Memantine for Pediatric Patients Receiving Cranial Irradiation: A Pilot Study

Abstract

While memantine has become standard in certain adults receiving brain RT to decrease the cognitive impacts of RT, it is unknown whether pediatric patients can take and tolerate memantine or experience benefit. In this prospective single-arm feasibility study, we hypothesized pediatric patients receiving brain RT would tolerate memantine with good treatment adherence. Patients aged 4-18 years with a primary CNS malignancy (excluding WHO Grade IV astrocytoma and glioblastoma) receiving intracranial RT were eligible. A 6-month course of memantine was given during and after RT. Dosing began once daily at 5 mg with up-titration in 5 mg increments over 4 weeks to a weight-based maximum (0.4 mg/kg to the closest 5 mg), not to exceed 10 mg BID. To reduce patient and clinical research associate (CRA) burden, medication adherence was tracked via the Medisafe Pill and Reminder application which study staff helped install on the patient or parent's smart phone. A paper pill diary was provided for those unable to use the app. The primary endpoint was to achieve 80% adherence rate to memantine in 80% of patients measured 1-month post-RT. Eighteen patients (14 male and 4 female, median age 11.5 years (range: 4-18)) were enrolled from 2020-2022. The study closed early after enrolling 18 of 20 planned patients to avoid competing with the phase III randomized Children's Oncology Group (COG) study AACL2031. One patient withdrew for cognition-altering substance-use, leaving 17 patients with data available for analysis. Histologies included germ cell tumor (n = 6), craniopharyngioma (n = 3), choroid plexus papilloma (n = 2), ependymoma (n = 2), glial/astrocytoma (n = 2), medulloblastoma (n = 1), and meningioma (n = 1). Thirteen had surgery, and 9 received chemotherapy. Eight received craniospinal irradiation (CSI). Median RT dose was 54 Gy (range 36-59.4) in 30 fractions (range: 20-33). At data freeze, all 17 had passed the 1-month post-RT time point. One patient discontinued memantine after a single dose due to nausea. Pill-reports were available for 14 of the remaining 16; two patients did not complete digital pill logs. For those with complete logs, all adherence rates were above 80%, with a median of 99.32% pill completion rate (range: 92.67-100). Seven (50%) took 100% of prescribed doses. Irrespective of adherence for the 2 unavailable for evaluation, the primary endpoint was still achieved. Grade 1 toxicities included headache (n = 6, 35%) and constipation (n = 1, 6%); there were no grade 2+ toxicities. At last follow-up, 15/16 have completed the full 6-month memantine course. Secondary endpoints including neurocognitive evaluations have not yet been met and will be the subject of future reports. Memantine is a feasible and well-tolerated addition to multi-modality treatment for pediatric brain tumors. Secondary endpoints of this study and results of the ongoing COG study are awaited to define the value of memantine in this population.