Erythropoietin may increase risk of thromboembolism

Last Updated: 2006-05-25 16:30:19 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Treatment with recombinant human erythropoietin reduces the need for transfusion among patients with cancer, but it may also increase the risk of thromboembolic events or tumor progression, results of a meta-analysis suggest.

Dr. Julia Bohlius, from University Hospital of Cologne, Germany and her colleagues scrutinized the literature for randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone among patients with cancer, published between 1985 and 2005.

They identified 57 trials involving 9353 patients. The authors note that the current analysis updates a previous meta-analysis that involved 27 of the studies published between 1985 and 2001.

In the present analysis, reported in the Journal of the National Cancer Institute for May 17, patients treated with either agent had a reduced need for transfusion (relative risk 0.64) and a greater chance of achieving a hemoglobin increase of 2 g/dL (RR 3.43).

However, the occurrence of thromboembolic events -- transient ischemic attacks, stroke, pulmonary emboli, deep vein thrombosis or MI - rose from a median of 1.4% among controlls to 4.5% among those receiving either of the erythropoietins (RR 1.67).

The authors also failed to observe significantly reduced mortality when the drugs were used. In fact, the hazard ratio for mortality of 1.08 suggests that epoetin or darbepoetin may actually decrease survival.

These findings differ from the earlier meta-analysis. Dr. Bohlius and her team point out that trials in the updated review tended to include patients with higher baseline hemoglobin levels or to use higher doses of epoetin or darbepoetin and to target hemoglobin levels > 13 g/dL.

These observations "raise concerns that the relationship (between higher hemoglobin levels and risk of thromboembolism) may be causal," the authors write, or that the drugs may be thrombogenic by mechanisms independent of hemoglobin levels.

They also theorize that erythropoietin may diminish survival by stimulating proliferation of cancer cells that express erythropoietin receptors.

They therefore suggest that "treatment with epoetin or darbepoetin to target hemoglobin levels beyond that of anemia (i.e., > 12 g/dL) among cancer patients is potentially harmful and should be considered only in an experimental setting."

Furthermore, they add, "caution is advised when using epoetin or darbepoetin in combination with chemotherapeutic agents that are known to be thrombogenic or for cancer patients who are at high risk for thromboembolic events."

J Natl Cancer Inst 2006;98:708-714.

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