Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: a systematic review.
BACKGROUND
Fluoropyrimidine-based chemotherapy is considered standard treatment of advanced colorectal cancer. Recent studies indicate benefit to the addition of bevacizumab, a recombinant monoclonal antibody targeting vascular endothelial growth factor.


METHODS
Medline, EMBASE, Cochrane Library, and conference proceedings were searched to identify randomized trials in advanced colorectal cancer comparing chemotherapy plus bevacizumab with chemotherapy alone. A meta-analysis of published data was carried out.


RESULTS
Five trials comparing chemotherapy plus bevacizumab with chemotherapy alone as first- or second-line treatment were identified. Our meta-analysis indicates an advantage in favor of the addition of bevacizumab to chemotherapy in terms of overall survival (OS) [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69-0.90; P = 0.0005], progression-free survival (PFS) (HR 0.63; 95% CI 0.49-0.81, P = 0.0004), and response rate (RR 1.50; 95% CI 1.06-2.10, P = 0.02). The most commonly observed adverse effects related to bevacizumab included hypertension, proteinuria, bleeding, and thrombosis. Gastrointestinal perforation and poor wound healing were also observed; however, their incidence was rare.


CONCLUSIONS
For patients with advanced colorectal cancer receiving first- or second-line fluoropyrimidine-based chemotherapy, the addition of bevacizumab improves PFS and OS at the expense of increased incidence of toxicity. The magnitude of benefit may differ based on the chemotherapy regimen with which bevacizumab is partnered.
Welch
S
S
Division of Medical Oncology, London Regional Cancer Centre, London, Ontario. Electronic address: stephen.welch@lhsc.on.ca.
Spithoff
K
K
Department of Clinical Epidemiology and Biostatistics, Cancer Care Ontario's Program in Evidence-Based Care, McMaster University, Hamilton, Ontario.
Rumble
R B
RB
Department of Clinical Epidemiology and Biostatistics, Cancer Care Ontario's Program in Evidence-Based Care, McMaster University, Hamilton, Ontario.
Maroun
J
J
Division of Medical Oncology, Ottawa Hospital Regional Cancer Centre, Ottawa, Ontario, Canada.
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002277:Carcinoma / Q000473:pathology / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D018450:Disease Progression; D006801:Humans; D007167:Immunotherapy / Q000379:methods
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab