贝伐珠单抗治疗转移性结直肠癌不良反应的Meta分析

Adverse Events of Bevacizumab in Patients with Metastatic Colorectal Cancer: A Meta-analysis

关键词:  结直肠癌  贝伐珠单抗  不良反应  Meta分析

Key words:  colorectal cancer  bevacizumab  adverse event  Meta-analysis

摘要:

目的 评价贝伐珠单抗联合化疗在转移性结直肠癌(mCRC)中不良反应的发生率，并分析各种不良反应的总体风险。方法 制定文献纳入、排除标准，全面检索Cochrane Library，Pubmed，EMBASE，CNKI，CBM以及万方数据库，纳入相关文献。采用Cochrane协作网提供的RevMan 5.1专用软件进行数据合并与统计分析。结果 共纳入7项研究(n=3 493)，贝伐珠单抗联合化疗组患者1 889例，单纯化疗组患者1 604 例。比较各项不良反应的发生率，结果接受贝伐珠单抗治疗的mCRC患者患高血压(RR=3.93，P<0.001)、蛋白尿(RR=3.76，P=0.009)、胃肠穿孔和瘘管(RR=4.10，P=0.02)、3~4级的出血(RR=1.94，P=0.01)和血栓栓塞(RR=1.33，P=0.008)的危险性增高；肺栓塞(RR=0.78，P=0.44)、中性粒细胞减少(RR=1.15，P=0.14)和腹泻(RR=1.17，P=0.09)等风险在两组中无明显差别。所有3~4级的不良反应(RR=1.16，P<0.001)在贝伐珠单抗联合化疗组轻度增加。两组mCRC患者中治疗相关的致死性不良反应发生率相当(RR=1.09，P=0.74)，贝伐珠单抗治疗组患者因不良反应中断治疗(RR=1.25，P=0.003)的风险更高。结论 与单纯接受化疗相比，接受贝伐珠单抗联合化疗治疗的mCRC患者出现高血压、蛋白尿、胃肠穿孔、血栓栓塞和出血的危险性更高，但并未增加致死性不良反应发生率。

Abstract:

OBJECTIVE To quantify the risk of bevacizumab-related adverse effects in patients with metastatic colorectal cancer (mCRC). METHODS Randomized controlled clinical trials (RCTs) of bevacizumab plus chemotherapeutic agents for patients with mCRC from the databases of Cochrane Library, Pubmed, EMBASE, CNKI, CBM and Wanfang Database for investigating side effects were retrieved. Then the methodological quality of included studies were evaluated. Meta-analysis was performed with the Review Manager 5.1. RESULTS It was retrieved seven out of 198 eligible papers encompassing 3 493 patients. The relative risk of hypertension (RR=3.93, P<0.001), gastrointestinal perforations (RR=4.10, P=0.02), proteinuria (RR=3.76, P=0.009), thrombosis events (RR=1.33, P=0.008) and bleeding (RR=1.94, P=0.010) were significantly increased in the bevacizumab group. There was no statistical difference in pulmonary embolism (RR=0.78, 95% CI 0.42-1.46, P=0.44), leukopenia (RR=1.15, 95% CI 0.95-1.40, P=0.14), grade 3-4 diarrheas (RR=1.17, 95% CI 0.98-1.40, P=0.09) between both groups. The grade 3-4 adverse events slightly increased in the bevacizumab group (RR=1.16, 95% CI 1.09-1.24, P<0.001). There was no statistical difference in fatal adverse events between both groups. CONCLUSION These results show that the risks of hypertension, gastrointestinal perforations, thrombosis, proteinuria and bleeding of bevacizumab group were higher than the chemotherapy alone group. However, bevacizumab did not increase the incidence of fatal adverse events compared with chemotherapy alone.