Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups

A wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen.Six trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS) and progression-free survival (PFS) (HR = 0.84; CI: 0.77-0.91; P < 0.00001 and HR = 0.72; CI: 0.66-0.78; P < 0.00001, respectively). However, heterogeneity of results was very high for both outcomes, and subgroup analyses supported the OS advantage with bevacizumab restricted to irinotecan-based regimens. Infusional fluorouracil subsets involved a minor proportion, and did not demonstrate statistical benefit in PFS or OS. Regarding toxicity, higher rates of grades 3-4 hypertension, bleeding, thromboembolic events and proteinuria were uniformly observed with bevacizumab, leading to increased treatment interruptions (HR = 1.47; P = 0.0004).Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.Colorectal cancer is currently the third most diagnosed cancer in men and the second in women worldwide, with an estimate of over 1.2 million new cases and 608,700 deaths in 2008 [1]. In the attempt of disease control, target therapy has been a matter of extensive research. Anti-angiogenesis is one of the pivotal theories involved in this approach, ever since the discovery of increased vascularity as a probable key for tumour progression [2,3]. One of the main pathways associated with the anti-angiogenic process is the vascular endothelial growth factor (VEGF) family, with high expression of its receptors observed not only in colorectal neoplasms, but in a wide variety o