title: Enzalutamide versus abiraterone acetate for the treatment of men with metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  Over the past decade, treatment options for men with metastatic castration-resistant prostate cancer (CRPC) have expanded with the addition of abiraterone acetate (AA), enzalutamide, sipuleucel-T, radium-223, docetaxel and cabazitaxel. The optimal sequencing of therapies in the context of efficacy and known cross-resistance remains uncertain.
  
  
  METHODS
  We review the development of enzalutamide (MDV3100, Xtandi), a novel second-generation androgen receptor (AR), and AA (Zytiga), a selective, irreversible inhibitor of cytochrome P17. In addition to discussing the clinical evidence, we also address evolving evidence of mechanisms of resistance and clinical cross-resistance during sequential therapy with these agents.
  
  
  CONCLUSIONS
  AA and enzalutamide have both demonstrated tolerability and clinical benefit for multiple outcomes in patients with CRPC, in both post-chemotherapy and pre-chemotherapy settings. Both agents target the androgen-signaling pathway and have similar efficacy; however, they differ in prednisone use and their toxicity profiles, impacting the decision of upfront therapy. Mechanisms of resistance emerging after treatment include both alterations in AR signaling as well as mechanisms that bypass the AR. Retrospective analyses have demonstrated evidence that sequential treatment with these agents results in limited clinical benefit, supporting mechanisms of cross-resistance. Trials are ongoing to determine optimal timing, sequence and combination of these agents.
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Division of Medical Oncology, Department of Medicine , DUMC 3841, Durham, NC 27710 , USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.forename: Jason
authors.initials: J
authors.lastname: Zhu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Armstrong
mesh_terms: D000069501:Abiraterone Acetate; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000736:Androstenes / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*
chemical_list: D000726:Androgen Antagonists; D000736:Androstenes; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; D013254:Steroid 17-alpha-Hydroxylase; D000069501:Abiraterone Acetate
keywords: abiraterone acetate; androgen receptor-V7; castration-resistant prostate cancer; cross-resistance; enzalutamide; resistance