title: A Meta-Analysis and Indirect Comparison of Endothelin A Receptor Antagonist for Castration-Resistant Prostate Cancer.
abstract: BACKGROUND
  Endothelin A (ET-A) receptor antagonists including zibotentan and atrasentan, have been suggested as a treatment for castration-resistant prostate cancer (CRPC). Our aim was to conduct a meta-analysis and indirect comparison to assess the efficacy and safety of ET-A receptor antagonists for treatment of CRPC.
  
  
  METHODS
  We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science from inception to November 2014 to identify randomized controlled trials (RCTs) which assessed ET-A receptor antagonists for treatment of CRPC. Meta-analysis was conducted by STATA version 12.0 software.
  
  
  RESULTS
  Eight RCTs were identified, involving 6,065 patients. The results of direct comparison showed that compared with placebo, there was no statistically significant difference in the improvement of progression-free survival (PFS), overall survival (OS), time to disease progression (TTP), and total adverse events (AEs) with ET-A receptor antagonist treatment for CRPC. The results of ET-A receptor antagonists plus docetaxel versus docetaxel alone were similar. The indirect comparisons showed that there were no significant differences between zibotentan plus docetaxel versus atrasentan plus docetaxel when compared with docetaxel alone or zibotentan versus atrasenta compared with placebo in the improvement of PFS, OS, TTP, and total adverse events.
  
  
  CONCLUSIONS
  There were no significant benefits for ET-A receptor antagonists with or without docetaxel in the improvement of PFS, OS, TTP, and overall AEs. And there were no significant differences between zibotentan and atrasentan. Single-agent docetaxel should remain as one of the standard treatments.
authors.affiliation: Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China; Department of Clinical Laboratory, The Second Hospital of Lanzhou University, Lanzhou 730030, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Qi
authors.affiliation: Department of Urology, GanSu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China.
authors.forename: Li-xiu
authors.initials: LX
authors.lastname: Zhang
authors.affiliation: Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China; Key Laboratory of Urological Diseases in Gansu Province, Lanzhou 730030, China.
authors.forename: Rui-xia
authors.initials: RX
authors.lastname: Song
authors.affiliation: Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China; Department of Neurosurgery, The Second Hospital of Lanzhou University, Lanzhou 730030, China.
authors.forename: Zhen-hua
authors.initials: ZH
authors.lastname: He
authors.affiliation: Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China; Key Laboratory of Urological Diseases in Gansu Province, Lanzhou 730030, China.
authors.forename: Zhi-ping
authors.initials: ZP
authors.lastname: Wang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077868:Atrasentan; D018572:Disease-Free Survival; D000077143:Docetaxel; D065130:Endothelin A Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D065130:Endothelin A Receptor Antagonists; D011759:Pyrrolidines; D043823:Taxoids; C511404:ZD4054; D000077143:Docetaxel; D000077868:Atrasentan