Antiandrogens Show Potential Against Prostate Cancer
MDV3100, a diarylthiohydantoin, linked to prostate specific antigen decrease in small group of men
TUESDAY, April 14 (HealthDay News) -- Two compounds that bind to androgen receptors in prostate cancer cells may hold promise as therapies for advanced prostate cancer, according to research published online April 9 in Science.
Chris Tran, of the Memorial Sloan-Kettering Cancer Center in New York City, and colleagues discuss the resistance to antiandrogen therapy that often develops in men treated for advanced prostate cancer. After screening for non-steroidal antiandrogens that maintain their activity during increased androgen receptor expression, the authors chose the diarylthiohydantoins RD162 and MDV3100 for further investigation.
In mice, both RD162 and MDV3100 were associated with tumor regression in models of castration-resistant prostate cancer (CRPC), the researchers report. In a phase I/II clinical trial, 30 men with CRPC whose disease progressed on first-line antiandrogens were given either 30 or 60 milligrams of MDV3100 daily. Twenty-two showed a decline in prostate specific antigen levels over at least 12 weeks; in 13 of the patients, prostate specific antigen fell by more than half. The treatment appeared to be well-tolerated, the report indicates.
"Treatment of advanced prostate cancer is limited by the development of resistance to antiandrogen therapy. Castration-resistant prostate cancer is commonly associated with increased levels of androgen receptor gene expression, which can occur through androgen receptor gene amplification or other mechanisms. Elevated androgen receptor levels are necessary and sufficient to confer resistance to antiandrogen therapy in mouse xenograft models," the authors write.
Several co-authors are co-inventors on patent applications related to RD162 and MDV3100, and disclosed financial relationships with Medivation, Inc.