Department of Infectious diseases, Changzheng Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
Eur J Clin Pharmacol. 2011 Jun;67(6):613-23. doi: 10.1007/s00228-010-0988-x. Epub 2011 Jan 18.
High-grade bleeding is a serious adverse event associated with bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor and widely used in the current cancer treatments. The aim of this study was to gain a better understanding of the overall incidence and risk of high-grade bleeding in cancer patients who receive bevacizumab therapy.
We performed a meta-analysis of relevant randomized controlled trials (RCTs) identified in PubMed, Cochrane library, Embase, and American Society of Clinical Oncology conferences. Overall relative risks (RRs), incidence rates, and 95% confidence intervals (CIs) were calculated using a random-effects model. The primary clinical endpoint was high-grade bleeding (grade 3 or above).
A total of 14,277 patients with a variety of solid tumors from 22 RCTs were included in the present analysis. The addition of bevacizumab to cancer chemotherapy significantly increased the risk of high-grade bleeding (RR 1.60, 95% CI 1.19-2.15), with RRs of high-grade bleeding among patients receiving bevacizumab at 2.5 and 5 mg/kg per week of 1.27 (95% CI 0.95-1.71) and 3.02 (95% CI 1.85-4.95), respectively. The overall incidence of high-grade bleeding among patients receiving bevacizumab was 2.8% (95% CI 2.1-3.8). Higher risks were observed in patients with non-small-cell lung cancer (RR 3.41, 95% CI 1.68-6.91), renal cell carcinoma (RR 6.37, 95% CI 1.43-28.33), and colorectal cancer (RR 9.11, 95% CI 1.70-48.79) who were receiving bevacizumab at 5 mg/kg per week.
Among the patients included in the trials analyzed in this meta-analysis, the addition of bevacizumab to cancer chemotherapy significantly increased the risk of high-grade bleeding. The risk may be dose-dependent and may vary with tumor type.
贝伐珠单抗是人源化单克隆抗体，靶向血管内皮生长因子，广泛用于目前的癌症治疗，其与高级别出血严重不良事件相关。本研究旨在更好地了解接受贝伐珠单抗治疗的癌症患者中高级别出血的总体发生率和风险。
我们对 PubMed、Cochrane 图书馆、Embase 和美国临床肿瘤学会会议中确定的相关随机对照试验（RCT）进行了荟萃分析。使用随机效应模型计算总体相对风险（RR）、发生率和 95%置信区间（CI）。主要临床终点为高级别出血（等级 3 或以上）。
本分析共纳入来自 22 项 RCT 的 14277 例各种实体瘤患者。贝伐珠单抗联合癌症化疗显著增加了高级别出血的风险（RR 1.60，95%CI 1.19-2.15），每周每公斤 2.5mg 和 5mg 接受贝伐珠单抗治疗的患者中高级别出血的 RR 分别为 1.27（95%CI 0.95-1.71）和 3.02（95%CI 1.85-4.95）。接受贝伐珠单抗治疗的患者中高级别出血的总体发生率为 2.8%（95%CI 2.1-3.8）。非小细胞肺癌（RR 3.41，95%CI 1.68-6.91）、肾细胞癌（RR 6.37，95%CI 1.43-28.33）和结直肠癌（RR 9.11，95%CI 1.70-48.79）患者接受每周每公斤 5mg 贝伐珠单抗治疗时，风险更高。
在本荟萃分析中纳入的试验患者中，贝伐珠单抗联合癌症化疗显著增加了高级别出血的风险。风险可能呈剂量依赖性，并可能因肿瘤类型而异。
