Donepezil and vitamin E for preventing cognitive dysfunction in small cell lung cancer patients: Preliminary results and suggestions for future study designs

Background: Up to 90% of small cell lung cancer (SCLC) patients suffer cognitive dysfunction. Since donepezil and vitamin E have been somewhat successful in treating other dementias, this study tested the hypothesis that these agents can prevent cognitive decline in SCLC patients. Because accrual was poor, this trial also offered opportunities for suggesting other study designs for future clinical trials on cognitive dysfunction in this group of patients. Methods: This double blind, placebo controlled trial tested oral donepezil 5 mg/day (with dose escalation to 10 mg after 1 month) and oral vitamin E 1,000 IU/day in SCLC patients after completion of all cancer therapy, including prophylactic cranial irradiation (PCI). Cognition, adverse events, and quality of life were assessed throughout the study period. Results: Only nine of 104 patients enrolled over 15 months (four donepezil and vitamin E-treated versus five placebo-exposed), and thus no definitive conclusions could be drawn. Nonetheless, the only patient who manifested a precipitous decline in cognition was taking donepezil and vitamin E. There was also a slight trend of increased gastrointestinal side effects among donepezil and vitamin E-treated patients. There were no notable differences in cognitive stability, adverse events, or quality of life between treatment arms. Conclusion: These preliminary findings do not provide enthusiasm for testing donepezil and vitamin E in the manner undertaken here for preventing cognitive dysfunction in SCLC patients. Eligibility criteria and timing of trial intervention are discussed as potential impediments to successful trial completion.