BLOODBATH OVER ESAs?

July 23, 2007

New studies suggest that widely used antianemia drugs may seriously harm cancer patients.

How should pharmacists and physicians respond to new studies suggesting that widely used anti-anemia drugs may seriously harm cancer patients? In March, the Food & Drug Administration reacted to the new data by placing boxed warnings on the drug labels of ESAs (erythropoiesis-stimulating agents), urging doctors to use the smallest dosage possible-just enough to avoid the use of blood transfusions. The warnings followed study findings that higher risks accompanied higher doses of ESAs. The risks included worsening cancer, more frequent cardiovascular events, and a greater number of deaths than expected. These disturbing results emerged most often when the drugs were aggressively administered off-label to target a hemoglobin of >12 g/dL.

Pazdur and other government experts emphasized at the ODAC meeting that blood transfusions are safer than they used to be but that currently no one knows for sure if ESA benefits continue to be greater than the risks of transfusions. For example, FDA pointed out that five randomized clinical trials showed shorter survival times in cancer patients receiving ESAs than in controls getting red blood cell transfusions. Also, three randomized trials showed poorer tumor outcomes in cancer patients receiving ESAs versus traditional blood transfusions. However, FDA guidelines were not followed in these experimental trials.

As a result of these and similar data, ODAC members voted to further tighten the reins on ESAs. Notably, they voted 15 to 2 to further restrict use of anti-anemia drugs in general pending the results of further safety studies. They also voted 12 to 5 to withhold the agents from patients with "certain types of cancer"-not specified but assumed by some attendees to be head and neck cancer, non-small cell lung cancer, and breast cancer-since the trial results with these cancers were unfavorable. Also, they voted 16 to 1 to stop administering anemia drugs when chemotherapy was finished and to reevaluate the patient's needs.

The FDA usually heeds ODAC's recommendations, but Pazdur said after the meeting that it was too soon for the agency to make any statements about its future actions.

All quiet in Cincinnati

Asked to comment on the controversy, Jane Pruemer, Pharm.D., BCOP, associate professor of clinical pharmacy practice, University of Cincinnati College of Pharmacy, told Drug Topics there is no controversy in Cincinnati. "Our guidelines have been in place since 2004," she said. They include: