Ocular Toxicity in Metastatic Melanoma Patients Treated With Mitogen-Activated Protein Kinase Kinase Inhibitors: A Case Series
Ocular Toxicity in Metastatic Melanoma Patients Treated With Mitogen-Activated Protein Kinase Kinase Inhibitors: A Case Series
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DOI：
10.1016/j.ajo.2015.07.035
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发表时间：
2015-11-01
影响因子：
4.2
通讯作者：
Guida, Michele
中科院分区：
文献类型：
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作者：
Niro, Alfredo;Strippoli, Sabino;Guida, Michele
目的：报道4例晚期黑色素瘤患者丝裂原活化蛋白激酶激酶抑制剂相关眼部副作用的临床特点和处理方法，并复习文献。设计：介入性病例系列。方法：4例晚期皮肤黑色素瘤患者分别使用丝裂原活化蛋白激酶（MEK）抑制剂单独治疗或与v-raf小鼠肉瘤病毒癌基因同源物B1 （BRAF）抑制剂联合治疗。所有患者定期或根据需要进行眼科检查，包括视力、眼压、外眼检查和眼底镜检查。当发现病理结果时，患者接受视野检查、光学相干断层扫描（OCT）和/或荧光素血管造影。根据不良事件通用术语标准评估和处理眼毒性。结果：治疗早期出现眼部不良事件。在3例患者中，OCT显示中央凹下神经视网膜升高，通常无症状，也在停止和重新启动MEK抑制剂后。2例患者出现血管损伤，1例患者在停药和使用全身治疗后视野缺损减少。1例前房出现炎症反应。视觉症状通常轻微且短暂。结论：MEK抑制剂单独使用或与BRAF抑制剂联合使用可引起短暂性视网膜病变，伴时间依赖性复发，通常伴有轻度视觉症状。血管损伤是可以观察到的，其处理在临床实践中是必不可少的。重要的是要调查所有以前的眼部疾病，全身性疾病，以及MEK抑制剂的药理学相互作用，这些可能会促进相关眼部效应的发生。(C) 2015年Elsevier Inc.版权所有。
PURPOSE: To report the clinical features and management of mitogen-activated protein kinase kinase inhibitor-associated ocular side effects in 4 patients with advanced melanoma and a review of literature.DESIGN: Interventional case series.METHODS: Four patients with advanced cutaneous melanoma were treated with a mitogen-activated protein kinase kinase (MEK) inhibitor as single therapy or together with a v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor. All patients underwent ophthalmologic examinations at regular intervals or as needed, including visual acuity, intraocular pressure, external eye examination, and funduscopy. When pathologic findings were found, patients underwent visual field examination, optical coherence tomography (OCT), and/or fluorescein angiography. Ocular toxicity was assessed and handled according to the Common Terminology Criteria for Adverse Events.RESULTS: Ocular adverse events appeared early in the treatment. In 3 patients OCT revealed subfoveal neuroretinal elevation, often asymptomatic, also after discontinuation and re-starting of MEK inhibitor. Vascular injury appeared in 2 patients, in 1 case associated with a visual field defect reduced after discontinuation of the drug and use of systemic therapy. In 1 case an inflammatory reaction was observed in the anterior chamber. Visual symptoms were usually mild and short-lived.CONCLUSIONS: MEK inhibitor as a single agent or in combination with BRAF inhibitor induces transient retinopathy with time-dependent recurrence and usually mild visual symptoms. Vascular injuries can be observed and their management is essential in clinical practice. It is important to investigate all previous ocular disorders, systemic conditions, and pharmacologic interactions of MEK inhibitor that could facilitate the onset of associated ocular effects. (C) 2015 by Elsevier Inc. All rights reserved.