title: Current clinical trials in castrate-resistant prostate cancer.
abstract: Seven years passed since docetaxel/prednisone demonstrated and overall survival benefit, leading to its approval by the FDA for metastatic castration resistant prostate cancer. In 2010, two new treatments, sipuleucel-T and cabazitaxel, were approved by the United States Food and Drug Administration for men with castration-resistant prostate cancer, based upon improvement in overall survival. The progress that has been made in understanding the biological basis of disease progression, particularly the role of the continued activation of the androgen receptor, have led to new treatments that will further improve survival in these patients. Abiraterone, a drug that depletes both intracellular and extracellular sources of testosterone, demonstrated a 3.9-month improvement in survival in patients who failed docetaxel-based chemotherapy. Other drugs targeting the androgen-receptor axis, such as TAK-700 and MDV3100, have demonstrated significant activity in phase 1 and 2 studies, and are currently in phase 3. Agents that target angiogenesis, bone, and novel apoptotic proteins currently are under investigation, either as single agents or in combination with chemotherapy. The challenge for the development of clinical trials will be how these compounds will be sequenced in the future.
authors.affiliation: Department of Medicine, Division of Oncology, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. dpp5@columbia.edu.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
mesh_terms: D000736:Androstenes; D000737:Androstenols / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D000077143:Docetaxel; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D014020:Tissue Extracts / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D000737:Androstenols; D018931:Antineoplastic Agents, Hormonal; D001549:Benzamides; D009570:Nitriles; D043823:Taxoids; D014020:Tissue Extracts; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C552428:cabazitaxel; C511774:sipuleucel-T; C540278:enzalutamide; D017430:Prostate-Specific Antigen; C089740:abiraterone; D011241:Prednisone