title: Toxicity and efficacy of the acetylcholinesterase (AChe) inhibitor donepezil in childhood brain tumor survivors: a pilot study.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Pediatrics, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA. scastell@wakehealth.edu
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Castellino
authors.forename: Janet A
authors.initials: JA
authors.lastname: Tooze
authors.forename: Lynn
authors.initials: L
authors.lastname: Flowers
authors.forename: Debbie F
authors.initials: DF
authors.lastname: Hill
authors.forename: Kevin P
authors.initials: KP
authors.lastname: McMullen
authors.forename: Edward G
authors.initials: EG
authors.lastname: Shaw
authors.forename: Susan K
authors.initials: SK
authors.lastname: Parsons
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy*; D002648:Child; D002800:Cholinesterase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000139:chemically induced*; D000077265:Donepezil; D056344:Executive Function / Q000187:drug effects; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008568:Memory / Q000187:drug effects*; D009483:Neuropsychological Tests; D010865:Pilot Projects; D010880:Piperidines / Q000009:adverse effects* / Q000627:therapeutic use*; D017741:Survivors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil