green tea or polyphenon e in preventing lung cancer in former smokers with chronic obstructive pulmonary disease

Conditions: Lung Cancer Prevention

Summary: rationale: chemoprevention is the use of certain substances to keep cancer from forming, growing, or coming back. the use of green tea or polyphenon e may prevent cancer from forming in former smokers with chronic obstructive pulmonary disease. purpose: this randomized phase ii trial is studying how well green tea or polyphenon e work in preventing lung cancer in former smokers with chronic obstructive pulmonary disease.

objectives: primary * evaluate the effects of high-level oral consumption of defined green tea (four 12-oz servings/day) or polyphenon e capsules (4 capsules/day) on markers of cellular oxidative damage, as measured by 8-hydroxydeoxyguanosine (8-ohdg) and 8-f_2-isoprostanes (8-epi-pgf2) in former smokers with chronic obstructive pulmonary disease. secondary * evaluate the effects of high-level oral consumption of defined green tea or polyphenon e capsules on body antioxidant status (carotenoids, vitamins a and e, ascorbic acid \[vitamin c\] and antioxidant enzymes \[catalase and glutathione peroxidase\]) in blood in these patients. * evaluate the effects of high-level oral consumption of defined green tea or polyphenon e capsules on gene expression of markers of proliferation and apoptosis in induced sputum in these patients. tertiary * evaluate the effects of high-level oral consumption of defined green tea or polyphenon e capsules on lung function in these patients. * evaluate the relative adherence to use of green tea beverage vs polyphenon e capsules in these patients. outline: this is a randomized, double-blind, placebo-controlled study. patients are stratified according to gender and inhaled steroid usage (yes vs no). all patients receive placebo tea beverage and placebo capsules 4 times a day for 2 weeks. patients are randomized to 1 of 3 treatment arms after successful completion of the 2-week period. * arm i (green tea beverage): patients receive oral green tea beverage and oral polyphenon e placebo daily for 6 months. * arm ii (green tea capsule \[polyphenon e\]): patients receive oral green tea beverage placebo and oral polyphenon e daily for 6 months. * arm iii (placebo): patients receive oral green tea beverage placebo and oral polyphenon e placebo daily for 6 months. patients undergo blood, urine, exhaled breath condensate (ebc), induced sputum, and buccal cell collection at baseline and periodically during study for biomarker/laboratory analysis. blood samples are analyzed for 8-hydroxydeoxyguanosine (8-ohdg), glutathione peroxidase, and catalase. urine is examined for f_2-isoprostanes, 8-ohdg, and tea polyphenols. induced sputum broncho-epithelial cells are analyzed for gene expression of genes implicated in cellular growth and apoptotic pathway via reverse transcriptase-polymerase chain reaction. ebc samples are examined for f_2-isoprostane levels. buccal cells are stored for future analysis. projected accrual: a total of 195 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * diagnosis of chronic obstructive pulmonary disease * fev_1/fvc ≤ 78 * history of smoking ≥ 1 pack daily for 30 years or 2 packs daily for 15 years * stopped smoking for ≥ 1 year * no previously diagnosed bronchiectasis * no history of \> 1 acute emphysema exacerbation within the past 3 months patient characteristics: * ecog performance status 0-1 * wbc ≥ 3,500/mm³ * platelet count \> 130,000/mm³ * hemoglobin ≥ 11 g/dl (female) or 12 g/dl (male) * ast and alt normal * bilirubin ≤ 1.5 mg/dl (unless gilbert's disease present) * creatinine ≤ 1.5 mg/dl * alkaline phosphatase ≤ 2 times upper limit of normal * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no invasive cancer within the past 5 years * able and willing to consume caffeinated beverages * able to produce induced sputum * able to perform forced expiratory maneuver during spirometry testing * no immunosuppression by virtue of medication or disease including, but no limited to, any of the following: * organ transplantation * liver or kidney failure * autoimmune diseases * oral steroids * chemotherapy * no serious concurrent illness that could preclude study compliance, such as uncontrolled high blood pressure, heart disease, or poorly controlled diabetes * no myocardial infarction within the past 6 weeks prior concurrent therapy: * at least 2 weeks since prior and no concurrent dietary supplements or herbal products, including any of the following: * herbal tea * ginkgo biloba \> 60 mg/day * melatonin \> 3 mg/day * echinacea \> 300 mg/day * hypericum perforatum (st. john's wort) \> 300 mg/day * dhea mustard \> 5 mg/day * at least 2 weeks since prior and no concurrent nontrial tea or tea products * more than 3 weeks since prior chest or abdominal surgery * more than 3 months since prior participation in chemoprevention or clinical intervention trials * at least 3 months since prior and no concurrent megadoses of vitamins, defined as \> 4,000 iu of vitamin a, 400 iu of vitamin e, 400 iu of cholecalciferol (vitamin d), 60 μg of selenium, or 1,000 mg of ascorbic acid (vitamin c) per day * no regular consumption of ≥ 6 cups or glasses of tea per week * no concurrent nontrial caffeine at \> 1 serving/day (1 serving defined as 12 oz of regular soda or 8 oz of coffee) * no concurrent participation in another interventional clinical trial

Keywords: lung cancer prevention green tea former smokers