Clinical Drug Investigation

, Volume 33, Issue 11, pp 779–788 | Cite as

Safety of Bevacizumab in Treating Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis of All Randomized Clinical Trials

  • Fei Dai
  • Lixing Shu
  • Yangfang Bian
  • Zhuo Wang
  • Zhangwei Yang
  • Wengong Chu
  • Shen Gao
Systematic Review


Background and 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).


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.


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]).


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.



No sources of funding were used in the preparation of this manuscript. The authors have no potential conflicts of interest that are directly relevant to the content of this article. The data collection for this study was conducted by Fei Dai and Lixin Shu; the data analysis and manuscript writing were performed by Fei Dai, Yanfang Bian, Zhuo Wang and Zhangwei Yang; and the study was designed by Wengong Chu and Shen Gao.


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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Fei Dai
    • 1
    • 2
  • Lixing Shu
    • 2
  • Yangfang Bian
    • 1
  • Zhuo Wang
    • 1
  • Zhangwei Yang
    • 1
  • Wengong Chu
    • 2
  • Shen Gao
    • 1
  1. 1.Pharmacy Department of Changhai HospitalThe First Affiliated Hospital of Second Military Medical UniversityShanghaiChina
  2. 2.Department of Pharmaceutical AdministrationSecond Military Medical UniversityShanghaiChina

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