Shaw, E.G., Rosdhal, R., D’Agostino, R.B., Lovato, J. Naughton, M.J., Robbins, M.E., & Rapp, S.R. (2006). Phase II study of donepezil in irradiated brain tumor patients: Effect on cognitive function, mood, and quality of life. Journal of Clinical Oncology, 24(9), 1415–1420.

The study was conducted to determine whether donepezil improved cognitive functioning, mood, and quality of life in patients who had irradiated brain tumors.

All participants received 5 mg/day of donepezil for 6 weeks, then 10 mg/day of donepezil for 18 weeks, followed by a washout period of 6 weeks where no treatment was administered. 

• The total number of enrolled participants was 35, with 24 completing all outcome assessments.
• The participants were 54% male and 46% female.
• The participants were 92% Caucasian and 8% black.
• 23 participants had glioma (about half low-grade), 4 participants had meningioma, 7 patients had other primary brain tumors, and 1 patient had metastatic disease).

This was a prospective, open-label, phase II study.

• Mini-Mental State Examination (MMSE) for global cognitive functioning
• Trail Making Test Parts A and B (TMT-A and TMT-B) for visual attention, motor speed, and cognitive flexibility
• Digit Span Test for attention and concentration
• Revised Rey-Osterrieth Complex Figure Test for visual construction skills and figural memory
• Controlled Oral Word Association Test for verbal fluency
• California Verbal Learning Test-II for verbal memory
• Health-Related Quality of Life (HRQOL) measures for health-related quality of life
• Karnofsky Performance Status Scale (KPS) for general well-being; scores range from 0 (death) to 100 (perfect health with no complaints or signs of disease)
• Functional Assessment of Cancer Therapy-Brain (FACT-Br) for cancer-related quality of life for patients with brain tumors
• Profile of Mood States assessment for subscales in depression, anxiety, anger, subjective confusion, fatigue, and vigor, as well as an overall mood score for distress

Significant improvement was noted between the pre-treatment baseline  and week 24 on measures of attention/concentration, verbal memory, figural memory, and a trend for verbal fluency (all p < 0.05). Confused mood was also improved from baseline to 24 weeks (p = 0.03). Health-related quality of life improved from baseline to 24 weeks in brain-specific concerns (p = 0.003), emotional functioning (p = 0.04), and social functioning (p = 0.02), with a trend for improvement in total health-related quality of life (p = 0.07).

Ten of 21 participants, or 48% of those who completed the study through the 30-week assessment, chose to go back on donepezil. A total of 63 toxicities ranging from grade 1 to grade 3 were reported.

Mood, health-related quality of life, and cognitive functioning (attention/concentration, verbal memory, and figural memory) were significantly improved following a 24-week course of donepezil.

• The study had a small sample size.
• The study had no control group for comparison. 
• Participants who completed the entire study differed significantly from those who dropped out in terms of age (p = 0.04). No control comparison.
• The repeated measures study did not address practice effects.
• Other co-occurring events may explain improvements in cognitive functioning. These events include concurrent tumor shrinkage, resolution of radiation-induced fatigue, and repair and recovery from radiation-induced brain damage.