Yang Yong, Liu Yi-Hua, Sun Xu, Yu Ming-Wei, Yang Lin, Cheng Pei-Yu, Yang Guo-Wang, Wang Xiao-Min
a Graduate School, Beijing University of Chinese Medicine , Beijing, PR China.
b Department of Oncology , Beijing Hospital of Traditional Chinese Medicine, Capital Medical University , Beijing, PR China.
Curr Med Res Opin. 2017 Sep;33(9):1663-1675. doi: 10.1080/03007995.2017.1349657. Epub 2017 Jul 20.
MEK inhibitors are a group of drugs that have shown reliable effects in the treatment of metastatic melanoma and non-small-cell lung cancer. Peripheral edema is an adverse event associated with MEK inhibitors; however, there has been no systematic attempt to evaluate peripheral edema data observed with these agents. This meta-analysis aimed to determine the risk of peripheral edema in cancer patients treated with MEK inhibitors.
The authors searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov without language restriction. The final search was conducted on January 9, 2017. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. Heterogeneity was calculated and reported via Tau, Chi, and I analyses.
A total of 13 eligible studies were obtained. Patients treated with MEK inhibitors (Trametinib and Selumetinib) had an increased risk overall of peripheral edema (RR = 3.05, 95% CI = 1.98-4.70; p < .00001), but the MEK inhibitors (Trametinib and Selumetinib) did not increase the risk of high grade edema (RR = 1.88, 95% CI = 0.66-5.35; p = .24). Sub-group analysis, based on cancer type (melanoma vs non-melanoma), found that the peripheral edema risk in melanoma patients is higher than that in non-melanoma patients (p = .03). However, no significant difference was observed in terms of high-grade edema and other sub-groups (trametinib vs selumetinib; monotherapy vs combination). Due to the absence of cobimetinib data, the result about cobimetinib was not involved.
This meta-analysis reveals that the use of MEK inhibitors is associated with an increased risk of peripheral edema in cancer patients. Oncologists should be aware of the risk and perform regular assessments.
MEK抑制剂是一类在转移性黑色素瘤和非小细胞肺癌治疗中显示出可靠疗效的药物。外周水肿是与MEK抑制剂相关的不良事件；然而，尚未有系统地尝试评估使用这些药物时观察到的外周水肿数据。本荟萃分析旨在确定接受MEK抑制剂治疗的癌症患者发生外周水肿的风险。
作者检索了PubMed、Cochrane图书馆、EMBASE和临床试验.gov，无语言限制。最终检索于2017年1月9日进行。对二分数据计算95%置信区间（CI）的风险比（RR）。通过Tau、Chi和I分析计算并报告异质性。
共获得13项符合条件的研究。接受MEK抑制剂（曲美替尼和司美替尼）治疗的患者总体外周水肿风险增加（RR = 3.05，95% CI = 1.98 - 4.70；p <.00001），但MEK抑制剂（曲美替尼和司美替尼）未增加重度水肿风险（RR = 1.88，95% CI = 0.66 - 5.35；p =.24）。基于癌症类型（黑色素瘤与非黑色素瘤）的亚组分析发现，黑色素瘤患者的外周水肿风险高于非黑色素瘤患者（p =.03）。然而，在重度水肿和其他亚组（曲美替尼与司美替尼；单药治疗与联合治疗）方面未观察到显著差异。由于缺乏考比替尼数据，未纳入关于考比替尼的结果。
本荟萃分析表明，使用MEK抑制剂与癌症患者外周水肿风险增加相关。肿瘤学家应意识到这一风险并进行定期评估。
