Lawrence, J.A., Balcueva, E.P., Groteluschen, D.L., Samuel, T.A., Lesser, G.J., Naughton, M.J., . . . Rapp, S.R. (2016). A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy. Journal of Cancer Survivorship, 10, 176–184.

DOI Link

Study Purpose

To evaluate the feasibility of taking daily donepezil, an acetylcholinesterase inhibitor, to improve cognitive function in women who report cognitive impairment one to five years after completing adjuvant chemotherapy for breast cancer

Intervention Characteristics/Basic Study Process

This study evaluated the feasibility of a randomized, controlled trial of 24 weeks of donepezil (5 mg/day for 6 weeks, then 10 mg/day for 18 weeks) versus placebo. Potential participants were prescreened for moderate-to-severe self-reported cognitive impairment, and those enrolled were stratified by menopausal status and time since chemotherapy. Self-reported cognitive function, co-occurring symptoms, and quality of life were measured before the trial, halfway through the trial (i.e., 12 weeks), and at the completion of the trial (i.e., 24 weeks). Neuropsychological testing was conducted at baseline and 24 weeks.

Sample Characteristics

N = 47
MEDIAN AGE = 56 years
AGE RANGE = 39–79 years
FEMALES: 100%
CURRENT TREATMENT: Other
KEY DISEASE CHARACTERISTICS: Nonmetastatic invasive breast cancer
OTHER KEY SAMPLE CHARACTERISTICS: Of the patients, 90% were Caucasian, 71% were married, 98% had completed high school, 95% were perimenopausal or postmenopausal, and 68% were on hormonal therapy (primarily an aromatase inhibitor). All patients had completed adjuvant chemotherapy one to five years (X = 2.5 years) before enrollment. Excluded current poor performance status, severe fatigue, and untreated major depressive disorder, as well as a history of major neurological or psychological disorders

Setting

SITE: Multi-site
SETTING TYPE: Outpatient
LOCATION: A university medical center and 15 community clinical oncology programs in the Southeastern United States

Phase of Care and Clinical Applications

PHASE OF CARE: Late effects and survivorship
APPLICATIONS: Elder care

Study Design

Double-blind, randomized, controlled trial of donepezil versus placebo with repeated measures

Measurement Instruments/Methods

Cognitive Impairment: Standardized neuropsychological tests of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity/speed. Functional Assessment of Cancer Therapy (FACT)-Cognition (COG), version 3, for self-reported cognitive function

Other measures: Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (F) subscale, PROMIS 7-item Fatigue Scale, Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), RAND-36 Health Survey (health-related quality of life)

Results

Feasibility: 76% of participants completed the study. Self-reported adherence was 98%. Two participants taking donepezil reported severe insomnia.

Cognitive Impairment: No differences were found between the groups in cognitive function at baseline. Objectively measured memory was better for participants taking donepezil than controls at 24 weeks (p < 0.05). No other group differences were found for objectively measured or self-reported cognitive function at the completion of the trial. Participants with poorer executive function at baseline who took donepezil had better executive function than controls at 24 weeks (p = 0.007). No differences were found related to aromatase inhibitor status.

Other outcomes: Higher levels of anxiety were found midway through the trial among participants taking donepezil (p = 0.049), but this potential side effect resolved by the end of the trial. No other differences in co-occurring symptoms or health-related quality of life were found.

Conclusions

Donepezil may have some benefit for patients related to changes in cognitive function. Further research is needed to provide strong evidence.

Limitations

Small sample (< 100)
Findings not generalizable
Subject withdrawals ≥ 10%
This feasibility study of a randomized, controlled trial was not powered to detect group differences.

Nursing Implications

This study primarily showed that future large studies of donepezil in women with breast cancer are feasible. The findings suggest that donepezil may improve memory in breast cancer survivors who report moderate-to-severe cognitive problems. Executive function may improve for some women. Anxiety and insomnia are potential side effects.