Green Tea or Polyphenon E in Preventing Lung Cancer in Former Smokers With Chronic Obstructive Pulmonary Disease

Sherry Chow

Status and phase: Completed; Phase 2

Conditions: Lung Cancer Prevention

Treatments: Other: placebo; Dietary Supplement: green tea; Drug: Polyphenon E

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00363805

P30CA023074 (U.S. NIH Grant/Contract)

UARIZ-HSC-0353

CDR0000487501

U01CA101204 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 178 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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178 participants in 3 patient groups, including a placebo group

Green Tea

Experimental group

Description:

Patients receive green tea beverage and placebo capsules for 6 months.

Treatment:

Dietary Supplement: green tea

Polyphenon E

Experimental group

Description:

Patients receive placebo beverage and Polyphenon E capsules daily for 6 months.

Treatment:

Drug: Polyphenon E

Placebo

Placebo Comparator group

Description:

Patients receive placebo beverage and placebo capsules daily for 6 months.

Treatment:

Other: placebo