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.