A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy

Abstract

Purpose Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. Methods Women who received adjuvant chemotherapy 1–5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. Results Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory—the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p=0.033) and HVLT-R Discrimination (p=0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. Conclusion Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. Implications for Cancer Survivors Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results.

Cognitive Effects of Chemotherapy and Cancer-Related Treatments in Older Adults

“…115,116 Additionally, a study in breast cancer survivors suggested improved verbal memory in those who had poorer cognitive functioning at baseline. 117 Cholinesterase inhibitor studies provide support for the cholinergic system as a therapeutic target for improving cognitive functioning in CRCI. 115–117 More selective cholinergic stimulation may potentially be useful for certain cognitive symptoms.…”

“…117 Cholinesterase inhibitor studies provide support for the cholinergic system as a therapeutic target for improving cognitive functioning in CRCI. 115–117 More selective cholinergic stimulation may potentially be useful for certain cognitive symptoms. For example, a randomized, placebo-controlled study evaluating the use of transdermal nicotine treatment as a therapeutic strategy for persistent CRCI is currently underway (NCT02312934).…”

Chemotherapy-related cognitive impairment in older patients with cancer

“…44,78–80 Additionally, most intervention studies have included only a small number of patients. These interventions can be grouped into pharmacological and non-pharmacological categories.…”

“…Examples of pharmacological agents investigated included donepezil, methylphenidate, modafinil and erythropoietin. 78,79,81,82 Non-pharmacological interventions include specific exercise programs and cognitive training. 80,83,84 Selected studies are shown in Table 4.…”

Chemotherapy-induced prospective memory impairment in breast cancer patients with different hormone receptor expression

“…[1–3] As several studies have shown, memory impairment is the most prominent presentation of chemotherapy-induced cognitive impairment (CICI) in patients with breast cancer, [2,4,5] and acts as an important factor affecting the long-term quality of life in these patients. [6] …”