Bevacizumab plus chemotherapy as first-line therapy for metastatic colorectal cancer: a systematic review of the efficacy and safety / 肿瘤

ABSTRACT

Objective:To systematically assess the efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents as first-line therapy for metastatic colorectal cancer (mCRC). Methods:We retrieved randomized controlled clinical trials (RCTs) of BEV plus chemotherapeutic agents as first-line therapy for mCRC from the databases of PubMed (1966 to August 2009), Embase (1974 to August 2009), Cochrane Library (Issue 3, 2009), China Journal Full Text Database (CJFD, 1994 to August 2009), Chinese Bio-medical Literature Database(CBM, 1978 to August 2009) and Chinese Scientific Journals Full Text Database (CSJD, 1989 to August 2009). Then we evaluated the methodological quality of included studies. Meta-analysis was performed using RevMan 5.0 software developed by the Cochrane Collaboration. Results:Only 6 clinical studies were selected and 2 646 eligible patients were included in the systematic review. Meta-analysis showed that BEV plus chemotherapy increased the overall response rate (complete response+partial response) compared with chemotherapy alone. The relative risk was 1.27 (95%CI 1.00-1.61, P=0.05), and the median survival time and progression-free survival (PFS) were longer. In terms of safety, there was a significant difference in the frequency of grade 3/4 adverse events, grade 3/4 hypertension, adverse events-induced study discontinuation and gastrointestinal perforation between the two groups. The relative risk was 1.12 (95%CI 1.07-1.61), 4.51 (95%CI 2.81-7.23), 1.37 (95%CI 1.16-1.63)and 4.32(95% CI1.24-15.05), respectively. There was no statistical difference between the two groups in the incidence of grade 3/4 bleeding, 60-day all-cause mortality, grade 3/4 proteinuria, grade 3/4 diarrhea, grade 3/4 leukopenia and pulmonary embolism. The relative risk was 1.50(95%CI 0.87-2.57), 0.71(95%CI 0.45-1.11), 2.26(95%CI 0.69-7.33), 1.18(95%CI 0.99-1.41), 1.17 (95%CI 0.97-1.42)and 0.84(95%CI 0.46-1.53), respectively. Conclusion:BEV plus chemotherapeutic agents as first-line the-rapy increases the response rate and prolongs PFS and median survival time of mCRC patients, but results in a higher incidence of any grade 3/4 adverse event, grade 3/4 hypertension and gastrointestinal perforation.