Chemotherapy for advanced hormone refractory prostate cancer

Abstract

Men with metastatic prostate cancer treated with androgen ablation respond rapidly and often dramatically to therapy, with improvement of bone pain, regression of soft tissue metastases, and declines in serum prostate-specific antigen (PSA). Unfortunately, few treatment options are available to men who progress after hormone therapy. Recent studies in the mechanism of anticancer drug action have focused on the proteins that regulate apoptosis or programmed cell death as a target for the treatment of hormone-resistant prostate cancer. New treatments are now being designed with both resistance and apoptotic pathways in mind. US Food and Drug Administration (FDA) approval of the combination of mitoxantrone and prednisone for the palliation of bone pain in men with hormone refractory prostate cancer demonstrates that chemotherapy can be effective. Two randomized trials have demonstrated the superiority of mitoxantrone combined with a corticosteroid over corticosteroid therapy in alleviating bone pain. The combination of estramustine with vinblastine, or VP-16, is commonly used in clinical practice with both regimens demonstrating significant PSA declines. When estramustine is combined with either paclitaxel or docetaxel in vitro, greater than additive in vitro cytotoxicity is noted. Phase I and II studies of taxane-based therapy in hormone refractory prostate cancer demonstrate improved survival when compared with historical controls, but phase III studies are necessary to confirm these preliminary observations.