Green Tea or Polyphenon E 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.

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