使用Memantine减少儿童放射后认知障碍：一项评估Memantine在放疗后儿童中减少认知障碍可行性的初步研究

Memantine to Reduce Cognitive Impairment After Radiation in Children: A Pilot Study Evaluating the Feasibility of Memantine in Reducing Cognitive Impairment in Pediatric Patients after Radiation Therapy for Central Nervous System Tumors

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS

影响因子:6.5

分区:医学1区 Top / 肿瘤学2区核医学2区

发表日期:2024 Nov 15

作者: Elizabeth L McKone, William G Breen, Nathan R Foster, Aaron W Bogan, Margaret A Connors, Reece A Alstat, Jonathan D Schwartz, Anita Mahajan, Safia K Ahmed, Nadia N Laack

DOI: 10.1016/j.ijrobp.2024.05.031

摘要

Memantine在接受脑部放射治疗（RT）的部分成人中已成为减少认知影响的标准治疗，但尚不清楚儿童是否可以服用、耐受和/或从中获益。在这项前瞻性单臂可行性研究中，我们假设接受中枢神经系统（CNS）放疗的儿童患者能够耐受Memantine并具有良好的依从性。符合条件的患者年龄为4至18岁，患有原发性CNS恶性肿瘤（不包括世界卫生组织4级星形细胞瘤、胶质母细胞瘤），接受颅内RT。给予为期6个月的Memantine，治疗期间及治疗后进行剂量递增，目标最大剂量为每公斤体重0.4 mg，最多不超过每日两次10 mg，递增5 mg每4周。主要终点是在RT后1个月内达到80%的药物依从率，且80%的患者达标。次要目标包括评估Memantine在3和6个月的可行性。2020至2022年间，有18名患者入组并接受Memantine联合RT。由于避免与儿童肿瘤科学联盟（Children's Oncology Group）ACCL2031第3阶段随机研究冲突，研究提前关闭，未达到预设停止规则。分析中，1名患者因认知改变相关药物退出，其余17名患者中，8名患者在RT后1个月达到了100%的服药依从率（范围74%-100%；9/17患者完全依从），其中94%（15/16）依从率超过80%。在RT后3和6个月的次要指标中，依从率的中位数分别为100%（范围55%-100%）和96%（范围33%-100%）。最常见的不良反应为1至2级疲劳、头痛和恶心，可能与药物相关，未出现3级及以上事件。Memantine作为多模态治疗的一部分在儿童中表现出可行、安全且耐受良好的特点。期待ACCL2031的结果以评估Memantine在该人群中的价值。

Abstract

Memantine is standard in certain adults receiving brain radiation therapy (RT) to decrease cognitive impacts, but it is unknown whether pediatric patients can take, tolerate, and/or benefit from memantine. In this prospective single-arm feasibility study, we hypothesized that pediatric patients receiving central nervous system (CNS) RT would tolerate memantine with good adherence.Patients aged 4 to 18 years with a primary CNS malignancy (excluding World Health Organization grade 4 astrocytoma, glioblastoma) receiving intracranial RT were eligible. A 6-month memantine course was given during and after RT, with dose titration in 5 mg increments over 4 weeks targeting a weight-based maximum (0.4 mg/kg to the closest 5 mg), not to exceed 10 mg twice a day. The primary endpoint was to achieve 80% drug adherence rate in 80% of patients measured 1 month after RT. Secondary objectives included memantine feasibility at 3 and 6 months.Eighteen patients enrolled from 2020 to 2022 and were prescribed memantine with RT. The study closed early to avoid competing with the phase 3 randomized Children's Oncology Group study ACCL2031. No predefined stopping rules were met. One patient withdrew for cognition-altering substance use, leaving 17 patients available for analysis. One patient discontinued memantine after one dose due to nausea. For the remaining 16 patients, there was a median of 100% pill completion rate (range, 74%-100%; n = 9/17 with 100% adherence) at 1 month after RT, with 15/16 (94%) with adherence rates >80%. At the 3- and 6-month post-RT time points for secondary endpoints, the median adherence rates were 100% (range, 55%-100%) and 96% (range, 33%-100%), respectively. Grade 1 to 2 fatigue, headache, and nausea were the most common toxicity events, at least possibly related to the study drug (n = 27), without attributable grade 3+ events.Memantine is a feasible, safe, and well-tolerated addition to multimodality treatment for pediatric CNS malignancies. Results of ACCL2031 are awaited to define the value of memantine in this population.