title: Evolving standards in the treatment of docetaxel-refractory castration-resistant prostate cancer.
abstract: The management of men with metastatic castration-resistant prostate cancer (CRPC) has taken several leaps forward in the past year, with the demonstration of improved overall survival with three novel agents (sipuleucel-T, cabazitaxel with prednisone and abiraterone acetate with prednisone), and a significant delay in skeletal-related events observed with denosumab. The pipeline of systemic therapies in prostate cancer remains strong, as multiple agents with a diverse array of mechanisms of action are showing preliminary signs of clinical benefit, leading to more definitive phase III confirmatory trials. In this review, which represents part 1 of a two-part series on metastatic CRPC, we will summarize the mechanisms of resistance to hormonal and chemotherapies and discuss the evolving landscape of treatment options for men with CRPC, with a particular focus on currently approved and emerging treatment options following docetaxel administration, as well as prognostic factors in this post-docetaxel state. As docetaxel remains the standard initial systemic therapy for men with metastatic CRPC for both palliative and life-prolonging purposes, knowledge of these evolving standards will help to optimize delivery of care and long-term outcomes.
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231-1000, USA. eantona1@jhmi.edu
authors.forename: E S
authors.initials: ES
authors.lastname: Antonarakis
authors.forename: A J
authors.initials: AJ
authors.lastname: Armstrong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007167:Immunotherapy; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery*; D016032:Randomized Controlled Trials as Topic; D011944:Receptors, Androgen / Q000378:metabolism; D059039:Standard of Care; D043823:Taxoids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017211:Treatment Failure; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D043823:Taxoids; D000077143:Docetaxel