New standards in the chemotherapy of metastatic hormone-refractory prostate cancer

Abstract

Hormone-refractory prostate cancer (HRPC) is a major issue in Western countries and the second leading cause of cancer death in North American men. In the prostate-specific antigen era, most HRPCs are currently diagnosed in asymptomatic patients based on biochemical failure, with increasing demand for active treatment. Until recently, chemotherapy for HRPC patients was not considered a standard of care due to the absence of clear data evidencing an overall survival benefit. In fact, few Phase III studies conducted in the 1980s and early 1990s had documented a superiority over corticosteroids alone in terms of biochemical response (declines in serum prostate-specific antigen levels) and quality of life, but not survival. Due to their impact on pain control, mitoxantrone and prednisone were long considered the best regimen for symptomatic HRPC patients. In recent years, more chemotherapeutic agents have been tested, among which the microtubule inhibitors (vinca alkaloids and taxanes) have obtained the most promising results in Phase II trials and have entered Phase III testing. Two well-designed randomized trials have changed this scenario. Both compared docetaxel (with or without estramustine) against mitoxantrone and prednisone, and demonstrated a significant advantage not only in terms of response, pain control and quality of life, but also in terms of overall survival. Which patients need to be treated, the regimen of choice and duration of chemotherapy will be the next questions to be answered in the coming years in the field of HRPC, along with the role of new signal transduction inhibitors and other targeted therapies.