scholarly journals Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial

2015 ◽  
Vol 33 (15) ◽  
pp. 1653-1659 ◽  
Author(s):  
Stephen R. Rapp ◽  
L. Doug Case ◽  
Ann Peiffer ◽  
Michelle M. Naughton ◽  
Michael D. Chan ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Cognitive Function ◽  
Adult Brain ◽  
Composite Score ◽  
Phase Iii ◽  
Cognitive Test ◽  
Controlled Clinical Trial ◽  
Motor Speed ◽  
Whole Brain Irradiation ◽  
Brain Irradiation

Purpose Neurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function. Patients and Methods A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. Results Of this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment. Conclusion Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments.

scholarly journals P05.01 the efficacy of donepezil on cognitive function in postoperative brain tumor patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii33-iii34
Author(s):  
Y Diansari ◽  
Y Harun ◽  
S Marisdina ◽  
Y Felistia
Keyword(s):  
Cognitive Impairment ◽  
Brain Tumor ◽  
Cognitive Function ◽  
Acetylcholinesterase Inhibitor ◽  
Primary Brain Tumor ◽  
Adult Brain ◽  
Cognitive Domain ◽  
Cognitive Test ◽  
Tumor Patients ◽  
Old Patients

Abstract BACKGROUND Cognitive impairment is frequently found in brain tumor patients. More than 90% of patients with brain tumor have at least one cognitive domain disturbance. Decline in cognitive function could happen before due to the tumor or after the treatment because of surgery, radiotherapy or chemotherapy. Until now there is no available standard treatment for patients with cognitive impairment due to brain tumor. Moreover, Donepezil is an acetylcholinesterase inhibitor known to be useful for improving cognitive function in patients with dementia. This clinical study aims to determine the cognitive effects of donepezil therapy in patients with brain tumors following surgery. MATERIAL AND METHODS This is a pilot study with total of 20 adult brain tumor patients were double blinded randomly assigned to receive a single daily dose (5mg for 12 weeks) of donepezil or placebo. The inclusion criteria were patients with primary brain tumor who had undergone surgery with cognitive impairment at the initial evaluation and age range 18 to 65 years old. Patients with previous cognitive problem, other diseases that can cause cognitive decline e.g. stroke and history of taking donepezil, memantine, methylphenidate, ginkgo biloba, and modafinil were excluded. A cognitive test using Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment Indonesia Version (MoCA-INA) assessing memory, attention, language, visuospatial, verbal fluency, and executive functions were administered before random assignment and at 4, 8 and 12 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. Furthermore, side effects and adverse events were also recorded. RESULTS Of this mostly middle-age (30–60 years old), female, meningioma as primary brain tumor with frontal and temporal lobe are the most frequent locations. After 12 weeks of treatment, the composite scores did differ significantly between groups (MMSE P=0.027, MoCA-INA P=0.024). Furthermore, the significant differences favouring donepezil were observed for orientation and recall domains using MMSE with p value 0.017 and 0.006 respectively. Visuospatial (P=0.034) and delayed recall domains (P=0.004) were significant through MoCA-INA evaluation. In addition, Mean MMSE score for pre-donepezil administration was 14.60 ± 4.47 and after 3 months was 20.40 ± 4.24 (P=0.000). Mean MoCA-INA score for pre-donepezil administration was 9.30 ± 3.65 and after 3 months was 15.30 ± 4.24 (P=0.000). However, there was no differences in the placebo group (MMSE P= 0.066, MoCA-INA P=0.313). CONCLUSION Three months treatment with donepezil significantly improve the cognitive functions among post-operative brain tumor patients with no reported side effect. Moreover, further research is needed for longer duration of follow-up and possibility of increased doses.

scholarly journals Induction of NSCs Quiescence and Neurogenesis Preservation in Mouse Adult Brain after FLASH Whole Brain Irradiation

2016 ◽  
Vol 118 ◽  
pp. S75-S76
Author(s):  
P-G. Montay-Gruel ◽  
B. Petit ◽  
V. Favaudon ◽  
J. Bourhis ◽  
M.-C. Vozenin
Keyword(s):  
Adult Brain ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation

Phase III randomized, double-blind, placebo-controlled trial of donepezil in irradiated brain tumor survivors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2006-2006 ◽  
Author(s):  
Stephen R. Rapp ◽  
Doug Case ◽  
Ann Peiffer ◽  
Michelle Joy Naughton ◽  
Volker W. Stieber ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Digit Span ◽  
Verbal Learning ◽  
Forest Community ◽  
Phase Iii ◽  
Dominant Hand ◽  
Primary Tumors ◽  
Brain Irradiation ◽  
Significant Difference

2006 Background: This RCT assessed the effect of 24 weeks of 5-10 mg per day of donepezil, an acetyl cholinesterase inhibitor, on cognitive functioning (primary endpoint) and fatigue, mood and QOL in long-term brain tumor survivors following partial or whole-brain irradiation. Cognitive results are reported herein. Methods: From 2/08-12/11,198 adult primary and metastatic brain tumor survivors > 6 months post radiation treatment (>30 Gray) recruited at 24 sites affiliated with the Wake Forest Community Clinical Oncology Program Research Base, 3 CTSU sites and M.D. Anderson Cancer Center were randomly assigned to receive donepezil (n=99) or placebo (n=99). Cognitive function was assessed at baseline, 12 and 24 weeks with Hopkins Verbal Learning Test-Revised, Rey-Osterreith Complex Figure, Trail Making Test, Digit Span, Controlled Oral Word Association, and Grooved Pegboard. A Cognitive Composite (CC) score was the primary outcome. Results: The sample was 91% White, 54% female, and median age was 55 yrs. 66% had primary tumors, 27% brain metastases and 8% PCI. Median time since diagnosis: 38 mos. 95% had 0-1 ECOG performance status scores. 74% completed the study. CC score improved significantly by 24 weeks in both arms (p < .01); however, there was not a statistically significant difference between groups (p = .57). Donepezil group performed better than placebo on HVLT Recognition (p = .03) and Discrimination (p = .01) and GP-Dominant Hand (p = 0.02). Significant interactions were found between treatment arm and baseline cognitive scores for: CC (p = .01), HVLT Immed. Recall (p = .03), HVLT %Savings (p < .01), Digit Span Forward (p = .01), ROCF Copy (p = .03), TMT-B (p = .05) and GP-Dominant (p < .01). In all cases, the benefit of donepezil, relative to placebo, was greater for those with worse baseline scores. Conclusions: Long-term brain tumor survivors treated with brain irradiation who have cognitive impairment can benefit from 5-10mg of donepezil for 24 weeks. Improvements in verbal memory, working memory, visuo- and psychomotor performance and executive functioning were observed in this group. (Study supported by NIH/NINR grant 5R01NR009675-04, NIH/NCI grant 2 U10 CA 81851-09-13 and Eisai, Inc.) Clinical trial information: NCT00369785.

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