title: Phase III trials of standard chemotherapy with or without bevacizumab for ovarian cancer: a meta-analysis.
abstract: BACKGROUND
  Platinum-based standard chemotherapy improves survival of ovarian cancer (OC), but the five-year survival rate remains below 50%. Antiangiogenic agents (7.5 or 15 mg/kg Bevacizumab, Bev) plus to standard chemotherapy improve progression-free survival (PFS) not overall survival (OS) in completed randomized controlled trials (RCTs). The efficacy and safety of two doses of Bev + standard chemotherapy remain controversial.
  
  
  METHODS
  MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane databases and ClinicalTrials.gov were searched. The outcomes of eligible RCTs included PFS, OS and toxicities. Hazard ratio (HR) and relative risk (RR) were used for the meta-analysis and were expressed with 95% confidence intervals (CIs).
  
  
  RESULTS
  Bev + chemotherapy improved PFS (HR, 0.82; 95% CI, 0.75 to 0.89; P = .000) and OS (HR, 0.87; 95% CI, 0.77 to 0.99; P = .026) in newly diagnosed OC (2 trials, 2776 patients), and PFS (HR, 0.48; 95% CI, 0.41 to 0.57; P = .000) in recurrent OC (2 trials, 845 patients). Bev + chemotherapy increased non-CNS bleeding (RR, 3.63; 95% CI, 1.81 to 7.29; P = .000), hypertension grade ≥ 2 (RR, 4.90; 95% CI, 3.83 to 6.25; P = .000), arterial thromboembolism (RR, 2.29; 95% CI, 1.33 to 3.94; P = .003), gastrointestinal perforation (RR, 2.90; 95% CI, 1.44 to 5.82; P = .003), and proteinuria grade ≥ 3 (RR, 6.63; 95% CI 3.17 to 13.88; P = .000). No difference was observed between the two Bev doses in PFS (HR, 1.04; 95% CI, 0.88 to 1.24) or OS (HR, 1.15, 95% CI, 0.88 to 1.50), but 15 mg/kg Bev increased toxicities.
  
  
  CONCLUSIONS
  Bev + standard chemotherapy delayed progression for newly diagnosed and recurrent OC, and improved survival for newly diagnosed OC. The 7.5 mg/kg dose appeared to be optimal for newly diagnosed OC patients with high risk for progression.
authors: Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China ; Seven-Year Academic Program for Master, China Medical University, Shenyang, China.
authors: Mingyi
authors: M
authors: Zhou
authors: Ping
authors: P
authors: Yu
authors: Xiujuan
authors: X
authors: Qu
authors: Yunpeng
authors: Y
authors: Liu
authors: Jingdong
authors: J
authors: Zhang
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab