title: Efficacy and toxicity of anti-VEGF agents in patients with castration-resistant prostate cancer: a meta-analysis of prospective clinical studies.
abstract: BACKGROUND
  Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC.
  
  
  METHODS
  The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimates of the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline ≥50%) were calculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progression- free survival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doublets were compared by two-sided Student's t test.
  
  
  RESULTS
  A total of 3,841 patients from 19 prospective studies (4 randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis. The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-based combinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response rate was 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinations vs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months with weighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001) for anti-VEGF monotherapy vs. anti-VEGF-based doublets.
  
  
  CONCLUSIONS
  With available evidence, this pooled analysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefits gained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy.
authors.affiliation: Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Shanghai Cancer Center, Shanghai, China E-mail : fushen2014@sina.com.
authors.forename: Wei-Xiang
authors.initials: WX
authors.lastname: Qi
authors.forename: Shen
authors.initials: S
authors.lastname: Fu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiao-Mao
authors.initials: XM
authors.lastname: Guo
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D008297:Male; D011446:Prospective Studies; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A