Assessing how quickly the body metabolizes the drug midazolam combined with genotyping could help to optimize irinotecan chemotherapy, according to a new study.

Irinotecan has been approved for use as part of first- and second-line chemotherapy for colorectal cancer and also has moderate activity against breast cancer, relapsed or refractory non-Hodgkin lymphoma, and lung cancer. Response to the drug varies in different people because of variations in the enzymes that metabolize the drug, including cytochrome P450 3A4 (CYP3A4) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1).

Alex Sparreboom, Ph.D., of the National Cancer Institute, and colleagues demonstrated in 30 cancer patients that the speed at which the body metabolizes the drug midazolam was associated with CYP3A4 phenotype and is closely related to how quickly the body metabolizes irinotecan. They also found that a specific UGT1A1 mutation was associated with increased amounts of the active inrinotecan metabolite. They conclude that combining CYP3A4 phenotyping with UGT1A1 genotyping could assist with the optimization of irinotecan chemotherapy. The method is currently undergoing validation in a prospective study.

Contact: National Cancer Institute Press Office, 301-496-6641, NCIPressOfficers@mail.nih.gov

Height, Obesity, and Activity Level Associated With Endometrial Cancer Risk

Greater height and obesity and lower levels of physical activity are all associated with an increased risk of endometrial cancer, according to a new study.

Obesity is an established risk factor for endometrial cancer, and there has been some evidence that body mass at younger ages, weight change, height, and physical activity may also be associated with a woman's risk of this cancer. To investigate these possible associations, Leo J. Schouten,
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Contact: Sarah L. Zielinski
jncimedia@oupjournals.org
301-841-1287
Journal of the National Cancer Institute
2-Nov-2004