Pharmacy Department of Changhai Hospital, The First Affiliated Hospital of Second Military Medical University, Shanghai, China.
Clin Drug Investig. 2013 Nov;33(11):779-88. doi: 10.1007/s40261-013-0125-6.
The incidence rates of colorectal cancer (CRC) are increasing in a number of different regions, and recent studies have indicated that addition of bevacizumab to CRC therapy is beneficial. To better understand the relative risk (RR) of adverse events associated with use of bevacizumab, we systematically reviewed published clinical trials that studied use of bevacizumab in treatment of patients affected by metastatic CRC (mCRC).
The National Library of Medicine PubMed, MEDLINE, Ovid, Cochrane Library and Chinese Biomedicine databases were searched. The RR and number needed to harm (NNH) values for major side effects with 95% confidence intervals (CIs) were calculated in a fixed-effects model and a random-effects model, where appropriate.
Fifteen controlled trials totalling 6,937 patients were eligible for this analysis. Compared with the control group, the bevacizumab treatment group had a slightly higher risk of any severe adverse event (pooled RR 1.07 [95% CI 1.02-1.12]). The pooled risk difference was 5% [95% CI 2-9%], with an NNH of 20 treated patients. Analyses showed a statistically significantly higher risk of secondary endpoints, including the discovery that bevacizumab was associated with a threefold higher risk of hypertension (pooled RR 3.06 [95% CI 2.45-3.83]), a twofold higher risk of gastrointestinal haemorrhage/perforation and a lower risk of neutropenia (pooled RR 0.75 [95% CI 0.26-2.19]).
Bevacizumab has efficacy in all treatment regimens for advanced CRC. However, our meta-analysis raises safety concerns regarding an increased risk of serious adverse events associated with use of bevacizumab among patients with mCRC. Our findings warrant cautious use of bevacizumab in clinical oncology.
在许多不同地区，结直肠癌（CRC）的发病率正在上升，最近的研究表明，贝伐珠单抗联合 CRC 治疗有益。为了更好地了解与贝伐珠单抗使用相关的不良事件的相对风险（RR），我们系统地综述了已发表的研究贝伐珠单抗治疗转移性 CRC（mCRC）患者的临床试验。
检索了美国国立医学图书馆的 PubMed、MEDLINE、Ovid、 Cochrane 图书馆和中国生物医学文献数据库。在固定效应模型和随机效应模型中，计算了主要副作用的 RR 和危害人数（NNH）值及其 95%置信区间（CI）。
符合纳入标准的 15 项对照试验共纳入 6937 例患者。与对照组相比，贝伐珠单抗治疗组发生任何严重不良事件的风险略高（汇总 RR 1.07[95%CI 1.02-1.12]）。汇总风险差异为 5%[95%CI 2-9%]，NNH 为 20 例治疗患者。分析显示，次要终点的风险显著增加，包括发现贝伐珠单抗与高血压风险增加三倍相关（汇总 RR 3.06[95%CI 2.45-3.83]）、胃肠道出血/穿孔风险增加两倍以及中性粒细胞减少症风险降低（汇总 RR 0.75[95%CI 0.26-2.19]）。
贝伐珠单抗在所有晚期 CRC 治疗方案中均有效。然而，我们的荟萃分析对 mCRC 患者使用贝伐珠单抗相关严重不良事件风险增加提出了安全性担忧。我们的研究结果需要在临床肿瘤学中谨慎使用贝伐珠单抗。
