Donepezil and Vitamin E to Prevent Side Effects Caused By Radiation Therapy to the Head in Patients Receiving Treatment for Small Cell Lung Cancer

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.

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