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

Abstract

BACKGROUND:

Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

• Authors: Ligia Traldi Macedo, Andre Bacellar da Costa Lima, Andre Deeke Sasse
• Journal: BMC cancer (BMC Cancer) Vol. 12 Pg. 89 (Mar 13 2012) ISSN: 1471-2407 [Electronic] England
• PMID: 22414244 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized
• Organoplatinum Compounds
• Pyridines
• oxiplatin
• Bevacizumab
• Irinotecan
• Fluorouracil
• Camptothecin

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab
• Camptothecin (administration & dosage, analogs & derivatives)
• Colorectal Neoplasms (drug therapy, mortality)
• Fluorouracil (administration & dosage)
• Humans
• Irinotecan
• Organoplatinum Compounds (administration & dosage)
• Pyridines (administration & dosage)
• Randomized Controlled Trials as Topic
• Survival Analysis