Rapp, S.R., Case, L.D., Peiffer, A., Naughton, M.M., Chan, M.D., Stieber, V.W., . . . Shaw, E.G. (2015). Donepezil for irradiated brain tumor survivors: A phase III randomized placebo-controlled clinical trial. Journal of Clinical Oncology, 33, 1653–1659.
To evaluate the effects of 24 weeks of donepezil versus placebo on objectively measured cognitive function starting at least six months after whole- or partial-brain irradiation
This clinical trial tested donepezil at 5 mg daily for six weeks followed by 10 mg daily for 18 weeks compared to a placebo. Study outcome measurements were collected before randomization, and 12 and 24 weeks after randomization.
PHASE OF CARE: Late effects and survivorship
Randomized, double-blinded, placebo-controlled trial
Self-reported adherence to the dose was approximately 92%, which did not differ between groups. The donepezil group reported more diarrhea (25%, p = 0.005) than the control. At baseline, both groups had poorer verbal memory, motor speed and dexterity, attention, and executive function compared to population norms. There was no improvement in overall cognitive function with 24 weeks of donepezil, but improvements were found for individual measures of memory (p = 0.007, 0.027) and motor speed and dexterity (p = 0.016). Donepezil showed greater improvement in overall cognitive function for patients with poorer cognitive function at baseline (p = 0.01).
For patients who received whole or partial brain irradiation, 24 weeks of donepezil improved memory and motor and speed dexterity. Greater improvements in multiple cognitive domains, including significant improvement in overall cognitive function, were found for patients with poorer cognitive function at baseline.
For patients who receive partial- or whole-brain irradiation for primary brain tumors or brain metastases, donepezil may improve memory and motor speed and dexterity. Patients with poorer cognitive function may have greater benefit, including improvement in overall cognitive function. Educate patients about the risk for diarrhea and appropriate management.