BACKGROUND Plexiform neurofibromas (PN) are the most frequent tumors associated with Neurofibromatosis type 1 (NF-1). PN can cause significant complications, including pain, functional impairment, and disfigurement. There is no efficient medical treatment and, surgical resection of large PN is frequently infeasible. Selumetinib (AZD6244/ARRY-142886) is a mitogen-activated protein kinase enzyme (MEK1/2) inhibitor and works by targeting the MAPK pathway. It is an investigational treatment option for inoperable symptomatic PN associated with NF-1. Herein, we describe a single institutional experience with selumetinib for inoperable PN in NF-1. METHODS Case series study of demographics, clinical, baseline characteristics, treatment effect, and follow-up of consecutive genetically confirmed NF1 patients with inoperable PN associated with significant or potential significant morbidity treated with selumetinib (April 2018 to April 2019). RESULTS Nineteen patients were treated with selumetinib. Predominant target locations were head and neck (31.6%, 6/19), chest (26.3%, 5/19) and pelvis (21%, 4/19) and the most important comorbidities were disfigurement (47.4%, 9/19) and pain (26.3%, 5/19). The mean follow-up time was 223 days (range 35-420 days). All but one had sustained clinical improvement, mainly in the first 60-90 days of treatment. In one patient, the treatment was suspended after 168 days (lack of clear benefit and left ventricular ejection fraction drop). There were no adverse effects leading to treatment suspension. CONCLUSIONS In the first observational study of selumetinib for NF-1 associated PN we showed that the drug was associated with clinical and radiological improvement. Our study also confirms the safety described in the clinical trials.

中文翻译：

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Selumetinib用于1型神经纤维瘤病中的丛状神经纤维瘤

背景技术丛状神经纤维瘤（PN）是与1型神经纤维瘤病（NF-1）相关的最常见的肿瘤。PN可引起严重的并发症，包括疼痛，功能障碍和毁容。没有有效的治疗方法，大PN的手术切除通常是不可行的。Selumetinib（AZD6244 / ARRY-142886）是一种促分裂原激活的蛋白激酶（MEK1 / 2）抑制剂，通过靶向MAPK途径发挥作用。它是与NF-1相关的无法操作的症状性PN的研究性治疗选择。在本文中，我们描述了selumetinib用于NF-1中不可操作的PN的单一机构经验。方法人口统计学，临床，基线特征，治疗效果，并接受selumetinib治疗的连续经遗传学确诊的NF1不能手术的PN与显着或潜在显着发病率相关的患者的随访（2018年4月至2019年4月）。结果19例患者接受了selumetinib治疗。主要目标位置是头部和颈部（31.6％，6/19），胸部（26.3％，5/19）和骨盆（21％，4/19），最重要的合并症是毁容（47.4％，9/19）。和疼痛（26.3％，5/19）。平均随访时间为223天（范围35-420天）。除了一个人以外，所有其他人的临床症状都得到了持续改善，主要是在治疗的最初60-90天。一名患者在168天后停药（缺乏明显获益，左心室射血分数下降）。没有导致治疗暂停的不良影响。结论在selumetinib对NF-1相关性PN的第一个观察性研究中，我们表明该药物与临床和放射学改善有关。我们的研究还证实了临床试验中描述的安全性。