MEDICAL MINUTES Code Gray program helps nurses cope with grief
ONS CONGRESS Managing bisphosphonaterelated jaw necrosis
CANCER CENTER PROFILE H. Lee Moffitt Cancer Center & Research Institute emphasizes personalized care
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JULY/AUGUST 2008 • VOL. 1, NO.3
www.theoncologynurse.com
ONS CONGRESS
SUPPORTIVE CARE
© Bridget Laudien
Opioid-induced Constipation: Effects on Patients’ Quality of Life and Nursing Management An interview with Judith C. Lentz, RN, MSN, NHA
O
Oncology nurses attend the opening session of the pioids are the mainstay of nurses and other caregivers. Among CEO of the Hospice and Palliative 33rd Annual Congress of the Oncology Nursing Society.
pain management for patients with advanced cancer and other conditions, but their side effects not only adversely impact patients’ quality of life but also make caring for them more difficult for
the most frequent and troublesome complications is constipation, which sometimes necessitates modification or even discontinuation of needed pain therapy. In this interview, Judith C. Lentz, RN, MSN, NHA, who is
Nurses Association, discusses the effects of opioid-induced constipation (OIC) on patients and caregivers and pharmacologic and nonpharmacologic approaches to management.
page 6 Complimentary CE Credit
Continued on page 11
HEMATOLOGIC MALIGNANCIES
CONFERENCE NEWS
IMF Guidelines on Management of Side Effects of Novel Therapies for
ASCO:
College of Nursing
Bisphosphonate Prolongs Cancerfree Survival in Endocrinesensitive Breast Cancer
Program #08CE059b: Calculating the Dosage of Anticancer Drugs in Obese Patients:
Multiple Myeloma
T
he Nurse Leadership Board (NLB) of the International Myeloma Foundation (IMF) presented the first comprehensive guidelines for managing side effects associated with novel therapies for multiple myeloma at a satellite symposium during the recent Oncology Nursing Society’s 33rd Annual Congress in Philadelphia. “We believe this presentation
CHICAGO—The addition of biannual infusions of zoledronic acid to hormone therapy improves diseasefree survival and recurrence-free survival in premenopausal women with hormone-sensitive early-stage breast cancer, reported Michael Gnant, MD, at the 44th
Continued on page 8
Continued on page 19
PRESORTED STANDARD
U.S. POSTAGE
PAID LEBANON JUNCTION, KY
PERMIT #651
Continuing Nursing Education
A Clinical Challenge
page 16
NURSING LIFE Your Financial Future: Choosing a financial planner
ALTERNATIVE AND COMPLEMENTARY THERAPIES Acupuncture reduces pain after neck dissection
page 22 © 2008 Green Hill Healthcare Communications, LLC
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MEDICAL MINUTES
Medical Minutes BY JOHN SCHIESZER
Medication May Help Prevent Depression in Patients with Head and Neck Cancer John Schieszer is an award-winning national journalist and radio broadcaster of The Medical Minute. He can be reached at medminutes@aol.com.
Taking the antidepressant citalopram before beginning treatment for head and neck cancer may help prevent depression during therapy, according to Nebraska researchers. Studies have documented that psychiatric morbidity in these patients is frequent and underdiagnosed. Major depressive disorder may occur in up to 40% of patients with head and neck cancer and typically occurs within the first 12 weeks of diagnosis. William Lydiatt, MD, of the University of Nebraska Medical Center and Nebraska Methodist Hospital, Omaha, and his colleagues conducted a randomized clinical trial involving patients with head and neck cancer. Before beginning treatment, 15 participants were randomly assigned to receive 40 mg of citalopram daily, and 13 were randomly assigned to take placebo. The patients took the medication for 12 weeks, during which time they underwent cancer treatment and were screened for depres-
sion every 4 weeks. A total of 22 patients were assessed at week 12, and 23 patients completed a final study visit 4 weeks after stopping the medication. Five (50%) of 10 patients taking placebo compared with two (17%) of 12 taking citalopram met the predefined cutoff criteria for depression during the 12 weeks of active study. No patients in the citalopram group became suicidal compared with two of those in the placebo group. Quality of life, as measured by a self-administered questionnaire, deteriorated in both groups during treatment but less so in the group taking citalopram. The researchers concluded from this pilot trial that prevention of major depressive disorder in patients undergoing treatment for head and neck cancer may be an attainable goal. They report that all measures of psychiatric well-being favored the group taking citalopram (Arch Otolaryngol Head Neck Surg. 2008;134:528-535).
©iStockphoto.com/Valentine Casarsa
July/August 2008
G REEN H ILL H EALTHCARE C OMMUNICATIONS
1
MEDICAL MINUTES
The death of a patient and dealing with the family’s grief are help the families and also be there for our other patients,” explained among the most stressful situations encountered by oncology nurses. Ms Sendlak, who described this new program at the 33rd Annual A cancer center in New York has created a program called “Code Congress of the Oncology Nursing Society. Gray” that can provide emergency emotional support for nurses She said evaluation of the Code Gray program has yielded positive immediately after a patient’s death. feedback in terms of immediacy, quality of support, and overall effec“It has been successful. We are now expanding the program to tiveness. She said oncology nurses have to be in the right state of other floors. The primary nurse has to wrap the bodies and take them mind to do their jobs and to take care of patients. This type of proto the morgue and then go back to work, and since the day I started gram, she said, is long overdue. here that has bothered me. I have been a nurse for more than 20 “I don’t see why every hospital couldn’t adopt this. We didn’t run years. We get close to our patients, and it can make a person dis- into any barriers, and the hospital supervisors were very supportive,” traught,” said Deborah Sendlak, RN, who helps run the program at said Ms Sendlak. “We are all taking care of each other. It is not a long the Roswell Park Cancer Institute, Buffalo, New York. break but enough to help. We try to give them 20 minutes, but if they The Code Gray program provides immediate support for the direct need longer we are going to cover them.” care staff within the work environment, rather than the more often delayed support group format. The system involves interA Potential New Tool for Cervical Cancer Screening vention during the acute phase of grief and provides peer-based support immediately Investigators at the University of North after a patient’s death. Carolina at Chapel Hill have found that perWhen a death occurs, the charge nurse sistent infection with human papillomavirus initiates a procedure that includes emotion(HPV) might be a useful clinical marker for al assessment of the immediate and followincreased risk of cervical cancer, the second up support needs of the nurse involved. The most common cancer in women worldwide. program also allows for the nurse to take Currently, Papanicolaou (Pap) smear time off from the unit and to meet with a tests are widely used in screening programs member of the multidisciplinary Code Gray aimed at detecting changes in the cervix which are responsible for about 70% of invasupport team or just spend time off the unit. before a cancer develops. However, testing sive cervical cancer and 50% of high-grade The program was named Code Gray for for HPV infections has the potential to be lesions worldwide. the emotional “gray zone” that pulls nurses more sensitive for future cervical cancer “The next step will be to develop a consenbetween the need to grieve and the need to screening programs. sus definition of HPV ‘persistence’ that can provide uninterrupted patient care, accordThe North Carolina researchers re- then usefully inform clinical practice for future ing to Ms Sendlak. “When a patient dies, viewed 41 existing studies including more cervical cancer screening programs,” said Dr we have to take care of ourselves so we can than 22,500 women to systemically evalu- Smith. “Additionally, we need more informaate the association between HPV persist- tion on whether the persistence of specific ence and high-grade lesions or cervical HPV types, such as 16 or 18, is associated with cancer. “We found that a persistent HPV relative differences in increased risk.” infection of 6 months to 1 year was consisShe said in the future measuring persistence tently associated with a woman’s increased of HPV infection may optimize screening for risk of high-grade cervical lesions or cervi- cervical cancer by increasing sensitivity while cal cancer,” said senior study author maintaining specificity comparable to Pap Jennifer Smith, PhD, who is a research smear testing. “What that means essentially is assistant professor of epidemiology at the that we might be better able to identify University of North Carolina, Chapel Hill. potential cervical cancer cases that could There are approximately 14 high-risk types otherwise go undetected,” Dr Smith of HPV that cause invasive cervical cancer. explained (Koshiol J, et al. Am J Epidemiol. The two most common types are 16 and 18, 2008;168:123-137).
©iStockphoto.com/Loren Rodgers
Code Gray Program May Help Oncology Nurses in Grief Situations
Vol. 1, No. 3
Departments
Feature Articles CONTENTS
6
Conference News
1
Reports from the 33rd Annual Congress of the Oncology Nursing Society
3
16 Continuing Education Calculating the dosage of anticancer drugs in obese patients
19 Conference News Reports from the 44th annual meeting of the American Society of Clinical Oncology
H. Lee Moffitt Cancer Center & Research Institute
Oncology Nurse
™
EDITORIAL BOARD EDITOR-IN-CHIEF
Beth Faiman, RN, MSN, APRN, BC, AOCN Cleveland Clinic Taussig Cancer Institute Cleveland, OH Isabell Castellano, RN Bristol-Myers Squibb Children’s Hospital Robert Wood Johnson University Hospital New Brunswick, NJ Deena Damsky Dell, RN, MSN, AOCN, BC Fox Chase Cancer Center Philadelphia, PA Wendy DiSalvo, BSN, MSN, FNP, AOCN Dartmouth Hitchcock Medical Center Norris Cotton Cancer Center Lebanon, NH
CONTENTS
Denice Economou, RN, MN, AOCN City of Hope National Medical Center Duarte, CA Amy Ford, RN, BSN, OCN Creative Cancer Concepts, Inc. Rockwall, TX
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22
News Notes Cartoon Nursing Life
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24 Alternative/Complementary Therapies
The Official Newspaper of Record for the Hem/Onc Nurse
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Medical Minutes
25 Meetings
21 Cancer Center Profile
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Lyssa Friedman, RN, MPA, OCN Veracyte, Inc South San Francisco, CA
Lori Stover, RN, BSN Western Pennsylvania Cancer Institute Pittsburgh, PA
Marilyn L. Haas, PhD, RN, CNS, ANP-C Mountain Radiation Oncology Asheville, NC Cassandra J. Hammond, RN, MSN, CRNP Avid Education Partners, LLC Sharpsburg, MD Taline Khoukaz, NP, MSN, ACNP-C University of Southern California Norris Cancer Center & Hospital Los Angeles, CA
Joseph D. Tariman, RN, MN, ARNP-BC, OCN University of Washington School of Nursing Seattle, WA Pamela Hallquist Viale, RN, MS, CS, ANP, AOCN Saratoga, CA Connie Visovsky, RN, PhD, APRN University of Nebraska, College of Nursing Omaha, NE Jeanne Westphal, RN Meeker County Memorial Hospital Litchfield, MN
Sandra E. Kurtin, RN, MS, AOCN, ANP-C Arizona Cancer Center Tucson, AZ
Frank P. Whyte, RN, OCN Mount Carmel Hospital—St. Ann’s Westerville, OH
Ann McNeill, MSN, RN, NP-C, OCN The Cancer Center at Hackensack University Medical Center Hackensack, NJ
Rita Wickham, OCN, PhD, RN Rush University College of Nursing Rush-Presbyterian-St. Luke’s Medical Center Chicago, IL
Kena C. Miller, RN, MSN, FNP Roswell Park Cancer Institute Buffalo, NY
Karla Wilson, RN, MSN, FNP-C, CPON City of Hope National Medical Center Duarte, CA
Dolores “Jeff” Nordquist, RN, MS, CS, FNP Mayo Clinic Rochester, MN
OTHER SPECIALTIES Susan Goodin, PharmD, FCCP, BCOP Cancer Institute of New Jersey New Brunswick, NJ
Melinda Oberleitner, RN, DNS, APRN, CNS College of Nursing and Allied Health Professions University of Louisiana Lafayette, LA
Barbara Savage, LISW Cleveland Clinic Taussig Cancer Institute Cleveland, OH
Lisa Schulmeister, MN, RN, APRN-BC, OCN, FAAN New Orleans, LA
G REEN H ILL H EALTHCARE C OMMUNICATIONS
Amanda Saldivar, MS, RD, LD Cleveland Clinic Taussig Cancer Institute Cleveland, OH
July/August 2008
■ Antioxidants May Reduce Effectiveness of Cancer Treatments
Patients with cancer who are receiving chemotherapy or radiation therapy should avoid use of supplements containing high levels of antioxidants, according to a new report. Many cancer patients take antioxidant supplements because they believe they will increase the effectiveness of their treatment. Researchers from the Naval Medical Center in San Diego, California, however, found that these supplements may, in fact, reduce the effectiveness of chemotherapy or radiation, or even increase toxicities. The researchers reviewed data from published randomized clinical trials that examined the use of antioxidants by patients undergoing cytotoxic therapy. Although the findings were inconclusive, the researchers suggest that antioxidants may protect cancer cells just as they do normal cells, thereby decreasing the effectiveness of chemotherapy and radiation (Lawenda BD, et al. J Natl Cancer Inst. 2008;100:773-783).
Antioxidants may protect cancer cells just as they do normal cells.
all cases of cancer reported in children who are taking the drugs (MedPage Today. June 4, 2008).
■ QOL Scores Predict Survival for Patients with Head and Neck Cancer
Low quality-of-life (QOL) scores may indicate poor survival for patients with head and neck cancer, according to a
recent study. A total of 495 patients with head and neck cancer completed a questionnaire, which assessed physical and emotional QOL. The University of Michigan investigators found a high association between general physical health and QOL issues and survival. Patients with difficulty with pain, eating, and speech were significantly less likely
to survive than were other patients. The researchers concluded that QOL instruments may be valuable screening tools to identify patients who are at high risk for poor survival and should be followed more closely (Karvonen-Gutierrez CA, et al. J Clin Oncol. 2008;26:2754-2760). Continued on page 4
NEWS NOTES
News Notes
POWER AND PERFORMANCE VIDAZA hits MDS with the strength of transfusion independence.1,2 • 44% of red blood cell (RBC) transfusion-dependent patients achieved RBC transfusion independence.1* • Median time to RBC transfusion independence was about 2.5 months.1 • In responding patients,† transfusion independence was durable, lasting a median of 330 days.2
■ Possible Link Between Pediatric Cancer and TNF Blockers Investigated
July/August 2008
Important Safety Information • VIDAZA is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol and in patients with advanced malignant hepatic tumors. • In clinical studies, the most commonly occurring adverse reactions by SC route were nausea (70.5%), anemia (69.5%), thrombocytopenia (65.5%), vomiting (54.1%), pyrexia (51.8%), leukopenia (48.2%), diarrhea (36.4%), fatigue (35.9%), injection site erythema (35.0%), constipation (33.6%), neutropenia (32.3%), and ecchymosis (30.5%). Other adverse reactions included dizziness (18.6%), chest pain (16.4%), febrile neutropenia (16.4%), myalgia (15.9%), injection site reaction (13.6%), aggravated fatigue (12.7%), and malaise (10.9%). The most common adverse reactions by IV route also included petechiae (45.8%), weakness (35.4%), rigors (35.4%), and hypokalemia (31.3%). • Because treatment with VIDAZA is associated with neutropenia and thrombocytopenia, complete blood counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle. • Because azacitidine is potentially hepatotoxic in patients with severe preexisting hepatic impairment, caution is needed in patients with liver disease. In addition, azacitidine and its metabolites are substantially excreted by the kidneys 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, it may be useful to monitor renal function. • VIDAZA may cause fetal harm. While receiving treatment with VIDAZA, women of childbearing potential should avoid becoming pregnant, and men should avoid fathering a child. In addition, women treated with VIDAZA should not nurse.
VIDAZA is FDA-approved for the treatment of all myelodysplastic syndrome (MDS) subtypes2‡: RA or RARS (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), RAEB, RAEB-T, or CMMoL. 9221 Study Design: A randomized, open-label, phase III study comparing the efficacy and safety of VIDAZA plus supportive care vs supportive care alone. 191 patients (132 male, 59 female, age 31–92) with all 5 subtypes of MDS classified according to the French, American, British (FAB) classification system were studied. VIDAZA was administered to patients subcutaneously at a dose of 75 mg/m2 daily for 7 days every 4 weeks. Dosage adjustments were allowed based on response or adverse events. The primary study endpoint was response rate. Response Criteria: Complete response was defined as <5% blasts in the bone marrow, absence of blasts in the peripheral circulation, and normal CBC (if abnormal at baseline) maintained for at least 4 weeks. Partial response was defined as at least a 50% decrease in bone marrow blasts and improvement of bone marrow dyspoiesis (for RAEB, RAEB-T, and CMMoL only) plus, for all subtypes, at least a 50% restoration in the deficit from normal of baseline white cells, hemoglobin, and platelets (if abnormal at baseline) and no blasts in the peripheral circulation maintained for at least 4 weeks. For CMMoL, if white cells were elevated at baseline, PR also required at least a 75% reduction in the excess count over the upper limit of normal, maintained for at least 4 weeks.
Please see the brief summary of prescribing information on the adjacent page.
*Of the 66 VIDAZA-treated patients who were RBC transfusion dependent at baseline, 29 (44%) achieved RBC transfusion independence.1 CR + PR = 16%. ‡ According to the FAB Classification System.
VIDAZA is a registered trademark of Pharmion Corporation. © 2007 Pharmion Corporation. All rights reserved. 2007288 May 2007 Printed in the USA.
References: 1. Data on file. Pharmion Corporation. 2. VIDAZA full prescribing information.
NEWS NOTES
The US Food and Drug Administration (FDA) is investigating a possible link between pediatric cancer and the use of tumor necrosis factor (TNF) blockers in light of recently diagnosed cases of lymphoma and other cancers in children and young adults. During the past 10 years, the FDA has learned of about 30 cases of cancer in children taking TNF blockers, including infliximab, etanercept, and adalimumab, which are prescribed for such autoimmune disorders as juvenile idiopathic arthritis, rheumatoid arthritis, psoriatic arthritis, and Crohn’s disease. The link between TNF blockers and cancer is not new, as all four drugs already carry warnings about the possible risks, but the FDA is now requiring all of the manufacturers of TNF blockers indicated for pediatric use to provide information about
†
G REEN H ILL H EALTHCARE C OMMUNICATIONS
3
NEWS NOTES ■ Oncology Reimbursement
NEWS NOTES
Solutions Aims to Improve Billing Efficiency
US Oncology, Inc has announced the introduction of Oncology Reimbursement Solutions (ORS), an oncologyfocused billing and reimbursement service. ORS offers community oncology practices a comprehensive revenue cycle management program to ensure accurate reimbursement for their services. Because
Brief Summary of Prescribing Information VIDAZA (azacitidine for injection) only For subcutaneous and intravenous use only INDICATIONS AND USAGE VIDAZA is indicated for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. CONTRAINDICATIONS VIDAZA is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol. VIDAZA is also contraindicated in patients with advanced malignant hepatic tumors. (See PRECAUTIONS). WARNINGS Pregnancy - Teratogenic Effects: Pregnancy Category D VIDAZA may cause fetal harm when administered to a pregnant woman. Early embryotoxicity studies in mice revealed a 44% frequency of intrauterine embryonal death (increased resorption) after a single IP (intraperitoneal) injection of 6 mg/m (approximately 8% of the recommended human daily dose on a mg/m basis) azacitidine on gestation day 10. Developmental abnormalities in the brain have been detected in mice given azacitidine on or before gestation day 15 at doses of ~3–12 mg/m (approximately 4%–16% the recommended human daily dose on a mg/m basis). In rats, azacitidine was clearly embryotoxic when given IP on gestation days 4–8 (postimplantation) at a dose of 6 mg/m (approximately 8% of the recommended human daily dose on a mg/m basis), although treatment in the preimplantation period (on gestation days 1–3) had no adverse effect on the embryos. Azacitidine caused multiple fetal abnormalities in rats after a single IP dose of 3–12 mg/m (approximately 8% the recommended human daily dose on a mg/m basis) given on gestation day 9, 10, 11 or 12. In this study azacitidine caused fetal death when administered at 3-12 mg/m on gestation days 9 and 10; average live animals per litter was reduced to 9% of control at the highest dose on gestation day 9. Fetal anomalies included: CNS anomalies (exencephaly/ encephalocele), limb anomalies (micromelia, clubfoot, syndactyly, oligodactyly), and others (micrognathia, gastroschisis, edema, and rib abnormalities). There are no adequate and well-controlled studies in pregnant women using VIDAZA. 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. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with VIDAZA. Use in Males Men should be advised to not father a child while receiving treatment with VIDAZA. (See PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility for discussion of premating effects of azacitidine exposure on male fertility and embryonic viability.) PRECAUTIONS General Treatment with VIDAZA is associated with neutropenia and thrombocytopenia. Complete blood counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle. After administration of the recommended dosage for the first cycle, dosage for subsequent cycles should be reduced or delayed based on nadir counts and hematologic response as described in DOSAGE AND ADMINISTRATION. Safety and effectiveness of VIDAZA in patients with MDS and hepatic or renal impairment have not been studied as these patients were excluded from the clinical trials. Because azacitidine is potentially hepatotoxic in patients with severe preexisting hepatic impairment, caution is needed in patients with liver disease. Patients with extensive tumor burden due to metastatic disease have been rarely reported to experience progressive hepatic coma and death during azacitidine treatment, especially in such patients with baseline albumin <30 g/L. Azacitidine is contraindicated in patients with advanced malignant hepatic tumors (See CONTRAINDICATIONS). Renal abnormalities ranging from elevated serum creatinine to renal failure and death have been reported rarely in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents for nonMDS conditions. In addition, renal tubular acidosis, defined as a fall in serum bicarbonate to <20 mEq/L in association with an alkaline urine and hypokalemia (serum potassium <3 mEq/L) developed in 5 patients with CML treated with azacitidine and etoposide. If unexplained reductions in serum bicarbonate <20 mEq/L or elevations of BUN or serum creatinine occur, the dosage should be reduced or held as described in DOSAGE AND ADMINISTRATION. Patients with renal impairment should be closely monitored for toxicity since azacitidine and its metabolites are primarily excreted by the kidneys (see DOSAGE AND ADMINISTRATION section). Information for Patients Patients should inform their physician about any underlying liver or renal disease. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with VIDAZA. Men should be advised to not father a child while receiving treatment with VIDAZA. Laboratory Tests Complete blood counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each cycle. Liver chemistries and serum creatinine should be obtained prior to initiation of therapy. Drug Interactions No formal assessments of drug-drug interactions between VIDAZA and other agents have been conducted. (See CLINICAL PHARMACOLOGY.) ®
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■ Practice Management Models
proper denial management is essential for an efficient revenue cycle process, ORS will resolve the reasons that claims are initially denied, helping to ensure they are approved when they are first submitted. ORS also provides a curriculum of oncology billing and coding education that includes web-based articles, audio conferences, and webcasts, and helps in accessing patient assistance programs. Last year, the ORS Patient Assistance Support team obtained more than $14 million in funding for disadvantaged patients with cancer.
Continued from page 3
Carcinogenesis, Mutagenesis, Impairment of Fertility The potential carcinogenicity of azacitidine was evaluated in mice and rats. Azacitidine induced tumors of the hematopoietic system in female mice at 2.2 mg/kg (6.6 mg/m , approximately 8% the recommended human daily dose on a mg/m basis) administered IP 3 times per week for 52 weeks. An increased incidence of tumors in the lymphoreticular system, lung, mammary gland, and skin was seen in mice treated with azacitidine IP at 2.0 mg/kg (6.0 mg/m , approximately 8% the recommended human daily dose on a mg/m basis) once a week for 50 weeks. A tumorigenicity study in rats dosed twice weekly at 15 or 60 mg/m (approximately 20%–80% the recommended human daily dose on a mg/m basis) revealed an increased incidence of testicular tumors compared with controls. The mutagenic and clastogenic potential of azacitidine was tested in in vitro bacterial systems Salmonella typhimurium strains TA100 and several strains of trpE8, Escherichia coli strains WP14 Pro, WP3103P, WP3104P, and CC103; in in vitro forward gene mutation assay in mouse lymphoma cells and human lymphoblast cells; and in an in vitro micronucleus assay in mouse L5178Y lymphoma cells and Syrian hamster embryo cells. Azacitidine was mutagenic in bacterial and mammalian cell systems. The clastogenic effect of azacitidine was shown by the induction of micronuclei in L5178Y mouse cells and Syrian hamster embryo cells. Administration of azacitidine to male mice at 9.9 mg/m (approximately 9% the recommended human daily dose on a mg/m basis) daily for 3 days prior to mating with untreated female mice resulted in decreased fertility and loss of offspring during subsequent embryonic and postnatal development. Treatment of male rats three times per week for 11 or 16 weeks at doses of 15–30 mg/m (approximately 20%–40%, the recommended human daily dose on a mg/m basis) resulted in decreased weight of the testes and epididymides, and decreased sperm counts accompanied by decreased pregnancy rates and increased loss of embryos in mated females. In a related study, male rats treated for 16 weeks at 24 mg/m resulted in an increase in abnormal embryos in mated females when examined on day 2 of gestation. (See WARNINGS.) Pregnancy Teratogenic Effects: Pregnancy Category D. (See WARNINGS.) Nursing Mothers It is not known whether azacitidine or its metabolites are excreted in human milk. Because of the potential for tumorigenicity shown for azacitidine in animal studies and the potential for serious adverse reactions, women treated with azacitidine should not nurse. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Of the total number of patients in the 3 clinical studies described in CLINICAL STUDIES, above, 62% were 65 years and older and 21% were 75 years and older. No overall differences in effectiveness were observed between these patients and younger patients. In addition there were no relevant differences in the frequency of adverse events observed in patients 65 years and older compared to younger patients. Azacitidine and its metabolites are 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, it may be useful to monitor renal function (see DOSAGE AND ADMINISTRATION section). ADVERSE REACTIONS Overview Adverse Reactions Described in Other Labeling Sections: neutropenia, thrombocytopenia, elevated serum creatinine, renal failure, renal tubular acidosis, hypokalemia, hepatic coma. Most Commonly Occurring Adverse Reactions (SC or IV Route): nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, fatigue, injection site erythema, constipation, neutropenia, ecchymosis. The most common adverse reactions by IV route also include petechiae, rigors, weakness and hypokalemia. Adverse Reactions Most Frequently (>2%) Resulting in Clinical Intervention (SC or IV Route): Discontinuation: leukopenia (5.0%), thrombocytopenia (3.6%), neutropenia (2.7%). Dose Held: leukopenia (4.5%), neutropenia (4.5%), febrile neutropenia (2.7%). Dose Reduced: leukopenia (4.5%), neutropenia (4.1%), thrombocytopenia (3.2%). Discussion of Adverse Reactions Information The data described below reflect exposure to VIDAZA in 268 patients, including 116 exposed for 6 cycles (approximately 6 months) or more and 60 exposed for greater than 12 cycles (approximately 1 year). VIDAZA was studied primarily in supportive-care-controlled and uncontrolled trials (n = 150 and n = 118, respectively). The population in the subcutaneous studies (n = 220) was 23 to 92 years old (mean 66.4 years), 68% male, and 94% white, and had MDS or AML. The population in the IV study (n = 48) was 35 to 81 years old (mean 63.1 years), 65% male, and 100% white. Most patients received average daily doses between 50 and 100 mg/m . The following table presents the most common adverse events, whether or not considered drug related by investigators, occurring in at least 5% of patients treated with VIDAZA in the supportive-care-controlled trial and the uncontrolled subcutaneous trial combined. It is important to note that duration of exposure was longer for the VIDAZA-treated group than for the observation group: patients received VIDAZA for a mean of 11.4 months while mean time in the observation arm was 6.1 months. 2
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G REEN H ILL H EALTHCARE C OMMUNICATIONS
Show Benefits for Oncology Practices
A practice management model, created by US Oncology for oncology practices, has been shown to be beneficial in enhancing patient access to advanced cancer care while improving efficiency for the practice. The model, using an approach often found in manufacturing settings, is focused on defining and measuring a problem; determining the problem’s cause; and initiating change and maintaining improvements. Oncology
Table 4: Most Frequently Observed Adverse Events a (>5% in All VIDAZA) Continued
Table 4: Most Frequently Observed Adverse Events a (>5% in All VIDAZA) Preferred Term
b
All VIDAZA (N=220) At least 1 TEAE 219 (99.5) Nausea 155 (70.5) Anemia 153 (69.5) Thrombocytopenia 144 (65.5) Vomiting 119 (54.1) Pyrexia 114 (51.8) Leukopenia 106 (48.2) Diarrhea 80 (36.4) Fatigue 79 (35.9) Injection site erythema 77 (35.0) Constipation 74 (33.6) Neutropenia 71 (32.3) Ecchymosis 67 (30.5) Cough 65 (29.5) Dyspnea 64 (29.1) Weakness 64 (29.1) Rigors 56 (25.5) Petechiae 52 (23.6) Injection site pain 50 (22.7) Arthralgia 49 (22.3) Headache 48 (21.8) Anorexia 45 (20.5) Pain in limb 44 (20.0) Pharyngitis 44 (20.0) Back pain 41 (18.6) Contusion 41 (18.6) Dizziness 41 (18.6) Edema peripheral 41 (18.6) Erythema 37 (16.8) Chest pain 36 (16.4) 36 (16.4) Epistaxis Febrile neutropenia 36 (16.4) Myalgia 35 (15.9) Weight decreased 35 (15.9) Abdominal pain 34 (15.5) Pallor 34 (15.5) Nasopharyngitis 32 (14.5) Pitting edema 32 (14.5) 32 (14.5) Skin lesion Dyspnea exertional 31 (14.1) Injection site bruising 31 (14.1) Rash 31 (14.1) Injection site reaction 30 (13.6) Anxiety 29 (13.2) Appetite decreased 28 (12.7) Fatigue aggravated 28 (12.7) 28 (12.7) Hypokalemia Upper respiratory tract 28 (12.7) infection Pruritus 27(12.3) Abdominal tenderness 26 (11.8) Depression 26 (11.8) Productive cough 25 (11.4) Insomnia 24 (10.9) Malaise 24 (10.9) Pain 24 (10.9) Pneumonia 24 (10.9) Abdominal pain upper 23 (10.5) Crackles lung 23 (10.5) Sweating increased 23 (10.5) Cardiac murmur 22 (10.0) 22 (10.0) Rhinorrhea Gingival bleeding 21 (9.5) Lymphadenopathy 21 (9.5) Herpes simplex 20 (9.1) Hematoma 19 (8.6) Night sweats 19 (8.6) Rales 19 (8.6) Tachycardia 19 (8.6) Wheezing 19 (8.6) Cellulitis 18 (8.2) Dysuria 18 (8.2) Breath sounds 17 (7.7) decreased Lethargy 17 (7.7) Oral mucosal 17 (7.7) petechiae Stomatitis 17 (7.7) Urinary tract infection 17 (7.7) Peripheral swelling 16 (7.3) Dyspepsia 15 (6.8) 15 (6.8) Hemorrhoids Hypotension 15 (6.8) Injection site pruritus 15 (6.8) Transfusion reaction 15 (6.8) Pleural effusion 14 (6.4) Abdominal distension 13 (5.9) Muscle cramps 13 (5.9) Post procedural 13 (5.9) hemorrhage
c
d
Observation (N=92) 89 (96.7) 16 (17.4) 59 (64.1) 42 (45.7) 5 (5.4) 28 (30.4) 27 (29.3) 13 (14.1) 23 (25.0) 0 6 (6.5) 10 (10.9) 14 (15.2) 14 (15.2) 11 (12.0) 19 (20.7) 10 (10.9) 8 (8.7) 0 3 (3.3) 10 (10.9) 6 (6.5) 5 (5.4) 7 (7.6) 7 (7.6) 9 (9.8) 5 (5.4) 10 (10.9) 4 (4.3) 5 (5.4) 9 (9.8) 4 (4.3) 2 (2.2) 10 (10.9) 12 (13.0) 7 (7.6) 3 (3.3) 9 (9.8) 8 (8.7) 15 (16.3) 0 9 (9.8) 0 3 (3.3) 8 (8.7) 4 (4.3) 12 (13.0) 4 (4.3) 11 (12.0) 1 (1.1) 7 (7.6) 4 (4.3) 4 (4.3 1 (1.1) 3 (3.3) 5 (5.4) 3 (3.3) 8 (8.7) 2 (2.2) 8 (8.7) 2 (2.2) 4 (4.3) 3 (3.3) 5 (5.4) 0 3 (3.3) 8 (8.7) 6 (6.5) 2 (2.2) 4 (4.3) 2 (2.2) 1 (1.1) 2 (2.2) 3 (3.3) 0 5 (5.4) 5 (5.4) 4 (4.3) 1 (1.1) 2 (2.2) 0 0 6 (6.5) 4 (4.3) 3 (3.3) 1 (1.1)
Preferred Termb
All VIDAZA (N=220) At least 1 TEAE 219 (99.5) Postnasal drip 13 (5.9) Rhonchi 13 (5.9) Syncope 13 (5.9) Urticaria 13 (5.9) Anemia aggravated 12 (5.5) Loose stools 12 (5.5) Nasal congestion 12 (5.5) Atelectasis 11 (5.0) Chest wall pain 11 (5.0) Dry skin 11 (5.0) Dysphagia 11 (5.0) Dyspnea exacerbated 11 (5.0) Hypoesthesia 11 (5.0) Injection site 11 (5.0) granuloma Injection site 11 (5.0) pigmentation changes Injection site swelling 11 (5.0) Mouth hemorrhage 11 (5.0) Post procedural pain 11 (5.0) Sinusitis 11 (5.0) Skin nodule 11 (5.0) Tongue ulceration 11 (5.0)
c
d
Observation (N=92) 89 (96.7) 3 (3.3) 2 (2.2) 5 (5.4) 1 (1.1) 5 (5.4) 0 1 (1.1) 2 (2.2) 0 1 (1.1) 2 (2.2) 3 (3.3) 1 (1.1) 0 0 0 1 (1.1) 2 (2.2) 3 (3.3) 1 (1.1) 2 (2.2)
a Mean VIDAZA exposure = 11.4 months. Mean time in observation arm = 6.1 months. b Multiple reports of the same preferred terms for a patient are only counted once within each treatment group. c Includes events from all patients exposed to VIDAZA, including patients after crossing over from observation. d Includes events from observation period only; excludes any events after crossover to VIDAZA. For SC VIDAZA administration, nausea, vomiting, diarrhea, and constipation all tended to increase in incidence with increasing doses of VIDAZA. Nausea, vomiting, injection site erythema, constipation, rigors, petechiae, injection site pain, dizziness, injection site bruising, anxiety, hypokalemia, insomnia, epistaxis, and rales tended to be more pronounced during the first 1-2 cycles of SC VIDAZA treatment compared with later cycles of treatment. There did not appear to be any adverse events that increased in frequency over the course of treatment. There did not appear to be any relevant differences in adverse events by gender. Overall, adverse reactions were qualitatively similar between the IV and SC studies. Adverse reactions that appeared to be specifically associated with the IV route of administration included infusion site reactions (e.g., erythema or pain) and catheter site reactions (e.g., infection, erythema, or hemorrhage). In clinical studies of either SC or IV VIDAZA, the following serious treatment-related adverse events occurring at a rate of <5% (not described in Table 4) were reported: Blood and lymphatic system disorders: agranulocytosis, bone marrow depression, splenomegaly. Cardiac disorders: atrial fibrillation, cardiac failure, cardiac failure congestive, cardiorespiratory arrest, congestive cardiomyopathy. Gastrointestinal disorders: diverticulitis, gastrointestinal hemorrhage, melena, perirectal abscess. General disorders and administration site conditions: catheter site hemorrhage, general physical health deterioration, systemic inflammatory response syndrome. Hepatobiliary disorders: cholecystitis Immune system disorders: anaphylactic shock, hypersensitivity. Infections and infestations: abscess limb, bacterial infection, blastomycosis, injection site infection, Klebsiella sepsis, pharyngitis streptococcal, pneumonia Klebsiella, sepsis, Staphylococcal bacteremia, Staphylococcal infection, toxoplasmosis. Metabolism and nutrition disorders: dehydration. Musculoskeletal and connective tissue disorders: bone pain aggravated, muscle weakness, neck pain. Neoplasms benign, malignant and unspecified: leukemia cutis. Nervous system disorders: convulsions, intracranial hemorrhage. Psychiatric disorders: confusion. Renal and urinary disorders: hematuria, loin pain, renal failure. Respiratory, thoracic and mediastinal disorders: hemoptysis, lung infiltration, pneumonitis, respiratory distress. Skin and subcutaneous tissue disorders: pyoderma gangrenosum, rash pruritic, skin induration. Surgical and medical procedures: cholecystectomy. Vascular disorders: orthostatic hypotension. Manufactured for: Pharmion Corporation Boulder, CO 80301 Manufactured by: Ben Venue Laboratories, Inc. Bedford, OH 44146 Edition Date: 9 January 2007 Brief Summary of Prescribing Information VIDAZA is a registered trademark of Pharmion Corporation. © 2007 Pharmion Corporation. All rights reserved. VIDB010907A January 2007 Printed in USA.
practices that are using the models have seen overall declines in patient wait times of 33%; increased efficiency of chemotherapy staff and infusion room resources by 16%; improvements ranging from 12% to 16% in the timeliness and completeness of orders; and improved efficiency for physicians of about 10% to 15%.
Erratum
I
n the article “KRAS Mutations Predictive of Response to Panitumumab Monotherapy in mCRC” in the May issue, the number of patients with KRAS mutations was inadvertently misstated. The corrected article appears in its entirety below:
KRAS Mutations Predictive of Response to Panitumumab Monotherapy in mCRC KRAS status should be considered when determining whether patients with metastatic colorectal cancer (mCRC) are candidates for panitumumab monotherapy because KRAS mutations are predictive of lack of clinical response to the epidermal growth factor inhibitor. This finding comes from a phase 3 study comparing panitumumab monotherapy with best supportive care (BSC) in patients with chemotherapy-refractory mCRC. The investigators used polymerase chain reaction on DNA from tumor secretions to detect KRAS mutations, and they compared the effect of panitumumab monotherapy on progression-free survival (PFS) in patients with mutant versus wild-type (WT; ie, nonmutated) KRAS. Of 463 patients originally enrolled, 427 (92%) were included in the KRAS analyses. KRAS mutations were identified in 184 (43%) of these 427 patients. The effect of panitumumab on PFS was significantly greater (P < .0001) in patients with WT KRAS than in those with mutant KRAS. In the WT KRAS group, median PFS was 12.3 weeks for panitumumab-treated patients compared with 7.3 weeks for those who received BSC. Seventeen percent of patients with WT KRAS but none of those with mutant KRAS responded to panitumumab. Overall survival was longer in the WT KRAS group than in the mutant KRAS group. Consistent with longer exposure to the drug, more grade III treatment toxicities were observed in the WT KRAS group. No significant differences in toxicity were found between the WT KRAS group and the overall population (Amado RG, et al. J Clin Oncol. 2008; 26:1626-1634.) July/August 2008
BETH FAIMAN, RN, MSN, APRN, BC, AOCN
EDITOR-IN-CHIEF
The
Oncology Nurse
The Official Newspaper of Record for the Hem/Onc Nurse
Y
™
To the Editor
ou asked, “What would a cancer patient’s life be like without an oncology nurse?” As an oncology nurse, I would say that without us, they would not get excellent quality care. I work in an outpatient oncology practice with five physicians, who each have a nurse. We answer the phones, and this simple act provides our patients with the reassurance that someone is always there. Our patients and their caregivers are grateful that we respond to calls and voice mails very efficiently compared with other physician’s office. Patients have often complained that they have called a primary care physician about symptoms of an upper respiratory infection, or urinary tract infection, or other problem and they do not get a return call. Or if they do, it is often too late and the problem is more difficult to treat. Sometimes patients may suffer a delay in chemotherapy treatment or end up in the hospital. The patient often will say, “I am so glad I called you; you’re always there!” This is a very good reason why I believe we need oncology nurses. With our specialized training, we can pinpoint issues early and ensure quality and continuity of care for our patients. Sincerely, Jennifer Dana RN MIMA CANCER CENTER, Melbourne, FL
Life without an oncology nurse Oncology nurses play many essential roles in the care and support of patients with cancer and their caregivers. Write to Karen@greenhillhc.com to share your thoughts on what a cancer patient’s life would be like without an oncology nurse. July/August 2008
As reports from ONS, ASCO, and other recent meetings make evident, providing high-quality care does not end with making a diagnosis and prescribing a treatment. Nurses and other members of the healthcare team often need to make modifications in treatment regimens and work with patients and caregivers to lessen the many possible adverse effects of therapy and provide support and encouragement. Multiple myeloma is a case in point. Novel therapies have greatly improved the prognosis for patients with myeloma, but they can have multiple side effects. The newly developed guidelines of the Nurse Leadership Board of the International Myeloma Foundation provide guidance on coping with the challenges faced by patients undergoing treatment for multiple myeloma. Also in this issue, reports from the annual meetings of ONS and ASCO provide updates on advances in prevention and management of side effects, such as rashes, lymphedema, and oral mucositis, which can interfere with a patient’s ability to tolerate needed therapy. Nurses have to attend to their own personal and professional needs as well as those of their patients. New columns will offer practical suggestions on how to improve your leadership and communication skills and make sound plans for your financial future. Upcoming issues of The Oncology Nurse will continue to provide up-to-date information on clinical and professional issues. Write to us (Karen@greenhillhc.com) and let us know what would be useful to you in your practice and your professional life.
EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, The Oncology Nurse™, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. E-mail: karen@greenhillhc.com. YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $105.00; institutions, $135.00; single issues $17.00. Orders will be billed at individual rate until proof of status is confirmed. Prices are subject to change without notice. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed to REPRINT PERMISSIONS DEPARTMENT, Green Hill Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205C, Monroe Twp, NJ 08831. The ideas and opinions expressed in The Oncology Nurse™, do not necessarily reflect those of the Editorial Board, the Editorial Director, or the Publisher. Publication of an advertisement or other product mention in The Oncology Nurse™, 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. ISSN #Applied for in April 2008. The Oncology Nurse™, is published 6 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 ©2008 by Green Hill Healthcare Communications, LLC. All rights reserved. The Oncology Nurse™ logo is a trademark of Green Hill Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America.
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EDITOR’S LETTER
ith all sorts of exciting advances in oncology—gene therapy, new high-tech diagnostic and treatment methods—it is still important to pay attention to more commonplace issues such as constipation, which can seriously impact a cancer patient’s quality of life and adherence to therapy. In the interview in this issue, Judith C. Lentz, RN, MSN, NHA, CEO of the Hospice and Palliative Nurses Association, provides insights into how opioid-induced constipation affects end-of-life care for cancer patients and their caregivers and discusses current approaches to treatment, including a new agent that is proving effective in refractory cases. The CE article this month addresses an important issue for oncology nurses and other healthcare professionals. With the prevalence of obesity in our society, it is critical to determine how best to calculate drug dosages in overweight and obese patients to achieve optimal results. Research is also needed on what modifications in therapy may be needed for other groups — women, children, the elderly, those with comorbidities, and others with special needs. Personalizing therapy to meet the particular needs of individual patients is, in fact, a major emphasis at the H. Lee Moffitt Cancer Center in Tampa, Florida. Their Total Cancer Care initiative aims to create personalized cancer care for patients with different types of cancer through genetics. The initiative also seeks to address the needs of family members and to follow patients throughout the continuum of care.
EDITOR’S LETTER
A Letter from the Editor W
CONFERENCE NEWS
CONFERENCE NEWS
ONS:
Wound Care Gel Shows Promise for EGFRI–associated Rash Symptoms PHILADELPHIA—A collagen and aloe vera–based wound care gel with 2% lidocaine hydrochloride, known as Regenecare, seems to be a safe and effective adjunct treatment for rash symptoms, such as pain and itching, that are commonly linked to the use of epidermal growth factor receptor (EGFR) inhibitors, according to preliminary results reported at the 33rd Annual Congress of the Oncology Nursing Society. Patricia Gowland, RN, BSN, OCN, CCRC, director of the Cancer Research Center at Ingalls Memorial Hospital in Harvey, Illinois, presented findings in 20 patients with grade 1 to 2 rash symptoms
who received the gel for cutaneous toxicity while undergoing EGFR inhibitor treatment. Patients were enrolled in an ongoing trial that has a target enrollment of 35 patients. EGFR inhibitors have been shown to be effective in treating a range of malignancies, including breast, lung, head and neck, and colorectal cancers, because they are more tumor-specific and their adverse side effects are easier to manage than those associated with standard chemotherapy, Ms Gowland pointed out. Treatment is, however, limited by the onset of a rash in about 90% of patients, which typically appears on the face, upper chest, back, hands, legs, and feet and resembles acne but is instead a reaction of the drug to epidermal antigens. The rash may be severe enough to necessitate a dose reduction or treatment postponement or termination. The good news is that the onset of rash serves as evidence of the drug’s effectiveness. In the study, patients were instructed to apply the gel four times per day to rash areas. Nurses assessed rash severity using the National Cancer Institute Common Toxicity Criteria which determined the grade of acne from rash/desquamation. According to this grading system, grade 1 refers to macular or papular eruption or erythema without associated symptoms. Grade 2 indicates macular or papular eruption or erythema with pruritus or other associated symptoms along with localized desquamation or other lesions covering less than 50% of the body’s surface. Patients completed quality-of-life questionnaires weekly and at the end of treatment cycles. At the end of the 6 weeks, 92.9% of patients reported that the gel was extremely effective in decreasing itching, and 85.7% of patients reported that the gel was extremely effective in reducing pain. Notably, patients said that symptom improvement generally occurred within 15 to 30 minutes after application of the gel. —Jill Stein
© Bridget Laudien
ONS:
Mucositis Treatment Scores High Marks From Patients and Clinicians
CONFERENCE NEWS
PHILADELPHIA—Patients with head and neck cancer, as well as their healthcare practitioners, report favorable results using a supersaturated electrolyte oral rinse (Caphosol) to treat oral mucositis (OM), according to results released at the 33rd Annual Congress of the Oncology Nursing Society. The US Food and Drug Administration– approved rinse lubricates tissues, minimizes friction, and decreases ulceration pain by replacing the normal ionic and pH balance in the oral cavity. Marilyn L. Haas, PhD, CNS, ANP-BC, nurse practitioner/outcomes analyst with Mountain Radiation Oncology in Asheville, North Carolina, presented results of the Caphosol Oral Mucositis Followup Observational Registry Trial (COMFORT), which was conducted at 26 radiation/medical oncology sites throughout the United States over a recent 6-month period. The study included 47 head and neck cancer patients who were undergoing chemotherapy and high-dose radia6
tion and were therefore considered to be at high risk of OM. Practitioners and patients completed questionnaires that evaluated symptoms before and after treatment. Historically, documented overall OM rates in patients with head and neck cancer receiving radiation range from 80% to 97%, with 34% to 57% experiencing grade 3 or 4 OM. In the present study, patients were instructed to rinse with the electrolyte solution four times per day and were allowed to rinse up to 10 times per day when symptoms increased. Severity was scored using National Cancer Institute toxicity scales and widely validated pain rating scales. Data showed that grade 1 or less OM was present in 47% of patients, and grade 4 oral mucositis was present in only one (2%) patient. Grade 1 or less pain occurred in 43% of patients, and dysphagia in 38% of patients. Overall, 76% of patients said they were satisfied or very satisfied with treatment, and 77% of healthcare providers rated treatment as satisfactory to excellent. The study also showed high levels of treatment compliance. On 96% of days, patients rinsed one or more times. On 90% of days, patients rinsed between two and six times.
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Marilyn L. Haas, PhD, CNS, ANP-BC “Speaking from a radiation therapy standpoint, while the literature talks about [a rate of] 97%, I would say that 100% of my head and neck cancer patients experience OM,” Dr Haas said in an interview. “Unfortunately, the toxicity and severity have intensified over the years because patients are receiving combined chemoradiation. So it’s important to be able to prevent OM or at least treat symptoms aggressively once they do occur.” Based on the COMFORT findings, Dr Haas recommends starting use of the advanced electrolye solution “early in the course of cancer therapy for patients at high risk for oral mucositis because it minimizes the onset and severity of symptoms.”
ONS:
New Drug Delivery System Cuts Breakthrough Cancer Pain PHILADELPHIA—BioErodible MucoAdhesive Fentanyl (BEMA) is a rapidly effective and well-tolerated treatment for breakthrough cancer pain, according to phase 3 results released at the 33rd Annual Congress of the Oncology Nursing Society. The BEMA drug delivery system consists of a small, dissolvable polymer disk that is formulated with the opioid fentanyl for application to the buccal membranes. “The new formulation is very palatable for the patient,” said W. D. Charlie Hill, RN, study coordinator at the Cancer Center at InVisions Consultants, LLC, in San Antonio, Texas. “Although oral medications are commonly used, oral medications are not always fast-acting and may not be ideal for patients who have difficulty in swallowing or have nausea or other gastrointestinal problems. You can place BEMA in the vascular oral mucosal surface, where it’s rapidly absorbed and the patient obtains timely pain relief.” The new results are from a phase 3 trial in cancer patients who were taking around-theclock opioids, and regularly experiencing one to four daily breakthrough pain episodes that required additional opioids for pain control. Participants initially underwent a 2- to 14-day open-titration phase in which they identified a fentanyl dose (ranging from 200 to 1200 µg) that adequately controlled their breakthrough pain episodes. Afterwards, they were randomized to six BEMA and three placebo doses, in randomized order, for up to 14 days. The study included 80 adults with cancer. A total of 394 episodes of breakthrough cancer pain were treated with BEMA, and 191 with placebo. The sum of pain intensity differences (SPID) at 30 minutes, the primary study end point, was significantly greater with BEMA than placebo. Also, SPID values significantly favored BEMA at all time points from 15 minutes through 60 minutes, which was the final time that pain was assessed. The mean overall satisfaction score was significantly higher for BEMA versus placebo at 60 minutes after dosing or at the time of rescue medication use. Overall, 67% of patients rated the relief from breakthrough pain with BEMA as good, very good, or excellent across all doses compared with 47% for placebo. All five dose levels of BEMA were safe and well tolerated, with no unexpected safety concerns. The most commonly reported treatmentrelated side effects were sleepiness in 6% of patients, nausea in 5.3% of patients, dizziness in 4.6% of patients, and vomiting in 4% of patients, all of which are typical of opioid use. There were no cases of treatment-related mucositis or respiratory depression. “As a practicing registered nurse, I hope this becomes front-line therapy, if approved,” Mr Hill said. “All of our patients were on background opioids with current rescue medications, and they verbalized their acceptance of this particular product because of its ease of use and superior effectiveness.” As many as two thirds of patients with chronic cancer-related pain experience breakthrough cancer pain, he added.
—JS July/August 2008
CONFERENCE NEWS
CONFERENCE NEWS
ONS:
APNs Need to “Bone Up” on Bisphosphonaterelated Jaw Osteonecrosis PHILADELPHIA—Advanced practice nurses (APNs) need to ensure that they are up-to-date on how to best assess and manage osteonecrosis of the jaw secondary to bisphosphonate treatment, investigators advised at the 33rd Annual Congress of the Oncology Nursing Society. “Bisphosphonate-related osteonecrosis of the jaw may cause painful exposure of the jawbone and interfere with the patient’s ability to chew and swallow food, thereby causing a significant deterioration in quality of life,” said Marlene McGuire, RN, MA, APN, of The Cancer Institute of New Jersey in New Brunswick. Bisphosphonate-related osteonecrosis of the jaw, which was initially described in 2003, occurs in about 1% to 10% of cancer patients receiving bisphosphonates (AAOMS Position Paper on Bisphosphonaterelated Osteonecrosis of the Jaws. www.aaoms.org/docs/position_papers/ osteonecrosis.pdf) and results from an alteration in bone homeostasis including inhibition of angiogenesis, Ms McGuire explained. Bisphosphonates act by interfering with osteoclast intercellular biochemical pathways (Strewler GJ. N Engl J Med. 2004;350:1172-1174). Risk factors are local, patient-related, or drug-related. Ms McGuire and her colleague Jacquelyn Lauria, RN, MS, APN, described these risk factors in a poster presentation.
Local risk factors • Recent dental surgery, including dental extractions, dental implants, periapical surgery, periodontal surgery, and dentoalveolar surgery • History of inflammatory dental disease, such as periodontal disease and dental abscesses
CONFERENCE NEWS
Did you
Know?
Women who are working when they are diagnosed with breast cancer lose an average of 27% of their income in the year after diagnosis. Source: J Natl Cancer Inst. Feb 26, 2008
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Patient-related risk factors High-risk groups include: • Whites undergoing treatment for multiple myeloma • Patients with a history of cancer, osteopenia, and/or osteoporosis • Patients who are receiving corticosteroids or who are diabetic; patients who have peripheral vascular disease, and patients who are smokers or excessive drinkers • Patients with poor dental health and patients who are receiving multiple chemotherapeutic agents Drug-related risk factors • Potency of the prescribed drug. Zoledronic acid, which is administered intravenously (IV), is more potent than pamidronate, which is also administered IV. Both drugs are more potent than oral bisphosphonates, such as alendronate and ibandronate sodium. • Route of administration. IV administration results in higher drug exposure and increased risk. • Duration of therapy. The longer the duration of therapy, the higher the risk. In general, risk is significantly increased after 3 years of treatment. Clinical features and management of osteonecrosis Clinical features of osteonecrosis include the following: • Exposed bone under the teeth, which occurs in the mandible in approximately two thirds of cases and in the maxilla in about one third of cases. • Pain, swelling, or gum infection
• Loose teeth or hard, rough areas on the jawbone • Poor healing of gums after a dental procedure • Sensation of heaviness or numbness in the jaw • Patients may be asymptomatic. There is no standard protocol for the management of bisphosphonate-related jaw osteonecrosis, Ms McGuire noted. Panoramic or cross-sectional imaging Marlene McGuire, RN, MA, APN, and Jacquelyn is usually recommended to determine the degree of Lauria, RN, MS, APN, present poster on bisphosphonecrosis and the presence nate-related jaw osteonecrosis. of a sequestrum or osteomyelitis. Treatment depends on the this devastating side effect,” Ms osteonecrosis stage and involves con- McGuire said. trolling pain using analgesics as well as Ms McGuire and Ms Lauria recomhalting lesion progression and limiting mend that their patients maintain good infectious complications using antibi- communication with their entire otics and surgical debridement. Patients healthcare team. Patients are advised to are advised to rinse daily with a 0.12% inform their dentist that they are being chlorhexidine solution. treated for cancer. Likewise, they should Ms McGuire and Ms Lauria have tell their oncology team about their launched a program at their institution dental history. Patients are provided that aims to ensure that all bisphospho- with a handout that includes the follownate-treated patients undergo a dental ing recommendations: examination and complete necessary • Schedule a dental check-up and dental work before starting treatment cleaning before you start cancer for their cancer. “Patients need to be in treatment and periodically during their optimal dental state before cancer the course of treatment. Always treatment,” Ms McGuire stressed. The check with your oncology team program also emphasizes the importance before scheduling these appointof routine oral assessment of patients ments. If your blood count is low, taking bisphosphonates, which will you may be told to avoid schedulallow for early identification of probing a dental appointment during lems with prompt referral to a dentist or this timeframe. oral surgeon. “A proactive approach is • Be certain to tell your dentist that the key to preventing and managing you are taking a bisphosphonate
NEW IMF GUIDELINES Continued from cover
at a major medical meeting represents a groundbreaking opportunity for these nurses, validating the valuable services the NLB provides,” said Susie Novis, president and cofounder of the IMF. “Myeloma patients and their families face unique challenges during the course of their treatment. The NLB guidelines provide nurses with the specific information they need to support their patients during these critical periods in their care.” The guidelines have also been published in the June 2008 supplement to The Clinical Journal of Oncology Nursing. Both the presentation, Consensus on SUSIE NOVIS Care: New Insights on Novel Therapies in Multiple Myeloma, and the guidelines are available through the IMF web site at www.myeloma.org.
Meeting a need The NLB was created by the IMF, a not-for-profit advocacy organization, in recognition of the essential role nurses play in managing patient care. The NLB includes 20 oncology nurses from leading cancer centers and community practices in the United States who care for patients with multiple myeloma. The NLB identified the need for strategies to manage the side effects of the novel agents used to treat multiple myeloma— lenalidomide, thalidomide, and bortezomib. At its inaugural meeting, the NLB chose five key side effects to address with
G REEN H ILL H EALTHCARE C OMMUNICATIONS
educational information for both nurses and their patients. These side effects are myelosuppression, including anemia, neutropenia, and thrombocytopenia; thromboembolic events, including deep vein thrombosis and pulmonary embolism; peripheral neuropathy; gastrointestinal side effects, including constipation, diarrhea, nausea, and vomiting; and steroid-associated side effects. Steroids have been a mainstay of myeloma treatment for decades, and are often administered in combination with the novel therapies. The consensus statements for side effect management are designed to be used by healthcare providers in any type of medical facility. Each of the five side effect management guidelines includes a patient education sheet. The supplement also includes an editorial by Brian G.M. Durie, MD, as well as a manuscript describing the formation of the NLB and process for development of the consensus statements. NLB member Beth Faiman, RN, MSN, APRN, BC, AOCN, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, chair of the NLB symposium, says the level of interest in the guidelines is high. As first author on the steroid management manuscript, she observed, “There was no clear consensus on how to manage steroids, which are integral to therapy for patients with myeloma. Newer clinical trials may show that lower doses of steroids may be safer and more effective, and show the best way to use steroids in combination ther- BETH FAIMAN, RN, apies. Although the NLB steroid guide- MSN, APRN, BC, lines target historical, higher dose AOCN July/August 2008
ONS:
Nurses Help Ensure Safety of Patients Undergoing Radiofrequency Ablation PHILADELPHIA–Nurses play an invaluable role in optimizing the safety of percutaneous radiofrequency ablation (RFA) in patients with malignant liver tumors who are not eligible for surgical resection, according to a presentation here at the 33rd Annual Congress of the Oncology Nursing Society. “Nurses have important responsibilities both before and after RFA, including patient education, assessment, and symptom management,” said Lisa M. Wall, RN, PhD, OCN, clinical nurse specialist at Memorial
Sloan-Kettering Cancer Center in New York. Although surgical resection remains the best treatment option for patients with primary or metastatic disease in the liver, many patients are not surgical candidates, she said. In patients with unresectable lesions, percutaneous RFA can be the sole treatment method or an adjunct to chemotherapy to reduce tumor burden in the liver. RFA may be indicated when: • the patient has primary liver cancer or limited metastatic disease in the liver • surgical resection is not an option because of the location of the tumor(s) or the presence of comorbidities • the tumor has recurred after surgical resection and further resection is not an option “An ideal candidate may be the patient with primary liver cancer, such as a hepatoma, who has a few small lesions that can be treated. RFA works best in tumors that are less than 4 cm in diameter.” Dr Wall said. Patients with metastatic colorectal cancer are also ideal candidates, she added. “I am referring to patients who develop one or two lesions in the liver, and you just want to give them a local treatment. They are not showing disease elsewhere, and they have already had chemotherapy, but the disease has recurred and you want to do a local treatment only in
the area where the disease has recurred.” With RFA, the patient undergoes conscious sedation to reduce movement during the procedure. Using computerized tomography, an interventional radiologist inserts an electrode probe through the abdomen and directly into the tumor. The tip of the probe is heated to 110 to 120 degrees Fahrenheit and held in place to burn the tumor. The hospital stay is generally 1 to 2 days. Potential outcomes of the procedure include cure or control of primary liver cancer, a reduction in tumor burden in both primary and Lisa M. Wall, RN, PhD, OCN, presents metastatic liver tumors, and pallia- poster on RFA Safety. tion of disease-related symptoms. Before RFA, nurses explain to After RFA, nurses assess the patient patients the purpose of the procedure for potential complications, including and describe the preparation for the bleeding, infection, and injury to the procedure (for example, the impor- liver and adjacent organs, and they evaltance of avoiding anticoagulants and uate electrolytes and hepatic and renal not eating or drinking after midnight function. They also inform the patient of on the day of the procedure). Nurses the postprocedure follow-up requirealso evaluate platelet and prothrom- ments and timetable for evaluation of bin times before the procedure since disease status. The procedure can be many patients with malignant liver repeated multiple times if necessary. tumors have low platelet counts due “RFA is a very effective tool to treat to cirrhosis or recent chemotherapy, localized and limited disease in the which increases their bleeding risk. liver and patients tolerate it well,” Dr They may also have compromised Wall said. “Nurses play an integral role hepatic function due to a high Child- in preparing patients for percutaneous Pugh score (resulting from ascites, RFA as well as their postprocedure encephalopathy, low albumin, pro- management and evaluation.” longed prothrombin time, or elevated bilirubin). —JS
regimens, the guidelines are still pertinent and necessary for patients and nurses.” Steroid side effects vary with the patient and dose. Although these side effects have been well documented, how to manage them has not. When Ms Faiman and her group searched, they found little in the literature. “It was exciting to collaborate between the NLB and IMF to produce something useful,” she said. “We are pleased that our work was validated by the myeloma experts, Dr Brian Durie and Dr Robert Kyle, as well as through the peer review process.”
you can get a heads-up on how to manage them, it makes it easy for patients. Some of the teaching tools included in our guidelines are based on common sense, some on experience, and they include pharmacologic and nonpharmacologic interventions. We don’t mind being one-upped,” she said, offering a challenge to those treating patients with other tumor types and other new therapies. “You can do this, too,” she concluded, suggesting both breast cancer and prostate cancer as possible topics for guidelines.
Offering a challenge Kena C. Miller, RN, MSN, FNP, Roswell Park Cancer Institute, Buffalo, New York, was also on the symposium faculty. Ms Miller noted that the NLB set out to summarize for oncology nurses and for nurses in general what the NLB members have found useful based on their familiarity with using the novel agents for myeloma, as well as what patients have found helpful. As multiple myeloma becomes a chronic disease as a result of the availability of effective newer agents, patients will be dealing with side effects for years to come, she said. “If side effects can be managed now, it will help in both the short term and the long term,” she explained. “The best point to make is that other nurses who deal with different side effects from treatments for other cancers may use the NLB guidelines as a springboard for disseminating information about newer agents for those cancers, as well as to improve on what the NLB has done,” Ms Miller said. “As new drugs are approved, if
Looking ahead Teresa Miceli, RN, BSN, Mayo Medical Center, Rochester, Minnesota, the NLB member who was first author on the myelosuppression guidelines, treats patients with hematologic malignancies. She suggests guidelines for patients with lymphoma would be a logical next topic. She also recognizes that long-term survivorship issues, especially for major cancer types, and patient advocacy and insurability issues are all important. She notes that many patients with myeloma have been told not to go back to work. Many are alive years after their diagnosis and are on disability and have a sense of purposelessness. She would like to see patients get back to a sense of normalcy and look ahead. A longterm care plan is one of the next goals for the NLB. Ms Miceli says that having myeloma doesn’t give patients a “get out of cancer free card,” meaning they remain susceptible to other primary malignancies, as well as coronary heart disease, diabetes, and hypertension. Patients will also continue to have health issues related to their
July/August 2008
myeloma or other cancer therapies, for example osteoporosis or obesity if they cannot exercise. This means patients must be involved with primary care physicians, not just their hematologist or oncologist. Ms Miceli runs a support group that includes patients who are long-term survivors. “I think a long-term care plan will have an even wider applicability and open eyes. If patients hear that information, they will have more hope,” she said. She also thinks that improvements in identifying different subtypes of myeloma in terms of molecular genetic risk factors and the therapies that they will respond to will improve treatment. “This will be huge. I hope and pray that myeloma over the next 10 years sees the type of advances that have been made in other cancers, like acute leukemias. I hope we find therapies that target the higher risk types of myelomas,” Ms Miceli concluded. The NLB is already anticipating a need for additional recommendations to manage side effects of therapies currently in development for myeloma whose mechanisms of action are different from the novel therapies, as well as side effects unique to new combinations of therapies. The NLB Long Term Care Task Force intends to address bone health, functional mobility and safety, chronic pain, sexuality and sexual dysfunction, renal complications, and health maintenance. The Nurse Education, Patient Education, and Publication Task Forces will make sure that the nurses and other healthcare providers will receive future NLB guidelines in a timely fashion. —Lynne Lederman
G REEN H ILL H EALTHCARE C OMMUNICATIONS
9
CONFERENCE NEWS
RFA works best in tumors that are less than 4 cm in diameter.
CONFERENCE NEWS
and therefore need to avoid dental surgery. • Discuss all dental procedures, such as tooth extraction or insertion of dental implants, with your oncologist. • Have your dentist check and adjust removable dentures periodically while receiving cancer treatment. • Use a mirror to check your teeth and gums daily for any changes such as sores or bleeding. • Maintain good oral hygiene to reduce your risk of infection. • Tell your oncology team about any bleeding, pain, or unusual feeling in your teeth or gums, or any dental infections.
The
Oncology Nurse
The Official Newspaper of Record for the Hem/Onc Nurse
The
™
Oncology
The Official Newspaper of Record for the Hem/Onc Pharmacist
Pharmacist
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Presents The First Annual 2008 Curriculum for
CONSIDERATIONS IN MULTIPLE MYELOMA A Newsletter Series for Cancer Care Professionals Center of Excellence Media, along with Editor-in-Chief Sagar Lonial, MD, of Emory University, will proudly offer the multidisciplinary cancer team at your center a series of newsletters focusing on the challenges in treating patients with multiple myeloma.
SAGAR LONIAL, MD Associate Professor of Hematology and Oncology Emory University
H Earn Continuing Education Credits H Each newsletter will feature:
Clinical Topics: • Renal Dysfunction • Hard-to-Treat Patients • Treatment-Naive Patients • Health Economics • Side Effect Management
• Contributions from thought-leading physicians, pharmacists, and nurses • Continuing Education credits available to physicians, pharmacists, and nurses
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Call 732-656-7935 or visit www.coexm.com
About Multidisciplinary Cancer Care Multidisciplinary Cancer Care newsletters provide a forum for sharing expert interdisciplinary treatment perspectives on patient care with the ultimate goal of promoting ongoing professional education to physicians, nurses, and pharmacists in the hematology/oncology community. Target Audience This educational publication is designed for physicians, nurses, and pharmacists who wish to enhance their knowledge concerning the management of patients with multiple myeloma and renal dysfunction.
Learning Objectives At the completion of this educational activity, you should be able to: • Describe the prevalence of renal insufficiency among patients with multiple myeloma (MM) • Recognize the special challenges in pharmacologic treatment of the many patients with MM who also have renal insufficiency, especially those requiring dialysis • Discuss the results of studies showing treatments that are active and safe in MM patients with renal impairment, including those with advanced renal failure requiring dialysis
Accreditation Physicians This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of CME Consultants and Center of Excellence Media. CME Consultants is accredited by the ACCME to provide continuing medical education for physicians. CME Consultants designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Supported by an educational grant from Millennium Pharmaceuticals, Inc.
Pharmacists CME Consultants is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This activity has been designated for 1 contact hour (0.100 CEU). In order to receive credit, all participants must complete an evaluation, request for credit form, and a posttest. Statements of Credit will be mailed to participants within six weeks. ACPE #309-999-08-012-H01-P Initial Release Date: 05/07/08. Planned Expiration Date: 05/07/09. Nurses CME Consultants is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. CME Consultants designates this program for 1 contact hour. Participants should claim only those contact hours actually spent in the educational activity. In order to receive credit for this program, each participant must complete the evaluation form, posttest, and certificate request form. Certificates will be mailed to program participants in approximately four to six weeks after receipt of the completed evaluation form, posttest, and certificate request form.
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OPIOID-INDUCED CONSTIPATION Continued from cover
this, the side effects create Figure 2 major problems for them.
How Does OIC Affect End-of-life Care and Patients’ Quality of Life? What are the most % Agree (Somewhat/Strongly) troublesome side effects of opioids? The side effect that is most OIC diminishes specifically noted when people terminally ill patients’ 97% are taking opioids is constipaquality of life tion (Figure 1) because opioids slow gastrointestinal motility. Nurses Nearly 100% of individuals OIC makes it more who are taking opioids for pain difficult to provide 90% management will have constigood end-of-life care pation. There are other side effects that are less frequent. Sometimes there is some nauOIC indicates opioid-induced constipation Source: Strategy One. sea, vomiting, or cramping. But, for the most part, if you manage the patient effectively in a and fiber to the patient’s diet. We also Are there any prescription proactive way, you can prevent most of use suppositories and enemas when nec- drugs to treat OIC? Several prescription drugs are availessary. The least popular way of controlthese side effects. able, and many of them are effective to Patients need to understand the value ling constipation is disimpaction. When people are very ill, as in the a certain degree. For success with preof being proactive in managing their bowel function so that they do not expe- population we’re talking about, your scription or nonprescription medicarience the terrible constipation that can ability to control their dietary and fluid tions, a proactive approach is needed. intake and their physical mobility is When an opioid is started, the person limited, and so you have to be very cre- needs to be started immediately on a OIC negatively affects patients’ quality of prevention and management regimen, ative in trying to manage the OIC. and both the patient and the home carelife and makes it more difficult to provide giver need to be educated about how How does OIC affect overall good end-of-life care. important it is to adhere to this regimen. patient management? A new drug—methylnaltrexone Management is particularly difficult What are some measures that occur when taking opioids. But, often when the patient doesn’t understand bromide (Relistor)—was recently patients are nonadherent, and we’re not both the benefits of the opioids and approved for treatment of OIC [see can help to lessen their physias successful at controlling OIC as we the side effects they can cause. In a sidebar].2 Although I personally was cal symptoms and improve recent study of pain management in not involved in the studies leading up would like to be. their quality of life? terminally ill patients, nurses said that to its approval, I can tell you anecdotalThe symptom that is most important more than 71% of their patients had ly that many of the nurses who particito control is pain. We have wonderful What are some of the measways to manage an individual’s pain, but ures currently used to control switched, reduced, or actually stopped pated in the phase 1/2 studies were very their medication because of OIC.1 impressed. They were pleased that we need to make sure that the patient OIC? Usually we use a combination of When that happens, the patients’ pain there was something they could rely on understands what that management consists of and how to prevent and man- pharmacologic and nonpharmacologic is not managed and they are not able for patients with refractory OIC. measures. One of them is to increase to participate in the activities that Methylnaltrexone was not developed age any side effects that may occur. as a primary intervention. But, when Opioids are a variety of agents that fluid intake. Another is to have the enhance their quality of life. OIC is tremendously stressful to you have a patient or caregiver who can control pain effectively, allowing patient be as mobile as possible, but patients to live the way they want to when patients are very ill, that is very both caregivers and to nurses. In our does not adhere to the preventive registudy, the vast majority of nurses said men and neither nonpharmacologic live, but they do have side effects. difficult to achieve. So we rely on things like laxatives that OIC negatively affects patients’ nor pharmacologic interventions are Although they are essential for controlling pain, and patients are aware of and stool softeners and try to add bulk quality of life and makes it more diffi- working, it is good to know that there cult to provide good end-of-life is a medication that can cause laxation to occur and relieve the patient’s discare (Figure 2). Figure 1 Many caregivers find it difficult comfort. Methylnaltrexone is the agent to discuss the constipation issue of choice for refractory situations. with the patient because they view Side Effects of Opioids That Patients Find the Most Frustrating it as a private matter. When the Because it is injectable, does it caregiver is embarrassed to ask the have to be administered in the 80% Constipation question, the patient is embar- hospital or in the physician’s rassed to share the information office, or could it be adminis43% Increased sleepiness tered by caregivers at home? with the caregiver. It definitely can be administered by From a nursing point of view, 25% Nausea it is also difficult because we caregivers in the home. Just as we teach know that we can achieve good patients to administer other injectable 23% Confusion outcomes of pain management if medications, such as insulin, we certainPatients the patient is adherent. We have ly can teach the caregiver how to give 14% Jerking of limbs and torso to resolve the problem whether methylnaltrexone. it is that the patient is not taking 10% Difficulty urinating the pain medication and experi- Is it used in addition to or encing pain as a result, or taking instead of other laxatives or 9% Vomiting the pain medication and having other measures? We would recommend that methconstipation as a result. A lot of 7% Decreased breathing time and energy center on this ylnaltrexone be used for refractory OIC. particular aspect of care, impact- It should be given only once in a 245% Other ing a great number of individuals hour period. In the phase 1/2 trials, laxat that particular point in their Source: Strategy One. disease process. Continued on page 14
July/August 2008
G REEN H ILL H EALTHCARE C OMMUNICATIONS
SUPPORTIVE CARE
SUPPORTIVE CARE
What do end-stage cancer patients and their caregivers perceive as the greatest challenges to maintaining their quality of life? Our experience, and this certainly includes my oncology experience prior to working in end-of-life care, has been that managing the stressors is what is most important to patients. The stressors can come from a variety of domains; there are physical, emotional, financial, and spiritual stressors. If we do not manage the stressors of the physical domain, we are unable to manage stressors in other domains. Therefore, physical symptom management is our priority when addressing patients’ needs so that they can have the quality of life that they’re striving to achieve. They want the focus to be on living with the disease, not dying from it.
11
CRs Correlate with Clinical Benefit in APEX1 OVERALL SURVIVAL STRATIFIED BY QUALITY OF RESPONSE 1.0
Proportion of Patients
0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0
0
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
32
34
36
38
Time (months) CR (n=27)
PR with e90% decrease (n=31)
PR with e50% and <90% decrease (n=77)
All other (n=180)
CLINICAL BENEFIT OF VELCADE® BY QUALITY OF RESPONSE* CR
PR
PR
(e90% M-protein reduction)
(e50% and <90% M-protein reduction)
Patients, n (%)
27 (9)
31 (10)
77 (24)
Median cycles
8
10
10
Treatment-free interval (months)
24.1 (9.7, 24.4)
6.9 (5.5, 11.1)
6.4 (4.4, 10.3)
Time to next treatment (months)
27.1 (15.2, 32.0)
13.6 (10.0, 17.3)
14.0 (12.6, 16.1)
Time to progression (months)
9.7 (7.8, 17.7)
10.8 (8.1, 14.4)
8.5 (7.0, 9.9)
Not yet reached
Not yet reached
Not yet reached
Overall survival
▼ CRs deliver greater clinical benefit than any other responses *In APEX, 315 VELCADE patients were evaluable for response. Responses were based on criteria established by the European Group for Blood and Marrow Transplantation (EBMT). Complete response (CR) required 100% disappearance of the original myeloma protein from blood and urine on at least 2 determinations 6 weeks apart by immunofixation, <5% plasma cells in the bone marrow, stable bone disease, and normal calcium. Partial response was stratified into 2 categories; M-protein reduction of either ≥ 90% or of ≥ 50% and <90% determined on at least 2 occasions, 6 weeks apart. Both categories required ≥ 90% reduction in urine myeloma protein upon at least two determinations six weeks apart, stable bone disease and normal calcium.
VELCADE® (bortezomib) for Injection is indicated for the treatment of patients with multiple myeloma who have received at least 1 prior therapy. VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. References: 1. Data on file. Millennium Pharmaceuticals, Inc.
Please see Brief Summary of full Prescribing Information on adjacent page, also available at www.VELCADE.com.
Millennium Pharmaceuticals, Inc., Cambridge, MA 02139 Š2008 Millennium Pharmaceuticals, Inc. All rights reserved.
Printed in USA
V0921A
03/08
CONFERENCE NEWS
SUPPORTIVE CARE
ONS: Early Nursing Intervention Important for Optimal Lymphedema Management PHILADELPHIA—Prompt recognition of upper extremity lymphedema and the implementation of effective strategies are needed for optimal management of this frequently devastating side effect of breast cancer treatment, researchers advised at the 33rd Annual Congress of the Oncology Nursing Society. Mattie J. Sennett McDowell, RN,
BSN, a research nurse in the Department of Breast Medical Oncology at M.D. Anderson in Houston, Texas, and her colleagues reviewed recent medical literature to identify evidence-based strategies for the prevention and treatment of lymphedema. According to the American Cancer Society, lymphedema accounts for 15% to 20% of breast cancer complications and has been estimated to develop in 10% to 33% of patients with breast cancer who undergo surgery and radiation therapy, Ms McDowell pointed out. There are more than 100 million cases of lymphedema worldwide. Lymphedema not only decreases physical functional but also impairs quality of life.
OPIOID-INDUCED CONSTIPATION Continued from page 11
New agent approved for treatment of OIC
SUPPORTIVE CARE
In April, the US Food and Drug Administration approved methylnaltrexone bromide (Relistor; Wyeth and Progenics) subcutaneous injection for treatment of opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient. The binding of opioids to receptors in the gastrointestinal (GI) tract can cause dysfunction, leading to OIC. Methylnaltrexone bromide is a peripherally acting mu-opioid receptor antagonist that blocks the binding of opioids to peripheral mu-opioid receptors outside the central nervous system, such as those in the GI tract. It reduces the constipating effects of opioids without decreasing their analgesic effect. The safety and efficacy of the drug were demonstrated in two phase 3 studies of patients with advanced illness, most of whom had a primary diagnosis of incurable cancer. Patients included in the studies had been receiving palliative opioid therapy and had OIC. They continued on a stable opioid regimen throughout the study as needed and maintained their regular laxative regimen. Both studies showed a statistically significant response to methylnaltrexone compared with placebo in the primary end points. In study 301, a single-dose trial, 62% of patients receiving subcutaneous methylnaltrexone 0.15 mg/kg had a bowel movement within 4 hours after the first dose compared with only 14% of those receiving placebo. In study 302, a 14-day trial, 48% of patients receiving methylnaltrexone had a bowel movement within 4 hours of receiving the first dose compared with 16% of those receiving placebo. Also, in study 302, 52% of patients responded to at least two of four doses of methylnaltrexone. No patients in either the treated or control group had clinically relevant changes in pain scores from baseline. Methylnaltrexone is contraindicated in patients with known or suspected GI obstruction. The most common side effects are abdominal pain, flatulence, and nausea.
There are two types of lymphedema: primary lymphedema, which is a congenital anomaly of lymph vessels; and secondary lymphedema, which is acquired through precipitating factors, such as heat exposure, surgery, radiation, obesity, and environmental factors. Lymphedema is classified into four stages (Table). Although several methods of lymphedema prevention have been validated, “the literature does not reflect a standardized system for preventing lymphedema,” Ms McDowell pointed out. The various methods involve skin care measures aimed at preventing infection, avoidance of limb constriction, use of compression garments, and avoidance of extreme tempera-
ation has occurred within 30 minutes to 4 hours after drug administration. Once patients have achieved laxation, we would recommend that they make a change in the pharmacologic and nonpharmacologic interventions they had been using to try to prevent a refractory situation from reoccurring. If constipation continues to be a problem, methylnaltrexone can be given every other day in addition to routine measures. It is important to educate the patient and the caregiver so that they understand the importance of these preventive measures. We can teach through videos, or written material, or by sitting down and going through a schedule with the caregiver.
Quality of life is really the focal point of everyone involved. In your survey, did you look at how effective management of OIC affects patients’ and caregivers’ quality of life? More than 70% of those who responded to the survey said that once they could manage constipation, they were able to have good pain management, and this then allowed them to participate in social activities that improved their quality of life exponentially. We received very positive feedback from both patients and caregivers, who find it very reassuring to know that there are ways to resolve constipation when it is refractory to all the other measures we’ve offered them. Many of the nursing participants in the survey indicated that OIC has been a problem in their nursing care. They try very hard to meet patients’ other needs and reduce the social, emotional, financial, and spiritual stresses they’re experiencing, but they cannot begin to work on those aspects of their quality of life until they can achieve good symptom management. Quality of life is really the focal point of everyone involved—the caregiver, the patient, and the nurse. Having a way of resolving issues that hamper quality of life and being able to assure patients that something can be done to improve it gives them great hope. The focus of hospice and palliative care is always on the patient. We strive to meet the needs that they have expressed to us and abide by their desires and choices on how to live with the disease they have. References 1. The compassion compromise: trade-offs in pain management for patients with terminal illness. Executive summary. Research conducted by Strategy One. April 2008. http://www.hpna.org. Accessed July 16, 2008. 2. Methylnaltrexone bromide (Relistor). [package insert]. Philadelphia, PA; Wyeth Pharmaceuticals Inc, and Terrytown, NY: Progenics Pharmaceuticals 2008.
Table. Stages of Lymphedema • Stage 0–Absence of tissue swelling, can last for several months or even years before edema is evident.
• Stage 1–Swelling of the tissues, and sometimes pitting edema. The swelling can be temporarily decreased by limb elevation, but swelling soon returns. Additional swelling, fibrosis, and infections/skin problems are possible.
• Stage 2–Fluid accumulation that cannot be reduced by limb elevation. Tissues feel firm, hard, and nonpitting. Additional swelling may occur along with fibrosis and additional infections/skin problems.
• Stage 3–Swelling and tissue fibrosis that causes the skin to thicken and lose normal elasticity. This process may produce tissue folds, which limit mobility, increase the risk of fungal infection with open wounds resistant to healing, and may, ultimately, be disfiguring. tures. Additional practices include the wearing of footwear and hosiery that fits properly and the avoidance of standing, sitting, or crossing one’s legs for a long time. Nurses should familiarize themselves with these measures and routinely discuss them with patients with lymphedema during their clinic visits, Ms McDowell advised. A variety of methods have been used to manage lymphedema, she said. These include limb elevation, exercises, compression therapy (which includes compression bandages, gradient compression devices, or pneumatic compression devices), and surgery. “Although multiple treatment modalities were identified, there was inconsistency on the utilization of a standardized method or measurement tool,” Ms McDowell said. The literature review revealed unanimous support for increased awareness of lymphedema for oncology nurses through educational forums and didactic learning modules. Ms McDowell added her own recommendation—more nursing involvement in clinical trials of lymphedema. “As the number of treatment modalities for breast cancer increases, there is a corresponding increase in the number of side effects from treatments,” she said. “Lymphedema is poorly understood and under-researched, and oncology nurses need to take a more proactive role in preventing and managing its often significant sequelae.”
—Karen Rosenberg —JS
14
G REEN H ILL H EALTHCARE C OMMUNICATIONS
July/August 2008
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For additional information, visit www.gelclair.com or call 1-877-GELCLAIR. Ingredients: Water, Maltodextrin, Propylene Glycol, Polyvinylpyrrolidone (PVP), Sodium Hyaluronate, Potassium Sorbate, Sodium Benzoate, Hydroxyethylcellulose, PEG-40 Hydrogenated Castor Oil, Disodium Edetate, Benzalkonium Chloride, Flavoring, Saccharin Sodium, Glycyrrhetinic Acid. Contents: 15 mL per single-use packet. Commercial boxes contain 15 single-use packets. (NDC 24477-010-15) Indications: GELCLAIR® has a mechanical action indicated for the management of pain and relief of pain by adhering to the mucosal surface of the mouth, soothing oral lesions of various etiologies, including oral mucositis/stomatitis (may be caused by chemotherapy or radiation therapy), irritation due to oral surgery, traumatic ulcers caused by braces or ill-fitting dentures, or disease. Also indicated for diffuse aphthous ulcers. Contraindications: The administration of GELCLAIR® is contraindicated in any patient with a known or suspected hypersensitivity to any of its ingredients. Side effects: At the time of producing this leaflet, no adverse effects have been reported in clinical trials with the use of GELCLAIR®. Postmarketing reports have included infrequent complaints of burning sensation in the mouth. Reference: 1. Innocenti M, Moscatelli G, Lopez S. Efficacy of Gelclair® in reducing pain in patients with oral lesions: preliminary findings from an open pilot study. J Pain Symptom Manage. 2002;24:455-457. GELCLAIR® is a registered trademark of Helsinn Healthcare SA, Lugano, Switzerland. Manufactured for Helsinn Healthcare SA, Lugano, Switzerland. Marketed and distributed by EKR Therapeutics, Inc., Cedar Knolls, NJ 07927.
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Continuing Education Program #08CE059b • RELEASE DATE: August 1, 2008 • EXPIRATION DATE: July 31, 2009
Calculating the Dosage of Anticancer Drugs in Obese Patients: A Clinical Challenge BY SHARYN D. BAKER, PHARMD, PHD, AND DAVID GREGORNIK, PHARMD, BCNSP Pharmaceutical Sciences, St. Jude’s Children’s Research Hospital, Memphis, Tennessee
HOW TO RECEIVE NURSING CREDIT To receive continuing education credit, learners must: • Read the article in its entirety • Take the CE self-assessment test and complete the evaluation test: 1. Log onto www.theoncologynurse.com. 2. Click on UNMC logo on homepage. 3. Register to participate. 4. Enter program number 08CE059b. • Complete and submit the evaluation form online (enter program number 08CE059b). Nurses must answer at least 70% of the questions on the post-test correctly. If Internet access is not available, please fax a request for an evaluation form to 402-559-6379, attn: Anji Wittman, (please include return fax number) or e-mail concne@unmc.edu • The estimated time to complete this activity is 1 hour. Your continuing education certificate can be printed by following the directions online after successful completion of the post-test. DISCLAIMERS The opinions or views expressed in this continuing education activity are those of the faculty and do not necessarily reflect the opinions or recommendations of the University of Nebraska Medical Center College of Nursing Continuing Nursing Education.
D
osing recommendations for cancer drugs are ordinarily drawn from studies in patients thought to best represent those who are most likely to receive the drug in clinical practice. Unfortunately, the obese patient is usually not considered the typical candidate for the drug. Thus, at least for now, dosing recommendations for obese patients are less grounded in science than for nonobese patients. In the absence of standardized dosing guidelines for cancer drugs in obese patients, dosing recommendations are often extrapolated to this population arbitrarily when the dose must be standardized to a particular patient variable such as body surface area (BSA) to minimize the risk of toxicity. The problem is compounded by the lack of information on the effect of obesity on the pharmacokinetics and pharmacodynamics of anticancer drugs. In the clinical setting, drug doses for obese patients are calculated using a variety of empiric dosing regimens, ranging from using the patient’s BSA up to an arbitrary cut-off or relying on an alternate estimate of the patient’s weight, such as predicted normal weight, among others. Because these dosing regimens are untested, patients are at significant risk of being underdosed, which introduces the potential for suboptimal treatment outcomes. With a growing number of obese adults with cancer, it becomes increasingly important to identify reliable means of calculating dosages of anticancer drugs in this population. FACULTY/PLANNER DISCLOSURES All planners and faculty participating in continuing education activities provided by the University of Nebraska Medical Center, College of Nursing Continuing Nursing Education are expected to disclose to the audience any significant support or substantial relationship(s) with providers of commercial products and/or devices discussed in this activity and/or with any commercial supporters of the activity. In addition, all faculty are expected to openly disclose any off-label, experimental, or investigational use of drugs or devices discussed in their presentation. The planners and faculty and have been advised that this activity must be free from commercial bias
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David Gregornik, PharmD, BCNSP St Jude Children’s Research Hospital Memphis, TN 38105-2794
While the University of Nebraska Medical Center College of Nursing Continuing Nursing Education is an ANCC accredited organization, this does not imply endorsement by the UNMC or ANCC of any commercial products affiliated with this activity. PROGRAM GOAL To educate oncology nurses about the incidence, prevention, and treatment of severe hypersensitivity reactions to cetuximab. LEARNING OBJECTIVES After completing this activity, the reader should be better able to: • Describe current methods of calculating dosage of anticancer drugs for obese patients • Summarize the findings of studies of eight anticancer drugs in lean and obese patients • Evaluate the potential utility of alternative weight descriptors in dose calculation for obese patients TARGET AUDIENCE Advanced practice nurses, registered nurses, and other interested healthcare professionals, especially those caring for cancer patients. COST This program is complimentary for all learners.
To address this question, we need to better understand the physiologic effects of obesity on drug disposition. My coworkers and I re-evaluated data from published studies of eight anticancer drugs that enrolled a total of 1206 adult cancer patients and compared findings in obese and lean patients. Patients were classified as obese if their body mass index (BMI) was e30 kg/m2, whereas lean patients had a BMI <25 kg/m2. Using actual area under the curve (AUC) in lean patients as the target standard, we aimed to define the weight descriptor that provides the same AUC in an obese patient as in a lean patient. The weight descriptors we looked at included predicted normal weight, lean body mass, adjusted ideal body weight (IBW), and the mean of IBW and actual body weight (ABW). The anticancer agents included carboplatin, cisplatin, docetaxel, doxorubicin, irinotecan, paclitaxel, topotecan, and troxacitabine.
Kimberly S. Hamilton, RN, BSN Chronic Leukemia and Myeloma Program Cleveland Clinic Cleveland, OH 44195 Robert J. Ignoffo, PharmD, FASHP Touro University Vallejo, CA PLANNING COMMITTEE Lisa Anzai, RN, MA Nurse Planner University of Nebraska Medical Center College of Nursing 985330 Nebraska Medical Center Omaha, Nebraska 68198-5330 Catherine Bevil, RN EdD Director, Continuing Nursing Education and Evaluation University of Nebraska Medical Center College of Nursing 985330 Nebraska Medical Center Omaha, Nebraska 68198-5330 Lara J. Reiman Managing Editor Green Hill Healthcare Communications, LLC 241 Forsgate Drive Monroe Twp, NJ 08831 Karen Rosenberg Editorial Director Green Hill Healthcare Communications, LLC 241 Forsgate Drive Monroe Twp, NJ 08831 REVIEWER Cass Hammond, RN, MSN, CRNP Avid Education Partners 18071 Crampton Lane Sharpsburg, MD 21782
Findings • The disposition of some, but not all, drugs is significantly altered in obese patients. • The absolute clearance of cisplatin, paclitaxel, and troxacitabine was significantly increased in obese patients. However, this was not seen with carboplatin, docetaxel, irinotecan, or topotecan. • With doxorubicin, systemic clearance was significantly reduced by approximately 30% in obese women but not in obese men.
and based upon all the available scientifically rigorous data from research that conforms to accepted standards of experimental design, data collection, and analysis. The following authors, reviewers, and planning committee members listed below have stated they have no significant or substantial relationship with providers of commercial products and/or devices discussed in this activity and/or with any commercial supporter of this activity. • Lisa Anzai, RN, MA • Catherine Bevil, RN, EdD • Cass Hammond, RN, MSN, CRNP
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EDITORIAL BOARD Sharyn D. Baker, PharmD, PhD Department of Pharmaceutical Sciences St Jude Children’s Research Hospital Memphis, TN 38105-2794
• • • • • •
Lara J. Reiman Karen Rosenberg Sharyn D. Baker, PharmD, PhD David Gregornik, PharmD, BCNSP Kimberly S. Hamilton, RN, BSN Robert J. Ignoffo, PharmD, FASHP
CONTINUING NURSING EDUCATION ACCREDITATION AND CONTACT HOURS STATEMENT The University of Nebraska Medical Center College of Nursing Continuing Nursing Education is accredited as a
provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. This activity is provided for 1.0 contact hours under ANCC criteria. Provided for 1.2 contact hours under Iowa Provider #78. Provider Approved by the California Board of Registered Nursing, Provider #13699 for 1.2 contact hours.
July/August 2008
Continuing Education Program #08CE059b • RELEASE DATE: August 1, 2008 • EXPIRATION DATE: July 31, 2009 Table. Antineoplastic Chemotherapy Protocol Weeks 0, 3, 6, and 26 • Ifosfamide 2650 mg/m2 on days 1 to 3 of the course • *Carboplatin target area under the curve (AUC) = 8 mg* min/mL on day 1
• Prospective studies are needed to refine dosing strategies in obese patients for individual chemotherapeutic agents. • Pharmacokinetic studies are needed to clarify whether different subgroups of obese patients have different drug dispositions. For more information on this topic, see Sparreboom A, et al. Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J Clin Oncol. 2007;25:4707-4713.
Week 9
• Ifosfamide 2650 mg/m2 on days 1 to 3 • Doxorubicin 25 mg/m2 on days 1 and 2
Weeks 17 and 26 • *Carboplatin target AUC = 8 mg* min/mL on day 1* • Ifosfamide 2650 mg/m2 day 1 to 3
Weeks 20, 29, and 35 • *Carboplatin target AUC = 8 mg* min/mL on day 1 • Doxorubicin 25 mg/m2 days 1 and 2 *Glomerular filtration rate (GFR) was estimated by assessment of 99Tc-DTPA renal clearance and used to target the carboplatin AUC using a modified Calvert formula: Dose of carboplatin (mg/m2) = AUC × [(GFR (in mL/min/m2) × 0.93) + 15]
Recommendations • For most of the drugs we evaluated, weight scalars used to calculate BSA should take into account ABW, irrespective of size. In fact, ABW is the most accurate and precise descriptor for calculating anticancer drug doses for obese patients. For example, a BSA that uses ABW seems to be the best strategy for calculating the dose for cisplatin, paclitaxel, and troxacitabine.
When choosing an alternate size descriptor for dose calculation in the obese, it is important to consider the particular agent and the patient’s sex. • The use of lean body mass or IBW is probably the best dosing scalar for doxorubicin in obese women and docetaxel in both men and women. • For carboplatin, the average of ABW and IBW is the best predictor of carboplatin clearance within the Bénézet/Chatelut formula that uses serum creatinine to calculate dose. • When choosing an alternate size descriptor for dose calculation in the obese, it is important to consider the particular agent and the patient’s sex. • The data do not support arbitrary dose capping in obese patients for any of the eight drugs studied. • The data do not support the practice of empiric dose reduction because of obesity. July/August 2008
A 21-year-old obese white woman (height, 160.7 cm; weight, 106.6 kg; body mass index, 41.3 kg/m2; BSA, 2.22 m2) presented with osteosarcoma of the left femur.1 The patient reported that approximately 1 year before diagnosis she began to experience disturbances in her gait, when her left leg involuntarily began to “swing out” while walking. Six months before diagnosis, she experienced intermittent left leg pain localized to her femur. This
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• Doxorubicin 25 mg/m2 on days 1 to 3
Weeks 14, 23, and 32
Case Report
Calculating the Dosage of Anticancer Drugs in Obese Patients: A nurse’s perspective BY KIMBERLY S. HAMILTON RN, BSN Cleveland Clinic Foundation, Cleveland, Ohio
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study of US adults in 2002 showed that 31% were obese (with a body mass index [BMI] of e30 kg/m2) compared with 23% in 1994.1 Studies have shown that cancers of the colon, breast (postmenopausal), endometrium, kidney, and esophagus are associated with obesity. Links between obesity and cancers of the gallbladder, ovaries, and pancreas have also been found, and obese adults may be at increased risk for other types of cancer as well.2 With the increasing incidence of obesity among US adults, it is imperative to find ways to treat these individuals effectively and safely when they do develop cancer. Historically, appropriately conducted clinical trials have provided information on drug efficacy, safety, and tolerability through several phases, which then translates into clinical practice, before a drug is considered for approval by the US Food and Drug Administration. Phase 1 trials include a smaller group of patients, and the drug is dosed based on preclinical research in nonhuman models. Drugs given to patients enrolled in a phase 1 study may be used for several tumor types, with the goal of determining the maximum tolerated dose of the drug in humans. Phase 2 trials provide data on efficacy and tumor response in a larger group of patients. Information gathered from phase 2 trials suggests effective dosing in a specific tumor type. Finally, phase 3 trials often include a randomized design, comparing the new therapy with a standard therapy, to prove superiority of one treatment over the other. In my own experience in treating patients enrolled in clinical trials, I have found that often patients are not excluded from clinical trials because of their obesity, but rather because of the comorbidities associated with obesity. Exclusion criteria for many clinical trials include uncontrolled hypertension, cardiovascular disease, and an Eastern Cooperative Oncology Group performance status e2. Although several patients that I have treated would be considered obese with a BMI >30 kg/m2, it is not clear how different response to treatment is in this special population compared with those with a lower BMI.
To deliver the appropriate and effective treatment dose to patients, especially when calculating the dosage of most intravenous therapies, the patient’s weight is somewhat accounted for by dosing per the body surface area or area under the curve calculations, given the current model. There are dose limits and precautions to prevent against the toxicity associated with many anticancer drugs. It is very interesting that the findings reported by Baker and colleagues showed differences in the disposition and absolute clearance of some of the drugs that were studied in the obese patients. It is evident that more clinical trials are needed to decipher how body weight, sex, and other characteristics of individual patients affect the dosing of their treatment regimen. Although these questions may be answered by a clinical trial, it would be specifically challenging in any given trial, depending on the study end points, to do subset analyses of patients with a BMI >30 kg/m2 or to randomize patients who have a greater BMI to different dose levels. In addition, many tumor types are rare, and larger trials are difficult to conduct for these tumor types. Another aspect to consider would be the flat dosing of many novel oral agents for obese patients. Several oral anticancer therapies are dosed at a specific standard amount for a disease process based on doses determined in the clinical trial setting. For example, lenalidomide at the 25-mg dose is prescribed for patients with multiple myeloma. We adjust the dose for renal impairment, but seldom make dose adjustments based on the weight of the patient. The study by Baker and colleagues will raise awareness of the need for more clinical trials with an emphasis on the effects of obesity and other factors that may influence the appropriate dose of anticancer drugs for each patient. References 1. Flegal KM, Carroll MD, Ogden CL, et al. Prevalence and trends in obesity among U.S. adults, 1999-2000. JAMA. 2002;288:17231727. 2. Vainio H, Bianchini F. IARC Handbooks of Cancer Prevention. Vol. 6: Weight control and physical activity. Lyon, France: IARC Press; 2002.
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Continuing Education Program #08CE059b • RELEASE DATE: August 1, 2008 • EXPIRATION DATE: July 31, 2009 continued for 4 months until she was examined by her general practitioner, who prescribed anti-inflammatory medications. The patient returned to her general practitioner after 18 days, complaining of worsening pain, mild night sweats, and a decrease in appetite. Her general practitioner referred the patient to an orthopedic specialist, who ordered a radiograph of the left leg followed by magnetic resonance imaging and a bone scan. The results of the diagnostic imaging studies led to referral to our institution.
Carboplatin was dosed based on the patient’s GFR, which would account for obesity-related changes in renal function. After the diagnosis of osteosarcoma was confirmed, the patient was enrolled on the front-line investigational protocol for osteosarcoma (Table). As stipulated in the protocol, IBW was used to calculate all chemotherapy doses. This patient’s IBW was estimated to be 57.5 kg. Using IBW in the Gehan-George BSA equation, the patient’s dosing BSA was calculated to be 1.6 m2, a decrease of 28%. Despite this conservative approach to dosing her chemotherapy, the patient experienced appreciable toxicity during her therapy, including two admissions to the intensive care unit for hypotension and sepsis, prolonged thrombocytopenia resulting in delayed therapy, and significant nausea and emesis. Carboplatin was dosed based on the patient’s glomerular filtration rate, which would account for obesity-related changes in renal function. Based on the analysis by Sparreboom and colleagues,2 the use of lean body mass or IBW was recommended when calculating a doxorubicin dose for obese women; information on ifosfamide dosing in the obese patients was not included in this analysis. The patient completed her final course of therapy approximately 40 weeks after the original diagnosis. A computed tomography scan of the chest immediately after completion of her chemotherapy was positive for a new small lung nodule. A follow-up image 2 months later revealed new nodules in the right lung and a slight increase in size of the original nodule. The patient underwent thoracotomy with resection of the nodules. Gross residual disease involving the diaphragm remained after surgery. Pathologic examination of the nodules showed metastatic osteosarcoma. The patient received salvage chemotherapy with several different regimens. Unfortunately, her disease progressed through this therapy, and she died 2 years after her original diagnosis. References 1. Gehan EA, George SL. Estimation of human body surface area from height and weight. Cancer Chemother Rep. 1970;54:225-235. 2. Sparreboom A, Wolff AC, Mathijssen RH, et al. Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J Clin Oncol. 2007;25:4707-4713.
To receive complimentary CE credit: 1. Log onto www.theoncologynurse.com. 2. Click on UNMC logo on homepage. 3. Register to participate. 4. Enter program number 08CE059b. 18
C O M M E N TA R Y
Calculating the Dosage of Anticancer Drugs in Obese Patients: A Clinical Dilemma: A pharmacist’s perspective BY ROBERT J. IGNOFFO, PHARMD, FASHP Touro University, Vallejo, California, and the University of California, San Francisco
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f all the therapeutic challenges facing the oncologist, the dosing of anticancer drugs in the obese cancer patient is one of the most difficult. Only a few studies have addressed this issue in a systematic fashion. This research has resulted in dosing guidelines for specific drugs but not a generalized standard dosing guideline that can be applied to all anticancer drugs. No one patient variable stands out as a key factor in the dosing of these agents. The use of body surface area (BSA), a standard (although unproven in a clinical study) for dosing of anticancer drugs in the nonobese patient, does not correlate with the pharmacokinetics or pharmacodynamics of these toxic agents. A study by Baker and colleagues1 attempts to address the issue of reliable dosing of anticancer drugs in the obese cancer patient. They used alternative weight descriptors (lean body weight, geometric mean between actual and lean body weight, ideal body weight, and predicted normal weight) in the calculation of a patient’s BSA and then monitored drug area under the curve (AUC) to determine differences in obese and nonobese cancer patients. Unfortunately, their results varied by individual agent and even individual class (the taxanes in particular). While absolute clearance was increased for all drugs studied in obese patients (cisplatin, paclitaxel, and troxcitabine were significantly increased), there was no difference in clearance when values were standardized to BSA. The use of actual body weight in the BSA formula for dosing docetaxel and doxorubicin resulted in AUCs that were 33% and 25% significantly higher than 1.0, respectively. This was apparently due to changes in disposition of these drugs in women, because men did not have significantly higher AUC ratios. Using lean body weight in both men and women resulted in no difference in AUC ratios. Capping the BSA to 2.0 m2 resulted in a significantly higher AUC ratio only for women receiving doxorubicin, but the authors did not specifically discuss this. BSA capping, however, produced lower AUC ratios for other agents and, in general, is discouraged by the authors. This is consistent with the study of Joerger and colleagues,2 who showed that for each increase in BSA of 0.2m2, paclitaxel elimination was increased by almost 10%, suggesting that capping the BSA would result in lower drug exposure for this agent.
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With regard to carboplatin, they confirmed that the use of the mean of actual and lean body weight in the Bénézet-Chatelut formula leads to the most accurate prediction of drug exposure. The authors noted that this result was similar to that in the study performed by Bénézet and colleagues.3 This is further supported by a case report by de Jonge and colleagues,4 who reported extremely high drug exposures in a 130-kg patient receiving high-dose cyclophosphamide, thiotepa, and carboplatin. They used adjusted body weight for carboplatin, which lowered the AUC into the normal range. The study by Baker and colleagues is an important addition to the scientific literature and brings to light many of the issues that should be considered in the dosing of anticancer drugs, including sex, type of body weight to incorporate into dosing formulas, flat dosing, dose capping, and empiric dose reduction. It appears that physiochemical properties of the particular drug do not significantly affect the pharmacokinetic parameter of drug exposure for the drugs studied.
Recommendations • I agree with Drs Baker and Gregornik’s bulleted recommendations in their review of this article. I would add further that ideal body weight is not a good weight scalar for any of the drug studies, and it led to a significant decrease in drug exposure for cisplatin and paclitaxel. • Because the world is experiencing a global epidemic in obesity, extensive further research on dosing strategies along with the evaluation of pharmacokinetics of anticancer drugs is needed in obese patients. This work should be linked to the pharmacogenomics of anticancer drug effects. • Studies should be performed on other commonly used anticancer drugs, including cyclophosphamide, thiotepa, capecitabine, other anthracyclines, and hormonal agents. References 1. Sparreboom A, Wolff AC, Mathijssen RH, et al. Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J Clin Oncol. 2007;25:4707-4713. 2. Joerger M, Huitema AD, van den Bongard DH, et al. Quantitative effect of gender, age, liver function, and body size on the population pharmacokinetics of Paclitaxel patients with solid tumors. Clin Cancer Res. 2006;12:2150-2157. 3. Bénézet S, Guimbaud R, Chatelut E, et al. How to predict carboplatin clearance from standard morphological and biological characteristics in obese patients. Ann Oncol. 1997;8:607-609. 4. de Jonge M, Mathôt RA, Van Dam SM, et al. Extremely high exposures to in an obese patient receiving high-dose cyclophosphamide, thiotepa and carboplatin. Cancer Chemother Pharmacol. 2002;50:251-255.
July/August 2008
annual meeting of the American Society of Clinical Oncology. Data obtained from a large randomized clinical trial add to preclinical findings that zoledronic acid may have an anticancer effect. Zoledronic acid is currently indicated for the treatment of patients with multiple myeloma and documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy.
• Tamoxifen (20 mg/day) • Tamoxifen (20 mg/day) plus zoledronic acid (4 mg intravenous [IV] every 6 months) • Anastrazole (1 mg/day) • Anastrazole (1 mg/day) plus zoledronic acid (4 mg IV every 6 months) Treatment duration was 3 years; median follow-up was 5 years. Overall disease-free survival was 94%, and overall survival was 98.2%. There was no difference in the primary end point— disease-free survival—between patients
Zoledronic acid basically reduced events in all of the subcategories, not only bone metastasis. The Australian Breast and Colorectal Cancer Study Group Trial 12 was designed to compare the efficacy of tamoxifen and anastrazole with or without zoledronic acid in women with endocrine-responsive stage I or II breast cancer with <10 positive nodes. All 1803 women enrolled underwent surgery to remove the primary tumor and ovarian suppression with goserelin acetate (3.6 mg subcutaneously every 28 days for the duration of the trial) before being randomized to one of four treatment arms:
randomized to tamoxifen or anastrazole (P = .59). Women randomized to zoledronic acid had a 36% reduction (P = .11) in the risk of a relapse event compared with women not randomized to zoledronic acid. “When you further subdivide the results and look at event subcategories…zoledronic acid basically reduced events in all of the subcategories, not only bone metastasis, which one might have anticipated, but also locoregional recurrences, distant non-bone metastases, and also contralateral breast can-
ASCO:
Low Vitamin D Associated with Worse Outcomes in Patients with Breast Cancer CHICAGO—Vitamin D deficiency is associated with worse outcomes in women with early breast cancer. In addition, high-dose vitamin D supplementation can provide relief of symptoms, such as joint pain and fatigue, related to vitamin D deficiency from aromatase inhibitor therapy in postmenopausal women with breast cancer. These findings come from two separate studies presented at the 44th annual meeting of the American Society of Clinical Oncology.
July/August 2008
A study of 512 consecutively enrolled patients between 1989 and 1996 with newly diagnosed breast cancer, conducted at three hospitals in Toronto, showed that 38% of the patients had vitamin D deficiency, and another 39% had levels considered to be insufficient, said Patricia J. Goodwin, MD, one of the investigators. Low vitamin D levels were associated with tumor grade and adjuvant chemotherapy. Compared with patients with sufficient vitamin D levels, those with insufficient levels had a 94% decrease (P = .02) in distant disease-free survival and a 73% worse (P = .02) overall survival at 10 years. Nonetheless, high-dose vitamin D supplementation is premature in patients with breast cancer, said Dr Goodwin, chair in breast research, Mount Sinai Hospital, Toronto. She added that more current research should be conducted to ascertain whether vitamin D deficiency exists at the level it did during enrollment of patients into this study. Vitamin D supplementation is, however, justified in women with invasive breast cancer who are vita-
cer,” said Dr Gnant, professor of surgery, Medical University of Vienna. “This is in fact an indication that zoledronic acid exerts its benefit through a variety of mechanisms…kind of creating a tumor-hostile environment in our patients that helps to kill micrometastases, or dormants (as we call them), everywhere in the body.” Recurrence-free survival was improved by 35% (P = .015) by adding zoledronic acid to endocrine therapy compared with endocrine therapy alone. There was a nonsignificant trend (P = .10) toward improved overall survival in the zoledronic acid group. Zoledronic acid was generally well tolerated. Notably, there were no confirmed cases of osteonecrosis of the jaw, “which is very reassuring,” Dr Gnant said. Osteonecrosis of Michael Gnant, MD, speaking at ASCO. the jaw has been reported in cancer patients who are treated with survival and overall survival in the IV bisphosphonates, although many study with endocrine therapy and zolepatients who have developed osteo- dronic acid mean that women with necrosis of the jaw while receiving bis- endocrine-responsive early breast canphosphonate therapy were also receiv- cer can be spared the side effects of ing chemotherapy and corticosteroids. cytotoxic therapy after locoregional There was also no evidence of renal treatment, Dr Gnant concluded. toxicity with zoledronic acid. The overall excellent disease-free —Wayne Kuznar
min D-deficient when starting an aromatase inhibitor, said Qamar J. Khan, MD, who presented a study in which high-dose but not standard-dose vitamin D relieved joint pain and fatigue in vitamin D-deficient women taking letrozole. “All women starting an aromatase inhibitor should be screened for vitamin D deficiency, and attempts should be made to optimize vitamin D levels,” said Dr Khan, associate professor of oncology, Cancer Center of Kansas, Wichita. About one fourth of women with invasive breast cancer who receive adjuvant aromatase inhibitors experience joint pain or stiffness. About one fourth also report fatigue while being treated with an aromatase inhibitor. In a 16-week prospective study, 60 women with invasive breast cancer who were candidates for aromatase inhibitor therapy had serum vitamin D levels measured at baseline, 10 weeks, and 16 weeks. All women were started on 2.5 mg/day of letrozole and 1200 mg/day of calcium plus 600 IU/day of vitamin D. Women who had serum vitamin D levels d40 ng/mL at week 4 had their vitamin D dosage increased to 50,000 IU/day for the next 12 weeks. Fatigue, pain severity, joint pain disability, and menopausal symptoms were assessed via questionnaire at baseline, week 4, and week 16. Sixty-four percent of the women
had vitamin D deficiency (<32 ng/mL) at baseline; 49 of the 50 women who received high-dose vitamin D had serum vitamin D levels >32 ng/mL by week 10. With standard-dose (600 IU/day) vitamin D, serum vitamin D levels dropped in seven of nine women. During standard-dose vitamin D, joint pain improved in only 8% of women and worsened in 34%. During weeks 4 through 16, when the vitamin D-deficient women at week 4 were switched to high-dose vitamin D, joint pain improved in 21% and worsened in 32%. Similarly, fatigue scores were more likely to improve during high-dose vitamin D therapy and were more likely to worsen during standard-dose vitamin D therapy. “Given that these women are being subjected to an aromatase inhibitor, which causes bone loss, just for the bone health alone they should have optimal levels of vitamin D,” said Dr Khan. Health Assessment Questionnaire II scores, designed to study the effects of an intervention on activities of daily living, were stable from baseline to week 4 (during standard-dose vitamin D therapy) but declined (improved) from weeks 4 to 16 (during high-dose vitamin D therapy). —WK
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Cancer Center & Research Institute Photo courtesy of The Moffitt Cancer Center
Moffitt Facts: Number of beds: 162 Number of inpatients: 726 Number of outpatients: 264,523 Number of staff: 3800 employees (800+ research faculty, 300+ physicians)
Executive Director: William S. Dalton, MD, PhD
Publication: Cancer Control Journal (peer-reviewed journal with a readership of 13,000)
Funding: For 2008, Moffitt received approximately $66 million in grants.
Research programs: Molecular oncology, immunology, drug discovery, experimental/therapeutic, genetic immunotherapy, behavior oncology, cancer screening, prevention, and detection, digital imaging, tobacco research and intervention, molecular screening July/August 2008
patient referrals. Moffitt has also earned the honor of being named in US News & World Report as one of America’s Best Hospitals. In addition to its main campus in Tampa, the center has 15 affiliates in Florida, one in Georgia, and two in Puerto Rico. The Moffitt Cancer Center provides the most marrow and blood transplants in the Southeastern United States.
Personalized cancer care In its vision to “be the leader in scientific discovery and translation into compassionate care, cures, and prevention of cancer,” the center is constantly growing, expanding, and evolving to keep current and remain innovative. The center’s latest initiative is to expand its personalized oncology research. The center started collaborating with Merck & Co in 2006 to develop more personalized treatment for different types of cancers that affect individuals. This Total Cancer Care initiative was started to test every tumor and 30,000 genes of patients with cancer. The goal is to create personalized individual cancer care through genetics and to help save more lives by 2010. Working in conjunction with the University of Florida and Shands Healthcare, the partnership will encompass the spectrums of patient care, research, and education. The goals of this collaboration include quality improvement in cancer care, helping to address the needs of surviving family members, and, lastly, tissue/data collection to create more custom-tailored therapies for each patient. Executive Director, Willian S. Dalton, MD, PhD, stated at a media conference, “Total Cancer Care is intended to streamline pathways to cancer care and to follow the patient through screening, diagnosis, and treatment of cancer, incorporating translational research at each step along this continuum of care.” Caring for the caregiver One of the initiatives of note at Moffitt is a program called Caring for the Caregiver, which provides stress management training, nutritional counseling, and advice on problem-solving techniques and communication strategies to family members of patients who live at home. Another unique service on offer is Cancer Answers, a toll-free telephone service staffed by registered nurses, who answer queries on such matters as cancer detection, prevention, risk, diagnosis, treatment, and research. Robert Bradbury, RPh, the clinical coordinator of the pharmacy has been a pharmacist since 1975, and has been on staff at Moffitt for 20 years. There are 65 pharmacists on staff at the center, and they work in various areas, such as the central pharmacy, retail pharmacy, and on clinical trials. There are also rounding pharmacists integrated into different areas and different roles. All are board-certified in oncology. According to Bradbury, Florida has the most boardcertified pharmacists in the nation. He says, “We take pride in being integrated with the patient care model at Moffitt so the patients have an advocate for their drug therapy.” Bradbury enjoys his interaction with patients, saying, “No one is more pleasant to work with than cancer patients. They’re very thankful for our interaction. It’s a great opportunity to be of comfort and to improve outcomes for our patients. One person can really make a difference.” Nurse Serena Moody has been on staff at Moffitt
Photo courtesy of The Moffitt Cancer Center
for a little over a year, and gives rave reviews of her professional experience there, with both other staff members and patients. She speaks warmly about her patients and their families, saying how grateful she is to be able to provide care and comfort for them, and how positive their interactions are. Many cancer patients and their families are glad to be at Moffitt, she says, and this creates a positive environment. She admits, however, that her job can be emotionally strenuous and is grateful for the support that Moffitt provides for its staff. Not only are ongoing professional workshops provided, but there is an extensive mentoring program for new nurses.
Encouraging oncology certification In recognition of its efforts to encourage staff nurses to seek oncology certification, the Moffitt Cancer Center received the 2008 Employer Recognition Award from the Oncology Nursing Certification Corporation. All nursing position descriptions indicate that, depending on the position, oncology certification is either preferred or required. To support certification, the center provides reimbursement for test fees and renewal of certification. The center also provides on-site, accredited continuing education programs, paid time to attend review courses, and reimbursement for nurses who participate in external review courses. Moffitt nurses receive a $1,000 bonus at the time of initial certification and on renewal of certification, and salary increases are tied to certification. Nurses are encouraged to participate in professional development activities and receive paid time to do so. The center recognizes certified nurses in a variety of ways, including Nurses Week celebrations, announcements in internal and external publications, and recognition plaques in patient care units. —Amy Johansson
G REEN H ILL H EALTHCARE C OMMUNICATIONS
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CANCER CENTER PROFILE
W
hen H. Lee Moffitt, then a Florida State Representative, conceived of the center that now bears his name back in 1978, he had no idea that 30 years later his name would be synonymous with innovative and comprehensive cancer care. Moffitt, a cancer survivor, was alarmed by Florida’s high rate of cancer. The state needed a center that would help eradicate cancer as a public health threat through patient care, education, and research. Florida ranks second in the nation for its rates of cancer incidence and mortality. Initially, Moffitt’s vision was met with resistance—where would the funding come from? But with the help of the Floridian government, he was able to raise $70 million dollars initially. In 1981, the Florida legislature passed a bill to secure the planning for the H. Lee Moffitt Cancer Center & Research Institute on the Tampa campus of the University of South Florida. Notably, funding for the initial $70 million needed for construction of the center came mainly from the state’s cigarette tax. In 1983, the center celebrated its groundbreaking, and by 1986, the center started admitting patients. The success was inspiring, and the center continued to grow, in physical size and in reputation. In 1998, the center expanded its research and clinical areas thanks to a $100 million grant from the Florida legislature. This was followed by earning the status of a National Cancer Institute Cancer Center. Earning this highly regarded distinction has translated into doubled research funding and a 130% increase in
CANCER CENTER PROFILE
H. Lee Moffitt
Nursing Life NURSING LIFE
Preheat oven to 375 degrees. Mix together the peaches, pinch of salt, nutmeg, cinnamon, ¼ cup flour, vanilla, lemon juice, and ½ cup sugar. Place in a 6”×10” baking dish. Sift together 3 cups flour, ½ tsp salt and 2 tsp. baking powder. In a separate bowl, combine the eggs, ½ cup sugar, milk, and melted butter.
Cinnamon Peach Cobbler Courtesy of Jay Weinstein
One of the great things about baking peaches is that you need not peel the skin, since it becomes more tender when cooked. This cobbler should be fully cooked, bubbling all throughout before it’s taken from the oven.
For the Filling: 10 large peaches, pitted and sliced into 1-inch wedges Pinch of salt ¼ tsp ground nutmeg 1 capful vanilla extract 1 ½ tsp ground cinnamon ½ cup sugar ¼ cup flour Juice of ½ lemon For the Biscuit Topping: 3 cups flour ½ tsp salt 2 tsp. baking powder 2 eggs ½ cup sugar ⅔ cup milk 6 oz melted butter
Add the wet ingredients to the dry, mixing only until they are well combined. Do not over-mix. Batter should have consistency of thick oatmeal. Adjust with milk if necessary. Spread batter over fruit, as evenly as possible with your hands. Some holes are natural, and will make for a more attractive presentation. Bake on bottom shelf of 375-degree oven for 90 minutes, turning halfway through, and checking after 1 hour. Fruit should be bubbling thoroughly, and biscuit topping should be nicely browned. Allow to cool at least 15 minutes before serving with vanilla ice cream and a sprig of fresh mint. What’s Your Favorite Healthy Recipe? With a little creativity, healthy foods can be delicious as well as nutritious. Do you have a favorite healthy recipe that you would like to share with your colleagues and patients? Send your recipe and its source (family recipes are welcome) to Karen@greenhillhc.com. Peach photos—Upper left: ©iStockphoto.com/Alina Pavlovava Bottom right: ©iStockphoto.com/Jill Fromer
Cartoon courtesy of Joseph Farris
CARTOON
NURSING LIFE
“There’s one side effect. It may kill you.” 22
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Your Financial Future By Sylvia Maurin
T
his column provides money management information and strategies that may help you gain greater control over your finances, reduce anxiety associated with financial decisions, and enable you to enjoy an enhanced sense of well-being about your financial future.
People and their money The relationship between people and their money tends to be deeply emotional, even irrational at times. For some, having money in hand rather than spending it is a source of power. For others, if there is no spending in progress, there is no success. Even for those in the big middle where moderate fiscal behavior is the norm, there seems to be a general and ever-present anxiety associated with money. The aim of this article is to provide information about how to identify and locate a financial planning professional, a great first step toward clearer financial objectives and lessening of financial anxiety. Understanding the acronyms While more education produces better-trained, more knowledgeable professionals, sorting through and understanding the various designations can be a daunting task. There are about 90 designations, certifications, and degrees available to financial services professionals. Some financial professionals believe there is a “Big Four” that stand out among the group: Certified Financial Planner (CFP), Certified Public Accountant (CPA), Chartered Financial Analyst (CFA), and Masters in Business Administration (MBA). All the professionals in these groups tend to have had broadbased financial education and training, and all have passed rigorous examinations. Many financial services professionals earn multiple designations and additionally seek specialty designations that are industry-specific. For example, there are those certified in longterm care (CLTC) as well as certified divorce financial analysts (CDFAs), and registered investment advisors (RIAs).
Taking action If you are starting out to find an advisor for the first time or are starting over after some time without ongoing financial advice, begin the process by asking friends, colleagues, and neighbors for referrals. The process is much the same as the one you would follow to locate a new physician or specialist. Locate three professionals and make an appointment with each for an initial no-cost consultation. Go to the appointment with some questions and pay particular attention to your gut sense of whether you can work easily with the professional under consideration. This aspect of the search process is much like a job interview; you are the hiring manager. You will want to select someone you think can do the job you need done. Ask about fees—all charges associated with the professional’s services and the fees for products he or she may sell; ask for three client references; and ask if the professional helps to both implement plans and work to keep plans current after the initial plan is completed. Either before or immediately after you hire a planner, be prepared to get actively involved in the process. Understand that you will need to spend time gathering all of your financial data so the planner can see what he or she has to work with and, importantly, be thoughtful and deliberate about setting your financial goals and objectives. Sylvia Maurin is president of Source One, LLC, a consulting services firm in Pittsburgh, Pennsylvania. Information presented in this column is general in nature. It is not intended to furnish or replace the expert guidance and/or advice of a financial planning professional familiar with your particular financial situation, goals, and objectives.
July/August 2008
Are You REALLY Listening? By Jim Barnoski
Focus in on the basic message Try to pinpoint the main ideas the person is expressing. Ask yourself what the speaker is trying to say. If you’re not sure, ask. “Mr. Jones, I believe what I heard is . . . Am I on track?” Understand what is being said Keep asking yourself if you understand what is being said. If you don’t, ask for clarification—and keep asking until you are sure you fully understand. “Mr. Jones, I’m not sure I understand how this relates to that. Can you help me out?” What you don’t understand, you can’t recall. Additionally, if you don’t understand what is being said, your mind is more likely to wander, and your listening effectiveness diminishes. Don’t get distracted Don’t let trivial things like the speaker’s appearance or random noises divert your attention from what he or she is saying. Listen to the speaker’s whole sentence. Listen not only for content, but context. Anytime you catch yourself being distracted by something that draws your attention away from the speaker’s words, make a conscious effort to focus back on the words. Do that by creating word images that match the speaker’s words. July/August 2008
Listen with your “gut” The speaker’s tone and body language will impart meaning. Body language accounts for 55% of communication and tonality 38%. The words are only 7% of the process. These subtle clues are quickly picked up by the unconscious mind and leave us with a particular feeling about the speaker. When you are left with a “feeling” about someone after a conversation— that they are sincere, they are hiding something, they can’t be trusted, etc— it is a sign that your unconscious mind has put two and two together and come up with an evaluation.
In summary, listen proactively There is more to listening than just passively hearing the words someone is speaking. Remember, neither questioning or listening is a passive activity. ©2008 Sandler Training, Inc. The Sandler Sales Institute is an international sales and management training/consulting firm since 1967. For more information go to www.sandler.com
Get Involved To keep your active attention on what is being said, offer comments. If the situation permits, offer your own perspective
Jim Barnoski is a trainer with Sandler Training Center.
Your subscription at NO CHARGE is just a signature away! Written by and for oncology nurses offering you the following: • Concise reviews of hot topics in the peer-reviewed literature by clinical specialists with key point ‘takeaways’ • Coverage of key research studies and on-the-scene reports from oncology medical meetings • Continuing education articles at no charge and post-tests, offering you a convenient way to obtain contact hours • Interviews with renowned thought leaders in the oncology nursing community • A “Policy Watch” column covering legislation and policy changes that affect cancer care in your areas of practice • Articles of special interest to student nurses, your future colleagues
NURSING LIFE
I
interview many professionals in all walks of life every week, and one question that always comes up is: How do you find out what your patient really needs when they don’t communicate well. The answer I often hear is “by listening.” Professionals in nursing, pharmacy, or any other business often forget that listening is a two-part exercise, neither of them passive. The first part of the exercise is planning and asking a variety questions that will get your patient thinking about his needs. After all, patients and clients are often busy people who, contrary to our perceptions, don’t spend a lot of time thinking about how our services might help them. They need some help getting started. So we have to ask the questions that will provoke thought and uncover the real problems. The second part is listening. Asking your patient all the correct questions is wasted if you don’t hear what he or she is saying, either in words, or more subtly, in tones or partial hints. Being a good listener requires more than just keeping quiet while the other person is talking. Sometimes we’re even thinking about our next question while they are answering our last question! Do you hear everything that is being said? Do you understand it completely? Here are some tips on how to become a more effective listener:
on what is being said. Ask a question or relate a relevant story that reinforces what the person is saying, or represents a different point of view. Ask yourself if what the person is saying relates to other situations or experiences. Third-party stories are an excellent way to confirm that you’ve got it right.
Become personally absorbed in what is being said. You can’t listen effectively if you are only “going through the motions.” Every subject has some interesting angle, some impact on you, or something you can learn. To uncover those elements, you must first abandon your prejudiced or preconceived ideas. If you enter into a conversation with the notion that the other person has nothing of interest or importance to say, you will miss what is important. An attitude of curiosity about a patient’s or coworker’s concerns and needs is flattering and can become both a bonding experience and a communications tool.
NURSING LIFE
Leadership and Communication Skills for Nurses
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Pediatric Oncologists Neglect to Query Patients about Alternative Therapies HONOLULU–Although pediatric oncologists believe it is important to know what complementary and alternative medicine (CAM) therapies their patients use, they only occasionally discuss the topic with their patients, according to the results of a study reported at the recent Pediatric Academic Societies 2008 meeting. The data also show that time constraints and a lack of knowledge about CAM are the main barriers to communication between pediatric oncology patients and oncologists regarding use of CAM. Michael Roth, MD, a resident in the Pediatrics Division at Albert Einstein College of Medicine in New York, presented findings from an online questionnaire completed by 83 pediatric oncologists in the United States. The 33-question survey is the first to document pediatric oncologists’ views of their patients’ use of CAM. “Even though CAM use by pediatric oncology patients is highly prevalent and CAM therapies may sometimes improve quality of life but also interact harmfully
with standard oncology therapy, pediatric oncologists are often not aware of what CAM therapies their patients are using,” Dr Roth pointed out. In the present study, 67% of oncologists reported that more than 25% of their patients use CAM, and 99% of oncologists maintained that it is important to know what CAM therapies their patients use, mostly to prevent potential harmful drug interactions and improve trust between physicians and patients. Nonetheless, only half of them ever ask their patients about CAM. Forty-nine percent of oncologists reported lack of time as a reason for the failure to ask patients about their CAM use, and 47% cited lack of knowledge about CAM. Three quarters of physicians said they believed that some forms of CAM might improve quality of life; massage therapy and prayer were most often cited. More than half of physicians thought that dietary supplements, herbal medicine, and antioxidants might be harmful.
©iStockphoto.com/Sean Locke
ALTERNATIVE AND COMPLEMENTARY THERAPIES
Alternative/Complementary Therapies
Dr Roth called for increased physician education on CAM and recommended the use of a brief CAM screening tool that may help physicians obtain information in limited time. He noted that nurses in pediatric oncology have an opportunity to ask patients and their families about their
Acupuncture May Reduce Pain and Dysfunction after Neck Dissection
ALTERNATIVE AND COMPLEMENTARY THERAPIES
CHICAGO—New data from a randomized, controlled trial have shown that acupuncture may significantly reduce pain, dysfunction, and xerostomia in patients with head and neck cancer after neck dissection. The findings were presented at the 44th Annual Meeting of the American Society of Clinical Oncology. Neck dissection is a common procedure for the treatment of head and neck cancer. Radical neck dissection involves complete removal of lymph nodes from one side of the neck and the muscle that helps turn the head as well as removal of a major vein and a nerve that is critical to full range of motion for the arm and shoulder. “Chronic pain and shoulder mobility problems are common after such surgery, adversely affecting quality of life as well as employability for certain occupations,” said lead study investigator David Pfister, MD, who is chief of the Head and Neck Medical Oncology Service at Memorial Sloan-Kettering Cancer Center (MSKCC), New York. Dr Pfister said physical therapy and antiinflammatory mediations are now widely prescribed to address the pain and shoulder dysfunction after neck dissection, but their efficacy is often disappointing or incomplete. In addition, postoperative radiation is frequently administered after neck dissection and this leads to xerostomia. Nerve-sparing and other modified radical techniques that preserve certain structures without compromising disease control reduce the incidence of these problems but do not eliminate them entirely. “Unfortunately, available conventional methods of treatment for pain and dysfunction following neck surgery often have limited benefits, leaving much room for improvement,” Dr Pfister said. 24
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For this study, 70 patients were randomized to receive either acupuncture or usual care, which included recommendations of physical therapy exercises and the use of anti-inflammatory drugs. For all the patients, at least 3 months had elapsed since their surgery and radiation treatments. The treatment group received four sessions of acupuncture over the course of approximately 4 weeks. Both groups were evaluated using the Constant-Murley Scale, a composite measure of pain, function, and activities of daily living. The investigators found that pain and mobility improved in 39% of the patients receiving acupuncture, compared with only 7% in the group that received usual care. An added benefit of acupuncture was significant reduction of xerostomia, which, until now, has been addressed with only limited success by mainstream means. “Like any other treatment, acupuncture does not work for everyone, but it can be extraordinarily helpful for many,” said study co-investigator Barrie Cassileth, PhD, who is chief of the Integrative Medicine Service at MSKCC. “It does not treat illness, but acupuncture can control a number of distressing symptoms, such as shortness of breath, anxiety and depression, chronic fatigue, pain, neuropathy, and osteoarthritis.” She cautioned, however, that patients with cancer should consult only acupuncturists who are certified by the National Certification Commission for Acupuncture and Oriental Medicine and who are trained in working with the special symptoms and problems caused by cancer and cancer treatment. —John Schieszer
use of CAM therapies and assist with opening a dialogue between physicians and patients. “In my experience, nurses very often are the first people the family will turn toward to discuss CAM,” he said. — JS
Coming Soon CE article: Treatment of Anemia in Cancer Patients with ESAs and IV Iron
New Approaches to the Treatment of Pediatric Neuroblastoma The Oncology Nurse as Patient Advocate Helping Children with Cancer Return to School Nutrition Screening of Oncology Patients Identifying Patients at High Risk for Fungal Infections Oncology Patient Participation in Clinical Trials For a free subscription go to
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July/August 2008
Meetings SEPTEMBER 2008 ©iStockphoto.com/Chris Pritchard
5–6
NEW YORK, NY NCCN 3rd Annual Congress: Hematologic Malignancies www.nccn.org
5 – 7 WASHINGTON, DC
2008 Breast Cancer Symposium www.astro.org
17 – 20
SAN FRANCISCO, CA 25th National Oncology Economics Conference www.accc-cancer.org
©iStockphoto.com/Tony Tremblay
OCTOBER 2008
16-18
©iStockphoto.com/Cheng Chang
MONTREAL, CANADA 9th Meeting of the International Society of Geriatric Oncology www.cancerworld.org/siog
17-18
ARLINGTON,VA 2008 ASTRO Translational Advances in Radiation Oncology and Cancer Imaging www.astro.org
July/August 2008
RITUXAN® (Rituximab) Brief summary—Please consult full prescribing information. WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) Infusion Reactions: Rituxan administration can result in serious, including fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Carefully monitor patients during infusions. Discontinue Rituxan infusion and provide medical treatment for Grade 3 or 4 infusion reactions [see Warnings and Precautions, Adverse Reactions]. Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non-Hodgkin’s lymphoma (NHL) patients with Rituxan [see Warnings and Precautions, Adverse Reactions]. Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan [see Warnings and Precautions, Adverse Reactions]. Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving Rituxan [see Warnings and Precautions, Adverse Reactions].
INDICATIONS AND USAGE Non-Hodgkin’s Lymphoma (NHL) Rituxan® (rituximab) is indicated for the treatment of patients with: Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent; Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy; Non-progressing (including stable disease), low-grade, CD20positive B-cell NHL, as a single agent, after first-line CVP chemotherapy; Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens. WARNINGS AND PRECAUTIONS Infusion Reactions Rituxan can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion with time to onset of 30–120 minutes. Rituxan-induced infusion reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, or anaphylactoid events. Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g., glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion reactions as needed. Depending on the severity of the infusion reaction and the required interventions, consider resumption of the infusion at a minimum 50% reduction in rate after symptoms have resolved. Closely monitor the following patients: those with preexisting cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (>25,000/mm3). [See Boxed Warning, Warnings and Precautions, Adverse Reactions.] Tumor Lysis Syndrome (TLS) Rapid reduction in tumor volume followed by acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia, can occur within 12–24 hours after the first infusion. Fatal TLS cases have occurred after administration of Rituxan. A high number of circulating malignant cells (*25,000/mm3) or high tumor burden confers a greater risk of TLS after rituximab. Consider prophylaxis for TLS in patients at high risk. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated. [See Boxed Warning.] Severe Mucocutaneous Reactions Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with Rituxan. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these reactions has varied from 1–13 weeks following Rituxan exposure. Discontinue Rituxan in patients who experience a severe mucocutaneous reaction. The safety of readministration of Rituxan to patients with severe mucocutaneous reactions has not been determined. [See Boxed Warning, Adverse Reactions.] Progressive Multifocal Leukoencephalopathy (PML) JC virus infection resulting in PML and death can occur in Rituxan-treated patients with hematologic malignancies or with autoimmune diseases for which Rituxan has not been approved. The majority of patients with hematologic malignancies diagnosed with PML received Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell transplant. The patients with autoimmune diseases had prior or concurrent immunosuppressive therapy and were diagnosed with PML within 12 months of their last infusion of Rituxan. Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue Rituxan and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. [See Boxed Warning, Adverse Reactions.] Hepatitis B Virus (HBV) Reactivation Hepatitis B Virus (HBV) reactivation with fulminant hepatitis, hepatic failure, and death can occur in patients with hematologic malignancies treated with Rituxan. The median time to the diagnosis of hepatitis was approximately 4 months after the initiation of Rituxan and approximately one month after the last dose. Screen patients at high risk of HBV infection before initiation of Rituxan. Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV infection for several months following Rituxan therapy. Discontinue Rituxan and any concomitant chemotherapy in patients who develop viral hepatitis, and institute appropriate treatment including antiviral therapy. Insufficient data exist regarding the safety of resuming Rituxan in patients who develop hepatitis subsequent to HBV reactivation. [See Adverse Reactions.] Other Viral Infections The following additional serious viral infections, either new, reactivated, or exacerbated, have been identified in clinical studies or postmarketing reports. The majority of patients received Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell transplant. These viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis C. In some cases, the viral infections occurred as late as one year following discontinuation of Rituxan and have resulted in death. [See Adverse Reactions.] Cardiovascular Discontinue infusions for serious or lifethreatening cardiac arrhythmias. Perform 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 Adverse Reactions.] Renal Severe, including fatal, renal toxicity can occur after Rituxan administration in patients with hematologic malignancies. Renal toxicity has occurred in patients with high numbers of circulating malignant cells (>25,000/mm3) or high tumor burden who experience tumor lysis syndrome and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and Rituxan is not an approved treatment regimen. Use extreme caution if this non-approved combination is used in clinical trials and monitor closely for signs of renal failure. Consider discontinuation of Rituxan for patients with a rising serum creatinine or oliguria. Bowel Obstruction and Perforation Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving Rituxan in combination with chemotherapy. In postmarketing reports, the mean time to documented gastrointestinal
13 – 18 CHICAGO, IL
16 – 19 WASHINGTON, DC
2008 Multidisciplinary Lung Cancer Symposium www.oncologymeetings.org
7th International Conference on Frontiers in Cancer Prevention Research www.aacr.org
perforation was 6 (range 1–77) days in patients with NHL. Perform a thorough diagnostic evaluation and institute appropriate treatment for complaints of abdominal pain, especially early in the course of Rituxan therapy. [See Adverse Reactions.] Immunization The safety of immunization with live viral vaccines following Rituxan therapy has not been studied and vaccination with live virus vaccines is not recommended. For NHL patients, the benefits of primary or booster vaccinations should be weighted against the risks of delay in initiation of Rituxan therapy. Laboratory Monitoring Because Rituxan binds to all CD20positive B lymphocytes (malignant and non-malignant), obtain complete blood counts (CBC) and platelet counts at regular intervals during Rituxan therapy and more frequently in patients who develop cytopenias [see Adverse Reactions]. The duration of cytopenias caused by Rituxan can extend months beyond the treatment period. ADVERSE REACTIONS The most common adverse reactions of Rituxan (incidence *25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia. The most important serious adverse reactions of Rituxan are infusion reactions, tumor lysis syndrome, mucocutaneous toxicities, hepatitis B reactivation with fulminant hepatitis, PML, other viral infections, cardiac arrhythmias, renal toxicity, and bowel obstruction and perforation. Clinical Trials Experience Non-Hodgkin’s Lymphoma Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to Rituxan in 1606 patients, with exposures ranging from a single infusion up to 6–8 months. Rituxan was studied in both single-agent and active-controlled trials (n = 356 and n = 1250). These data were obtained in adults with low-grade, follicular, or DLBCL NHL. Most patients received Rituxan as an infusion of 375 mg/m2 per infusion, given as a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 doses, or following chemotherapy for up to 16 doses. Infusion Reactions In the majority of patients with NHL, infusion reactions consisting of fever, chills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first Rituxan infusion. Infusion reactions typically occurred within 30 to 120 minutes of beginning the first infusion and resolved with slowing or interruption of the Rituxan infusion and with supportive care (diphenhydramine, acetaminophen, and intravenous saline). The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. [See Boxed Warning, Warnings and Precautions.] Infections Serious infections (NCI CTCAE Grade 3 or 4), including sepsis, occurred in less than 5% of patients with NHL in the single-arm studies. The overall incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal 1%). [See Warnings and Precautions.] In randomized, controlled studies where Rituxan was administered following chemotherapy for the treatment of follicular or low-grade NHL, the rate of infection was higher among patients who received Rituxan. In diffuse large B-cell lymphoma patients, viral infections occurred more frequently in those who received Rituxan. Cytopenias and hypogammaglobulinemia In patients with NHL receiving rituximab monotherapy, NCI-CTC Grade 3 and 4 cytopenias were reported in 48% of patients. These included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia was 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116 days). A single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences of hemolytic anemia following Rituxan therapy occurred during the single-arm studies. In studies of monotherapy, Rituxan-induced B-cell depletion occurred in 70% to 80% of patients with NHL. Decreased IgM and IgG serum levels occurred in 14% of these patients. Single-Agent Rituxan Adverse reactions in Table 1 occurred in 356 patients with relapsed or refractory, lowgrade or follicular, CD20-positive, B-cell NHL treated in single-arm studies of Rituxan administered as a single agent. Most patients received Rituxan 375 mg/m2 weekly for 4 doses. Table 1 Incidence of Adverse Events in *5% of Patients with Relapsed or Refractory, LowGrade or Follicular NHL, Receiving Single-agent Rituxan (N = 356)a,b
and 4 adverse reactions and serious adverse reactions. In Study 7, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs. 1.0% for CHOP). The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs. 7%) and lung disorder (6% vs. 3%). Other Grade 3 or 4 adverse reactions occurring more frequently among patients receiving RCHOP were viral infection (Study 7), neutropenia (Studies 7 and 8), and anemia (Study 8). 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, antihuman anti-chimeric 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 rituximab treated patients is unclear. Postmarketing Experience The following adverse reactions have been identified during postapproval 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. USE IN SPECIFIC POPULATIONS Pregnancy Category C: There are no adequate and well-controlled studies of rituximab in pregnant women. NonHodgkin’s lymphoma and severe rheumatoid arthritis are serious conditions that require treatment. Rituximab should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Rituximab is a genetically engineered IgG molecule, and IgG crosses the human placenta. 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. Other than target B lymphocytes, rituximab is not known to bind to any normal human tissues in an ex vivo assay. However, it is not known if binding occurs to unique embryonic or fetal tissue receptors in vivo. 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 gastrointestinal or limited systemic exposure to Rituxan should be weighed against the known benefits of breastfeeding. Pediatric Use The safety and effectiveness of Rituxan in pediatric patients have not been established. Geriatric Use Diffuse Large B-Cell NHL 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 All Grades (%) Grade 3 and 4 (%) All Grades (%) Grade 3 and 4 (%) frequently among elderly patients. Serious pulmonary adverse reactions were also Any Adverse Events 99 57 38 4 Respiratory System more common among the elderly, including pneumonia and pneumonitis. LowBody as a Whole Increased Cough 13 1 86 10 Rhinitis 12 1 Fever 53 1 Grade or Follicular Non-Hodgkin’s Lymphoma Clinical studies of Rituxan in Bronchospasm 8 1 Chills 33 3 low-grade or follicular, CD20-positive, B-cell NHL did not include sufficient Dyspnea 7 1 Infection 31 4 Sinusitis 6 0 Asthenia 26 1 numbers of patients aged 65 and over to determine whether they respond Metabolic and Nutritional Headache 19 1 Abdominal Pain 14 1 Disorders 38 3 differently from younger subjects. OVERDOSAGE There has been no experience Pain 12 1 Angioedema 11 1 with overdosage in human clinical trials. Single doses of up to 500 mg/m2 have Back Pain 10 1 Hyperglycemia 9 1 Throat Irritation 9 0 Peripheral Edema 8 0 been given in dose-escalation clinical trials. NONCLINICAL TOXICOLOGY Flushing 5 0 LDH Increase 7 0 Heme and Lymphatic System 67 Digestive System 48 37 2 Carcinogenesis, Mutagenesis, Impairment of Fertility No long term animal Lymphopenia 48 40 Nausea 23 1 Leukopenia 14 4 Diarrhea 10 1 studies have been performed to establish the carcinogenic or mutagenic potential Neutropenia 14 6 Vomiting 10 1 of Rituxan or to determine potential effects on fertility in males or females. Thrombocytopenia 12 2 Nervous System 32 1 Anemia 8 3 Dizziness 10 1 PATIENT COUNSELING INFORMATION Patients should be provided the Rituxan Skin and Appendages Anxiety 5 1 44 2 Musculoskeletal System Night Sweats 15 1 26 3 Medication Guide and provided an opportunity to read prior to each treatment Rash 15 1 Myalgia 10 1 session. Because caution should be exercised in administering Rituxan to patients Pruritus 14 1 Arthralgia 10 1 Urticaria 8 1 Cardiovascular System 25 3 with active infections, it is important that the patient’s overall health be assessed Hypotension 10 1 Hypertension 6 1 at each visit and any questions resulting from the patient’s reading of the Medication Guide be discussed. Rituxan is detectable in serum for up to six a b Adverse reactions observed up to 12 months following Rituxan. Adverse reactions graded for severity by months following completion of therapy. Individuals of childbearing potential NCI-CTC criteria. In these single-arm Rituxan studies, bronchiolitis obliterans occurred during and should use effective contraception during treatment and for 12 months after up to 6 months after Rituxan infusion. Rituxan in Combination With Rituxan therapy. Chemotherapy Adverse reactions information below is based on 1250 patients who received Rituxan in combination with chemotherapy or following chemotherapy. Rituxan in Combination With Chemotherapy for Low-Grade NHL In Study 4, patients in the R-CVP arm experienced a higher incidence of Revised 1/2008 (4835504) infusional toxicity and neutropenia compared to patients in the CVP arm. The Jointly Marketed by: following adverse reactions occurred more frequently (*5%) in patients receiving Biogen Idec Inc. 5200 Research Place San Diego, CA 92122 R-CVP compared to CVP alone: rash (17% vs. 5%), cough (15% vs. 6%), flushing Genentech USA, Inc. 1 DNA Way South San Francisco, CA 94080-4990 (14% vs. 3%), rigors (10% vs. 2%), pruritus (10% vs. 1%), neutropenia (8% vs. 3%), and chest tightness (7% vs. 1%). In Study 5, the following adverse reactions were reported more frequently (*5%) in patients receiving Rituxan following CVP compared to patients who received no further therapy: fatigue (39% vs. 14%), anemia (35% vs. 20%), peripheral sensory neuropathy (30% vs. 18%), infections (19% vs. 9%), pulmonary toxicity (18% vs. 10%), hepato-biliary toxicity (17% vs. ©2008 Biogen Idec Inc. and Genentech, Inc. 7140916 March 2008 7%), rash and/or pruritus (17% vs. 5%), arthralgia (12% vs. 3%), and weight gain (11% vs. 4%). Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more frequently (*2%) in the Rituxan arm compared with those who received no further therapy (4% vs. 1%). Rituxan in Combination With Chemotherapy for DLBCL In Studies 6 and 7, the following adverse reactions, regardless of severity, were reported more frequently (*5%) in patients age *60 years receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs. 46%), lung disorder (31% vs. 24%), cardiac disorder (29% vs. 21%), and chills (13% vs. 4%). Detailed safety data collection in these studies was primarily limited to Grade 3
G REEN H ILL H EALTHCARE C OMMUNICATIONS
MEETINGS
4–8
NEW YORK, NY Chemotherapy Foundation Symposium XXVI www.chemotherapyfoundation.org
MEETINGS
NOVEMBER 2008
25
For previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
When planning a treatment course for DLBCL
Take the essential path toward improved survival RITUXAN+CHOP is proven to prolong survival in DLBCL
47% INCREASE
in 7-year OS in GELA* trial 1,2
• At 7 years, 8 cycles of RITUXAN+ CHOP increased overall survival (OS) from 36% to 53% compared with CHOP alone1 • At 5 years, 8 cycles of RITUXAN+ CHOP increased OS from 46% to 58% compared with CHOP alone5
BOXED WARNINGS and Additional Important Safety Information The most important serious adverse reactions of RITUXAN are fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B reactivation with fulminant hepatitis, other viral infections, cardiovascular events, renal toxicity, and bowel obstruction and perforation. The most common adverse reactions of RITUXAN (incidence e25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia.5
RITUXAN in Combination with CHOP Chemotherapy for DLBCL: The following adverse reactions, regardless of severity, were reported more frequently (e5%) in patients age e60 years receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs 46%), lung disorder (31% vs 24%), cardiac disorder (29% vs 21%), and chills (13% vs 4%). In the GELA LNH 98-5 study, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs 1.0% for CHOP).5 The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs 7%) and lung disorder (6% vs 3%). Other Grade 3 or 4 adverse reactions reported more frequently among patients receiving R-CHOP were viral infection (GELA LNH 98-5 study), neutropenia (GELA LNH 98-5 and MInT studies), and anemia (MInT study).5
Please see brief summary of prescribing information on adjacent page. Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion. *GELA (Groupe d’Etude des Lymphomes de l’Adulte) LNH 98-5 trial: A Phase III trial of 399 previously untreated elderly (age e60 years) DLBCL patients.3,4 †CHOP: Cyclophosphamide, doxorubicin, vincristine, and prednisone. References: 1. Coiffier B, Feugier P, Mounier N, et al. Long-term results of the GELA study comparing R-CHOP and CHOP chemotherapy in older patients with diffuse large B-cell lymphoma show good survival in poor-risk patients. J Clin Oncol. 2007;25(suppl 18S):443s. Abstract 8009. 2. Coiffier B, Feugier P, Mounier N, et al. Long-term results of the GELA study comparing R-CHOP and CHOP chemotherapy in older patients with diffuse large B-cell lymphoma show good survival in poor-risk patients. Paper presented at: 43rd American Society of Clinical Oncology Annual Meeting; June 1-5, 2007; Chicago, Ill. Abstract 8009. 3. Coiffier B, Lepage E, Brière J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235-242. 4. Data on file, Genentech, Inc. 5. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2008.
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©2008 Genentech, Inc., and Biogen Idec Inc. All rights reserved. 3 Printed in USA on Recycled Paper 8974801 April 2008