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J Clin Oncol ; 33(15): 1653-9, 2015 May 20.
Article in English | MEDLINE | ID: mdl-25897156

ABSTRACT

PURPOSE: Neurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function. PATIENTS AND METHODS: A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. RESULTS: Of this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment. CONCLUSION: Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments.


Subject(s)
Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Cognition Disorders/drug therapy , Indans/therapeutic use , Piperidines/therapeutic use , Adult , Aged , Aged, 80 and over , Cholinesterase Inhibitors/therapeutic use , Cognition Disorders/etiology , Combined Modality Therapy , Donepezil , Double-Blind Method , Female , Humans , Learning/drug effects , Male , Memory/drug effects , Middle Aged , Neoplasm Metastasis , Neuropsychological Tests , Treatment Outcome , Young Adult
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