Researchers identify genetic markers to predict response to chemotherapy for colorectal cancer

06/03/04

One of the most common challenges facing oncologists today is determining the best course of treatment for their patients--one that would be effective and have the fewest possible side effects. In a study presented today at the 40th Annual Meeting of the American Society of Clinical Oncology in New Orleans, Fox Chase Cancer Center researchers have identified genetic markers in the blood that can help predict a patient's response to and side effects from irinotecan, a common chemotherapy drug for colorectal cancer.

Leslie E. Carlini, Ph.D., a research associate in the Fox Chase laboratory of Rebecca L. Blanchard, Ph.D., presented the findings. Their research focuses on genetic variations that influence the effect of medicines on different people--an area of study called pharmacogenetics. Ultimately, the goal is to improve the way drugs are prescribed by identifying individuals who are likely to benefit from a specific medicine or who are at increased risk of serious side effects.

"Our data suggest that variations in genes that help metabolize irinotecan may be useful predictors of how well colorectal cancer patients respond to this drug and how severe side effects will be," Carlini said.

To see how genetic variations affected response and side effects, the laboratory analyzed DNA in blood samples taken during a multi-site clinical trial to test an investigational combination chemotherapy regimen for metastatic colorectal cancer. The patients received intravenous irinotecan once a week and twice-daily tablets of the drug capecitabine for two weeks of a three-week treatment cycle.

The researchers looked at a family of genes called UGTs (UDP-glucuronosyltransferases), involved in breaking down irinotecan within the body and ultimately disposing of it. "Our research indicates that patients specific UGT1A7 or UGT1A9 genotypes will get more anti-tumor response from the chemotherapy combination. What's more, these patients should have fewer side effects," Carlini said.

There were no statistically significant associations between the other two UGT genes and either side effects or antitumor response. "In reality, physicians will soon be able to personalize cancer therapies based on the tumor's characteristics and the genetic profile of the person," said Carlini. "The ultimate goal is to tailor treatment that offers the most anti-tumor activity with the fewest side effects."

In a separate study based on the same clinical trial, Fox Chase researchers also discovered a protein marker to help predict response to combination chemotherapy with capecitabine and irinotecan. Medical oncologist Neal J. Meropol will present these results at the ASCO annual meeting in a Gastrointestinal (Colorectal) Cancer Session on Sunday, June 6 between 8 a.m. and 12 noon (Abstract # 3520, Poster #11).

In addition to Blanchard and Meropol, Carlini's colleagues in the study include Y.-M. Chen, Ph.D., T. Hill, and C. McGarry of Roche Labs, Nutley, N.J.; and P. J. Gold, M.D., of the Swedish Cancer Institute, Seattle, Wash.

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