Pilot study on the efficacy of an ondansetron- versus palonosetron-containing antiemetic regimen prior to highly emetogenic chemotherapy.

PURPOSE: Nausea and vomiting are among the most feared complications of chemotherapy reported by patients. The objective of this study was to establish the overall complete response (CR; no emesis or use of rescue medication 0-120 h after chemotherapy) with either ondansetron- or palonosetron-containing antiemetic regimens in patients receiving highly emetogenic chemotherapy (HEC). METHODS: This was a prospective, open-label, randomized, single-center, pilot study that enrolled patients receiving their first cycle of HEC. Patients were randomized to receive either palonosetron 0.25 mg IV (PAD) or ondansetron 24 mg orally (OAD) on day 1 prior to HEC. All patients received oral aprepitant 125 mg on day 1, then 80 mg on days 2 and 3, and oral dexamethasone 12 mg on day 1, then 8 mg on days 2, 3, and 4. Descriptive statistics were used to summarize the data. RESULTS: A total of 40 patients were enrolled, 20 in each arm. All patients were female, and 39 received doxorubicin/cyclophosphamide chemotherapy for breast cancer. For the primary endpoint, 65 % (95 % CI, 40.8-84.6 %) of patients in the PAD arm and 40 % (95 % CI, 19.1-63.9 %) of patients in the OAD arm achieved an overall CR. CONCLUSIONS: While CR rates for aprepitant and dexamethasone plus palonosetron or ondansetron-containing regimens have been published previously, this is the first documentation of CR rates with these regimens in the same patient population. These results may be used to design a larger, adequately powered, prospective study comparing these regimens.

Continued challenges with the use of erythropoiesis-stimulating agents in patients with cancer: perspectives and issues on policy-guided health care.

Erythropoiesis-stimulating agents (ESAs) are approved as an alternative to blood transfusions for treating anemia secondary to chemotherapy in patients with cancer. Recently, ESAs have been a source of controversy and confusion in the oncology community. This began when two European trials-the Breast Cancer Erythropoietin Survival Trial (BEST) and the Advanced Head-and-Neck Cancer Treated with Radiotherapy (ENHANCE) Study-raised safety concerns about decreased overall survival and increased venous thromboembolic events. In 2004, the United States Food and Drug Administration (FDA) convened its Oncologic Drugs Advisory Committee (ODAC) to review the data and reassess the risks and benefits of ESAs in patients with cancer. On May 10, 2007, ODAC reconvened when five trials (BEST, ENHANCE, AMG-20010103, AMG-20000161, and EPO-CAN-20) showed decreased overall survival. The briefing document noted that studies demonstrating detrimental effects on survival and/or tumor outcomes used an unapproved treatment regimen designed to maintain hemoglobin levels above 12 g/dl. On May 14, 2007, just days after the ODAC reconvened, the Centers for Medicare and Medicaid Services (CMS) released a proposed decision memo for a national coverage determination (NCD) imposing restrictions on ESAs. For health care providers, aspects of the proposed NCD were markedly inconsistent with FDA-approved ESA use and generally were considered ambiguous and unclear. Over objections of several professional associations and members of Congress, on July 30, 2007, CMS posted the final NCD and declared it effective immediately. When compared with FDA-approved labeling and professional society guidelines, the NCD revealed differences in ESA initiation, dosage escalation, dosage reduction, and definition of response. These discrepancies have generated confusion among health care providers, who are struggling over whether they can feasibly provide a dual system of care-one for Medicare patients and another for non-Medicare patients-that is evidence based. With this supplement, we hope to educate health care providers on the issues and challenges associated with policy-guided health care when discrepancies exist between the policy and evidence-based practice; offer guidance on implementing the NCD; and highlight the important role of pharmacists in the process.