DNA Test Predicts Harmful Effects Of Cancer Drug

Main Category: Cancer / Oncology
Also Included In: Genetics
Article Date: 29 Aug 2007 - 0:00 PST

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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 third most common form of cancer in the United States. The FDA currently 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, a blood disorder characterized by an abnormally low number of white blood cells, which decreases the body's ability to fight off infections.

In a paper published in the August 28 Journal of the National Cancer Institute, UNC's Dr. (PhD) and colleagues analyzed data from nine previous studies of irinotecan. They found that only 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 authorization to test all patients before treating them with irinotecan, even though many clinicians didn't think it was always necessary since low doses of the drug weren't causing problems," said Prof. Howard McLeod, 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. "Testing only becomes essential when the dosage increases and genetics become a larger factor in determining what side effects patients experience".

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 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 unnecessary tests and expenses."

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.

About the authors: McLeod is the Fred Eshelman Distinguished Professor at the UNC School of Pharmacy. Goldberg is the associate director of UNC's Lineberger Comprehensive Cancer Center and chief of the UNC Division of Hematology/Oncology. Hoskins is of the UNC School of Pharmacy. Qu and Ibrahim are of the UNC School of Public Health.

University of North Carolina at Chapel Hill
http://www.unc.edu