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MEK抑制剂治疗的眼部效应:文献综述、临床表现及缓解的最佳实践

Ocular Effects of MEK Inhibitor Therapy: Literature Review, Clinical Presentation, and Best Practices for Mitigation.

作者信息

Jeng-Miller Karen W, Miller Miles A, Heier Jeffrey S

机构信息

Ophthalmic Consultants of Boston, Boston, MA, USA.

Center for Systems Biology, Massachusetts General Hospital Research Institute, Boston, MA, USA.

出版信息

Oncologist. 2024 May 3;29(5):e616-e621. doi: 10.1093/oncolo/oyae014.

Abstract

MEK signaling pathway targeting has emerged as a valuable addition to the options available for the treatment of advanced cancers including melanoma and non-small cell lung cancer. Ophthalmologic monitoring of patients taking part in clinical trials of MEK inhibitors has shown that while ocular effects are common, generally emerging during the first days to weeks of treatment, the majority are either asymptomatic or have minimal visual impact and are benign, resolving without intervention or the need to reduce or stop MEK inhibitor therapy. However rare cases of serious, potentially vision-threatening ocular toxicities have been reported during MEK inhibitor therapy. There is currently no recommendation for routine ophthalmologic screening or monitoring of patients with advanced cancer who are initiating MEK inhibitor therapy. However, baseline ophthalmologic examination may be useful for all patients initiating MEK inhibitor therapy to allow the differentiation of preexisting pathology versus the development of MEK inhibitor-associated retinopathy in the event of the emergence of symptomatic ocular events. Regular ophthalmologic examination may be appropriate for patients at increased risk for ocular events, such as patients with a history of ocular inflammation, infection, or underlying macular/retinal disease. All patients reporting visual disturbance should be referred for prompt ophthalmologic review to determine the potential seriousness of any underlying abnormalities and whether there is a need for treatment modification or specific intervention. Understanding the potential consequences of ocular toxicities is of particular importance in the context of decision-making for the continuation of potentially life-prolonging medications such as MEK inhibitors.

摘要

靶向MEK信号通路已成为治疗包括黑色素瘤和非小细胞肺癌在内的晚期癌症的一种有价值的新选择。对参与MEK抑制剂临床试验的患者进行的眼科监测表明,虽然眼部影响很常见,通常在治疗的最初几天到几周内出现,但大多数要么无症状,要么对视力影响极小,且是良性的,无需干预或减少或停止MEK抑制剂治疗即可自行缓解。然而,在MEK抑制剂治疗期间,也报告了罕见的严重、可能威胁视力的眼部毒性病例。目前对于开始MEK抑制剂治疗的晚期癌症患者,没有常规眼科筛查或监测的建议。然而,基线眼科检查可能对所有开始MEK抑制剂治疗的患者有用,以便在出现有症状的眼部事件时,区分既往存在的病变与MEK抑制剂相关视网膜病变的发展。对于眼部事件风险增加的患者,如患有眼部炎症、感染或潜在黄斑/视网膜疾病史的患者,定期眼科检查可能是合适的。所有报告视力障碍的患者都应转诊进行及时的眼科检查,以确定任何潜在异常的潜在严重性,以及是否需要调整治疗或进行特定干预。在决定是否继续使用如MEK抑制剂这类可能延长生命的药物时,了解眼部毒性的潜在后果尤为重要。

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