Progesterone receptor antagonist therapy has therapeutic potential even in cancer restricted to males as evidenced from murine testicular and prostate cancer studies.

BACKGROUND Treatment with the progesterone receptor antagonist mifepristone has been shown to improve the length and quality of life in mice with spontaneous leukemia, breast cancer, and lung cancer. The present study evaluated the efficacy of mifepristone therapy in murine tumors restricted to males, i.e. testicular and prostate cancer. MATERIALS AND METHODS Eight-week-old mice with a strong predisposition to testicular or prostate cancer were gavaged with mifepristone. Olive oil was used in place of mifepristone in order to provide a control. Survival rates and body conditioning scores were compared after one year of treatment. RESULTS Non-significant trends in survival rates were found in both types of murine cancers. Mifepristone significantly reduced the number of sick days in mice with testicular cancer. There was a significant reduction of adverse events (i.e. a tumor >1 cm or bleeding from the penis) in those with prostate cancer treated with mifepristone. CONCLUSION These data support the hypothesis that various cancers may utilize a mechanism that is present in normal pregnancy that involves secretion of a progesterone-induced protein that blocks natural killer cell activity. The hypothesis that the cancer cells have the capacity to direct local progesterone production is supported by demonstrating the benefit of a progesterone receptor antagonist in tumors restricted to males.