Cancer patients who took drugs to cut the risk of anemia were twice as likely to develop blood clots in the lungs or legs as other patients, a decade-long study of more than 55,000 cancer patients has found.

The study adds to mounting evidence that the risks of the commonly used drugs -- known as erythropoiesis-stimulating agents or ESAs -- may outweigh the benefits.

ESAs stimulate bone marrow to increase the production of red blood cells. They were first approved in cancer patients in 1991 to reduce the number of blood transfusions needed during chemotherapy.

But despite widespread use of the drugs -- rising tenfold between 1991 and 2002 to nearly half of all cancer patients undergoing chemotherapy -- blood transfusion rates among these patients remained steady, Dr. Dawn Hershman of New York-Presbyterian Hospital/Columbia University Medical Center and colleagues reported on Tuesday in the Journal of the National Cancer Institute.

We dramatically increased the number of patients that received these agents, Hershman said in a telephone interview. In the entire time, the transfusion rate didn't change.

Sales of the drugs, including Amgen's Aranesp and Epogen and Johnson & Johnson's Procrit, have fallen sharply since a late 2006 study by J&J showed a higher risk of death and cardiovascular complications for aggressively treated patients.

In 2007, the U.S. Food and Drug Administration required a strong warning on ESAs and suggested limiting their use to patients with specific types of cancers with especially low red blood counts.

The U.S. Centers for Medicare and Medicaid Services or CMS, which runs the Medicare insurance program for the elderly and disabled, also proposed limiting coverage for the drugs, but they remain widely used.

From 2006 to 2008, worldwide annual Aranesp sales fell 24 percent to $3.1 billion. Procrit sales slid 23 percent to $2.46 billion over the same period.

Hershman said the drugs were approved in cancer patients based on carefully controlled clinical trial data that showed they reduce the need for blood transfusions.

But in her study, which involved real patients treated in community health centers, even the transfusion benefit was not apparent.

I think the take-home message is we really do need to think about how we look for long-term toxicity in patients, Hershman said.

In August, CMS said it would ask an advisory panel for input on the use of ESAs in patients with chronic kidney disease. That committee is expected to meet in March 2010.

Medicine