Jatoi, A., Kahanic, S.P., Frytak, S., Schaefer, P., Foote, R.L., Sloan, J., & Petersen, R.C. (2005). Donepezil and vitamin E for preventing cognitive dysfunction in small cell lung cancer patients: Preliminary results and suggestions for future study designs. Supportive Care in Cancer, 13(1), 66–69.

The study was conducted to test oral donepezil and oral vitamin E in patients with small-cell lung cancer after completion of all cancer therapy and prophylactic cranial irradiation.

A randomization procedure was conducted after participant stratification in the following ways.

• Baseline cognitive function on the Mini-Mental State Examination (MMSE) placed participants in three impairment groups: normal, mild to moderate, and severe.  
• Participants were categorized by age into two groups, 60 years or younger or older than 60 years.

The treatment group received 5 mg/day of oral donepezil, which increased to 10 mg/day after one month of therapy if tolerated well. Treatment group participants also received 1000 IU/day of oral vitamin E. The control group was given an identical oral placebo. Assessments were performed at study enrollment, one month, and every three months until cancer recurrence or treatment failure.

• The total number of participants enrolled over 15 months was 9.
• There were 4 participants in the treatment group and 5 participants in the control group.  
• All participants had a diagnosis of small-cell lung cancer.
• All participants had a limited disease status and similar prophylatic carnial irradiation.  
• All participants had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2.
• The mean age of the treatment group was 67, with a range of 65–69.
• The mean age of the control group mean was 67, with a range of 60–76.
• The treatment group was 100% male; the control group was 80% male and 20% female.

The study took place at the North Central Cancer Treatment Group and the Mayo Clinic.

The study was a double-blind, placebo-controlled trial.

• The Mini-Mental State Examination (MMSE) was used to measure global cognitive functioning. A three-point drop indicated treatment failure.
• A five-point drop on the Blessed Dementia Scale indicated treatment failure.
• The Common Terminology Criteria for Adverse Version 2.0 was also used. 

There were no notable differences in cognitive stability, adverse events, or quality of life between treatment arms. Only one patient, who received donepezil and vitamin E, manifested a three-point drop in cognitive scores as measured by the MMSE. There was a slight trend of increased gastrointestinal side effects among patients treated with donepezil and vitamin E.

The median time spent in the study was 42 or 69 days for the treatment or control group, respectively.

Due to low enrollment and retention, the effect of oral doses of vitamin E and donepezil on cognitive function could not be determined. 

• The study had a small sample size.
• Inclusion criteria seriously limited eligibility and enrollment.
• Participant withdrawal tended to occur sooner in the study for those receiving the medication intervention than among those in the control group. No explanation for subject withdrawals was provided.