Pioglitazone for Lung Cancer Chemoprevention

Pioglitazone for Lung Cancer Chemoprevention

This is a chemoprevention trial evaluating the diabetic agent pioglitazone. Non-diabetic subjects at risk for lung cancer (based on smoking history, lung function testing, and atypical cells in a sputum sample) receive either placebo or pioglitazone and have chest computerized tomography (CAT) scans and examinations of their airways with a bronchoscope at the start of the trial and after 6 months on treatment. Compensation will be provided to the subject after completing the trial.

This trial evaluates the oral peroxisome proliferator-activated receptor gamma (PPARgamma) agonist pioglitazone in a double-blind placebo controlled trial. The high risk current and former smokers qualify based on tobacco exposure, airflow limitation on lung function testing, and sputum cytologic atypia. Subjects have a quantitative high resolution thoracic CT scan and a fluorescent bronchoscopy at study entry and after 6 months on drug or placebo. Biologic samples are collected at both time points. The primary outcome is endobronchial histology and determining if pioglitazone can retard progression. Secondary endpoints related to the PPAR gamma signaling pathway will also be analyzed.

Inclusion Criteria:

• Current or former smoker (at least 10 pack years);
• One or more of the following:
• Mild or worse sputum atypia
• Airflow Limitation (FEV1/FVC<70% predicted)
• Biopsy proven airway dysplasia

Exclusion Criteria:

• myocardial infarction (MI) with ejection fraction < 50%;
• severe/unstable angina;
• history of coronary or peripheral arterial bypass grafting;
• New York Heart Association (NYHA) class III or IV congestive heart failure;
• hypoxemia (less than POX 90 with supplemental oxygen); Diabetes type I or II; severe COPD (GOLD stage III or IV); clinically significant edema requiring diuretic therapy;
• life expectancy < 6 months; history of bladder cancer
• pregnant or breast feeding; inability to give informed consent