Lung Cancer Prevention
Conditions
Keywords
lung cancer, prevention, green tea, former smokers
Brief 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.
Detailed 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.
Interventions
Sponsors
National Cancer Institute (NCI)
Sherry Chow
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary 8-hydroxydeoxyguanosine Levels | Baseline and 6 months | the urinary concentrations of 8-hydroxydeoxyguanosine were normalized by the urinary creatinine concentrations to correct for variations in urine dilution/production and the change in urinary 8-hydroxydeoxyguanosine levels was calculated as the 6 months levels minus the baseline levels |
| Change in Urinary 8-F2-isoprostanes Levels | Baseline and 6 months | the urinary concentrations of 8-F2-isoprostanes were normalized by the urinary creatinine concentrations to correct for variations in urine dilution/production and the change in urinary 8-F2-isoprostanes levels was calculated as 6 months levels minus baseline levels |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Green Tea Patients receive green tea beverage and placebo capsules for 6 months. | 42 |
| Polyphenon E Patients receive placebo beverage and Polyphenon E capsules daily for 6 months. | 63 |
| Placebo Patients receive placebo beverage and placebo capsules daily for 6 months. | 73 |
| Total | 178 |
Baseline characteristics
| Characteristic | Polyphenon E | Placebo | Green Tea | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 38 Participants | 26 Participants | 93 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 35 Participants | 16 Participants | 85 Participants |
| Age Continuous | 63.6 years STANDARD_DEVIATION 8.5 | 64.3 years STANDARD_DEVIATION 7.8 | 66.8 years STANDARD_DEVIATION 9.2 | 64.7 years STANDARD_DEVIATION 8.5 |
| Region of Enrollment United States | 63 participants | 73 participants | 42 participants | 178 participants |
| Sex: Female, Male Female | 31 Participants | 37 Participants | 21 Participants | 89 Participants |
| Sex: Female, Male Male | 32 Participants | 36 Participants | 21 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 42 | 14 / 63 | 21 / 73 |
| serious Total, serious adverse events | 4 / 42 | 4 / 63 | 7 / 73 |
Outcome results
Primary
Change in Urinary 8-F2-isoprostanes Levels
the urinary concentrations of 8-F2-isoprostanes were normalized by the urinary creatinine concentrations to correct for variations in urine dilution/production and the change in urinary 8-F2-isoprostanes levels was calculated as 6 months levels minus baseline levels
Time frame: Baseline and 6 months
Population: The number of participants analyzed was less than the number of participants completing the study because the analysis only included samples where the identity of the analyte was confirmed in the sample.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Green Tea | Change in Urinary 8-F2-isoprostanes Levels | -39.87 ng/mg creatinine | Standard Deviation 271.2 |
| Polyphenon E | Change in Urinary 8-F2-isoprostanes Levels | -35.80 ng/mg creatinine | Standard Deviation 261.7 |
| Placebo | Change in Urinary 8-F2-isoprostanes Levels | 0.71 ng/mg creatinine | Standard Deviation 266.4 |
Primary
Change in Urinary 8-hydroxydeoxyguanosine Levels
the urinary concentrations of 8-hydroxydeoxyguanosine were normalized by the urinary creatinine concentrations to correct for variations in urine dilution/production and the change in urinary 8-hydroxydeoxyguanosine levels was calculated as the 6 months levels minus the baseline levels
Time frame: Baseline and 6 months
Population: The number of participants analyzed was less than the number of participants completing the study because the analysis only included samples where the identify of the analyte was confirmed in the sample.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Green Tea | Change in Urinary 8-hydroxydeoxyguanosine Levels | 2.36 ng/mg creatinine | Standard Deviation 10.48 |
| Polyphenon E | Change in Urinary 8-hydroxydeoxyguanosine Levels | 5.20 ng/mg creatinine | Standard Deviation 36.2 |
| Placebo | Change in Urinary 8-hydroxydeoxyguanosine Levels | -1.08 ng/mg creatinine | Standard Deviation 25.41 |