背景:丝裂原活化蛋白激酶(MEK)抑制剂,整合RAS-RAF-MEK-ERK1/2通路的重要信号链,调节实体瘤患者的细胞功能,如分裂和增殖。然而,在临床治疗过程中,各种眼部不良反应(AE)会影响患者。本系统综述旨在评估MEK抑制剂联合靶向治疗或化疗治疗期间AE的发生情况。
方法:在PubMed,Cochrane图书馆,Embase,和几个中国数据库来确定随机对照试验。总的来说,眼AE被评估为主要终点;视力模糊,脉络膜视网膜病变,和视网膜脱离作为次要终点进行评估.
结果:共纳入17项随机对照试验。总的来说,与不使用MEK抑制剂的治疗相比,使用MEK抑制剂联合其他靶向抑制剂或化疗与总体眼部毒性风险增加近7.3%显著相关(风险比[RR],2.88;95%CI,1.42-5.85,P<0.05)。视力模糊的风险增加(RR,4.10;95%CI,2.55-6.58;P<.05),脉络膜视网膜病变(RR,8.36;95%CI,3.42-20.47;P<.05),和视网膜脱离(RR,8.98;95%CI,3.92-20.57;P<.05)。
结论:MEK抑制剂联合靶向药物或化疗治疗似乎会增加整体眼部不良事件。每当出现新的或恶化的眼部毒性时,建议进行更实用的算法来筛查眼部AE。
Mitogen-activated protein kinase (MEK) inhibitors, which integrate the important signaling chain of the RAS-RAF-MEK-ERK1/2 pathway, regulate cell functions such as division and proliferation for patients with solid tumors. However, various ocular adverse effects (AEs) affect patients during clinical treatment. This systematic
review aimed to assess the occurrence of AEs during treatment with MEK inhibitors plus targeted therapy or chemotherapy.
A scientific literature search was conducted in PubMed, the Cochrane Library, Embase, and several Chinese databases to identify randomized controlled trials. Overall, ocular AEs were assessed as the primary end point; blurred vision, chorioretinopathy, and retinal detachment were assessed as secondary end points.
Seventeen randomized controlled trials were included. Overall, the use of MEK inhibitors combined with other targeted inhibitors or chemotherapy was significantly associated with a nearly 7.3% increased risk of overall ocular toxicities vs therapy without MEK inhibitors (risk ratio [RR], 2.88; 95% CI, 1.42-5.85, P < .05). An increased risk of blurred vision (RR, 4.10; 95% CI, 2.55- 6.58; P < .05), chorioretinopathy (RR, 8.36; 95% CI, 3.42-20.47; P < .05), and retinal detachment (RR, 8.98; 95% CI, 3.92-20.57; P < .05) was demonstrated.
Treatment with MEK inhibitors combined with targeted drugs or chemotherapy seems to increase overall ocular AEs. A more practical algorithm for the screening of ocular AEs was suggested to be conducted whenever new or worsening ocular toxicities occur.