Phase II study of donepezil in irradiated brain tumor patients: Effect on cognitive function, mood, and quality of life

Purpose A prospective, open-label phase II study was conducted to determine whether dol a US Food and Drug Administration-approved reversible acetylcholinesterase inhibitor used to treat mild to moderate Alzheimer's type dementia, improved cognitive functioning, mood, and quality of life (QOL) in irradiated brain tumor patients. Patients and Methods Thirty-four patients received donepezil 5 mg/d for 6 weeks, then 10 mg/d for 18 weeks, followed by a washout period of 6 weeks off drug. Outcomes were assessed at baseline, 12, 24 (end of treatment), and 30 weeks (end of wash-out). All tests were administered by a trained research nurse. Results Of 35 patients who initiated the study, 24 patients (mean age, 45 years) remained on study for 24 weeks and completed all outcome assessments. All 24 patients had a primary brain tumor, mostly low-grade glioma. Scores significantly improved between baseline (pretreatment) and week 24 on measures of attention/concentration, verbal memory, and figural memory and a trend for verbal fluency (all P <.05). Confused mood also improved from baseline to 24 weeks (P =.004), with a trend for fatigue and anger (all P <.05). Health-related QOL improved significantly from baseline to 24 weeks, particularly, for brain specific concerns with a trend for improvement in emotional and social functioning (all P <.05). Conclusion Cognitive functioning, mood, and health-related QOL were significantly improved following a 24-week course of the acetylcholinesterase inhibitor donepezil, Toxicities were minimal. We are planning a double blinded, placebo-controlled, phase III trial of donepezil to confirm these favorable results.