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

Sharon M. Castellino, Janet A. Tooze, Lynn Flowers, Debbie F. Hill, Kevin P. McMullen, Edward G. Shaw, Susan K. Parsons

Research output: Contribution to journalArticle

30 Scopus citations


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 >23.5Gy 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.

Original languageEnglish (US)
Pages (from-to)540-547
Number of pages8
JournalPediatric Blood and Cancer
Issue number3
StatePublished - Sep 1 2012



  • AChe inhibitor
  • Childhood brain tumor
  • Donepezil
  • Executive function
  • Survivors

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Castellino, S. M., Tooze, J. A., Flowers, L., Hill, D. F., McMullen, K. P., Shaw, E. G., & Parsons, S. K. (2012). Toxicity and efficacy of the acetylcholinesterase (AChe) inhibitor donepezil in childhood brain tumor survivors: A pilot study. Pediatric Blood and Cancer, 59(3), 540-547.