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.

Formulary management strategies for type 3 serotonin receptor antagonists.

The efficacy of type 3 serotonin (5-hydroxytryptamin) (5-HT3) receptor antagonists in preventing nausea and vomiting associated with cancer chemotherapy, radiation therapy, and surgery and the role of practice guidelines for the use of these agents in controlling antiemetic drug costs without compromising patient care are described. Nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery can have a negative impact on quality of life and patient outcomes. The 5-HT3 receptor antagonists are effective for preventing nausea and vomiting from these causes. Oral 5-HT3 receptor antagonist therapy is as effective as intravenous therapy, while usually costing less. Various factors associated wtih the patient and the chemotherapy, radiation therapy, or surgery that increase the risk for nausea and vomiting have been identified. Practice guidelines have been developed in which 5-HT3 receptor antagonist therapy is reserved for patients at high risk for nausea and vomiting based on these various factors. The use of such practice guidelines at Memorial Sloan-Kettering Cancer Center limited antiemetic drug expenditures despite an increase in the number of patients receiving cancer treatment without compromising emetic control or quality of life. The use of special order forms improved compliance with the practice guidelines.