EORTC/NCI/AACR: Tamoxifen Phenotype Drug Probe Studied
Cough medicine ingredient dextromethorphan could identify poor tamoxifen metabolizers
WEDNESDAY, Nov. 24 (HealthDay News) -- Dextromethorphan, a known "probe drug" for both CYP2D6 and CYP3A4 metabolism, can be used as a phenotyping probe for tamoxifen metabolism in women who must take tamoxifen for breast cancer treatment, according to research presented at the European Organisation for Research and Treatment of Cancer/National Cancer Institute/American Association for Cancer Research Symposium on Molecular Targets and Cancer Therapeutics, held from Nov. 16 to 19 in Berlin.
Anne-Joy de Graan, of the Erasmus Medical Center in Rotterdam, Netherlands, and colleagues conducted a study of 40 breast cancer patients who had been taking tamoxifen for more than three weeks. Patients were given 30 mg of dextromethorphan (as liquid cough syrup) in addition to their oral tamoxifen dose. Blood was sampled over the next 24 hours to measure dextromethorphan and tamoxifen metabolites. The researchers then calculated how well dextromethorphan metabolism predicted and correlated with tamoxifen metabolism.
The researchers found that the clearances of dextromethorphan and endoxifen (the main metabolite of tamoxifen) were significantly correlated (R = −0.72), as were the daily trough endoxifen concentrations and dextromethorphan area under the curve (R = −0.70).
"We found that dextromethorphan is a very good way to predict endoxifen concentrations," de Graan said in a statement. "Tamoxifen is prescribed to women for as much as five years in the adjuvant setting, so it is highly important to know beforehand if the therapy is going to be effective. When it is known that a woman metabolizes tamoxifen poorly, a switch in drugs or an increase in dose can be considered."