Off-label use of cancer drugs risks potentially fatal toxicities

Food & Drug Administration policies prevent pharmaceutical manufacturers from informing patients about potentially fatal toxicities that occur with some cancer drugs –  policies that should be revised immediately, according to Andrew M. Evens, DO, instructor in medicine, and Charles L. Bennett, MD, professor of medicine, Northwestern University Feinberg School of Medicine, division of hematology/oncology.

The doctors, researchers at Northwestern’s Robert H. Lurie Comprehensive Cancer Center, have called for an immediate revision of these FDA policies, particularly since the drug thalidomide, which was approved by the FDA as an off-label cancer treatment in 1998, has been reported to have caused potentially fatal blood clots in the legs and the lungs in more than 190 cancer patients.

Thalidomide, banned initially in 1962, has had a remarkable resurgence since FDA approval for cancer, although its formal FDA approval is as a treatment of skin complication of the rare illness, leprosy. Virtually all patients who have received thalidomide over the past six years have received the drug for cancer, making this drug the only one in the country used exclusively off-label.

The FDA restricts discussion or dissemination of information to physicians and patients to “on label” indications, thus preventing the pharmaceutical manufacturer from advising cancer patients about the side effects of thalidomide when it’s used to treat cancer.

And, despite an FDA mandate that all health care personnel and patients involved with thalidomide treatments participate in the preventive System for Thalidomide Education and Prescribing Safety (STEPS) program, that program does not provide patients, pharmacists or health care providers with information on thromboembolisms.

The Research on Adverse Drug Events and Reports (RADAR) project, led by Bennett, is supported by a $5 million grant from the National Cancer Institute. Evens presented the RADAR data on the thalidomide-associated blood clots at the 46th Annual Meeting of the American Society of Hematology in early December.

The Northwestern study identified the occurrence of potential fatal blood clots in the legs and the lungs in up to 20% or more of cancer patients who received thalidomide. The highest rates of thromboembolism occurred in patients who received concurrent treatment with thalidomide plus chemotherapy (18%), versus blood clots associated with thalidomide-corticosteroid combinations (13%), and single-drug treatment (5 percent).

 “Given the current controversies about the FDA and pharmaceutical safety, our findings provide additional evidence that dramatic changes in the way the FDA address patient safety are needed,” Evens said.

SOURCE: Northwestern University Media Advisory, 20-Dec-2004.