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Caution against over-aggressive use of erythropoiesis-stimulating agents for cancer-related anemia

Published on May 1, 2007 at 8:17 AM · No Comments

Echoing recent FDA warnings, a research group from Northern Ireland cautions against over-aggressive use of a group of drugs called "erythropoiesis-stimulating agents" (ESAs) to treat anemia in some cancer patients, according to a commentary in the April issue of The Oncologist, published by AlphaMed Press.

The article by Dr. Terence R. Lappin and colleagues of Queen's University, Belfast, cites evidence that using ESAs to treat non-chemotherapy-related anemia in cancer patients could increase the risk of death, thromboembolic events, and perhaps even cancer growth. The authors write, "Overall these studies have raised concerns that ESAs could in certain circumstances adversely affect survival in cancer patients and have led to speculation that these agents may enhance thrombosis, tumor growth, and neovascularization."

The ESAs darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit) are genetically engineered forms of a protein called erythropoietin, which stimulates red blood cell production. The drugs are widely used to treat anemia: low levels of hemoglobin, the oxygen-carrying protein in the blood. They are approved for use in treating anemia in patients with chronic kidney disease and in cancer patients with anemia related to chemotherapy.

However, the FDA has recently issued alerts regarding possible hazards of ESA treatment for anemia in cancer patients not receiving chemotherapy. The alerts were based on problems reported in several studies of such "off-label" use of ESAs. One study showed a 25 percent increase in the risk of death for patients receiving darbepoetin alfa. Another reported that cancer patients treated with ESAs were at much higher risk of abnormal blood clots, or "thromboembolic events" -- including stroke and myocardial infarction.

In their commentary, Dr. Lappin and coauthors draw attention to an additional possibility: that ESAs could promote cancer growth. Several studies have identified molecular receptors of erythropoietin in the endothelial cells lining blood vessels and possibly in tumor cells as well. Because of their genetically modified characteristics, ESAs may have stronger effects on these receptors than natural erythropoietin does. If so, then it is possible that ESAs may promote abnormal formation of new blood vessels. This process, called neovascularization, is a key event in cancer growth and progression.

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