title: A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA. jalawren@wakehealth.edu.|Department of Hematology and Oncology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC, 27157, USA. jalawren@wakehealth.edu.
authors.forename: J A
authors.initials: JA
authors.lastname: Lawrence
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
authors.forename: L
authors.initials: L
authors.lastname: Griffin
authors.affiliation: Michigan CCOP, St. Mary's of Michigan, Saginaw, MI, 48602, USA.
authors.forename: E P
authors.initials: EP
authors.lastname: Balcueva
authors.affiliation: St. Vincent CCOP, Green Bay Oncology, Green Bay, WI, 54301, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Groteluschen
authors.affiliation: Medical College of Georgia MBCCOP, Augusta, GA, 30912, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Samuel
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.|Department of Hematology and Oncology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC, 27157, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Lesser
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Naughton
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Case
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
authors.forename: E G
authors.initials: EG
authors.lastname: Shaw
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Rapp
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D000077265:Donepezil; D005221:Fatigue / Q000139:chemically induced / Q000453:epidemiology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D010865:Pilot Projects; D010880:Piperidines / Q000627:therapeutic use*; D011788:Quality of Life; D057566:Self Report; D017741:Survivors / Q000523:psychology / Q000706:statistics & numerical data
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
keywords: Breast cancer survivors; Cognitive dysfunction; Donepezil; Memory