Anemia Meds Linked To Blood Clots And Deaths
1 CommentBy Ed Silverman // February 26th, 2008 // 4:27 pm
Treating anemia with ESAs, otherwise known as erythropoiesis-stimulating agents, is associated with an increased risk of death and venous thromboembolism (blood clots in the deep veins of the legs or in the lungs) among patients with cancer, according to an article in the lateset issue of the Journal of the American Medical Association.
Amgen’s Epogen and Aranesp, and Johnson & Johnson’s Procrit are widely used to treat anemia in patients with cancer. Some studies have indicated that there may be a higher risk of venous thromboembolism (VTE) with these medications, but it has not been known if there is an associated increased risk of death, according to the article. The study comes as the FDA next month holds an advisory committee to review further restrictions on the drugs.
The study examined the rate of blood clots and death associated with ESA administration for 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 to examine survival. Analysis of the data indicated that the risk of death was significantly higher for patients with cancer - 10 percent - who were treated with ESA compared with those given a placebo.
Venous thromboembolism was evaluated for 38 trials that included 8,172 patients. The researchers found that there was a significantly increased risk (57 percent) among patients treated with ESA (334 events among 4,610 patients treated with ESA vs. 173 events among 3,562 control patients).
“These risks are important given the prevalence of ESA use as a supportive care drug among patients with cancer as well as the dissemination of a series of safety advisories by the FDA and ESA manufacturers,” the authors write.
“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.”
Gregory D. Pawelski
Dr. Charles L. Bennett (in the NYT article), a professor at Northwestern University and an oncologist and hematologist, said he did not think that the higher risk of death came from those blood clots. Rather, he said, there is evidence that the drugs, which are synthetic forms of a natural hormone called erythropoietin, directly stimulate the growth and spread of tumors.
Pharmaceutical EPO can feed the growth of tumors in cancer patients (it is a “growth factor” afterall). A “growth factor” is about twenty small proteins that attach to specific receptors on the surface of stem cells in bone marrow and promote differentiation and maturation of these cells into morphotic constituents of blood. And blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). Problems with blood composition or circulation can lead to downstream tissue (which is made up of cells) dysfunction. If pharmaceutical EPO stimulates the bone marrow to make red blood cells, it could feed the growth of tumors in cancer patients.
The problem is that few drugs work the way oncologists think and few of them take the time to think through what it is they are using them for. Take medical oncologists out of the retail pharmacy business and force them to be cancer “doctors” again!