Background:
Children receiving irradiation for brain tumors are at significant risk for cognitive deficits that notably impact quality of life. This is the first randomized, controlled, investigation of the feasibility, acceptability, and preliminary efficacy of memantine (an NMDA receptor antagonist) for reducing cognitive late effects in children and adolescents undergoing radiotherapy.
Methods:
In a randomized, double-blind, controlled, pilot trial children and adolescents took memantine (20 mg/d) or placebo for 12 weeks. Adherence was assessed using pill counts and side effects monitored using structured interview. At baseline, 6 weeks (end of radiation therapy), 12 weeks (end of medication), and 1 year, participants completed cognitive assessments.
Results:
Thirty patients (age= 11.93±2.87 years; 47% male) were included; memantine (n= 16) and placebo (n= 14) groups did not differ in age, sex, race, socioeconomic status, or baseline IQ (p> 0.26). Study participation (71%) and medication adherence (88% completed 12 weeks; 97% of medication taken) were high. Side effects were minimal with no difference between memantine and placebo groups in increase in severity from baseline to any medication week (p> .23). At 12 weeks, effect sizes (ES) indicate the memantine group had better processing speed (Cogstate Identification ES= .61), academic fluency (Woodcock Johnson-IV Reading Fluency ES= .45; Math Fluency ES= .81), and fatigue (PedsQL Multidimensional Fatigue Scale ES= .72), with some benefits persisting one year post treatment (e.g., Woodcock Johnson-IV Reading Fluency ES= .65; Math Fluency ES= .71).
Conclusions:
Study findings from this randomized, controlled trial indicate memantine used as a neuroprotectant during irradiation for children and adolescents with brain tumors is feasible and acceptable, with preliminary evidence for better cognitive outcomes that requires validation in a larger trial.
