oltipraz in the prevention of lung cancer in people who smoke

Conditions: Lung Cancer

Summary: rationale: chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. purpose: randomized phase i trial to study the effectiveness of oltipraz in preventing lung cancer in people who smoke.

objectives: * determine the effect of oltipraz on the level of bp-7,8-diol-9,10-epoxide (bpde) dna adducts in the lung lining cells (macrophages and bronchial epithelial cells) of smokers. * determine the tolerability and toxicity of this treatment regimen in these patients. * determine the effect of this treatment regimen on the level of macromolecule adducts in the blood (e.g., bpde dna, bpde hemoglobin, and 8-hydroxy-deoxyguanine), oral lining cells (bpde dna), bladder lining cells (4-aminobiphenyl dna), and lung macrophages (8-hydroxy-deoxyguanine) in these patients. * determine the effect of this treatment regimen on the change (decrease) in activation of nnk as measured by change (increase) in urinary nnal plus nnal glucuronide in these patients. * determine the effect of this treatment regimen on the oxidative state, glutathione-s-transferase activity, and superoxide dismutase 3 and phase ii enzymes in the lungs and blood of these patients. * compare the changes in oxidative state and phase ii enzymes with changes in adduct levels in the lungs and blood of these patients. * determine the correlation between oltipraz-induced changes in phase ii enzymes and adduct formation with genotypic variation in glutathione-s-transferase isozymes in these patients. * compare the response to this treatment regimen in terms of oxidative state, phase ii enzymes, and adduct formation in the lungs vs the blood in these patients. outline: this is a randomized, double-blind, multicenter study. patients are stratified according to participating center. patients are randomized to one of three treatment arms. * arm i: patients receive an oral placebo weekly. * arm ii: patients receive low-dose oral oltipraz weekly. * arm iii: patients receive high-dose oral oltipraz weekly. treatment continues for 12 weeks in the absence of unacceptable toxicity. patients are followed at 4 weeks. projected accrual: a total of 66 patients (22 per treatment arm) will be accrued for this study within 21 months.

Eligibility criteria:
disease characteristics: * current cigarette smokers * at least 20 cigarettes a day * no variation of more than 10 in the number of cigarettes smoked per day within the past 3 months * at least 10 years of smoking any amount * failed to stop smoking after at least one attempt to quit within the last 3 years * prior stage i non-small cell lung cancer allowed if surgically resected with at least a lobectomy * no concurrent evidence of lung cancer * willing to undergo 2 bronchoscopies patient characteristics: age: * 18 and over performance status: * ecog 0 life expectancy: * not specified hematopoietic: * cbc normal * hemostasis normal hepatic: * pt and ptt normal renal: * blood chemistries normal * nonfasting glucose no greater than 200 mg/dl * no active renal disease * no urinary tract infection by urinalysis (trace protein allowed) cardiovascular: * ekg normal * no coronary artery disease requiring continuous medication pulmonary: * chest radiograph normal (postsurgical changes allowed) * no acute or significant chronic abnormality * fev1 greater than 1.8 l or 75% predicted * no chronic obstructive pulmonary disease requiring continuous medication other: * no known hypersensitivity or prior adverse reaction to oltipraz * no inmates or prisoners * no medical or psychological condition that would preclude study (e.g., acute psychosis) * no prior malignancy except nonmelanomatous skin cancer, cervical dysplasia, or curatively treated stage i or ii cancer of the head and neck * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 6 months after study prior concurrent therapy: biologic therapy: * not specified chemotherapy: * at least 3 months since prior potential chemoprevention agent (e.g., oltipraz, retinoids, or acetylcysteine) endocrine therapy: * not specified radiotherapy: * not specified surgery: * see disease characteristics

Keywords: non-small cell lung cancer small cell lung cancer