Department of Psychiatry & Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.
Department of Social Sciences & Health Policy, Wake Forest University School of Medicine, Winston-Salem, NC.
J Clin Oncol. 2024 Jul 20;42(21):2546-2557. doi: 10.1200/JCO.23.01100. Epub 2024 May 6.
To test efficacy of donepezil, a cognitive enhancer, to improve memory in breast cancer survivors who report cancer-related cognitive impairment 1-5 years postchemotherapy.
Adult female BCS exposed to ≥4 cycles of adjuvant chemotherapy 1-5 years before enrollment who reported cancer-related cognitive impairment were eligible. Participants, enrolled at sites affiliated with the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base, were randomly assigned to receive 5 mg of donepezil once daily for 6 weeks titrated to 10 mg once daily for 18 weeks or placebo. Cognition and self-report cognitive functioning was assessed at baseline, 12, 24 (end of intervention), and 36 (washout) weeks postrandomization. Mixed-effects repeated measures analysis of covariance models were used to assess treatment differences in immediate recall (primary outcome) on the Hopkins Verbal Learning Test-Revised (HVLT-R) and other cognitive domains (secondary outcomes) with covariates of treatment, time, time by treatment interaction, baseline outcome level, age stratification, and an unstructured covariance matrix to account for within participant correlation over time.
Two hundred seventy-six BCS from 87 NCORP practices (mean age, 57.1, standard deviation [SD], 10.5) who were at a mean of 29.6 months (SD, 14.2) postchemotherapy were randomly assigned to donepezil (n = 140) or placebo (n = 136). At 24 weeks, treatment groups did not differ on HVLT-R scores (donepezil mean = 25.98, placebo = 26.50, = .32). There were no statistically significant differences between treatments at 12, 24, or 36 weeks for attention, executive function, verbal fluency, processing speed, or self-reported cognitive functioning. Endocrine therapy and menopausal status did not affect results.
BCS 1-5 years after completing chemotherapy with documented memory problems, randomly assigned to 24 weeks of 5-10 mg of donepezil once daily, did not perform differently at the end of treatment on tests of memory, other cognitive functions, or subjective functioning than those randomly assigned to placebo.
测试多奈哌齐（一种认知增强剂）在化疗后 1-5 年内报告有癌症相关认知障碍的乳腺癌幸存者中的疗效，以改善其记忆力。
符合条件的患者为接受过≥4 个周期辅助化疗且在入组前 1-5 年内的成年女性乳腺癌幸存者，报告有癌症相关认知障碍。这些患者在与威克森林国家癌症研究所社区肿瘤学研究计划（NCORP）研究基地相关的站点入组，随机分配接受 5 毫克多奈哌齐每日 1 次，6 周内滴定至 10 毫克每日 1 次，共 18 周，或安慰剂。在随机分组后 12、24（干预结束）和 36 周（洗脱）时，评估认知功能和自我报告认知功能。采用混合效应重复测量协方差模型，根据治疗、时间、时间与治疗的交互作用、基线结局水平、年龄分层和无结构协方差矩阵等协变量，评估霍普金斯词语学习测试修订版（HVLT-R）即时回忆（主要结局）和其他认知领域（次要结局）的治疗差异。
共有 87 个 NCORP 实践点的 276 名乳腺癌幸存者（平均年龄 57.1 岁，标准差 10.5）入组，他们在化疗后平均 29.6 个月（标准差 14.2）时被随机分配至多奈哌齐组（n=140）或安慰剂组（n=136）。在 24 周时，多奈哌齐组和安慰剂组的 HVLT-R 评分无差异（多奈哌齐组的平均分数为 25.98，安慰剂组为 26.50， =.32）。在 12、24 或 36 周时，两组在注意力、执行功能、词语流畅性、处理速度或自我报告认知功能方面均无统计学差异。内分泌治疗和绝经状态对结果无影响。
在完成化疗后 1-5 年且有记忆问题的乳腺癌幸存者中，随机分配至多奈哌齐组（5-10 毫克，每日 1 次），与安慰剂组相比，在治疗结束时记忆、其他认知功能或主观功能的测试中无差异。
