ABSTRACT
BACKGROUND: The health-related quality of life (HRQL) and fatigue of brain cancer survivors treated with donepezil or placebo for cognitive symptoms after radiation therapy were examined. METHODS: One hundred ninety-eight patients who completed >30 Gy fractionated whole or partial brain irradiation at least 6 months prior to enrollment were randomized to either placebo or donepezil (5 mg for 6 weeks followed by 10 mg for 18 weeks) in a phase 3 trial. A neurocognitive battery, the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue, was administered at baseline, 12 weeks, and 24 weeks. RESULTS: At 12 weeks, donepezil resulted in improvements in only emotional functioning (P = .04), with no significant effects at week 24. Associations by level of baseline cognitive symptoms (above or below the median score of the baseline FACT-Br "additional concerns/brain" subscale), indicated that participants with more baseline symptoms who received donepezil versus placebo, showed improvements in social (P = .02) and emotional well-being (P = .038), other concerns/brain (P = .003) and the FACT-Br total score (P = .004) at 12 weeks, but not 24 weeks. However, participants with fewer baseline symptoms randomized to donepezil versus placebo reported lower functional well-being at both 12 (P = .015) and 24 weeks (P = .009), and greater fatigue (P = .02) at 24 weeks. CONCLUSIONS: The positive impact of donepezil on HRQL was greater in survivors reporting more baseline cognitive symptoms. Donepezil had significantly worse effects on fatigue and functional well-being among participants with fewer baseline symptoms. Future interventions with donepezil should target participants with more baseline cognitive complaints to achieve greater therapeutic impact and lessen potential side effects of treatment.
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.
