Researchers identify biomarker to predict response of colon cancer patients to chemotherapy regimen

Researchers at Fox Chase Cancer Center have identified a biomarker that can predict how well individual colon cancer patients will respond to a common chemotherapy regimen. This finding is a significant step forward in the goal of personalizing cancer treatment. Medical oncologist Neal J. Meropol, M.D., director of the gastrointestinal cancer program at Fox Chase, presented the study today in New Orleans at the 40th Annual Meeting of the American Society of Clinical Oncology.

The study involves an enzyme that is important in activating capecitabine. Capecitabine is a commonly used oral chemotherapy drug that is converted into its active form by the enzyme thymidine phosphorylase (TP). TP is found in some, but not all, cancers. Capecitabine (marketed by Roche under the name Xeloda) in combination with irinotecan ( marketed by Pfizer under the name Camptosar) is a chemotherapy regimen being developed to treat advanced colon cancer patients.

Meropol’s study was designed to see if a correlation exists between how well a patient with metastatic colorectal cancer responds to chemotherapy with capecitabine plus irinotecan, and whether or not the amount of TP in the tumor predicted success with therapy. The study included 67 patients, ranging in age from 40 to 81, who had received no prior chemotherapy for their metastatic disease.

Patients whose tumors had the enzyme TP, believed to be needed in the final step to convert capecitabine to its active form of 5-FU (fluorouracil), had a significantly higher response rate to the chemotherapy regimen. Specifically, the response rate for patients whose primary tumors tested positive for TP was 65 percent compared to 27 percent in patients whose primary tumors tested negative for TP. Among patients whose metastatic tumors expressed TP, the response rate was 61 percent compared to 14 percent in patients without TP in metastases.

“These data suggest that TP expression may be useful as a marker in predicting a positive response to chemotherapy with capecitabine plus irinotecan for colorectal cancer patients,” Meropol said. “With that information, we can begin personalizing treatment. If we know the enzyme is present to activate the drug, we may be able to identify those patients who should receive capecitabine.”

Capecitabine is also used for patients with breast cancer.

The American Cancer Society estimates that nearly 147,000 Americans will receive a diagnosis of colon or rectal cancer this year and about 56,730 people will die of colorectal cancer in 2004. Meropol’s colleagues in the study include P. J. Gold of the Swedish Cancer Institute, Seattle Wash.; R. B. Diasio of the University of Alabama, Birmingham; Y. Chen and T. Hill of Roche Labs, Nutley, N.J.; T. Godfrey of Loma Linda University, Loma Linda, Calif.; A. J. Kovatich of MDR Global Systems, Windber, Pa.; K. A. Lund of Rockwood Clinic, Spokane, Wash.; and E. Mitchell and R. Schwarting of Thomas Jefferson University, Philadelphia.

Fox Chase Cancer Center was founded in 1904 in Philadelphia, Pa. as the nation’s first cancer hospital. In 1974, Fox Chase became one of the first institutions designated as a National Cancer Institute Comprehensive Cancer Center. Fox Chase conducts basic, clinical, population and translational research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center’s web site at www.fccc.edu or call 1-888-FOX CHASE.