Clinical Drug Investigation

, Volume 33, Issue 11, pp 779–788

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

Authors

  • Fei Dai
    • Pharmacy Department of Changhai HospitalThe First Affiliated Hospital of Second Military Medical University
    • Department of Pharmaceutical AdministrationSecond Military Medical University
  • Lixing Shu
    • Department of Pharmaceutical AdministrationSecond Military Medical University
  • Yangfang Bian
    • Pharmacy Department of Changhai HospitalThe First Affiliated Hospital of Second Military Medical University
  • Zhuo Wang
    • Pharmacy Department of Changhai HospitalThe First Affiliated Hospital of Second Military Medical University
  • Zhangwei Yang
    • Pharmacy Department of Changhai HospitalThe First Affiliated Hospital of Second Military Medical University
    • Department of Pharmaceutical AdministrationSecond Military Medical University
  • Shen Gao
    • Pharmacy Department of Changhai HospitalThe First Affiliated Hospital of Second Military Medical University
Systematic Review

DOI: 10.1007/s40261-013-0125-6

Cite this article as:
Dai, F., Shu, L., Bian, Y. et al. Clin Drug Investig (2013) 33: 779. doi:10.1007/s40261-013-0125-6

Abstract

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).

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]).

Conclusion

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.

Copyright information

© Springer International Publishing Switzerland 2013