title: Safety of bevacizumab in treating metastatic colorectal cancer: a systematic review and meta-analysis of all randomized clinical trials.
abstract: OBJECTIVE
  The incidence rates of colorectal cancer (CRC) are increasing in a number of different regions, and recent studies have indicated that addition of bevacizumab to CRC therapy is beneficial. To better understand the relative risk (RR) of adverse events associated with use of bevacizumab, we systematically reviewed published clinical trials that studied use of bevacizumab in treatment of patients affected by metastatic CRC (mCRC).
  
  
  METHODS
  The National Library of Medicine PubMed, MEDLINE, Ovid, Cochrane Library and Chinese Biomedicine databases were searched. The RR and number needed to harm (NNH) values for major side effects with 95% confidence intervals (CIs) were calculated in a fixed-effects model and a random-effects model, where appropriate.
  
  
  RESULTS
  Fifteen controlled trials totalling 6,937 patients were eligible for this analysis. Compared with the control group, the bevacizumab treatment group had a slightly higher risk of any severe adverse event (pooled RR 1.07 [95% CI 1.02-1.12]). The pooled risk difference was 5% [95% CI 2-9%], with an NNH of 20 treated patients. Analyses showed a statistically significantly higher risk of secondary endpoints, including the discovery that bevacizumab was associated with a threefold higher risk of hypertension (pooled RR 3.06 [95% CI 2.45-3.83]), a twofold higher risk of gastrointestinal haemorrhage/perforation and a lower risk of neutropenia (pooled RR 0.75 [95% CI 0.26-2.19]).
  
  
  CONCLUSIONS
  Bevacizumab has efficacy in all treatment regimens for advanced CRC. However, our meta-analysis raises safety concerns regarding an increased risk of serious adverse events associated with use of bevacizumab among patients with mCRC. Our findings warrant cautious use of bevacizumab in clinical oncology.
authors: Pharmacy Department of Changhai Hospital, The First Affiliated Hospital of Second Military Medical University, Shanghai, China.
authors: Fei
authors: F
authors: Dai
authors: Lixing
authors: L
authors: Shu
authors: Yangfang
authors: Y
authors: Bian
authors: Zhuo
authors: Z
authors: Wang
authors: Zhangwei
authors: Z
authors: Yang
authors: Wengong
authors: W
authors: Chu
authors: Shen
authors: S
authors: Gao
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
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