title: Bevacizumab increases the risk of gastrointestinal perforation in cancer patients: a meta-analysis with a focus on different subgroups.
abstract: BACKGROUND
  The aim of this meta-analysis was to gather current data and evaluate not only the risk of gastrointestinal (GI) perforation with bevacizumab, but also the potential risk factors for this adverse event.
  
  
  METHODS
  We carried out a literature search in PubMed for randomized controlled trials (RCTs) reported from January 2000 to December 2013. Summary incidence, relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies.
  
  
  RESULTS
  A total of 26,833 patients from 33 RCTs were included in the meta-analysis. Bevacizumab-containing therapy significantly increased the risk of developing all-grade (RR 3.35, 95% CI 2.35-4.79, P < 0.001) and fatal GI perforation (RR 3.08, 95%CI: 1.04-9.08, P = 0.042). On subgroup analysis, no significant risk differences were found based on bevacizumab dosage, treatment duration, treatment line, type of clinical trial and median age. When stratified by tumor types, a significantly increased risk of GI perforation with bevacizumab was observed in colorectal cancer (RR 2.84, 95% CI 1.43-5.61, P = 0.003), gynecologic cancer (RR 3.37, 95% CI 1.71-6.62, P < 0.001) and prostate cancer (RR 6.01, 95% CI 1.78-20.28, P = 0.004). Additionally, the use of bevacizumab significantly increased the risk of GI perforation when used in conjunction with taxanes (RR 3.09, 95% CI 1.92-4.96, P < 0.001) or oxaliplatin (RR 2.85, 95% CI 1.07-7.57, P = 0.036).
  
  
  CONCLUSIONS
  Bevacizumab treatment is associated with a significantly increased risk of developing GI perforation, and clinicians should be aware of the risks of GI perforation with the administration of this drug in cancer patients.
authors.affiliation: Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China, qiweixiang1113@163.com.
authors.forename: Wei-Xiang
authors.initials: WX
authors.lastname: Qi
authors.forename: Zan
authors.initials: Z
authors.lastname: Shen
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Tang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000068258:Bevacizumab; D006801:Humans; D007416:Intestinal Perforation / Q000139:chemically induced*; D009369:Neoplasms / Q000188:drug therapy / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012306:Risk
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab