• INCLUSION CRITERIA:

  1. Adult patients with newly diagnosed stage Ia-IIb resectable non-small cell lung cancer who will be undergoing definitive surgery. If histologic confirmation of lung cancer has not previously been made, the baseline study bronchoscopy, as outlined in section 3.6.2, or CT-guided biopsy with tissue saved for protocol use may be used to document NSCLC, after obtaining informed consent. Should the bronchoscopy or CT-guided biopsy be negative for NSCLC, the patient will be taken off study prior to drug treatment. At NCI, histologic confirmation of the diagnosis will be performed by the NCI Laboratory of Pathology.
  2. Age greater than or equal to 18 years of age.
  3. Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
  4. Patients must have the capacity and willingness to sign a written informed consent and demonstrate willingness to comply with an oral regimen.
  5. The time between initial diagnosis and the scheduled surgery date allow for the subject to receive a minimum of 2 weeks or a maximum of 6 weeks treatment with pioglitazone. The maximum time between enrollment on this trial and surgery will be 6-weeks and there will be no delay between the end of pioglitazone treatment and surgery.
  6. Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count greater than or equal to 1,500/mL
• hemoglobin greater than 10 g/dL
• platelets greater than or equal to 100,000/mL
• Bilirubin less than 1.8 mg/dL
• AST/ALT less than 1.5 times upper limits of institutional normal

• creatinine less than 1.5 times upper limit of institutional normal

  7. Patients must agree to swallow oral tablets.

  8. Patients who will agree to undergo two bronchoscopies as detailed in section 3.6.2 (before treatment and at the time of surgery).

• For those patients who are undergoing mediastinoscopy as part of their standard-of-care, the pre-treatment bronchoscopy may be performed during the mediastinoscopy. If the patient remains eligible for definitive surgical resection after the mediastinoscopy, the patient may begin pioglitazone treatment on this protocol.

  9. Females are eligible to participate in the study if

• She is of non-childbearing potential as defined by having had a hysterectomy, a bilateral oopherectomy, a bilateral tubal ligation, or having been post-menopausal for greater than or equal to 1 year.
• She is of childbearing potential and has a negative pregnancy test within 2 weeks of the starting the study drug and agrees to the use of non-hormonal methods of birth control, e.g., barrier methods, for the duration of the study due to possible drug interactions.

EXCLUSION CRITERIA:

1. Pregnant or lactating women.
2. Patients who are undergoing chemotherapy, treatment with biologic agents, or radiation therapy. Prior chemotherapy, biologic agent treatment, or radiation therapy, greater than 1 year ago, is allowed.
3. Patients with greater than or equal to class II NYHA congestive heart failure or history of congestive heart failure.
4. Patients with greater than or equal to grade 2 (moderate) edema.
5. Patients with diabetes mellitus being treated with insulin or any pharmacologic therapy.
6. Patients taking gemfibrozil or rifampin, due to drug interactions with pioglitazone.
7. Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active liver disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.