Use of erythropoiesis-stimulating agents (ESAs) to treat anemia is associated with increased risk for venous thromboembolism and death in patients with cancer, according to an article in the February 27 issue of the Journal of the American Medical Association.

Erythropoietin and darbepoetin are widely used to treat anemia in patients with cancer. Some studies have indicated that there may be a higher risk of venous thromboembolism with these medications, but it has not been known if there is an associated increased risk of death, according to background information in the article.

Charles L. Bennett, MD, PhD, of Northwestern University Feinberg School of Medicine, Chicago, and colleagues examined the rate of venous thromboembolism and death associated with use of the agents as treatment of anemia among patients with cancer by conducting a review of phase III trials.

The researchers identified 51 clinical trials with 13,611 patients: Analysis of data indicated that the risk of death was significantly higher for patients with cancer who were treated with an erythropoiesis-stimulating agent than for patients in the placebo group.

Venous thromboembolism was evaluated for 38 trials involving 8,172 patients. The researchers found there was a significantly increased risk (57 percent) of venous thromboembolism among patients treated with an erythropoiesis-stimulating agent (334 events among 4,610 patients versus 173 events among 3,562 control patients).

"These risks are important given the prevalence of erythropoiesis-stimulating agent 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," the authors wrote.

"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."