Messaggi chiave
- WF-97116 è uno studio di fase III, randomizzato, in doppio cieco, controllato con placebo, che ha valutato l’uso di donepezil, un inibitore reversibile dell’acetilcolinesterasi, in 276 pazienti con carcinoma mammario (BC) esposte a ≥4 cicli di chemioterapia (CT) adiuvante che riferivano compromissione delle funzioni cognitive a 1-5 anni dal completamento della terapia. L’outcome primario era l’impatto del trattamento sulla memoria immediata misurata con l’Hopkins Verbal Learning Test-Revised (HVLT-R).
- A 24 settimane, non sono emerse differenze tra il gruppo sperimentale e il gruppo placebo nei punteggi HVLT-R (media, 25,98 vs 26,50 con donepezil rispetto a placebo; p = 0,32). Analogamente, non sono state osservate differenze statisticamente significative a 12, 24 o 36 settimane nei domini relativi a attenzione, funzione esecutiva, fluenza verbale e velocità di elaborazione, né nel funzionamento cognitivo riportato dalle pazienti. Terapia endocrina e stato menopausale non hanno influito sui risultati.
- A differenza di quanto osservato in alcune patologie non tumorali, donepezil non sembra apportare alcun beneficio in termini di miglioramento della memoria e di altre funzioni cognitive in pazienti BC sottoposte a CT adiuvante nei precedenti 1-5 anni. È auspicabile la conduzione di ulteriori studi che possano testare farmaci alternativi, differenti modalità di somministrazione (per esempio, in concomitanza con la CT o subito dopo il suo completamento) e/o interventi di natura non farmacologica.
Abstract
Purpose
- 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.
Patients and Methods
- 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.
Results
- 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, p = .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.
Conclusions
- 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.