FDA should amend the product information for irinotecan

Aug 29 2007

Not everyone needs a genetic test before taking the cancer drug irinotecan, and the U.S. Food and Drug Administration should modify its prescription guidelines to say so, according to researchers at the University of North Carolina at Chapel Hill.

Irinotecan, also known by its brand name Camptosar, is used mainly as a second-line treatment for colorectal cancer. The FDA recommends screening patients for a gene that could make them more susceptible to the harmful side effects of the drug, the most worrisome of which is neutropenia, an abnormally low number of white blood cells.

In a paper published in the Aug. 28, 2007 Journal of the National Cancer Institute, UNC researchers analyzed data from nine previous studies of irinotecan. They found that patients who received a medium or high dose of the drug had greater risk of neutropenia if they had two copies of a variation of the gene UGT1A1, known as UGT1A1*28. At lower doses, however, the risk was the same regardless of what UGT1A1 gene the patients had.

“Many institutions saw the FDA's recommendation as a mandate to test all patients before treating them with irinotecan even though many clinicians didn't think it was always necessary given that low doses of the drug weren't causing problems,” said Howard McLeod, Pharm.D., senior author of the study and director of the UNC Institute for Pharmacogenomics and Individualized Therapy.

“Our review showed that at low doses the drug is well tolerated and can be taken by most people,” McLeod said. “As the dosage increases, genetics become a larger factor in determining what side effects patients experience, and then testing becomes essential.”

Having a genetic test available for a medicine is valuable, but so is knowing when to use that test, said Dr. Richard Goldberg, a co-author of the study and physician in chief of the North Carolina Cancer Hospital.

“There are so many treatment options for cancer patients that the more information we have about matching the right therapy to the patient, the better off we all are,” Goldberg said. “Studies like this one give oncologists the tools needed to take better care of patients while avoiding tests and expenses that aren't needed.”

The authors recommended that the FDA amend the product information for irinotecan to describe the association between irinotecan dose and risk of hematologic toxicity among patients with two UGT1A1*28 genes.