Erythropoiesis Stimulating Agent (ESA) Use for Anemic Cancer and Chronic Kidney Disease (CKD) Patients in 2008: Advocacy for Conservative Use

The ESAs epoetin and darbepoetin were approved for treatment of chemotherapy-associated anemia in 1993 and 2002 and CKD-associated anemia in 1989 and 2001, respectively. In 2006, ESAs were the largest single pharmaceutical expenditure by the Center for Medicare and Medicaid Studies (CMS). Recently, a series of preclinical experiments, clinical trials, and meta-analyses of ESAs have been reported. The Food and Drug Administration (FDA), National Comprehensive Cancer Network (NCCN), American Society of Hematology (ASH)/American Society of Clinical Oncology (ASCO), and Kidney Disease Outcomes Quality Improvement (KDOQI) have issued guideline statements for ESAs, and CMS has implemented an ESA Monitoring Policy (EMP) to help ensure appropriate ESA claims. Herein, we analyze these actions and usage trends of ESAs for anemic cancer and CKD patients. Data sources included basic science studies, clinical trials, meta-analyses, notifications from CMS, ESA manufacturers, and the FDA, guidelines from the NCCN, ASH/ASCO, and KDOQI, and published reports regarding ESA usage reported between 2006 and 2008. Search terms included erythropoietin, darbepoetin, anemia, neoplasm, and CKD. Results from eight recent clinical trials and one 2008 meta-analysis for anemic cancer patients identified tumor progression and mortality risks with ESA versus placebo/control use. Analyses from one clinical trial and one 2008 meta-analysis for CKD patients identified mortality and cardiovascular risks when high hemoglobin levels were targeted. Guidelines, manufacturer notifications, and reimbursement policies have become increasingly conservative. ESA administration to anemic cancer and CKD patients has decreased. Among anemic cancer patients, red blood cell transfusions are increasing and ESA use is decreasing. Among anemic CKD patients, target and achieved hemoglobin levels and ESA doses have decreased. Regulatory, clinical and professional communities now advocate for conservative use of ESAs for anemic patients with cancer or CKD.