Millions of cancer patients take drugs to boost their red blood cells and health when they become anemic after chemotherapy.
But a new study by Northwestern University's Feinberg School of Medicine shows these drugs, called erythropoiesis-stimulating agents (ESAs), actually raise patients' risk of death, possibly by stimulating the growth of cancer cells.
A meta-analysis of 51 trials with 13,613 patients revealed a 10 percent increased risk of death among cancer patients taking ESAs compared to patients who did not take them. The study, lead by Charles Bennett, M.D., the A.C. Buehler Professor in Economics and Aging at the Feinberg School, will be published in the Journal of the American Medical Association Wednesday, February 27.
The Northwestern study is the first to demonstrate a quantifiable increased risk of death from EPAs and is based on the largest number of trials ever examined for this purpose.
"The FDA says if you use the drug in moderation, it should be safe," Bennett said. "But our findings, in conjunction with basic science studies, raise the concern that the drug may be stimulating cancer and shortening cancer patients' survival."
“It's troubling that 15 years after the drug came out, we finally came to this realization," said Bennett, who also is a hematologist and oncologist at Northwestern Memorial Hospital and the Jesse Brown VA Medical Center.
The JAMA paper is an update of a poster presentation Bennett made to the American Society of Clinical Oncology in June 2007.
One of the study's co-authors, Stephen Lai, M.D., assistant professor at the University of Pittsburgh Medical Center, tested the response of cancer cells to an ESA in the laboratory. Lai, a head and neck surgeon, saw a significant effect when he added an ESA called erythropoietin to head and neck cancer cells in tissue culture.
"We saw a dramatic change," Lai said. "Adding 'epo' (erythropoietin) to the cells increased their ability to migrate or invade. Our basic science findings and the clinical trial results suggest that giving cancer patients 'epo' for their anemia may actually cause their tumors to progress."
Lai's basic science study is part of a growing body of studies that demonstrate erythropoietin expression and function in a variety of human cancers as presented at a National Cancer Institute workshop on erythropoietin and tumor progression December 2007 in Bethesda, Md.
The FDA approved the ESAs erythropoietin and darbepoetin in 2003 as a treatment for anemic cancer patients to avoid blood transfusions. However, evidence linking these drugs to a higher risk of death has been mounting. In March 2007, the FDA issued a public health advisory on EPAs, warning of an increased risk of serious and life-threatening side effects.
Ironically, Bennett noted, "The later clinical trials were conducted to see if these drugs help people live longer. But, it turns out, this is not the case."
ESAs produced up to $6 billion in cancer-anemia related sales last year for pharmaceutical firms, Bennett said, and represented Medicare's largest pharmaceutical expenditure.