纪念碑减少儿童辐射后的认知障碍：一项试点研究，评估了美金素对中枢神经系统肿瘤放射治疗后纪念儿科患者认知障碍的可行性
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
影响因子:6.50000
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
摘要
在某些接受脑放射疗法（RT）以降低认知影响的成年人中，美容是标准的，但尚不清楚小儿患者是否可以服用，耐受和/或从美容中受益。在这项前瞻性的单臂可行性研究中，我们假设接受中枢神经系统（CNS）RT的儿科患者将耐受纪念碑的依从性良好。年龄在4至18岁之间的患者患有中枢神经系统恶性肿瘤（不包括世界卫生组织4级级4级星形胶质细胞瘤，胶质虫，glioblastoma），接受内核的内在群。在RT期间和之后进行了6个月的美金刚课程，剂量滴定在4周内以5 mg的滴定为目标，其靶向基于重量的最大值（最接近5 mg的0.4 mg/kg），每天不超过10 mg。主要终点是在RT后1个月测量的80％的患者中实现80％的药物依从率。次要目标包括3个月和6个月的美容性可行性。从2020年到2022年，有1名患者招收，并用RT开处方美金刚。这项研究很早就结束，以避免与第三阶段随机儿童肿瘤学组研究ACCL2031竞争。没有达到预定义的停止规则。一名患者撤回了用于改变认知的药物的使用，有17名患者可用于分析。一名患者因恶心而在一次剂量后停止美容。对于剩下的16名患者，在RT后1个月后，有100％的药丸完成率（范围为74％-100％； n = 9/17，有100％依从性），15/16（94％）的依从率> 80％。在次要终点的3个月和6个月后时间点，中值依从率分别为100％（范围为55％-100％）和96％（范围为33％-100％）。 1至2年级的疲劳，头痛和恶心是最常见的毒性事件，至少可能与研究药物有关（n = 27），而没有可归因于3级以上的事件。Memantine是可行，安全且宽容的多模态治疗的儿童恶性肿瘤。等待ACCL2031的结果定义了纪念品在该人群中的价值。
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.