Donepezil and vitamin E for preventing cognitive dysfunction in small cell lung cancer patients: preliminary results and suggestions for future study designs
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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.
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.
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.
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.
- Frytak S, Shaw JN, O’Neill BP, et al (1989) Leukoencephalopathy in small cell lung cancer patients receiving prophylactic cranial irradiation. Am J Clin Oncol 12:27–33
- Komaki R, Meyers CA, Shin DM, et al (1995) Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation. Int J Radiation Oncology Biol Phys 33:179–182 CrossRef
- Van Oosterhout AGM, Boon PJ, Houx PJ, et al (1995) Follow-up of cognitive functioning in patients with small cell lung cancer. Int J Radiat Oncol Biol Phys 31:911–914 CrossRef
- Ahles TA, Silberfarb PM, Herndon II J, et al (1998) Psychologic and neuropsychologic functioning of patients with limited small cell lung cancer treated with chemotherapy and radiation therapy with or without warfarin: A study by the Cancer and Leukemia Group B. J Clin Oncol 16:1954–1960
- Parageorgiou C, Dradoufas C, Kouloulias, et al (2000) Psychophysiological evaluation of short term neurotoxicity after prophylactic cranial irradiation in patients with small cell lung cancer: A study of event-related potentials. J Neurooncol 50:275–285 CrossRef
- Qizilbash N, Whitehead A, Higgins J, et al (1998) Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. JAMA 280:1777–1782 CrossRef
- Sano M, Ernesto C, Thomas RG, et al (1997) A controlled trial of selegine, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Group. N Engl J Med 24:1216–1222 CrossRef
- Selden NR, Gitelman DR, Salamon-Murayama N, et al (1998) Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain 121:2249–2257 CrossRef
- Erhola M, Nieminen MM, Ojala A, et al (1998) Human plasma antioxidant capacity during radiotherapy for lung cancer: a clinical study. J Exp and Clin Cancer Res 17:325–330
- Blessed G, Tomlinson BE, Roth M (1968) The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br. J Psychiatry 144;808–809
- Mahoney J, Drinka TJ, Abler R, et al (1994) Screening for depression: single question versus GDS. J Am Geriatric Soc 42:1006–1008
- Trotti A, Byhardt R, Stetz J, et al (2000) Common toxicity criteria, version 2.0 an improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Ohys 47:13–47 CrossRef
- Cmelak AJ, Choy H, Shyr Y, et al (1999) National survey on prophylactic cranial irradiation: differences in practice patters between medical and radiation oncologists. Int J Radiat Oncol Biol Phys 44:157–162 CrossRef
- Benowitz S. Despite challenges, cancer prevention and control programs on the rise (2003) J Natl Cancer Inst 95:1427–1428 CrossRef
- Tozzi V, Balestra P, Galgani S, et al (2003) Neurocognitive performance and quality of life in patients with HIV infection. AIDS Res Hum Retroviruses 19:643–652 CrossRef
- Donepezil and vitamin E for preventing cognitive dysfunction in small cell lung cancer patients: preliminary results and suggestions for future study designs
Supportive Care in Cancer
Volume 13, Issue 1 , pp 66-69
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- Author Affiliations
- 1. Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN, 55905, USA
- 2. Siouxland Hematology Oncology Associates, Sioux City, IA, USA
- 3. Toledo Community Hospital Program CCOP, Toledo, OH, USA