program were identified: • Comprehensive assessment of cancer survivors by a multidisciplinary team • Recommendations that promote a healthy lifestyle that will enhance remaining cancer-free • Establishment of a road map for future cancer surveillance by developing a survivorship report • Mechanism for receipt of routine health maintenance.

The TNMC cancer survivorship program was structured into two distinct practice elements: • The Comprehensive Assessment Survivorship Clinic • The Internal Medicine Survivorship Follow-Up Clinic.

Program design and description The Comprehensive Assessment Survivorship Clinic at TNMC is for survivors who have completed their chemotherapy and/or radiation treatment, and currently includes breast cancer, nonHodgkin lymphoma, and Hodgkin lymphoma patients. This clinic uses a multidisciplinary approach to identify a survivor’s needs and to design strategies to meet these needs. Survivors attend this clinic once for half a day, where they are evaluated by multidisciplinary team members in 30- to 45-minute intervals.

An internist, a nurse, a social worker, a physical therapist, a pharmacist, and a nutritionist are critical participants in the assessment. Other medical specialties and disciplines, such as psychology, are consulted when necessary. At the completion of this assessment, the multidisciplinary team meets to discuss specific recommendations for follow-up care and implementation strategies.

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Survivorship Program Based on team feedback, the physician creates a Survivorship Summary Report and Plan of Care (Figure 1).

This document provides a road map for future survivorship: • Summary of the survivor’s cancer diagnosis and treatment • Recommendations for follow-up of one’s specific cancer diagnosis • Recommendations for follow-up of long-term/late effects of treatment • Recommendations for overall healthcare maintenance • Other relevant referrals and resources.

The Internal Medicine Survivorship Follow-up Clinic at TNMC is designed to implement the Survivorship Summary Report and Plan of Care for individuals who do not have a primary care connection and to provide ongoing general medicine care to patients as requested by the medical oncologists.

ing templates, and patient education materials were designed and developed prior to program initiation to meet various documentation, educational, and research needs. Providing patient navigation through all assessment points, participating in comprehensive care planning, and consistently communicating on all aspects of the process are crucial func-

Only recently has the cancer community redefined the spectrum of cancer care to include the needs of the cancer survivor.

Team composition and roles Identifying key disciplines to assist in developing the model of care and creating the team was instrumental to the survivorship program effort. The role of the internal medicine physician is multifaceted. This provider is the director of the survivorship program and is pivotal in creating the vision, obtaining organizational commitment, leading program design, and designing ongoing evaluation. From a clinical perspective, the internist performs a history and physical examination focusing on the longterm/late effects of cancer treatment and strategies for surveillance, ensures that immunizations are up to date, and identifies other medical conditions, such as hypertension or diabetes, that require attention. The internist then incorporates the findings from the other members of the multidisciplinary team into an individualized survivorship plan of care.

The physician is responsible for collaborating on marketing initiatives to increase awareness among providers and secure patient recruitment through educational offerings, publications, brochure development, and media coverage.

Exploring funding opportunities through grants and administrative avenues are also key responsibilities.

The nurse serves as the survivorship case manager and coordinates many of the patient care activities. An introductory letter, data collection tools, schedul-

GREEN HILL HEALTHCARE COMMUNICATIONS

tions of the nurse to ensure the patient has a satisfying experience.

The social worker assesses the overall psychosocial state of the survivor. The patient is asked to complete the Brief Symptom Inventory 18, which measures psychosocial distress, and the Functional Assessment of Cancer Therapy—General, which measures overall adjustment

and well-being after a cancer diagnosis.3 Responses on these standardized tools are discussed with the survivor and used to identify high-risk areas and guide care planning.

The social worker collaborates with the survivor to explore the support systems and coping strategies used during Continued on page 25

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The result was a state-of-the-art infusion center with 20 recliners in a patientfocused environment that is open to serve patients 7 days a week. The medical staff of 3 physicians and 4 nurses, led by practice administrator Romel Colanta, MD, now delivers a broad array of outpatient oncology services, including chemotherapy, albumin, antiemetic, and iron therapy infusions. Additionally, the infusion center staff provides supportive cancer care services, including therapeutic phlebotomy, antibiotic infusion, and electrolyte replacement. They also provide multidisciplinary infusion services for patients referred to the center by gastroenterologists, neurologists, and infectious disease specialists.

With the high volume of oncology drugs required to treat their patient panel, the medical staff at Colanta had to make the decision as to how they would supply their patients with oncology medications. If they followed the traditional practice of hematology and oncology providers, they would “buy and bill” the

medications, meaning they would have the responsibility of sourcing and purchasing the medications, storing them, preparing and sometimes compounding them for patients, managing the inventory on an ongoing basis, and dealing with a bevy of insurance prior authorization and reimbursement procedures and requirements in order to get paid.

est clinical standards, deliver them just in time for treatment day (thereby eliminating waste), handle all the hassles of insurance prior authorization and reimbursement, and free the center from the challenges of safely storing and dispensing the drugs and the huge, capitalintensive “carry costs” that maintaining such an inventory requires.

“The partnership with OncoMed has enabled us to make better use of our capital.”

—Romel Colanta, MD Practice Administrator Colanta Hematology & Oncology Center

Although buy and bill traditionally had its benefits, including a substantial margin paid by Medicare and other commercial payers, changes that resulted from the Medicare Modernization Act lowered a margin that sometimes paid physicians 40% over the cost of the drug to just 6%.

The Colanta team decided there was a better way. They knew they could outsource the pharmacy function to a pharmacy that was highly specialized in oncology medications. This pharmacy would prepare the drugs under the high-

The outpatient infusion center at Colanta Hematology & Oncology Center comfortably serves patients.

Dr Colanta and his colleagues researched their options and chose OncoMed—The Oncology Pharmacy.

OncoMed is an oncology pharmacy, meaning that its sole business is oncology medications. Its specially trained and certified oncology pharmacists work in a technologically advanced pharmacy built exclusively for oncology pharmaceutical prescription processing and dispensing, including a USP <797>-compliant class 5 clean room. To protect the supply chain and ensure a complete and full drug pedigree, all inventories are purchased directly from pharmaceutical manufacturers. The company’s “just-intime treatment-day” service means that oncologists and hematologists in any state in the nation are guaranteed delivery of medications and all therapyspecific administration supplies within 24 hours of placing the order. Given the Colanta Hematology & Oncology Center’s close proximity to one of OncoMed’s regional oncology pharmacy sites, they were eligible to get same day and even emergency stat dose delivery when needed.

But what also set OncoMed apart from specialty pharmacies that concentrate on more than one class of pharmaceuticals is the OncoMed care management support team’s ability to work with insurers to get the authorizations that the Colanta Hematology & Oncology Center’s patients need. OncoMed’s team includes

patient care navigators and patient reimbursement specialists who have extensive experience working with insurers, oncology drug manufacturers, and medical foundations. These specialists always know where to go to search for needed funding for patients who are banking on that expertise for their recovery.

OncoMed has become a pivotal partner to the Colanta Hematology & Oncology Center by owning the pharmaceutical worry and letting the physicians focus solely on guiding their patients to remission.

We sat down with Dr Colanta and asked him about the new center and its partnership with OncoMed. Why did your infusion center choose to partner with OncoMed? The buy-and-bill model that oncologists have always worked under is no longer viable. Physicians can’t make an office run on a 6% margin. Under buy and bill, the average sales price (ASP) + 6% methodology can very quickly go to ASP + 4%, +2%, or -2% if we run into any obstacles in getting reimbursed. And with expensive drugs like chemotherapy, we cannot take that risk. Plus, OncoMed helps patients get funding for medication even after the patient’s insurer has denied coverage.

In addition to this new center, you now have 2 additional sites in New Jersey. How has the partnership with OncoMed enabled you to successfully launch and grow the center?

When we opened, 90% of what we infused in the clinic was oncolytics. As we have grown, we infuse a far broader array of medications. The backbone of our practice is still chemotherapy, but we have increased our nononcolytic infusions. For patients referred by gastrointestinal practitioners, we infuse infliximab, and for those referred by infectious disease physicians, we provide antibiotic infusions. Some of those drugs are still viable [under buy and bill], but not all. We have been able to devote money that has traditionally gone to purchasing medication and instead expand our services. The partnership with OncoMed has enabled us to make better use of our capital.

Continued on next page

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EVOLUTION IN ONCOLOGY PRACTICE MANAGEMENT™ Continued from from page page 22 24 Continued

How does the medication ordering and fulfillment process work with OncoMed? Having an efficient and focused process in place is very important. We have been able to institute a process where we have someone devoted to being our liaison with OncoMed. When a patient comes in and his or her benefits are precertified, we send the person’s case information to OncoMed, and the drugs are sent to us directly, along with all the administration supplies. We get them on a next-day basis, or sooner if needed, and everything is clearly labeled with patient-specific information. That makes a huge difference to us when dealing with OncoMed versus some specialty pharmacies that some insurers have imposed upon us to use, which get the drugs wrong, ship them late, and have no idea of the correct administration supplies.

How does the relationship with OncoMed allow you and your team to

focus on what is important?

I will give you a “before-and-after” example. Before we worked with OncoMed, 50% or more of our time was spent on managing drug costs and reimbursement. We had 5 people managing pharmacy at the 3 locations; we have been able to reduce that number of employees to 1. Before, we had to continually make sure that we were not underwater on drugs, as reimbursement rates and times fluctuated. OncoMed has made it possible to not devote time and effort on that.

Based on your experience, what would you say about OncoMed to hematologists and oncologists considering such a move?

It is definitely a relationship that every infusion center or oncologist has to explore. When dealing with narrowing reimbursement margins and delayed reimbursement, ultimately it will be beneficial to switch to OncoMed.

Pharmacists filling orders at the OncoMed facility.

THE LEADERSHIP OF ONCOMED – THE ONCOLOGY PHARMACY

Burt Zweigenhaft CEO, OncoMed

Kevin Askari, RPh President and Chief Clinical Pharmacist OncoMed

Ellen Scharaga, RPh Senior Vice President OncoMed

To learn more about OncoMed or to request a presentation, contact OncoMed at 1-877-662-6633, extension 1298 or marketing@oncomed.net, or go to www.oncomed.net.

Survivorship Program Bridging the Gaps in Cancer Care... Continued from page 23 and after treatment. Relationship changes and concerns, including intimacy, are discussed. Re-entry into practical and instrumental roles (eg, parent, spouse, employee) and anxiety regarding return to work, insurance coverage, and finances are explored. The social worker provides feedback on strengths and concerns of the survivor. If needed, a patient is referred for counseling or psychological intervention.

The relationship between diet and cancer recurrence is still evolving, but studies have shown that reducing fat by choosing leans meats and avoiding highfat and caloric foods, increasing intake of fruits and vegetables, and maintaining healthy body weight play a role in cancer prevention.4 The nutritionist re views the patient’s current diet and outlines methods to incorporate healthy eating. The survivor is counseled on dietary changes that can reduce the risk of chronic diseases, such as heart disease

and diabetes. A plan for weight management is another critical area, and advice is given on increasing, maintaining, or losing weight safely.

Patients often have numerous dietand supplement-related questions. The volume of information available to patients from many sources can make it difficult to discern scientifically based information from testimonials and fads.

The nutritionist assists with evaluating claims and products that promote cancer prevention or recurrence. The patient is given reputable sources and association contacts that provide accurate information on a variety of dietary claims.

The oncology pharmacist is a key member of the survivorship team. The pharmacist reviews past courses of therapy and provides a comprehensive list and cumulative doses of all chemotherapy the patient has received. Because antineoplastic agents administered during treatment can result in a wide range

GREEN HILL HEALTHCARE COMMUNICATIONS NO. 2

of toxicities, contributing to long-term side effects for the survivor, it is imperative to review this information.5 The pharmacist assesses all current medications, both prescription and over-the-counter products, that the patient is taking. It is important that herbal supplements and any home remedies be part of this comprehensive review. This assists in determining any potential drug–drug interactions that can occur with these seemingly harmless interventions and ensure maximum benefit from the medication regimen.

The physical therapist takes an active role in evaluating current physical state and outlining a program for optimal functioning. The therapist focuses on the overall level of physical activity and fatigue, bone health, and, when indicated, neuropathy and lymphedema management. The ability to perform daily activities and endurance are assessed.

Special instructions that range from spe-

cific exercises to a structured walking program may be delivered.

Maintaining bone health, especially in breast cancer and lymphoma survivors, requires use of bone density scans, ordered by the physician, to identify the presence of osteoporosis and osteopenia.6 If either of these conditions are present, weight-bearing exercises will be recommended by the physical therapist. All survivors are given information on ways to maintain healthy bones.

The physical therapist also assesses lymphedema and neuropathy. Individuals at risk for lymphedema are educated by the physical therapist on precautions and self-care techniques to reduce the risk. Those with symptoms are taught appropriate interventions, such as proper skin care, self-massage, and correct compression. Neuropathy assessments are performed based on specific regimens or patient symptoms.

Continued on page 32

SEpTEMbER 2010 I VOL 3, NO 6

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Models of Care

Resolving the Impending Supply-Demand Imbalance in Cancer Survivorship Care: A Need for New Models Craig A. Bunnell, MD, MPH, MBA1; Lawrence N. Shulman, MD2 1 Assistant Professor, Associate Chief Medical Officer; 2Associate Professor, Chief Medical Officer, Dana-Farber Cancer Institute, Boston

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Physician and infusion visits per patient per year during first year of therapy

he future of cancer care is about to confront the laws of supply and demand—and the outcome remains uncertain. Although cancer incidence rates have fallen modestly over the past 15 years, the absolute number of people diagnosed with invasive cancer has continued to increase, owing largely to a growing population and its aging demographic. At the same time, early detection and improved therapies have resulted in declining mortality rates, leaving the absolute number of patients dying of cancer essentially unchanged, and the number of survivors increasing.

Based on these trends, it is estimated that the number of living Americans with a history of cancer will increase by nearly 60%, from 11.4 million in 2005 to 18.2 million in 2020.1,2 Compounding the demands of this increasing number of cancer patients and survivors is the growing intensity and complexity of cancer care. Even previously worrisome estimates of the future projected number of cancer visits have failed to account for this increasing complexity, perhaps because these trends are difficult to predict and the data are not routinely collected or reported.2,3 The Dana-Farber Cancer Institute tracked these data and determined that from 2001 to 2009, the average number of physician visits per patient per year rose 28% during the first year of treatment and the number of infusion visits per patient during the first year of therapy increased by 147% [Lawrence N. Shulman, MD, personal communication, June 2010] (Figure). Given that ear-

14

Physician visits

12

Infusion visits

Craig A. Bunnell, MD, MPH, MBA

The expectation that ongoing follow-up care for cancer survivors might be transitioned to primary care physicians, allowing oncologists to care for patients undergoing active therapy, is grossly unrealistic. lier predictions that do not account for this increased complexity or intensity of care estimate an increase of more than 50% in the number of visits to medical oncologists by 2020, it seems likely that they underestimate future demand.

Shortage of oncologists predicted Exacerbating the growing imbalance of demand is the impending diminished relative supply of medical oncologists to provide necessary cancer care. A study conducted by the Association of American Medical Colleges predicts a critical shortage of oncologists to care for patients within the next decade.4 Given that this estimate also did not account for

10

the increasing complexity of oncologic care, it seems likely that the impending shortage will be realized earlier than expected. The expectation that ongoing follow-up care for cancer survivors might be transitioned to primary care physicians, allowing oncologists to care for patients undergoing active therapy, is grossly unrealistic. Much has been written about the current crisis in supply of primary care physicians and how the increasing demands and diminishing reimbursements are driving US medical students away from careers in family practice and internal medicine.5 Further, with US medical schools currently maintaining a near-zero growth rate in medical graduates, no coordinated strategy exists that is likely to produce a future supply of oncologists or primary care physicians sufficient to meet the needs of future cancer patients.6 Clearly, services currently provided by physicians will need to be provided by nonphysicians.7

8 6 4 2 0 01 20

02 20

03 20

04 20

05 20

06 20

07 20

08 20

Year Adapted with permission from Dana-Farber Cancer Institute.

Figure. Physician and Infusion Visits per Patient per Year During First Year of Therapy from 2001-2009

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Lawrence N. Shulman, MD

September 2010 I VOL 3, NO 6

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Innovative models of care needed Novel, innovative models of care will need to be explored.8 Several cancer centers and practices are developing collaborative models of care using “physician extenders,” such as nurse practitioners, physician assistants, and clinical nurse specialists. Partnering with these extenders allows physicians to care for new patients and those with complex medical needs, while the extenders follow patients in treatment and provide survivorship care. Indeed in some centers, advanced practice nurses and physi-

cian assistants see patients independently and bill for their services.

Such collaborative models are also being explored in survivorship clinics to assist in the transition from active treatment to follow-up care. Other areas of medicine, such as diabetes and cardiac care, have already explored such models.

In these scenarios, patients meet with the extenders at the end of active treatment to receive a formal end-of-treatment summary and evidence-based follow-up care plan. These follow-up plans facilitate the transition from the oncologist to the primary care physician or to the longitudinal survivorship clinic and serve as a mechanism for the patient and the primary care provider to identify relevant issues and provide guidance regarding the appropriate follow-up for the patient’s specific cancer, its treatment, and the attendant medical risks.

These and additional efforts to educate primary care physicians and primary care physician extenders about survivorship issues, and to cultivate relationships with primary care clinicians who have an interest in survivorship care, will also be critical to address the knowledge and coordination deficiencies accompanying the transition from active cancer treatment to ongoing follow-up. These efforts must eliminate duplicative care, increase efficiency, and maintain or improve medical outcomes. Only with forethought and the development of new and creative models of care, can we hope to provide for the needs and demands of future cancer patients. It will be critical, however, that these models be studied in a scientific manner to ensure that they accomplish their intended objectives. ● References 1. American Cancer Society. Cancer Facts & Figures 2010. Atlanta, GA: American Cancer Society; 2010.

2. Warren JL, Mariotto AB, Meekins A, et al. Current and future utilization of services from medical oncologists. J Clin Oncol. 2008;26:3242-3247.

3. Cooper RA. The medical oncology workforce: an economic and demographic assessment of the demand for medical oncologists and hematologist-oncologists to serve the adult population to the year 2020. November 2008. www.asco.org/ASCO/Downloads/Cancer%20 Research/Medical%20Oncology%20Workforce-Cooper %20Study.pdf. Accessed August 17, 2010.

4. Erikson C, Salsberg E, Forte G, et al. Future supply and demand for oncologists: challenges to assuring access to oncology services. J Oncol Pract. 2007;3:79-86.

5. Bodenheimer T. Primary care—will it survive? N Engl J Med. 2006;355:861-864.

6. Salsberg E, Grover A. Physician workforce shortages: implications and issues for academic health centers and policymakers. Acad Med. 2006;81:782-787.

7. Whitcomb ME. The shortage of physicians and the future role of nurses. Acad Med. 2006;81:779-780.

8. Shulman LN, Jacobs LA, Greenfield S, et al. Cancer care and cancer survivorship care in the United States: will we be able to care for these patients in the future? J Oncol Pract. 2009;5:119-123.

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Chronic Lymphocytic Leukemia The Essentials of Patient Care LOG ON TODAY TO PARTICIPATE www.coexm.com/ace02.asp Release Date: April 29, 2010 Expiration Date: April 28, 2011

TARGET AUDIENCE This activity is intended for hematologists, oncologists and others who are involved with the care of patients with Chronic Lymphocytic Leukemia (CLL).

STATEMENT OF NEED CLL is the most common type of leukemia in the United States, with over 15,000 new cases per year, characterized by the accumulation of monoclonal B cells in the bone marrow, peripheral blood, and lymphoid tissue. Primarily a disease of the elderly, the median survival for CLL varies substantially: many patients survive more than 10 years after diagnosis, but a subset of symptomatic patients have shorter life expectancies—in the range of 1.5 to 6 years. The clinical/research body of knowledge in CLL is rapidly changing and represents a challenge for the whole treatment team.

FACULTY Neil E. Kay, MD Professor Department of Medicine Mayo Clinic Rochester, Minnesota

Michael Keating, MD Course Chair Professor of Medicine Deputy Department Chairman Department of Leukemia M.D. Anderson Cancer Center Houston, Texas

EDUCATIONAL OBJECTIVES On completion of this activity, participants should be able to: • List the essential steps in diagnosis and treatment planning of the CLL patient • Select CLL treatment regimens based on patient characteristics • Define data supporting the benefit/risk ratio of upfront, relapsed, and refractory CLL setting • Define strategies to manage fludarabine-resistant CLL • Describe emerging therapies in CLL

This activity is supported by an educational grant from Genentech BioOncology and Biogen Idec.

This activity has been approved for 1.5 AMA PRA Category 1 Credits™.

For further information and to participate, please go to: www.coexm.com/ace02.asp

In collaboration with

TON_Sept 2010_steph_v4_TON 9/14/10 4:30 PM Page 28

Clinical challenge: Identification of patients with lower-risk MDS* and a poor prognosis Approximately two-thirds of patients with myelodysplastic syndromes (MDS) have lowerrisk disease, defined as Low- and Intermediate-1–risk per IPSS.* However, existing prognostic tools for MDS do not differentiate those patients with lower-risk disease who have a poor prognosis.1

The International Prognostic Scoring System (IPSS) The IPSS helps to estimate the overall survival of patients with MDS. Certain patients classified with lower-risk MDS by the IPSS system may benefit from the “wait and watch” approach currently used by many physicians. However, one limitation of the IPSS is that it does not identify patients with lower-risk MDS and poor prognosis who may be candidates for early therapeutic intervention.

A proposed prognostic scoring system for patients with lower-risk MDS This scoring system stratified patients with lower-risk MDS into 3 risk categories and evaluated the characteristics associated with survival.1 Following a multivariate analysis, the parameters below were found to be associated with decreased survival1: • Platelets (<50 x 109/L; 50–200 x 109/L) • Age (≥60 years) • Unfavorable cytogenetics† • Hemoglobin (<10 g/dL) • Percent of marrow blasts (≥4%–10%) The authors recommend the validation of this model by confirming the results in another patient population. Until these results are validated, the main use of this model will be to assign patients with poor prognoses to investigational clinical trials.1

Utility of proposed scoring system This scoring system may help to identify those patients with lower-risk MDS who may benefit from early therapy. Using this system, the authors determined that of the 673 patients in Risk Categories 2 and 3, 80% had a poor prognosis if untreated. They believed that the need to treat this population was further supported by the number of patients who died (90%) before their disease transformed to acute myelogenous leukemia.1 Results from 856 patients showed 31% of patients with a median survival of 14.2 months (1.2 years) (Risk Category 3), 48% with a median survival of 26.6 months (2.2 years) (Risk Category 2), and 21% with a median survival of 80.3 months (6.7 years) (Risk Category 1).1‡

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Estimated Survival of Lower-risk MDS Patients by Risk Category1

Assigned Score‡ 0-2 3-4 ≥5

Cumulative Proportion Alive

1.0

Survival Total (%) Dead (No.) Median (mo) 4-yr (%) 182 (21) 408 (48) 265 (31)

43 212 173

80 27 14

65 33 7

0.8 0.6 0.4 0.2 0 0

12

24

36

48

60

72

84

96

Months from Referral Reprinted with permission from Garcia-Manero et al (2008).1

This study indicated that it is possible to identify those lower-risk MDS patients with a poor prognosis (those in Risk Categories 2 and 3) who may benefit from early therapeutic intervention. The proposed prognostic tool based on the IPSS classification of this specific patient type may have a significant impact on1: • MDS treatment approaches • When to treat lower-risk MDS • Clinical trial development

This proposed model may have implications for clinical trial design and potentially for the treatment decision process for patients with lower-risk MDS.1

*MDS, myelodysplastic syndromes; lower-risk MDS, Low- and Intermediate-1–risk per International Prognostic Scoring System. † In this scoring system, only diploid and 5q were considered favorable cytogenetics; all others were considered unfavorable.1 ‡ Category scoring based on: Category 1 = score 0-2, Category 2 = score 3-4, Category 3 = ≥5. Assigned score: age (≥60 years) = 2; platelets (<50 x 109/L) = 2, platelets (50–200 x 109/L) = 1; hemoglobin (<10 g/dL) = 1; bone marrow blasts (≥4%–10%) = 1; unfavorable cytogenetics = 1.1 Reference: 1. Garcia-Manero G, Shan J, Faderl S, et al. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia. 2008;22(3):538-543.

©2010 Celgene Corporation

07/10

CELG10172T

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Survivorship Program

Developing a Psychosocial-focused Survivorship Program in a Community Cancer Center Scott D. Siegel, PhD, Cindy Waddington, RN, MSN, AOCN Helen F. Graham Cancer Center, Christiana Care Health System, Newark, Delaware

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his article describes a psychosocial model of survivorship developed at the Helen F. Graham Cancer Center (HFGCC) in Newark, Delaware. We developed this survivorship program to better address the needs of our patients as they transition to life after treatment. The sections that follow will provide an overview of our cancer center, the process through which we developed our program and why we chose to adopt a psychosocial model, the nuts and bolts of the program, and a brief review of some preliminary outcomes. We also consider future directions, both in terms of our specific survivorship program and with regard to the larger, national conversation about survivorship.

The Helen F. Graham Cancer Center HFGCC at Christiana Care is a 184,000-square-foot facility located in northern Delaware, approximately 40 miles southwest of Philadelphia.

HFGCC treats more than 3200 new cancer cases annually, providing care to patients from all of Delaware and parts of Pennsylvania, New Jersey, and Maryland. In 2007 HFGCC was selected to be one of 16 community hospitals in the National Cancer Institute Community Cancer Centers Program (NCCCP) pilot, a program that recently expanded to 30 hospitals.1 The primary goals of the NCCCP include: expanding clinical trials in the community setting, particularly among underserved populations; reducing cancer healthcare disparities; improving the collection and storage of biospecimens; and exploring the utility of a national database of electronic health records. In addition to these primary goals, NCCCP’s secondary goals include improving survivorship and palliative care initiatives.

Participation in the NCCCP significantly bolstered our survivorship program.

Developing the survivorship program Prompted in part by the 2005 Institute of Medicine (IOM) report, From Cancer Patient to Cancer Survivor: Lost in Transition,2 we set out to develop a survivorship program that met IOM recommendations and maintained a

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September 2010 I VOL 3, NO 6

survivor-centered philosophy. As a first step, we completed a baseline assessment to identify our strengths and areas for growth. We sought direction from the literature, input from the medical staff, and feedback from survivors through the use of self-report surveys and qualitative research. The results of our baseline assessment revealed that we most needed to address the life-aftertreatment phase of the continuum of care. Specifically, it was clear that our private physician practices provided quality follow-up medical care, but there was little infrastructure in place to connect survivors with our support services posttreatment. Finally, our survivors’ chief posttreatment needs were multidisciplinary and largely psychosocial in nature. Informed by these findings, we developed a psychosocial-focused Survivorship Multidisciplinary Center (MDC) that is offered to survivors on the conclusion of active treatment.

We have virtually eliminated the “doorknob phenomenon” in which a patient waits until the very end of an appointment to express a core concern.

Nuts and bolts Survivors are referred to our Survivorship MDC through one of a few mechanisms: self-referral (we advertise our program through brochures available throughout the cancer center), physician referral, or through our screening program. Currently, we screen survivors about 1 month after completion of treatment for a range of physical and psychosocial unmet needs. Survivors who express multiple or complicated needs are referred to the Survivorship MDC. Most survivors who participate in our Survivorship MDC attend both initial and follow-up appointments.

At the initial appointment, about 1 hour in length, we introduce each survivor to all the members of the MDC team, which includes a health psychologist, an oncology clinical nurse specialist, a holistic nurse certified by the American Holistic Nurses Association,

and a licensed clinical social worker. We then orient the survivor to the format of the initial appointment, which consists of two phases. In the first phase, we ask the survivor to tell his or her story. For most survivors, this is the first opportunity to reflect on the typically fast-paced and difficult period of time that started at diagnosis and continued to the end of treatment. It is not unusual for a survivor to become emotional while describing challenges, changes, and accomplishments. In fact, as a team, we pay a lot of attention to strong affect, because it usually guides us when making decisions about where to focus. For instance, it is not unusual for a survivor to come into our meeting presenting with one concern, but over the course of storytelling, to reveal several other more affectively charged concerns.

Emphasizing the story over the traditional taking of the patient history is one example of our decidedly nonmedical approach. Although taking 20 to 30 minutes to hear a survivor describe his or her chief complaint(s) may seem inefficient, we have learned that the opposite is true. It is not unusual, for instance, to hear from a survivor that he or she has sought help from multiple other providers without ever being asked about some core concern (eg, depression or pain). We have also virtually eliminated the “doorknob phenomenon” in which a patient waits until the very end of an appointment to express a core concern.

After a survivor completes his or her story, we begin to pivot to the second phase of the appointment, in which we gather more information, provide feedback to the patient, and document the treatment plan. The health psychologist may ask additional questions about psychiatric history, social history, and psychiatric symptoms. The oncology clinical nurse specialist pays particular attention to long-term and late side effects of treatment and other medical issues, including weight management, increasing physical activity, menopausal symptoms, nutrition, and smoking cessation. Our holistic nurse, who is also a massage practitioner and certified yoga instructor, often assesses the survivor’s interest in complementary medicine.

Then, the licensed clinical social worker listens for needs that may be met by community and government agencies, in addition to providing supportive counseling.

After gathering any additional necessary information, our team typically provides some brief education to the survivor (eg, expected recovery time from radiation treatment). The education can be useful in its own right, and it often helps to normalize the survivor’s experience, as it is not unusual that we hear a survivor ask some version of, “Oh, so I’m not the only one?”

Finally, we begin to work with the survivor to develop specific and realistic goals to help address self-identified concerns. These goals may include referrals to additional healthcare providers, such as a registered dietitian, counselor, psychiatrist, or wellness coach (all available either within our cancer center or on our medical campus). Given the survivor’s concerns and interests, we may also review specific evidence-based wellness and stress-management practices, such as establishing good sleep hygiene, learning diaphragmatic breathing and meditation, or developing a journaling practice. We conclude the intial visit by providing informational handouts, referral information, and scheduling the follow-up visit.

At the follow-up visit, usually scheduled for 6 weeks after the initial appointment, we check in with the survivor to assess for progress. In most cases, we see improvement. When we do, we usually offer our support and encouragement, and inquire about other unmet needs. In the few cases that show little or no improvement, we use our time as a “back to the drawing board” appointment.

Sometimes the treatment plan and goals we developed in the initial session were not adequate to meet the survivor’s needs. Other times, the survivor’s circumstances have changed, thus requiring a new approach. For survivors who need further help, we offer to schedule additional follow-up appointments as needed.

Preliminary outcomes To date, 90 survivors have participated in our Survivorship MDC. In reviewing the demographic descriptive statistics, our average participant is a white woman in her 50s with a history of breast cancer. Overall, there are significant disparities in gender, ethnicity, and tumor site—these statistics highlight the need to provide better access to men, to survivors of cancers other than breast cancer, and to ethnic minorities. All the survivors participat-

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Survivorship Program ing in the Survivorship MDC complete a validated, self-report measure of physical and psychosocial quality of life. In summary, the chief concerns among our survivors are fear of recurrence, general anxiety, fatigue and sleep changes, and pain.

our Survivorship MDC), and complete a treatment summary and care plan. It is also our hope that instead of relying on survivors to seek out our services, as we have in the past, our new navigator will be better able to reach out to underserved populations and reduce the disparities we reported.

Second, we hope to concentrate further on survivors’ fear of recurrence. We

Fear of recurrence can persist unabated for many years after treatment has concluded. Achieving better understanding of and ways of treating fear of recurrence is one of our future goals.

At the follow-up Survivorship MDC appointment, survivors repeat the same quality-of-life assessment. From the start, we acknowledge that our survivorship program is not a randomized, controlled trial and that we cannot conclude that any observed changes in quality of life are a result of participating in the Survivorship MDC. That said, we have found statistically significant improvements in overall quality of life, fatigue, sleep, general anxiety, and depression.

These changes may be the result of the passage of time and general recovery, participating in the Survivorship MDC, other factors, or some combination. We do not, however, find any statistically significant improvement in reported fear of recurrence. This is particularly noteworthy because fear of recurrence represents our survivors’ top concern, and neither the passage of time nor participating in our Survivorship MDC appears to help alleviate this concern. This finding is also consistent with reports in the literature, which document that fear of recurrence can persist unabated for many years after treatment has concluded.

Achieving better understanding of and ways of treating fear of recurrence is one of our future goals.

Future directions Looking ahead within our program, we have chosen to focus on two areas for the immediate future. First, we were recently awarded grant support from the NCCCP to fund a new full-time survivorship nurse navigator. Our new navigator will focus on building relationships with our survivors as they are completing treatment and providing education about the possible challenges associated with making the transition to life after treatment. The navigator will follow up with survivors after treatment has concluded to screen for unmet medical and psychosocial needs, making the appropriate referrals as indicated (including to

GREEN HILL HEALTHCARE COMMUNICATIONS

chose to make this a priority because fear of recurrence is the most frequently cited top concern of our survivors, fear of recurrence does not tend to improve over time,3 and currently there is no evidence-based treatment for fear of recurrence. Therefore, as a first step we have decided to develop an independent line of translational research to better understand fear of recurrence. In the

longer term, after we have had the opportunity to further refine our program, our goal is to evaluate the effectiveness of our Survivorship MDC in a randomized, controlled trial.

Looking forward at the national level, cancer survivorship is in many ways a frontier. With the ongoing development of different models of survivorContinued on page 32

CEU’s for PHARMACISTS at MOUNT SINAI ONCOLOGY MEETING

CHEMOTHERAPY FOUNDATION SYMPOSIUM INNOVATIVE CANCER THERAPY FOR TOMORROW ® November 9-13, 2010 Marriott Marquis, New York City

Tuesday, November 9

PEDIATRIC ONCOLOGY Wednesday-Friday, November 10-12

INNOVATIVE CANCER THERAPY FOR TOMORROW Practical Applications For The Clinical Oncologist New Agents, Clinical Trials and Emerging Therapies Saturday, November 13

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SEpTEMbER 2010 I VOL 3, NO 6

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Survivorship Program Bridging the Gaps in Cancer Care... Continued from page 25 Any patient who would benefit from further physical therapy interventions is scheduled for follow-up.

Survey Results Percent at “Very Good” rating

May 2007 - May 2008

Visit completion Upon completion of each team member’s assessment, a group session is held to share data and create a comprehensive survivorship plan for the patient. Recommendations are discussed with the survivor and summarized in a written document. A copy of this report is given to the survivor, the referring oncologist, and, if identified, the patient’s primary care provider to facilitate individualized follow-up care.

Outcomes To ensure ongoing success of the survivorship program, outcomes are tracked.

Patient and team satisfaction, financial results, and program volumes are trended and shared with the multidisciplinary team and the cancer service line administrator to evaluate current functioning and identify opportunities for improvement. A patient survey was developed to gather feedback on program elements, clinic flow, and team member functioning. Surveys are mailed 1 week after the visit. Initial results, outlined in Figure 2, revealed a high level of satisfaction with the program as evidenced by greater than 80% of participants rating many elements as “very good.” There were, however, opportunities for improvement.

Program improvements Areas identified for improvement included reducing the length of time in the assessment clinic, the wait between seeing team members, and the time

100 80 60 40 20 0

Continued from page 31

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4

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ship programs across the country, there is as yet no gold standard for addressing survivorship—and it is unlikely, we believe, that there will ever be a one-size-fits-all model.4 For instance, cancer centers in rural versus urban communities will most likely need to reach their survivors via different avenues. Furthermore, whether cancer centers first address surveillance, follow-up medical care, or psychosocial aspects of survivorship depends on resources available at the cancer center and in the surrounding community.

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10. Overall rating of care received during your visit 11. Length of the clinic visit 12. Is there anything specific you would like to see added to the clinic?

13. Did you find the Survivorship Summary Report and Plan of Care helpful?

14. Would you like to have education offerings during the breaks/lunch hour?

Figure 2. Comprehensive Assessment Survivorship Clinic Survey Results

Our responsibility to cancer patients does not required to complete the social work vivors to network with other survivors tools. There were requests for both formal while receiving an array of amenities, end with the conclusion of educational offerings and informal net- including massages, facials, make-up their treatment. working sessions. There were also suggestions for including other services.

Improvements that have been implemented focused on timely notification of patient readiness between interviews to decrease wait times between providers and distributing the inventory document upon arrival so it can be scored before the social worker assessment. An educational series on survivorship topics, development of a support group, the addition of massage therapy at the clinic location, and the hosting of a spa night have been added. The spa night is designed for sur-

Lessons learned

Next steps

Doing the necessary homework/obtaining consistent feedback from patients created a structure to truly meet their needs

Continue with refinement of outcome measures

Securing a physician champion established early credibility and assisted in gaining both provider and organizational buy-in

Determine areas that require customization for transition to other cancer diagnoses

Consistently communicating and establishing a format for evaluation allowed for timely program revision and increased satisfaction

Develop additional educational materials tailored to survivorship

Beginning with one patient population assisted in refining processes that were transferable to other cancer populations

Explore a variety of funding sources, including grants and philanthropic opportunities

Develop research focus around the tool results, compliance with Creating other offerings that complement the the established treatment plan, program is important to the survivor and identification of the critical success factors Marketing the program is needed to create growth and expand services

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1. Accommodations and comfort for visitors 2. Staff attitude toward your visitors 3. Time team spent with you 4. Concern for your questions and worries 5. How well team kept you informed 6. Friendliness/courtesy of team 7. Skill of team 8. How well staff worked together to care for you 9. Likelihood of your recommending this program to others

Table Lessons Learned and Next Steps

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Developing a Psychosocialfocused Survivorship...

Continue to create visibility of program through publications and educational seminars

applications, aromatherapy, and a light meal. The needs for physical therapy were greater than originally anticipated.

To meet this demand and to accommodate follow-up recommendations, physical therapy services were increased.

The survivorship program has been a successful journey for TNMC. The lessons learned and the next steps in development are listed in the Table.

Although great strides have been made, more will need to be done to ensure that cancer survivors have the knowledge and resources necessary to lead a satisfying life. We hope this review will serve as a guide for those committed to addressing the needs of survivors through the development of a comprehensive survivorship program. ● Acknowledgments The authors extend their appreciation to our team members: Deborah Darrington, MD; Tom Davis, PharmD, BCOP, RPh; Lisa Nichter, RD, LMNT, CDE; Betty Perez, PT, BS, MA, CLT; and Sue Stensland, LCSW. References 1. Jacobs AL, Palmer SC, Schwartz LA, et al. Adult cancer survivorship: evolution, research, and planning care.

CA Cancer J Clin. 2009;59:391-410.

2. Institute of Medicine. From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, DC: National Academies Press; 2005.

3. Peled R, Darmil D, Siboni-Samocha O, ShohamVardi I. Breast cancer, psychological distress and life events among young women. BMC Cancer. 2008;8:245.

4. American Institute Cancer Research. Reduce your cancer risk: diet. www.aicr.org/site/PageServer?page name=reduce_diet_home. Accessed June 30, 2010.

5. Floyd JD, Nguyen DT, Lobins RL, et al. Cardiotoxicity of cancer therapy. J Clin Oncol. 2005;23:7685-7696.

6. Chalasani P, Downey L, Stopeck AT. Caring for the breast cancer survivor: a guide for primary care physicians. Am J Med. 2010;123:489-495.

Where we do see a strong emerging consensus is in the recognition that our responsibility to cancer patients does not end with the conclusion of their treatment. To meet our responsibility of helping patients transition to life after treatment, we believe more attention needs to be given to allocating the appropriate resources for survivorship care, continuing to foster awareness of survivorship in both healthcare providers and cancer survivors, and developing best practices for providing medical and psychosocial care to survivors. ● Disclosure This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.

References 1. Clauser SB, Johnson MR, O’Brien DM, et al.

Improving clinical research and cancer care delivery in community settings: evaluating the NCI community cancer centers program. Implementation Science. 2009;4:63.

2. Institute of Medicine. From Cancer Patient to Cancer Survivor: Lost in Transition. Washington, DC: National Academies Press; 2005.

3. Skaali T, Fossa SD, Bremnes R, et al. Fear of recurrence in long-term testicular cancer survivors. Psychooncology.

2009;18:580-588.

4. Oeffinger KC, McCabe MS. Models for delivering survivorship care. J Clin Oncol. 2006;24:5117-5124.

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TON_Sept 2010_steph_v4_TON 9/15/10 12:21 PM Page 34

Survivorship Resource Guide Survivorship is an ever-evolving concept, as are guidelines for the care of this population. Survivorship can touch on medical, physiological, legal, and financial aspects of life. This list is a sampling of organizations that focus on survivorship, many of which offer links to multiple resources.

Organization

Phone number

Website

American Cancer Society

800.227.2345

www.cancer.org

American Institute of Cancer Research

800.843.8114

www.aicr.org

Association of Cancer Online Resources

212.226.5525

www.acor.org

Association of Oncology Social Work

215.599.6093

www.aosw.org

info@aosw.org

American Society of Clinical Oncology

888.651.3038

www.cancer.net/patient/survivorship

contactus@cancer.net

Camp Mak-a-Dream

406.549.5987

www.campdream.org

camp@montana.com

800.813.HOPE

www.cancercare.org

info@cancercare.org

www.cancerandcareers.org

cancerandcareers@cew.org

CancerCare Cancer and Careers

E-mail

aicrweb@aicr.org

Cancer Support Community (formerly The Wellness Community and Gilda’s Club)

888.793.9355

www.thewellnesscommunity.org

help@cancersupportcommunity.org

Cancer Survivors Unite

267.738.8760

www.cancersurvivorsunite.org

info@CancerSurvivorsUnite.org

Caring Ambassadors Program (CAP) Lung Cancer

503.632.9032

www.lungcancercap.org

cindy.langhorne@lungcancercap.org

Centers for Disease Control and Prevention (CDC) Cancer Survivorship

800.232.4636

www.cdc.gov/cancer/survivorship

cdcinfo@cdc.gov

Children’s Oncology Group’s Cure Search

800.458.6223

www.survivorshipguidelines.org

info@curesearch.org

626.256.HOPE ext. 63829

prc.coh.org

prc@coh.org

Disability Rights Legal Center

866.843.2572

www.disabilityrightslegalcenter.org

clrc@lls.edu

Fertile Hope (a LIVESTRONG initiative)

866.965.7205

www.fertilehope.org/healthcare professionals/index.cfm

First Descents

303.945.2490

www.firstdescents.org

info@firstdescents.org

888.GILDA.4U

www.gildasclub.org

info@gildasclub.org

www.journeyforward.org

info@journeyforward.org

City of Hope Pain & Palliative Care Resource Center

Gilda’s Club Worldwide Journey Forward Lance Armstrong Foundation

877.236.8820

www.livestrong.org

Leukemia & Lymphoma Society

800.955.4572

www.leukemia-lymphoma.org

Lymphoma Research Foundation

800.235.6848 (New York) 800.500.9976 (Los Angeles)

www.lymphoma.org

Memorial Sloan-Kettering Cancer Center

212.639.2000

www.mskcc.org

The Minnie Pearl Cancer Foundation

877.467.1936

www.minniepearl.org

pat@minniepearl.org

800.4.CANCER

dccps.nci.nih.gov/ocs

ncidccpspdrm@mail.nih.gov

National Coalition for Cancer Survivorship

888.650.9127

www.canceradvocacy.org

info@canceradvocacy.org

National Patient Advocate Foundation

202.347.8009

www.npaf.org

action@npaf.org

www.nursingcenter.com/library/ static.asp?pageid=721732

Customerservice@Nursing Center.com

www.thecancerjourney.org

clinical@ons.org

www.planetcancer.org

contactus@planetcancer.org

www.realtimecancer.org

hope@realtimecancer.org

National Cancer Institute Office of Cancer Survivorship

Nursing Center.com’s Prescription for Living Oncology Nursing Society’s The Cancer Journey

866.257.4ONS

Planet Cancer (a LIVESTRONG initiative) Real Time Cancer (Canada)

709.579.7325

Steps for Living

877.735.4673

Testicular Cancer Resource Center

helpline@lymphoma.org

getbusyliving@stepsforliving.org tcrc.acor.org

dougbank@alum.mit.edu info@thesamfund.org

The SAMFund for Young Adult Survivors of Cancer

866.439.9365

www.thesamfund.org

The Wellness Community

888.793.9355

www.thewellnesscommunity.org

888.393.FUND

www.ulmanfund.org

info@ulmanfund.org

818.508.5657

www.vitaloptions.org

info@vitaloptions.org

The Ulman Cancer Fund for Young Adults Vital Options International Working Against Cancer Young Survival Coalition Survivorship blog Pearlman Cancer Center

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www.workingagainstcancer.org/ index.html 877.YSC.1011

help@cancersupportcommunity.org

contactus@workingagainstcancer.org

www.youngsurvival.org

info@youngsurvival.org

Website survivorshipforum.blogspot.com

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CONTINUING EDUCATION CREDITS

Current activities at www.COEXM.com include:

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Survivorship News

Physical Activity to the Fore

By Daniel Denvir

WASHINGTON, DC—The role of physical activity and a healthy lifestyle was at the center of discussion at the 5th Biennial Cancer Survivorship Research Conference. Evidence increasingly points to the importance of exercise and a healthy diet in the years after treatment, and many researchers are currently exploring effective physical activity and weight loss interventions.

Melinda L. Irwin, PhD, MPH, of Yale School of Medicine, New Haven, Connecticut, gave an overview of the state of the research on how a healthy energy balance affects quality of life in survivorship, with lower cancer mortality and morbidity.

“The evidence is growing,” said Irwin, “and it’s pretty suggestive of an association between higher levels of activity and an improved survival.”

She pointed to a number of seminal studies over the past decade, including Calle and colleagues’ 2003 study, which established that obesity affects survival adversely1; and Ibrahim and AlHomaidh’s 2010 meta-analysis, which found a 50% reduction in breast cancer death with 2 to 3 hours per week of moderate physical activity.2 But the implementation of physical activity interventions in clinical care lags behind, Irwin said. “Unfortunately, current cancer therapies do not address the association of lifestyle factors on prognosis and survivorship.”

The Transdisciplinary Research on Energetics and Cancer Centers (TREC),

cers, genes, and other exposures; biomarkers; diverse cancer populations; and collaborations that allow for combined analyses. There is also a need for high-quality randomized clinical trials looking at survival, recurrence, and second primary outcomes; biomarker end points; diverse populations; and recruitment and adherence strategies.

New exercise guidelines There is hope that new exercise guidelines developed by an interdisciplinary team and released in the July 2010 issue Medicine & Science in Sports & Exercise will be a big step in the right direction. Anna L. Schwartz, FNP, PhD, FAAN, of Arizona State University, Phoenix, discussed the new guidelines in a presentation.

“This is the way the future is going to be. We’re going to diagnose people with cancer: ‘sorry, you’ve got Brand X cancer, you’re going to the cancer and exercise club to get part of your care.’”

For most cancer survivors, it is appropriate to follow the protocol laid out for older people in general, as described in the US Department of Health and Human Services’ Physical Activity Guidelines for Americans3: 150 minutes of moderate-intensity or 75 minutes of high-intensity exercise per week; and two to three sessions of resistance exercise per week. Above all, says Schwartz: “Avoid inactivity” and “do whatever you want to do, whatever it is you like to do.”

Schwartz also discussed the new can-

“Current cancer therapies do not address the association of lifestyle factors on prognosis and survivorship.”

—Melinda L. Irwin, PhD, MPH

a National Cancer Institute–funded 10year research initiative on “the biology, genomics, and genetics of energy balance to behavioral, socio-cultural, and environmental influences upon nutrition, physical activity, weight, energetics, and cancer risk” has been at the forefront of measuring such interventions, and Irwin reported a number of findings from TREC’s 2009 conference.

TREC has funded four sites, and six more will be funded in the coming year.

Irwin also pointed out a number of research gaps. There is a need for more cohort studies assessing the relationship between energy balance and prognosis; measured body composition; weight loss/gain and prognosis; subtypes of can-

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cer exercise trainer certification developed by the American College of Sports Medicine and the American Cancer Society.

Physical activity and weight loss interventions Cheryl Rock, PhD, RD, of the University of California, San Diego Medical Center, Moores Cancer Center, reviewed physical activity and weight loss interventions, which can have a positive affect across the board, including with “cardiovascular disease, diabetes, osteoarthritis, and all the other things that plague us as we get older, and certainly are highly prevalent in cancer survivors.”

©iStockphoto.com/kzenon

Unexplained weight loss can be a symptom of recurrence, so survivors sometimes feel apprehensive about slimming down—but many are starting out too heavy in the first place.

“Although it’s true that while going through treatments it’s important to be cognizant of not losing muscle mass and maintaining healthy weight, it’s also true that nowadays, given the higher prevalence of obesity in the United States, many cancer patients when they are diagnosed are actually overweight at that time,” she explained.

Body image issues can even mislead oncologists, she said. “The whole healthcare team has to be engaged in this process: Weight loss doesn’t necessarily mean wasting.”

Kathleen Y. Wolin, ScD, of Wash ington University, St. Louis, Missouri, presented an overview of studies on physical activity and cancer survivorship. Although Wolin was adamant in asserting the importance of exercise, there are still major research gaps to be filled: bone and fracture risk; cardiovascular effects; recurrence and survival end points; and the “dosage” questions—how many hours, how often, at what intensity?

She said that researchers should also focus on more newly prevalent types of exercise, such as the many varieties of yoga. There is also the question of how to make exercise accessible to a diverse group of people, including rural residents with no access to sidewalks or low-income people with less access to gyms. So far, research has largely focused on white and middle class sur-

vivors. Some studies also lack methodological rigor: too many before and after comparisons and nonrandomized trials.

That said, the benefits and low risk of exercise for cancer survivors are clear.

“If you take away nothing else from this presentation, it’s that exercise is safe for people to do during breast cancer treatment,” Wolin concluded.

Other presentations described innovative approaches for increasing physical activity among diverse populations of survivors.

Susan L. Beck, PhD, APRN, FAAN, of the University of Utah College of Nursing, Salt Lake City, and other researchers investigated the “Effect of Resistance Exercise for Older Cancer Survivors” and found “initial support for the feasibility and efficacy of eccentric exercise to improve fatigue and weakness in older adult cancer survivors,” although there was not a demonstrable effect on health status.

The study compared a 12-week eccentric resistance exercise program administered to 40 elderly survivors against a control group. Baseline measures on the General Fatigue Scale, General Weakness Scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF36) were compared with posttest measures. The group undergoing the exercise intervention registered a 0.98 mean change on the General Fatigue Scale, compared with 0.45 for the control group; the experimental group’s mean change on the General Weakness Scale was 1.01, compared with just 0.09 for Continued on page 38

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Survivorship News Physical Activity to the Fore Continued from page 36 the nonexercise group. The researchers call for the study to be expanded in a larger randomized clinical trial.

Kerri Winters-Stone, PhD, and her fellow researchers at the College of Health and Human Sciences, Oregon State University, Corvallis, are undertaking a randomized clinical trial comparing aerobic with resistance exercise in sedentary elderly breast cancer survivors (BCS). Preliminary findings after 3 months “show that short-term, low-intensity exercise of any type may improve endurance, strength, and function in older BCS, but gait speed may be more responsive to aerobic exercise,” although more differences between the exercises may only become clear later in the trial. Seventy-nine women are participating in either resistance, aerobic, or a controlled flexibility exercise group.

Encouraging cancer survivors to exercise and pursue a healthy lifestyle can be a challenge, especially because interventions must be tailored to factors such as age. Researchers Carolyn B. Rabin, PhD, and Bess H. Marcus, PhD, from the Miriam Hospital/Alpert Medical School of Brown University, Providence, Rhode Island, gathered qualitative and quantitative data from 10 young adult survivors (aged 18-39 years) in an effort to adapt a theoretically grounded webbased exercise intervention to their age group. In addition to goal setting, activity logging, tailored feedback, and other features already tested with sedentary adults, researchers considered the addition of a link to cancer survivor–specific exercise information and an online forum where survivors could communicate with one another. Most surveyed survivors rated the proposed additions positively; some suggested adding an “Ask the Expert” feature and more information on nutrition.

When encouraging exercise, is it better to emphasize the pitfalls of a sedentary lifestyle or the joys of fitness? In “The Effects of Framing on Exercise Levels in Colorectal Cancer Survivors,” Isaac M. Lipkus, PhD, and fellow researchers at Duke University, Durham, North Carolina, compared two minimal interventions (a mailed brochure), one with “gain” framing, and another with “loss.” Of the 149 eligible participants recruited from state cancer registries, 137 (92%) early-stage colorectal cancer survivors (6 months to 5 years after diagnosis) completed the 1-month follow-up survey. At baseline, participants engaged in moderate to vigorous exercise an average of 39 minutes per week, which increased to 115 minutes at follow-up. No difference was observed between the two different frames, however; and researchers con-

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cluded that “future research should investigate methods to increase the potency of these interventions to increase further physical activity in this population.”

Melissa F. Miller, PhD, MPH, of the Cancer Support Community’s Research and Training Institute, Washington, DC, looked into the way different factors influenced survivor response to Cancer Transitions, a 6-week program that provides cancer survivors exercise and nutrition support. The study evaluated a pilot program at 10 centers from 2007 to 2008. The program was already known to improve health-related quality of life and physical activity, but it was not known what factors made someone more or less receptive to the program.

The study investigated predictors of physical and emotional functioning and found that “several factors (weight status, program attendance, income, race, and time since treatment) predicted greater response to Cancer Transitions. Research is needed to evaluate the value of targeting and/or

ity and healthy eating can positively influence lifestyle behaviors and quality of life for African-American breast cancer survivors.”

Making physical activity promotion an integral part of follow-up care, rather than something separate or elective, could boost its efficacy. Bernardine M. Pinto, PhD, and fellow researchers at Miriam Hospital/Alpert Medical School of Brown University, Providence, Rhode Island, evaluated the efficacy of Moving Forward with Life, a program that provided oncologists and surgeons with training in giving brief physical activity advice during follow-up visits with BCS. All 192 women received the advice and took part in 12 weeks of telephone counseling. Then, they were randomized into either an extended advice intervention group (based on the Transtheoretical Model and Social-Cognitive Theory) or a brief advice control group. The researchers found that those receiving extended advice were more likely to exercise and increase the number of minutes exercising per week.

“If you take away nothing else from this presentation, it’s that exercise is safe for people to do during breast cancer treatment.”

—Kathleen Y. Wolin, ScD

tailoring healthy lifestyle support programs for cancer survivors.”

Race and culture can also play a role in survivorship care. M. Tish Knobf, PhD, RN, FAAN, AOCN, and fellow researchers at Yale University piloted a 6-week program to encourage healthy lifestyle and physical activity among African-American BCS. A convenience sample of 40 women was recruited from support groups, hospitals, and community outreach. Preliminary data were presented for 30 women measured for empowerment (Self Efficacy for Exercise), functional ability (MOS SF36), quality of life (Functional Assessment of Cancer Therapy-Breast), and healthy lifestyle (Health Promotion Lifestyle Profile II) at baseline, immediate postprogram, and 3 months later.

Improvements were found in quality of life, emotional well-being, health promotion, health responsibility, physical activity, nutrition, and spiritual growth, but not for empowerment or functional ability. The researchers suggest that “a culturally designed psychoeducational intervention focused on physical activ-

Jennifer R. Klemp, PhD, MPH, and fellow researchers at the University of Kansas Medical Center’s Breast Cancer Survivorship Center, Kansas City, presented preliminary evidence suggesting that a 6-month intervention focusing on diet, exercise, and behavioral weight loss in overweight postmenopausal BCS can be effective in reducing weight, achieving favorable biomarker changes, and improving quality of life. Of 84 BCS who had completed chemotherapy at least 3 months before and had a body mass index of 25 to 45, 52 agreed to participate and six did not complete the trial. Participants engaged in 225 minutes a week of moderate-intensity aerobic exercise, light resistance training, a 1200- to 1500-calorie-per-day diet, and group meetings on behavior modification.

The researchers used a number of measures to assess participants at baseline and postintervention, including anthropometrics, body composition (dual x-ray absorptiometry), serum biomarkers (insulin, leptin, and adiponectin), fitness test, and survey

questions on eating habits and quality of life. Preliminary data for 32 of the women showed significant weight loss, positive biomarker change, and improved quality of life.

Fewer studies have been conducted with lung cancer survivors for obvious reasons: the disease still has a high mortality rate and is characterized by shortness of breath and fatigue.

Preliminary findings from a new study show there are significant barriers to recruiting patients for such interventions. In “Feasibility of Implementing a Physical Activity Trial with Sedentary Survivors of Early State, Non–SmallCell Lung Cancer (NSCLC),” Jamie S. Ostroff, PhD, of Memorial SloanKettering Cancer Center, New York, and other researchers recruited 70 sedentary and disease-free survivors between 1 and 10 years after treatment. Participants were separated into a 12-week home-based physical activity program emphasizing walking, upper body and breathing exercises, or a wait-list control group. Of 51 eligible patients, just 28 enrolled. Patients who refused the program were of a similar average age and gender, and cited low motivation for exercise, travel distance to the cancer center, and health concerns. Similarly, in another study, researchers in Denmark found “that patients failed to comply with homebased exercise,” and that supervised exercise was preferable.

Emily Jo Rajotte, MPH, of the Fred Hutchinson Cancer Research Center’s Survivorship Program, Seattle, Wash ington, and other researchers undertook a study of a community-based exercise program. They found significant improvements in fatigue, physical function, musculoskeletal symptoms, mental health, social support, blood pressure, weight, waist circumference, strength, and flexibility. The program resulted in few injuries or lymphedema events, and 70% of participants reported continued exercise 6 months later. Exercise and Thrive was a 10-week group exercise program organized by the YMCA of Greater Seattle, Hutchinson Center’s Survivorship Program, and LIVESTRONG. Of 157 survivors observed, pre- and postsurvey and physiologic data were available for 68% of participants. ● References 1. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348:1625-1638.

2. Ibrahim EM, Al-Homaidh A. Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies. Med Oncol. April 22, 2010. Epub ahead of print.

3. 2008 Physical Activity Guidelines for Americans.

Washington, DC: US Dept of Health and Human Services; October 2008. ODPHP Publication No. U0036.

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value-focused www.ValueBasedCancer.com www.ValueBasedCancer.com

New NewTools ToolsArriving ArrivingtotoMeasure Measureand and NCCN NCCNRoundtable: Roundtable:Clinical Clinicaland and Manage Economic ManageChemotherapy ChemotherapyCare Care EconomicIssues IssuesImpacting Impacting Business, Cancer Business,clinical clinicalconcerns concernsnow nowconnected connectedinin CancerCare CareDelivery Delivery value-focused value-focusedapproach approach ByBy Daniel Denvir Daniel Denvir

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The application youcan’t can’tmanage manage The application ofofthis thisbelief beliefto tothetheoncology oncologysetting setting was of of thethe wasdemonstrated demonstratedat ata session a session Association AssociationofofCommunity CommunityCancer Cancer Cen ters’ 36th Annual National Cen ters’(ACCC) (ACCC) 36th Annual National Meeting.

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WeWe “It“It is is anan important topic, because dying young. important topic, because practice, practice,butbutthey they developed dying this is one of of those things, if we don’t on on clinical efficacy andand without innovations andand a cure,” he said. this is one those things, if we don’t based based clinical efficacy without need need innovations a cure,” he said. getget a handle on it, it’s going to happen regard to to costs.

At At a roundtable held thethe inadequacy of current treata handle on it, it’s going to happen regard costs. a roundtable held ButBut inadequacy of current treatments for cancer is no the the main to to us,” she said.

“People and groups during the NCCN’s 15th Annual us,” she said. “People and groups during the NCCN’s 15th Annual ments for cancer is longer no longer main and organizations areare going to to start Equally challenging, he sugproblem.

Equally challenging, he sugand organizations going start Conference, Conference, moderator moderator Clifford Clifford problem. is finding a means to pay for for dictating how wewe provide cancer care, PhD, Senior Vice President dictating how provide cancer care, Goodman, Goodman, PhD, Senior Vice President gested, gested, is finding a means to pay and we can’t let that happen.” at The Lewin Group, predicted, “The the ever-costlier care that threatens to and we can’t let that happen.” at The Lewin Group, predicted, “The the ever-costlier care that threatens to appropriate use of evidence-based bankrupt the healthcare system.

Continued on page 8 appropriate use of evidence-based bankrupt the healthcare system.

Continued on page 8 guidelines is on a collision course As society struggles to find soluAs society struggles to find soluguidelines is on a collision course with the financial nonsustainability of tions, “the ground is shaking beneath with the financial nonsustainability of tions, “the ground is shaking beneath the healthcare system.” us,” Dr Goodman commented. the healthcare system.” us,” Dr Goodman commented.

Value-Based Value-BasedCancer CancerCare Care will willbebeatatthe theASCO ASCOAnnual Annual Meeting, June 4-8, in Chicago.

Meeting, June 4-8, in Chicago.

Continued on page 19 Continued on page 19

Please visit usus atat booth 18121 Please visit booth 18121

SEER-Medicare SEER-MedicareDatabase DatabaseAnalysis Analysis Confirms Expensive Prostate Confirms Expensive Prostate Breast BreastCancer CancerSurvival SurvivalImproves, Improves, Cancers CancersGaining GainingSupremacy Supremacy Photo by © ASCO/Todd Buchanan 2009 Photo by © ASCO/Todd Buchanan 2009

Thanks ThankstotoNew NewTherapies Therapies

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Breast Cancer Conference (EBCC7).

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This improvement, the researchers By Rosemary Frei, MSc This improvement, the researchers By Rosemary Frei, MSc Barcelona—Survival for patients with suggest, is due to increased use of The 2010 Genitourinary Cancers Barcelona—Survival with anthracyclines suggest, is due to rise increased use of San Francisco, CA—The popularity of The 2010 Progress Genitourinary Cancers metastatic breast cancerfor haspatients improved and the of targeted Symposium: in Multi San Francisco, CA—The metastatic breast has improved anthracyclines and the rise of targeted minimally Symposium: Progresswas in held Multidramatically in the cancer last 20 years, espe- therapies.

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All HER2-positive tumors, according to mab (Herceptin), which targets the radiation therapy (IMRT), and of sions emphasized a multidisciplinarysesradiation therapy (IMRT), and of approach HER2-positive mab gene, (Herceptin), which important targets the brachytherapy sions emphasized a multidisciplinary research presentedtumors, at the 7thaccording European to HER2 is the most to care; a number of them combined with IMRT combined with IMRT research presented at the 7th European HER2 gene, is the most important forbrachytherapy approach to cost care;and a number of them brought out the value issues prostate cancer started to take off Continued on page 27 for 2002, prostate cancer started analysis to take off associated broughtwith out the cost for andgenitourivalue issues Continued on page 27 after caring a new database after 2002, a new database analysis associated with caring for genitourinary cancers. has confirmed. hasthe confirmed. nary cancers.

At American Society of Clinical At the American Society of Can Clinical Oncology’s 2010 Genitourinary - and Women’s Hospital, Harvard Oncology’s 2010Paul Genitourinary Can- Medical and Women’s Hospital, Harvard cers Symposium, L. Nguyen, School, Boston, and his cocerspresented Symposium, Nguyen, Medical School, his cofoundBoston, MIRP and jumped MD, the Paul resultsL. of his investigators MD, analysis presentedof the investigators found MIRP jumped team’s dataresults from of thehis from 1.5% of radical prostatectomies team’s analysis of dataand from from of 28.7% radicalinprostatectomies Surveillance, Epidemiology Endthe (RPs) in 1.5% 2002 to 2005. They Surveillance, Epidemiology and End also(RPs) in 2002 28.7% in 2005.

They Results (SEER)-Medicare database. found that to IMRT soared from also found that IMRT treatments soared from Results (SEER)-Medicare Dr Nguyen, director of database.

Prostate 8.7% of external radiation Dr Nguyen, director of Prostate for 8.7% of external radiation treatments prostate cancer to 81.7%. In addiBrachytherapy, Dana-Farber/Brigham Brachytherapy, Dana-Farber/Brigham for prostate cancer to 81.7%.

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A new publication for your new vocabulary

www.ValueBasedCancer.com

TON_Sept 2010_steph_v4_TON 9/15/10 12:18 PM Page 40

Survivorship News

Putting the Family Back into Family Practice

By Rosemary Frei, MSc

T

he National Cancer Institute (NCI) defines cancer survivors as “people who have been diagnosed with cancer and the people in their lives who are affected by their diagnosis including family members, friends, and caregivers.”

New research is reinforcing the fact that healthcare providers should strive to make families of cancer patients central to all communication with and care surrounding the ill individuals. Unfortunately, however, family caregivers are still largely a peripheral consideration in the management of patients with cancer, and it may take years to reorient the healthcare system accordingly. With the aging of the North American population, this time lag may turn into a crisis, some experts say.

“Who’s going to be left holding the bag when the number of people with cancer doubles in the next 15 years and the stripped-down healthcare system can’t cope? Family, friends, and neighbors,” noted Michelle M. Lobchuk, RN, PhD, an associate professor of nursing at the University of Manitoba in Winnipeg. “I used to be an acute medicine and palliative care nurse, and from that experience I know that families want to be involved [in their loved ones’ care]. You can see it in their eyes; mostly they’re pleading for information on the disease and how to help the patient cope and survive.”

Positive effects of family-based cancer care Another expert in this field, Barbara Given, PhD, RN, associate dean for research at Michigan State University College of Nursing in East Lansing, and her collaborators have been studying the importance of family involvement in oncology care for almost three decades. This information—along with that from other researchers active in the field—is gradually percolating throughout oncology.

Some of their most recent research demonstrates that caregivers are sensitive to patient symptoms but suggests that they can use help in improving their accuracy in gauging symptom severity (Chronic Illn. 2010;6:46-56).

Her team has also demonstrated that nurse-delivered, over-the-telephone coping and communication support for aging patients with advanced cancer and their family members can significantly impact cancer outcomes (Cancer Nurs. 2009;32:193-202).

Their research indicates that a good, attentive family member responding to a treatment-related adverse event can affect the clinical outcomes for the

40

September 2010 I VOL 3, NO 6

patient. For example, if an infection isn’t noticed for 3 to 4 days, it can be life-threatening rather than something that could have been managed simply by administering antibiotics. “I think physicians are beginning to recognize that, and to understand that it’s good for their [performance based on] clinical outcome indicators used to measure quality of care,” Given said. “It’s also good for the patients because it improves their survival and reduces their burden of illness, and it’s good for the family because it means they do not [have to cope with the patient’s] unnecessary symptoms and problems.”

She points to the NCI’s new web page on family caregivers in cancer— which calls them “the foundation of the health care system in the United States”—as evidence that her research and that undertaken by others is making an impact (www.cancer.gov/cancer topics/pdq/supportivecare/caregivers/ healthprofessional).

At an invited presentation at this year’s American Society of Clinical Oncology annual meeting, Given summarized the knowledge she has accumulated in the field. She noted that families play a central role in taking care of people with cancer, encompassing such things as symptom management, provision of emotional support, coordination of care, acquisition and administration of medication, advocacy, and record keeping. Yet the role is often taken on abruptly with little or no guidance from the cancer care system.

“Caregivers need information and skills not only at the diagnosis or hospitalization but at all times.”

—Barbara Given, PhD, RN

“Caregivers need information and skills not only at the diagnosis or hospitalization but at all times,” Given stressed. “Health professionals, therefore, need to assess the care demands

©iStockphoto.com/Jacob Wackerhausen

on the caregivers and provide them with the information they need to meet those demands, taking into account such things as the expected duration and level of care and the caregivers’ availability and capability.”

Significant remaining gaps in recognizing importance of family Lobchuk is conducting survey research that reveals just how deeply ingrained the attitude is, particularly among physicians, that families are peripheral to patient care.

As one physician told her, “I don’t go out of my way to contact or call in the family to include them in a discussion of colon cancer screening. If the loved one happens to be present at the time of a periodic health exam in the examining room, then they will be part of the discussion. …It’s never something that I’m proactively doing.”

Lobchuk notes that making family central to all aspects of cancer management and survivorship will require a major mental shift in thinking and practice. “Not only will healthcare providers need to relinquish power and control to patients and families, but we’ll also need to reorient healthcare systems in how they support decisionmaking that is based on a merging of scientific evidence and what people uniquely expect of health and healthcare for themselves,” she said. “This will require skill and comfort in embracing the notion of partnerships that involve ambiguity, trade-offs, and negotiation.”

Other conclusions based on her research include: • Value is added when family is included in the development of survivorship plans. “Shared goals foster following recommendations for care,” Lobchuk said.

• Physicians, nurses, and other

healthcare practitioners are in positions to create awareness of the concept of partnership between family members, the patient, and the healthcare providers.

• Nurses in particular are committed to such relationship-centered care and are empathetic, which includes helping patients and families tell the stories of their suffering and emotions, and acknowledging the validity of those experiences.

She believes more research is needed to clearly determine how best family can be included in acute- and long-term cancer care, including survivorship.

FOCUSing on family involvement Laurel L. Northouse, RN, PhD, of the University of Michigan School of Nursing, Ann Arbor, developed a family intervention nearly 10 years ago that integrates primary caregivers and other family members into a framework for optimal care of the cancer patient. The intervention is called FOCUS, which stands for family involvement, optimistic attitude, coping effectiveness, uncertainty reduction, and symptom management. It addresses many of the needs identified

by Lobchuk and Given.

The first component involves promoting open communication between the family members and the person affected by cancer, encouraging mutual support and teamwork, identifying family strengths, and helping the children in the family. The second component comprises practicing optimistic thinking, sharing fears and negative thoughts, and maintaining hope even in the face of death. Coping effectiveness includes encouraging healthy coping and lifestyle behaviors, whereas uncertainty reduction involves obtaining information about the disease

GreeN HILL HeALtHCAre COmmUNICAtIONS

TOP_Sept 2010:TOP 9/16/10 12:54 PM Page 41

Survivorship News process and treatments, learning to be assertive in dealing with healthcare professionals, and learning to live with uncertainty with respect to the course of the illness. Symptom management comprises assessing the symptoms experienced by patients and family members and teaching them self-care strategies.

Northouse and her colleagues originally created FOCUS for women with recurrent breast cancer and their family members (Oncol Nurs Forum. 2002;29: 1411-1419). Patients and family members in this initial study—which was funded by the American Cancer Society and involved three home-visit sessions and two phone sessions delivered by master’s-level nurses—reported high satisfaction with the FOCUS program.

They then adapted the FOCUS program for men with newly diagnosed, posttreatment, or advanced prostate cancer and their partners. They found in an NCI-supported randomized, clinical trial that at 4-month follow-up, intervention-targeted patients had less uncertainty and better communication with their partners than did control patients (Cancer. 2007;110:28092818). Their spouses reported higher quality of life, greater self-efficacy, better communication, and fewer negative feelings toward caregiving and toward their spouse’s emotional and physical state. Some of these effects were maintained at 8 and 12 months.

The materials Northouse and her team developed for the prostate cancer study can be downloaded free of charge (rtips.cancer.gov/rtips/programDetails. do?programId=102766).

Most recently, Northouse and her team have completed a randomized, controlled trial of the FOCUS intervention delivered in either three or six sessions to patients with advanced breast, prostate, colorectal, and lung cancers and their family caregivers.

“We were looking at the intervention dose—three versus six sessions— because we’re always trying to see if we can reduce the dose and hence make the program more cost-effective,” Northouse explained. “Our hypothesis is that people who report higher distress or who are at higher risk for distress would probably benefit more from the six- versus the three-session intervention, and that people receiving either dose would do better than controls.”

She said her team will present or publish the results some time next year.

They are also moving FOCUS onto the web. “Our hope is that by putting it onto the Internet we can deliver it to more people and that we can do so at much lower cost. There will be a master’s-level, advanced practice nurse available to answer users’ questions, but other than that nurse and the personnel needed to adapt FOCUS for the Net, there will be very few costs.”

People who report higher distress or who are at higher risk for distress would probably benefit more from the sixversus the three-session intervention, —Laurel L. Northouse, RN, PhD

RITUXAN® (Rituximab) Brief summary—Please consult full prescribing information. counts prior to each Rituxan course. During treatment with Rituxan and chemotherapy, obtain CBC and platelet counts at weekly to monthly intervals and more frequently in WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), patients who develop cytopenias. [See Adverse Reactions]. s The duration of cytopenias SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL caused by Rituxan can extend months beyond the treatment period. ADVERSE LEUKOENCEPHALOPATHY (PML) REACTIONS The most common adverse reactions of Rituxan (incidence ≥25%) Infusion Reactions: Rituxan administration can result in serious, including observed in clinical trials of patients with NHL were infusion reactions, fever, fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have lymphopenia, chills, infection, and asthenia. The most common adverse reactions of occurred. Approximately 80% of fatal infusion reactions occurred in Rituxan (incidence ≥25%) observed in clinical trials of patients with CLL were: infusion association with the first infusion. Carefully monitor patients during reactions and neutropenia. Clinical Trials Experience in Lymphoid Malignancies infusions. Discontinue Rituxan infusion and provide medical treatment for Because clinical trials are conducted under widely varying conditions, adverse reaction Grade 3 or 4 infusion reactions [see Warnings and Precautions, Adverse rates observed in the clinical trials of a drug cannot be directly compared to rates in the Reactions]. s Tumor Lysis Syndrome (TLS): Acute renal failure requiring clinical trials of another drug and may not reflect the rates observed in practice. The data dialysis with instances of fatal outcome can occur in the setting of TLS described below reflect exposure to Rituxan in 2282 patients, with exposures ranging from a single infusion up to 6–8 months. Rituxan was studied in both single-agent and following treatment of non-Hodgkin’s lymphoma (NHL) patients with Rituxan active-controlled trials (n = 356 and n = 1926). The population included 679 patients [see Warnings and Precautions, Adverse Reactions]. s Severe Mucocutaneous with low-grade follicular lymphoma, 927 patients with DLBCL, and 676 patients with Reactions: Severe, including fatal, mucocutaneous reactions can occur in CLL. Most NHL patients received Rituxan as infusion of 375 mg/m2 per infusion, given as patients receiving Rituxan [see Warnings and Precautions, Adverse a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 Reactions]. s Progressive Multifocal Leukoencephalopathy (PML): JC virus doses, or following chemotherapy for up to 16 doses. CLL patients received Rituxan 375 infection resulting in PML and death can occur in patients receiving Rituxan mg/m2 as an initial infusion followed by 500 mg/m2 for up to 5 doses, in combination with [see Warnings and Precautions, Adverse Reactions]. s fludarabine and cyclophosphamide. Seventy-one percent of CLL patients received 6 cycles and 90% received at least 3 cycles of Rituxan-based therapy. Infusion INDICATIONS AND USAGE Non-Hodgkin’s Lymphoma (NHL) Rituxan® (rituximab) is Reactionss In the majority of patients with NHL, infusion reactions consisting of fever, indicated for the treatment of patients with: Relapsed or refractory, low-grade or chills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, follicular, CD20-positive, B-cell NHL as a single agent; Previously untreated follicular, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first CD20-positive, B-cell NHL in combination with CVP chemotherapy; Non-progressing Rituxan infusion. Infusion reactions typically occurred within 30 to 120 minutes of (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after beginning the first infusion and resolved with slowing or interruption of the Rituxan first-line CVP chemotherapy; Previously untreated diffuse large B-cell, CD20-positive infusion and with supportive care (diphenhydramine, acetaminophen, and intravenous NHL in combination with CHOP or other anthracycline-based chemotherapy regimens. saline). The incidence of infusion reactions was highest during the first infusion (77%) Chronic Lymphocytic Leukemia (CLL) Rituxan® (rituximab) is indicated, in and decreased with each subsequent infusion. [See Boxed Warning, Warnings and combination with fludarabine and cyclophosphamide (FC), for the treatment of patients Precautions.] Infections Serious infections (NCI CTCAE Grade 3 or 4), including sepsis, with previously untreated and previously treated CD20-positive CLL. Limitations of use occurred in less than 5% of patients with NHL in the single-arm studies. The overall Rituxan is not recommended for use in patients with severe, active infections. incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal WARNINGS AND PRECAUTIONS Infusion Reactions Rituxan can cause severe, 1%). [See Warnings and Precautions.] In randomized, controlled studies where Rituxan including fatal, infusion reactions. Severe reactions typically occurred during the first was administered following chemotherapy for the treatment of follicular or low-grade infusion with time to onset of 30–120 minutes. Rituxan-induced infusion reactions and NHL, the rate of infection was higher among patients who received Rituxan. In diffuse sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, large B-cell lymphoma patients, viral infections occurred more frequently in those who pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, received Rituxan. Cytopenias and hypogammaglobulinemiaa In patients with NHL ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death. Premedicate receiving rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in patients with an antihistamine and acetaminophen prior to dosing. Institute medical 48% of patients. These included lymphopenia (40%), neutropenia (6%), leukopenia management (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia reactions as needed. Depending on the severity of the infusion reaction and the required was 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116 days). interventions, temporarily or permanently discontinue Rituxan. Resume infusion at a A single occurrence of transient aplastic anemia (pure red cell aplasia) and two minimum 50% reduction in rate after symptoms have resolved. Closely monitor the occurrences of hemolytic anemia following Rituxan therapy occurred during the singlefollowing patients: those with pre-existing cardiac or pulmonary conditions, those who arm studies. In studies of monotherapy, Rituxan-induced B-cell depletion occurred in experienced prior cardiopulmonary adverse reactions, and those with high numbers of 70% to 80% of patients with NHL. Decreased IgM and IgG serum levels occurred in 14% circulating malignant cells (≥25,000/mm3). [See Boxed Warning, Warnings and of these patients. Relapsed or Refractory, Low-Grade NHL Adverse reactions in Table 1 Precautions, Adverse Reactions.] Tumor Lysis Syndrome (TLS) Acute renal failure, occurred in 356 patients with relapsed or refractory, low-grade or follicular, CD20-positive, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, B-cell NHL treated in single-arm studies of Rituxan administered as a single agent. [See some fatal, can occur within 12–24 hours after the first infusion of Rituxan in patients Clinical Studies.] Most patients received Rituxan 375 mg/m2 weekly for 4 doses. with NHL. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burden Table 1 confers a greater risk of TLS. Administer aggressive intravenous hydration and anti- Incidence of Adverse Reactions in ≥5% of Patients with Relapsed or Refractory, Lowhyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, Grade or Follicular NHL, Receiving Single-agent Rituxan (N = 356)a,b monitor renal function and fluid balance, and administer supportive care, including dialysis as All Grades (%) Grade 3 and 4 (%) All Grades (%) Grade 3 and 4 (%) indicated. [See Boxed Warning.] Severe Mucocutaneous Reactions Mucocutaneous Any Adverse Events 99 57 Respiratory p y System y 38 4 reactions, some with fatal outcome, can occur in patients treated with Rituxan. These Bodyy as a Whole 86 10 Increased Cough 13 1 Fever 53 1 Rhinitis 12 1 reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid Chills 33 3 Bronchospasm 8 1 dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these Infection 31 4 Dyspnea 7 1 Asthenia 26 1 Sinusitis 6 0 reactions has varied from 1–13 weeks following Rituxan exposure. Discontinue Rituxan Headache 19 1 Metabolic and Nutritional in patients who experience a severe mucocutaneous reaction. The safety of Abdominal Pain 14 1 Disorders 38 3 Pain 12 1 Angioedema 11 1 readministration of Rituxan to patients with severe mucocutaneous reactions has not Back Pain 10 1 Hyperglycemia 9 1 been determined. [See Boxed Warning, Adverse Reactions.] Progressive Multifocal Throat Irritation 9 0 Peripheral Edema 8 0 Flushing 5 0 LDH Increase 7 0 Leukoencephalopathy (PML) JC virus infection resulting in PML and death can occur Heme and Lymphatic y p System y 67 48 Digestive g System y 37 2 in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases.

Lymphopenia 48 40 Nausea 23 1 Leukopenia 14 4 Diarrhea 10 1 The majority of patients with hematologic malignancies diagnosed with PML received Neutropenia 14 6 Vomiting 10 1 Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell Thrombocytopenia 12 2 Nervous System y 32 1 Anemia 8 3 Dizziness 10 1 transplant. The patients with autoimmune diseases had prior or concurrent Skin and Appendages Anxiety 5 1 pp g 44 2 immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of Night Sweats 15 1 Musculoskeletal System y 26 3 Rash 15 1 Myalgia 10 1 their last infusion of Rituxan. Consider the diagnosis of PML in any patient presenting Arthralgia Pruritus 14 1 10 1 with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited Urticaria 8 1 Cardiovascular System y 25 3 Hypotension 10 1 to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue Rituxan Hypertension 6 1 and consider discontinuation or reduction of any concomitant chemotherapy or a b immunosuppressive therapy in patients who develop PML. [See Boxed Warning, Adverse Adverse reactions observed up to 12 months following Rituxan. Adverse reactions graded for severity Reactions.] Hepatitis B Virus (HBV) Reactivation Hepatitis B virus (HBV) reactivation by NCI-CTC criteria. with fulminant hepatitis, hepatic failure, and death can occur in patients with hematologic In these single-arm Rituxan studies, bronchiolitis obliterans occurred during and up to malignancies treated with Rituxan. The median time to the diagnosis of hepatitis was 6 months after Rituxan infusion. Previously Untreated Low-Grade NHL In Study 4, approximately 4 months after the initiation of Rituxan and approximately one month after patients in the R-CVP arm experienced a higher incidence of infusional toxicity and the last dose. Screen patients at high risk of HBV infection before initiation of Rituxan. neutropenia compared to patients in the CVP arm. The following adverse reactions Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV occurred more frequently (≥5%) in patients receiving R-CVP compared to CVP alone: infection for several months following Rituxan therapy. Discontinue Rituxan and any rash (17% vs. 5%), cough (15% vs. 6%), flushing (14% vs. 3%), rigors (10% vs. 2%), concomitant chemotherapy in patients who develop viral hepatitis, and institute pruritus (10% vs. 1%), neutropenia (8% vs. 3%), and chest tightness (7% vs. 1%). In appropriate treatment including antiviral therapy. Insufficient data exist regarding the Study 5, the following adverse reactions were reported more frequently (≥5%) in safety of resuming Rituxan in patients who develop hepatitis subsequent to HBV patients receiving Rituxan following CVP compared to patients who received no further reactivation. [See Adverse Reactions.] Infections Serious, including fatal, bacterial, therapy: fatigue (39% vs. 14%), anemia (35% vs. 20%), peripheral sensory fungal, and new or reactivated viral infections can occur during and up to one year neuropathy (30% vs. 18%), infections (19% vs. 9%), pulmonary toxicity (18% vs. following the completion of Rituxan-based therapy. New or reactivated viral infections 10%), hepato-biliary toxicity (17% vs. 7%), rash and/or pruritus (17% vs. 5%), included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, arthralgia (12% vs. 3%), and weight gain (11% vs. 4%). Neutropenia was the only West Nile virus, and hepatitis B and C. Discontinue Rituxan for serious infections and Grade 3 or 4 adverse reaction that occurred more frequently (≥2%) in the Rituxan arm institute appropriate anti-infective therapy. [See Adverse Reactions.] Cardiovascular Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform compared with those who received no further therapy (4% vs. 1%). [See Clinical Studies.]

DLBCL In Studies 6 and 7, [see Clinical Studies] s the following adverse reactions, cardiac monitoring during and after all infusions of Rituxan for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina. [See regardless of severity, were reported more frequently (≥5%) in patients age ≥60 years Adverse Reactions.] Renal Severe, including fatal, renal toxicity can occur after Rituxan receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs. 46%), lung disorder administration in patients with NHL. Renal toxicity has occurred in patients who (31% vs. 24%), cardiac disorder (29% vs. 21%), and chills (13% vs. 4%). Detailed experience tumor lysis syndrome and in patients with NHL administered concomitant safety data collection in these studies was primarily limited to Grade 3 and 4 adverse cisplatin therapy during clinical trials. The combination of cisplatin and Rituxan is not an reactions and serious adverse reactions. In Study 7, a review of cardiac toxicity approved treatment regimen. Monitor closely for signs of renal failure and discontinue determined that supraventricular arrhythmias or tachycardia accounted for most of Rituxan in patients with a rising serum creatinine or oliguria. Bowel Obstruction and the difference in cardiac disorders (4.5% for R-CHOP vs. 1.0% for CHOP). The Perforation Abdominal pain, bowel obstruction and perforation, in some cases leading following Grade 3 or 4 adverse reactions occurred more frequently among patients in to death, can occur in patients receiving Rituxan in combination with chemotherapy. In the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs. postmarketing reports, the mean time to documented gastrointestinal perforation was 6 7%) and lung disorder (6% vs. 3%). Other Grade 3 or 4 adverse reactions occurring (range 1–77) days in patients with NHL. Perform a thorough diagnostic evaluation and more frequently among patients receiving R-CHOP were viral infection (Study 7), institute appropriate treatment for complaints of abdominal pain. [See Adverse neutropenia (Studies 7 and 8), and anemia (Study 8). CLL The data below reflect Reactions.] Immunization The safety of immunization with live viral vaccines following exposure to Rituxan in combination with fludarabine and cyclophosphamide in 676 s The age range was Rituxan therapy has not been studied and vaccination with live virus vaccines is not patients with CLL in Study 9 or Study 10 [see Clinical Studies]. recommended. Laboratory Monitoring In patients with lymphoid malignancies, during 30–83 years and 71% were men. Detailed safety data collection in Study 9 was limited treatment with Rituxan monotherapy, obtain complete blood counts (CBC) and platelet to Grade 3 and 4 adverse reactions and serious adverse reactions. Infusion-related

GREEN HILL HEALTHCARE COMMUNICATIONS

Her team is conducting a pre- and postintervention study, with this pilot leading to a randomized, controlled trial.

Together, the different areas of research on family involvement in cancer care can doubtlessly bolster the quality of life of both cancer patients and their family members in the decades to come. l adverse reactions were defined by any of the following adverse events occurring during or within 24 hours of the start of infusion: nausea, pyrexia, chills, hypotension, vomiting, and dyspnea. In Study 9, the following Grade 3 and 4 adverse reactions occurred more frequently in R-FC–treated patients compared to FC-treated patients: infusion reactions (9% in R-FC arm), neutropenia (30% vs. 19%), febrile neutropenia (9% vs. 6%), leukopenia (23% vs. 12%), and pancytopenia (3% vs. 1%). In Study 10, the following Grade 3 or 4 adverse reactions occurred more frequently in R-FC–treated patients compared to FC-treated patients: infusion reactions (7% in R-FC arm), neutropenia (49% vs. 44%), febrile neutropenia (15% vs. 12%), thrombocytopenia (11% vs. 9%), hypotension (2% vs. 0%), and hepatitis B (2% vs. <1%). Fifty-nine percent of R-FC–treated patients experienced an infusion reaction of any severity. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Rituxan with the incidence of antibodies to other products may be misleading. Using an ELISA assay, anti-human antichimeric antibody (HACA) was detected in 4 of 356 (1.1%) patients with low-grade or follicular NHL receiving single-agent Rituxan. Three of the four patients had an objective clinical response. The clinical relevance of HACA formation in Rituxan-treated patients is unclear. Postmarketing Experience The following adverse reactions have been identified during post-approval use of Rituxan in hematologic malignancies. 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. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Rituxan. Hematologic: prolonged pancytopenia, marrow hypoplasia, and late-onset neutropenia, hyperviscosity syndrome in Waldenstrom’s macroglobulinemia. Cardiac:: fatal cardiac failure. Immune/ Autoimmune Events: uveitis, optic neuritis, systemic vasculitis, pleuritis, lupus-like syndrome, serum sickness, polyarticular arthritis, and vasculitis with rash. Infection: viral infections, including progressive multifocal leukoencephalopathy (PML), increase in fatal infections in HIV-associated lymphoma, and a reported increased incidence of Grade 3 and 4 infections in patients with previously treated lymphoma without known HIV infection. Neoplasia:: disease progression of Kaposi’s sarcoma. Skin: severe mucocutaneous reactions. Gastrointestinal: bowel obstruction and perforation. Pulmonary: fatal bronchiolitis obliterans and pneumonitis (including interstitial pneumonitis). DRUG INTERACTIONS Formal drug interaction studies have not been performed with Rituxan. In patients with CLL, Rituxan did not alter systemic exposure to fludarabine or cyclophosphamide. USE IN SPECIFIC POPULATIONS Pregnancy Category C: There are no adequate and well-controlled studies of rituximab in pregnant women.

Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than six months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero. Non-Hodgkin’s lymphoma is a serious condition that requires treatment. Rituximab should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Reproduction studies in cynomolgus monkeys at maternal exposures similar to human therapeutic exposures showed no evidence of teratogenic effects. However, B-cell lymphoid tissue was reduced in the offspring of treated dams. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months of birth.

Nursing Mothers It is not known whether Rituxan is secreted into human milk.

However, Rituxan is secreted in the milk of lactating cynomolgus monkeys, and IgG is excreted in human milk. Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts. The unknown risks to the infant from oral ingestion of Rituxan should be weighed against the known benefits of breast-feeding. Pediatric Use The safety and effectiveness of Rituxan in pediatric patients have not been established. Geriatric Use Diffuse Large B-Cell NHLL Among patients with DLBCL evaluated in three randomized, active-controlled trials, 927 patients received Rituxan in combination with chemotherapy. Of these, 396 (43%) were age 65 or greater and 123 (13%) were age 75 or greater. No overall differences in effectiveness were observed between these patients and younger patients. Cardiac adverse reactions, mostly supraventricular arrhythmias, occurred more frequently among elderly patients.

Serious pulmonary adverse reactions were also more common among the elderly, including pneumonia and pneumonitis. Low-Grade or Follicular Non-Hodgkin’s Lymphoma Clinical studies of Rituxan in low-grade or follicular, CD20-positive, B-cell NHL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Chronic Lymphocytic Leukemia Among patients with CLL evaluated in two randomized active-controlled trials, 243 of 676 Rituxan-treated patients (36%) were 65 years of age or older; of these, 100 Rituxan-treated patients (15%) were 70 years of age or older. In exploratory analyses defined by age, there was no observed benefit from the addition of Rituxan to fludarabine and cyclophosphamide among patients 70 years of age or older in Study 9 or in Study 10; there was also no observed benefit from the addition of Rituxan to fludarabine and cyclophosphamide among patients 65 years of age or older in Study 10 [see Clinical Studies]. s Patients 70 years or older received lower dose intensity of fludarabine and cyclophosphamide compared to younger patients, regardless of the addition of Rituxan.

In Study 9, the dose intensity of Rituxan was similar in older and younger patients, however in Study 10 older patients received a lower dose intensity of Rituxan. The incidence of Grade 3 and 4 adverse reactions was higher among patients receiving R-FC who were 70 years or older compared to younger patients for neutropenia [44% vs. 31% (Study 9); 56% vs. 39% (Study 10)], febrile neutropenia [16% vs. 6% (Study 9)], anemia [5% vs. 2% (Study 9); 21% vs. 10% (Study 10)], thrombocytopenia [19% vs. 8% (Study 10)], pancytopenia [7% vs. 2% (Study 9); 7% vs. 2% (Study 10)] and infections [30% vs.

14% (Study 10)]. OVERDOSAGE There has been no experience with overdosage in human clinical trials. Single doses of up to 500 mg/m2 have been administered in clinical trials. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of Rituxan or to determine potential effects on fertility in males or females. PATIENT COUNSELING INFORMATION Patients should be provided the Rituxan Medication Guide and provided an opportunity to read prior to each treatment session. It is important that the patient’s overall health be assessed at each visit and the risks of Rituxan therapy and any questions resulting from the patient’s reading of the Medication Guide be discussed. Rituxan is detectable in serum for up to six months following completion of therapy. Individuals of childbearing potential should use effective contraception during treatment and for 12 months after Rituxan therapy.

Revised 02/2010 (4851501) Jointly Marketed by: Biogen Idec Inc. 5200 Research Place San Diego, CA 92122 Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990 ©2010 Biogen Idec Inc. and Genentech, Inc. 7140919 February 2010

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NOW IN THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

DRIVING BETTER OUTCOMES RITUXAN+FC improved median PFS in first-line and previously treated CLL1,2 In relapsed/refractory* CLL 2.1-year follow-up

In first-line CLL 1.7-year follow-up

39.8 months R-FC

vs

26.7 months

31.5 months

R-FC

FC

vs

21.7 months FC

8.3

5.0

month

month

improvement in median

improvement in median

PFS

PFS

CLL8 TRIAL (N=817)

REACH TRIAL (N=552) RITUXAN-NAIVE PATIENTS

In the CLL8 trial2 RITUXAN+FC more than doubled CR in first-line CLL compared with FC alone (36% vs 17%; p<0.0001)

In the REACH trial 2 Patients who responded to RITUXAN+FC (n=167) maintained their responses for nearly 2 years longer (48 months vs 27 months; p=0.0294) than those treated with FC alone (n=134)

Treatment considerations These trials were not designed or powered to detect a significant difference in PFS by age category. However, exploratory analyses defined by age suggest no observed benefit with the addition of RITUXAN to FC chemotherapy in previously untreated CLL patients 70 years of age or older and in previously treated CLL patients 65 years of age or older.1 *In the REACH trial, patients had received 1 prior therapy. Patients who had previously received RITUXAN or both fludarabine and cyclophosphamide, either sequentially or in combination, were excluded from the trial, as were fludarabine-refractory patients; alkylator-refractory patients were permitted.2 R=RITUXAN; FC=fludarabine and cyclophosphamide; PFS=progression-free survival; CR=complete response.

Indication RITUXAN® (Rituximab) is indicated, in combination with fludarabine and cyclophosphamide (FC), for the treatment of patients with previously untreated and previously treated CD20-positive CLL. RITUXAN is not recommended for use in patients with severe, active infections.

BOXED WARNINGS RITUXAN administration can result in serious, including fatal, adverse reactions. These include infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML)

Warnings and Precautions RITUXAN can also result in serious, including fatal, adverse reactions. These include hepatitis B reactivation with fulminant hepatitis and hepatic failure resulting in death; other infections, including bacterial, fungal, new or reactivated viral infections; cardiovascular events; severe, including fatal, renal toxicity; and abdominal pain, bowel obstruction and perforation, in some cases leading to death

Additional Important Safety Information The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with CLL were infusion reactions and neutropenia. Most patients treated with R-FC experienced at least one Grade 3 or 4 adverse reaction.

The most frequently reported Grade 3 or 4 adverse reaction was neutropenia In clinical trials, CLL patients 70 years of age or older who received R-FC had more Grade 3 and 4 adverse reactions compared with younger CLL patients who received the same treatment

For additional safety information, please see following page for brief summary of full prescribing information, including BOXED WARNINGS. Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.

References: 1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2010. 2. Data on file, Genentech, Inc. ©2010 Genentech USA, Inc., and Biogen Idec Inc. All rights reserved.

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