Toxicity and efficacy of the acetylcholinesterase (AChe) inhibitor donepezil in childhood brain tumor survivors: A pilot study

Background Neurocognitive deficits are a recognized late effect of curative brain tumor therapy. We evaluated the feasibility, tolerance, and impact of a pilot pharmacologic intervention with the acetylcholinesterase (AChe) inhibitor, donepezil, in pediatric brain tumor (BT) survivors at risk for neurocognitive dysfunction. Procedure A single institution open‐label pilot study was conducted in childhood BT survivors: ≥1 year from cancer treatment; and who received >23.5 Gy cranial radiation therapy (RT). Toxicity, adherence and neurocognitive outcomes were evaluated at baseline and serially during 24 weeks of donepezil, and following a 12‐week washout period off drug. Results From a pool of subjects, 13 were successfully contacted and screened, and 11 met all eligibility criteria to initiate donepezil at a median of 4.7 (1.9–11.9) years from RT. Seventy‐two percent of patients completed the 24‐week drug study visit. Despite transient gastrointestinal toxicity (vomiting and diarrhea) in 30% of patients there was no weight loss on donepezil. Significant improvement in performance was noted at 24 weeks on the Dellis–Kaplan Executive Function (D‐KEF) Tower test ( P  < 0.001), the Wide Range Assessment of Memory and Learning, 2nd Edition (WRAML‐2) Visual memory ( P  = 0.007), and the Number/Letter task ( P  = 0.018). Conclusions Donepezil was well tolerated among childhood BT survivors who had received substantial prior therapy. Based on improved executive function and memory performance in this pilot trial, a randomized placebo controlled trial of this pharmacologic agent is warranted to fully evaluate its efficacy in remediating neurocognitive dysfunction. Pediatr Blood Cancer 2012;59:540–547. © 2012 Wiley Periodicals, Inc.