Practical guide to the use of chemotherapy in castration resistant prostate cancer.
INTRODUCTION: Chemotherapy, once thought to be toxic and ineffective in men with castration resistant prostate cancer (CRPC), has a significant impact on survival and quality-of-life in these patients. This article summarizes recent studies performed with two Food and Drug Administration (FDA) approved agents which have improved survival in men with CRPC, docetaxel and cabazitaxel.
MATERIALS AND METHODS: The literature on cytotoxic chemotherapy for castration resistant prostate cancer was reviewed. The individual efficacy, mechanisms of chemotherapeutic action, and appropriate disease states of administration were identified. Recent clinical trial results of chemotherapy combined with targeted agents was also reviewed.
RESULTS: Front line cytotoxic therapy consists of docetaxel combined with prednisone. In two randomized trials, docetaxel based therapy demonstrated a 20%-24% improvement in survival over the palliative standard of care, mitoxantrone combined with prednisone. Eight randomized trials combining docetaxel/prednisone with other antiangiogenic, bone targeted, vaccine or metabolic therapies failed to demonstrate an improvement in survival over docetaxel alone. Cabazitaxel, an analogue of docetaxel which has activity in taxane resistant cell lines, is approved by the FDA, for use in CRPC patients who have previous exposure to docetaxel.
CONCLUSIONS: Docetaxel combined with prednisone remains the standard of care as first line cytotoxic therapy for CRPC. Cabazitaxel is an effective second line cytotoxic agent that improves survival; studies are underway comparing cabazitaxel to docetaxel as first line chemotherapy. Given its lack of survival benefit, as well as the emergence of new treatments for prostate cancer, mitoxantrone has a diminished role in the treatment of CRPC.