When given the same chemotherapy treatment, why did a group of Japanese lung cancer patients survive longer – yet with a higher rate of side effects – than their U.S. counterparts? A study spearheaded by the Southwest Oncology Group and led by David Gandara, director of clinical research at the UC Davis Cancer Center, suggests that the reasons lie in subtle variations in genes that govern how the body metabolizes chemotherapy drugs.
The discovery that Japanese and U.S. patients, matched in age, gender and other respects, had differences in key metabolism-related genes is the latest result from a seven-year collaboration between the Southwest Oncology Group and two clinical trials groups in Japan.
Researchers found that patients with a certain variation in the CYP3A4 gene responded more favorably to the chemotherapy drugs paclitaxel and carboplatin and that their lung cancers progressed more slowly. A variation in another gene, ERCC2, seemed to interfere with how well patients responded to treatment.
The study breaks new ground by exploring the possible role of ethnic patterns in the emerging science of pharmacogenomics, in which drug regimens are tailored to a patient's genetic profile.
The differences in outcomes corresponded with the patients' genetic makeup, rather than their ethnicity, because some individuals in each group possessed genetic variations not typical of their group. The study suggests that in the future, therapies need to be tailored to each individual based on analysis of their genetic makeup, not simply their ethnicity.