Awada Gil, Serruys Daphne, Schwarze Julia Katharina, Van De Voorde Lien, Duerinck Johnny, Neyns Bart
Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
Department of Medical Oncology, AZ Sint-Lucas Gent, Ghent, Belgium.
Case Rep Oncol. 2020 Sep 1;13(2):1031-1036. doi: 10.1159/000509773. eCollection 2020 May-Aug.
Patients with neurofibromatosis type 1 (NF1) have an increased lifetime risk for the development of nervous system tumors, including high-grade gliomas (glioblastoma). NF1 is associated with the loss of expression of neurofibromin 1 ( gene product). This hyperactivates the mitogen-activated protein kinase pathway, leading to cellular proliferation and survival. MEK-inhibitor monotherapy is a promising treatment strategy in this setting, but is associated with distinct adverse events, most prominently cutaneous toxicity. We report the case of a young NF1 patient with a recurrent, heavily pretreated mesencephalic glioblastoma who was treated with the MEK-inhibitor trametinib (2 mg once daily). A partial response was documented, but unfortunately, he developed dose-limiting cutaneous toxicity (rash, paronychia). Based on interim results of a phase 2 trial in advanced wild-type melanoma indicating that a low dose of the BRAF-inhibitor dabrafenib is able to counter trametinib-related cutaneous toxicity, dabrafenib 50 mg twice daily was added. The cutaneous adverse events gradually recovered after addition of dabrafenib to trametinib. The patient eventually achieved a durable complete response, has excellent tolerance of his treatment and remains fully active.
1型神经纤维瘤病（NF1）患者发生神经系统肿瘤（包括高级别胶质瘤，如胶质母细胞瘤）的终生风险增加。NF1与神经纤维瘤蛋白1（基因产物）表达缺失有关。这会过度激活丝裂原活化蛋白激酶途径，导致细胞增殖和存活。MEK抑制剂单药治疗在这种情况下是一种有前景的治疗策略，但会伴有明显的不良事件，最突出的是皮肤毒性。我们报告了1例年轻的NF1患者，患有复发性、经过多次治疗的中脑胶质母细胞瘤，接受了MEK抑制剂曲美替尼（每日1次，每次2 mg）治疗。记录到部分缓解，但不幸的是，他出现了剂量限制性皮肤毒性（皮疹、甲沟炎）。基于一项针对晚期野生型黑色素瘤的2期试验的中期结果，即低剂量的BRAF抑制剂达拉非尼能够对抗曲美替尼相关的皮肤毒性，遂加用达拉非尼，每日2次，每次50 mg。在曲美替尼中加用达拉非尼后，皮肤不良事件逐渐恢复。该患者最终实现了持久的完全缓解，对治疗耐受性良好，仍保持完全活动状态。
