Epoetin, darbepoetin linked to higher mortality, more VTEs in cancer patients

February 26, 2008

NEW YORK (Reuters Health) - Erythropoiesis-stimulating agents are associated with increased risk of venous thromboembolism (VTE) and higher mortality rates when used to treat anemia in patients with cancer, according to meta-analyses published in the Journal of the American Medical Association for February 27.

Previous overviews have linked erythropoietin and darbepoetin with increased incidence of VTE, but none have identified mortality risks associated with these agents, note Dr. Charles L. Bennett, from Northwestern University in Chicago, and his associates.

However, eight recently reported prospective trials individually identified increased rates of tumor progression or mortality with erythropoiesis-stimulating agents, the report indicates.

The authors' current analysis includes data from 38 phase III trials included in the 2006 Cochrane overview plus 13 new phase III trials reported since April 2005 (total 13,611 patients) that included survival information. VTE risk was evaluated for 8172 patients treated in 38 trials with relevant information.

The hazard ratio for mortality was significantly higher for patients treated with an erythropoiesis-stimulating agent compared with control patients (HR, 1.10, p = 0.03). No significant heterogeneity among trials was noted, and the association was not dominated by a small number of trials.

The relative risk for VTE was also elevated by treatment with erythropoietin or darbepoetin (RR, 1.57).

"Depending on the type of cancer, activation of the erythropoietin/erythropoiesis-receptor signaling axis results in measurable cellular effects, including proliferation, anti-apoptosis, and invasion," Dr. Bennett's group explains. "Additional research on erythropoiesis-stimulating agents' safety is clearly needed."

Dr. Bennett and his associates note that the US Food and Drug Administration has scheduled a meeting of its Oncologic Drug Advisory Committee in March, 2008, to review safety concerns related to erythropoiesis-stimulating agents.