Drugs used to combat anemia in cancer patients may do more harm than good according to a new study that finds these so-called erythropoiesis stimulating agents or ESAs increase the risk of blood clots. Researchers at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center examined more than 50,000 cancer patients. Their study, published online in the Journal of the National Cancer Institute, found that the use of ESAs failed to substantially reduce the number of blood transfusions required during chemotherapy as they were supposed to, but they did increase the risk of deep vein thrombosis or pulmonary embolism.

The researchers, however, noted they found no evidence of an increased risk of mortality when ESAs are given with chemotherapy.

“This analysis confirms the association between ESAs and venous thromboembolism, which was observed in previous meta-analysis," says Dawn Hershman, co-director of the breast cancer program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center. “This new finding is significant because where the meta-analysis looked at pooled data from randomized clinical trials, this data is from community practice – real-life clinical settings – where you can often see things that wouldn't necessarily show-up in a short-term, 12-week study. Additionally, this analysis included data from more than 50,000 patients– including those with more advanced cancer or high-risk status, who therefore might not have been candidates for clinical trials."

Based on previous findings, in the spring of 2007, the FDA required a black-box warning on ESAs including Amgen's Aranesp and Epogen and Johnson & Johnson's Procrit. The labels warned about the potential for venous thromboembolism, tumor promotion, and decreased survival in ESA users. The warning suggested limiting the use of ESAs to specific tumor types, durations, doses, and targeted hemoglobin levels. In addition, the Center for Medicare and Medicaid Services proposed eliminating or limiting coverage for ESAs as treatment for some cancers. Total U.S. sales of ESAs were $10 billion in 2006, accounting for a greater Medicare Part B expenditure than any other drug.

Hershman and her colleagues analyzed the association between use of ESAs and venous thromboembolism and overall survival in patients who were 65 years or older and diagnosed with colon, non-small cell lung, or breast cancer or diffuse large B-cell lymphoma, between 1991-2002. These cancers were chosen because they were thought to be common cancers for which ESAs were frequently used. Patients were identified in the Surveillance, Epidemiology, and End Results–Medicare database, which at the time contained records of patients diagnosed with cancer in regions that represented approximately 14 percent of the U.S. population.

Results demonstrated that more patients who received an ESA developed deep vein thrombosis or pulmonary embolism, as compared to patients who did not. Overall survival was similar in both groups. The number of patients receiving ESAs increased approximately 10-fold from 1991 through 2002, with approximately 50 percent of patients with advanced cancer undergoing chemotherapy receiving ESAs by 2002. The rate of blood transfusion per year during the same time period, however, remained constant at 22 percent.

"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 in the paper.