Cognitive/Functional Effects, Delirium, Depression, Lung Cancer, Radiation Toxicity
Conditions
Keywords
depression, delirium, cognitive/functional effects, radiation toxicity, limited stage small cell lung cancer, extensive stage small cell lung cancer, recurrent small cell lung cancer
Brief summary
RATIONALE: Donepezil and vitamin E may be able to decrease side effects caused by radiation therapy given to prevent brain metastases in patients with small cell lung cancer. It is not yet known if donepezil and vitamin E are effective in preventing side effects caused by radiation therapy to the head. PURPOSE: Randomized phase III trial to determine the effectiveness of donepezil and vitamin E in preventing side effects caused by radiation therapy given to prevent brain metastases in patients who have small cell lung cancer.
Detailed description
OBJECTIVES: * Compare the interval between completion of cancer treatment that included prophylactic cranial irradiation and onset of cognitive decline in patients with small cell lung cancer (SCLC) treated with donepezil and vitamin E vs placebo. * Determine the toxicity of donepezil and vitamin E in these patients. * Determine whether preserved cognitive function favorably impacts quality of life in these patients. * Determine the natural history of cognitive decline in these patients after cancer treatment. * Determine whether genotypes of apolipoprotein E predict decline in cognitive function among patients at risk for treatment-associated dementia and whether these genotypes predict duration of disease-free survival among patients who have achieved complete response after treatment for SCLC. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to cognitive function (normal vs mild to moderate dysfunction vs severe dysfunction) and age (60 and under vs over 60). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral donepezil daily and vitamin E twice daily. * Arm II: Patients receive oral placebos according to the same schedule as the study drugs in arm I. All patients begin treatment within 2 weeks after completion of prophylactic cranial irradiation. Treatment continues for a minimum of 1 month in the absence of disease progression, unacceptable toxicity, or a 3.0 point drop on the Mini Mental State Examination (MMSE) and/or a 5 point drop on the Blessed Dementia Scale. Cognition is assessed using the Blessed Dementia Scale and the MMSE at baseline and then every 3 months during study. Quality of life and depression are assessed at baseline and then every 3 months during study. Patients are followed every 6 months.
Interventions
DIETARY_SUPPLEMENTvitamin E
DRUGdonepezil hydrochloride
OTHERplacebo
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of small cell lung cancer (SCLC) * Must meet one of the following conditions: * Enrolled no more than 4 weeks before initiation of prophylactic cranial irradiation (PCI) OR * Enrolled no more than 10 days after initiation of PCI * Limited or extensive stage SCLC with complete response (CR) outside chest allowed * Must have CR or minimal disease after completion of intended course of chemotherapy * No disease progression since initiation of PCI * No prior or concurrent CNS metastases PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * ECOG 0-2 Life expectancy: * At least 12 weeks Hepatic: * Bilirubin no greater than 1.5 mg/dL Renal: * Creatinine no greater than 2 times upper limit of normal Cardiovascular: * No sick sinus syndrome or other symptomatic supraventricular conduction disorders even if symptoms currently controlled by antiarrhythmics Pulmonary: * No history of asthma or chronic obstructive pulmonary disease requiring chronic oxygen therapy Other: * No medical or psychiatric condition that would increase risk * No seizure disorder * No ongoing alcohol abuse PRIOR CONCURRENT THERAPY: Chemotherapy: * See Disease Characteristics * No concurrent anticancer chemotherapy Other: * No concurrent medications that would impair baseline cognitive function or are likely to be dose escalated over the next few months * No other concurrent vitamin E
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Compare the interval between completion of cancer treatment that included prophylactic cranial irradiation and onset of cognitive decline in patients with small cell lung cancer (SCLC) treated with donepezil and vitamin E vs placebo | Up to 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Quality of life | Up to 6 months |
Countries
United States
Outcome results
None listed