Using erythropoiesis-stimulating agents (ESAs) in the treatment of anemia increases the risk of venous thromboembolism (VTE) and death among cancer patients, according to an article in the February 27, 2008 issue of JAMA.
ESAs are a class of drugs that promote red blood cell production in the body. The ESAs erythropoietin and darbepoetin are commonly used in patients with cancer to treat anemia. Previous studies indicated that there might be a higher risk of VTE, blood clots in the deep veins of the legs of lungs. However, these studies did not conclude if an associated increased risk of death was created.
To determine the effect on mortality in these patients, Charles L. Bennett, M.D., Ph.D., of the Northwestern University Feinberg School of Medicine, Chicago, and colleagues reviewed phase 3 trials, examining instances of VTE and death with ESA administration for treatment of anemia in cancer patients.
51 trials were identified with 13,611 patients. Analysis of survivial within the data showed that patients who were treated with ESA were significantly more likely to die than patients in the placebo control group. 38 trials were evaluated for VTE, including 8,172 patients. In the analysis, the investigators found that a significantly increased risk of VTE was present in patients treated with ESA versus the control population.
This could have important implications, considering how common treatment using ESAs is. The authors write: “These risks are important given the prevalence of ESA use as a supportive care drug among patients with cancer as well as the dissemination of a series of safety advisories by the Food and Drug Administration (FDA) and ESA manufacturers.”
They continue: “Safety concerns account in large part for changes observed in patterns of use, reimbursement policies, clinical guidelines, and FDA-approved package inserts pertaining to ESAs in the oncology setting. Our findings, in conjunction with basic science reports on erythropoietin and erythropoietin receptors in solid cancers, raise concern about ESA safety for patients with cancer.”
Venous Thromboembolism and Mortality Associated With Recombinant Erythropoietin and Darbepoetin Administration for the Treatment of Cancer-Associated Anemia
harles L. Bennett, MD, PhD; Samuel M. Silver, MD, PhD; Benjamin Djulbegovic, MD, PhD; Athena T. Samaras, BA; C. Anthony Blau, MD; Kara J. Gleason, BS; Sara E. Barnato, MD; Kathleen M. Elverman; D. Mark Courtney, MD; June M. McKoy, MD, MPH, JD; Beatrice J. Edwards, MD; Cara C. Tigue, BA; Dennis W. Raisch, PhD; Paul R. Yarnold, PhD; David A. Dorr, MD, MS; Timothy M. Kuzel, MD; Martin S. Tallman, MD; Steven M. Trifilio, RPh; Dennis P. West, PhD; Stephen Y. Lai, MD, PhD; Michael Henke, MD
JAMA. 2008;299(8):914-924.
Written by Anna Sophia McKenney