Genetic biomarker that may improve quality of life during treatment for colorectal cancer

May 16 2005

A Mayo Clinic-led study has revealed a genetic biomarker that can predict which patients are most likely to experience unwanted side effects from one of the most commonly used and highly effective chemotherapy regimens designed to treat colorectal cancer.

Conducted by the North Central Cancer Treatment Group (NCCTG), the study involved 299 patients and collaborators from St. Louis, Mo.; Pittsburgh, Pa.; Ontario, Canada; and Chapel Hill, N.C. Mayo researchers will present these study results at the 2005 American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Fla.

The side effects associated with oxaliplatin (Eloxatin), a key component of modern chemotherapy for colorectal cancer, can include progressive nerve dysfunction with tingling, numbness, sensiti

vity to cold -- and over time, loss of manual dexterity needed for basic tasks of daily living such as buttoning shirts or tying shoelaces. While the work on this topic is early and further studies must be performed, its possible applications to patient care have significant potential for improving the quality of life during treatment. For example, identifying which patients are most vulnerable to these side effects before treatment would allow physicians to prescribe alternative treatments or take measures to counteract the nerve damage.

In their report, Mayo Clinic researchers describe for the first time finding variations in genes of certain patients that help predict which group of patients are at higher risk to develop side effects from oxaliplatin early in the course of their treatment. Because the variations occur in genes involved in detoxifying oxaliplatin, the researchers hypothesized that the variations could be used as biological markers -- biomarkers -- that would indicate which patients are most susceptible to oxaliplatin's negative side effects. Their results confirmed this.

Using genetic information from the patient to tailor treatment is referred to as pharmacogenomic medicine, and is among the newest developments in cancer research. Pharmacogenomic information is believed to be the key to making the most effective and easily tolerated treatment choices.

Says Axel Grothey, M.D., the Mayo Clinic medical oncologist who led the study, "Our research indicates that there is a group of patients who appear to have, based on genetic differences in an enzyme, a lower threshold to the toxic side effects of oxaliplatin. If our finding is confirmed in a second trial, this could be of great clinical importance because it would enable those patients with a genetic makeup that predicts early onset of nerve dysfunction to either seek alternative treatment options right away, or to receive agents that protect the nerves." Dr. Grothey emphasizes that the findings are preliminary and need further confirmation before they become widely available to patients.

Cancer of the colon or rectum is also called colorectal cancer. According to the National Institutes of Health, in the United States, colorectal cancer is the fourth most common cancer in both men and women. In men, skin, prostate and lung cancers are more prevalent. In women, skin, lung and breast cancer are more prevalent. While the exact cause is not known, risk factors associated with colorectal cancer include high-fat diets that are low in fruits and vegetables. The most common treatments are surgical removal of the diseased portion of the colon, chemotherapy and radiation treatments to halt cancer growth.

More and larger studies are needed to validate these findings. If the findings are confirmed, additional research will be needed to develop neuroprotective agents that can shield the nerves from the toxic effects of oxaliplatin and alternatives to oxaliplatin-based chemotherapy. Mayo Clinic researchers are investigating both possibilities.

In addition to Dr. Grothey, the Mayo Clinic research team included Erin Green; Daniel Sargent, Ph.D.; Scott Williamson; and Craig Fuchs. Collaborators from other institutions include Howard McLeod, M.D., of Washington University, St. Louis, Mo.; Ramesh Ramanathan, M.D., of the University of Pittsburgh; Brian P. Findlay, M.D., of the National Cancer Institute Canada, St. Catherine's, Ontario, Canada; and Richard M. Goldberg, M.D., of the University of North Carolina, Chapel Hill, N.C.

DISCLOSURE: This study was supported by grants from the National Cancer Institute (NCI) and the Sanofi-Aventis Group, and coordinated by the North Central Cancer Treatment Group (NCCTG), a national clinical research group sponsored by the NCI. NCCTG is a network of more than 400 community-based cancer treatment clinics in the United States, Canada and Mexico that work with Mayo Clinic to conduct clinical studies for advancing cancer treatment.