Cancer patients taking drugs to stimulate red blood cell production and cut the risk of anemia are twice as likely to develop blood clots in the lungs or legs, a decade-long study has found.

The study in the Journal of the National Cancer Institute adds to growing evidence that the risks of erythropoiesis-stimulating agents, or ESAs, might outweigh their benefits.

ESAs, such as erythropoietin and darbopoietin (sold under such names as Epogen, Procrit and Aranesp), stimulate red blood cell production and are thought to help reduce the number of blood transfusions patients need while undergoing chemotherapy.

But there have been concerns that the drugs raise the risks of potentially fatal blood clots, including deep vein thrombosis and pulmonary embolism. Nevertheless, use of the drugs has continued to grow.

Dr. Dawn L. Hershman of Columbia University Medical Center in New York, and colleagues looked at the links between ESA use and blood clots, as well as the overall survival rates of more than 56,000 patients. All were 65 years or older and had been diagnosed with colon, non-small cell lung, or breast cancer or diffuse large B-cell lymphoma between 1991-2002.

They found that more patients who received an ESA developed serious blood clots (technically called venous thromboembolism) than patients who did not take the medications.

Among the more than 12,000 patients who received either erythropoietin or darbepoietin during the study period, 14.3 per cent developed a thromboembolic event, compared with 9.8 per cent of the nearly 35,000 patients not treated with the medications.

The researchers also found that the number of patients receiving ESAs increased about 10-fold from 1991 through 2002, rising from 4.8 per cent in 1991 to 45.9 per cent in 2002. And yet, the rate of blood transfusion per year during the same time period remained constant, at about 22 per cent, the study found.

"Further efforts at monitoring use and long-term toxicity of expensive oncology drugs should be put in place to ensure that for any drug the benefits outweigh the risks in community practice," the authors write.

ESAs have come under scrutiny since a study in late 2006 showed a higher risk of death and cardiovascular complications for aggressively treated patients.

Shortly after, the U.S. Food and Drug Administration ordered that a strong warning be placed on ESAs, and suggested limiting their use to patients with specific types of cancers with especially low red blood counts.

In the initial trials of ESAs, transfusions for cancer patients were reduced by half, and no increased risk of blood clots was found. But as this study suggests, the "real world" use of medication can sometimes yield different results.

In discussing their findings, the researchers noted that when new reports of serious side effects emerge after medications have been approved, they undermine trust in the drug approval process and the medical establishment.

ESAs are "a prototypical example of the limitations of our current system," they write.