iloprost in preventing lung cancer in patients at high risk for this disease

Conditions: Lung Cancer; Precancerous Condition

Summary: rationale: chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. iloprost may be effective in preventing lung cancer. purpose: this randomized phase ii trial is studying how well iloprost works in preventing lung cancer in patients who are at high risk for this disease.

objectives: primary * compare the reversal of premalignant histological changes in the bronchial epithelium of patients at high risk for lung cancer (defined by \> 20 pack years of smoking and sputum atypia) treated with iloprost vs placebo. * determine whether this drug modulates ki-67 proliferation index (antigen ki-67) in these patients. * determine whether this drug affects prostaglandin metabolism in these patients. * determine the toxicity profile of this drug in these patients. secondary * determine whether this drug modulates a panel of biomarkers, including mcm-2(minichromosome maintenance protein: forms dna helicase), egfr (epidermal growth factor receptor: cell surface receptor for the epidermal growth factor family of proteins. mutations in egfr expression or activity can result in cancer.) , her2/neu (human epidermal growth factor receptor 2 her2 is a member of the egfr family), rarβ (retinoic acic receptor beta is a nuclear transcription regulator and a member of the thyroid-steroid hormone receptor superfamily), p53, fhit (fragile histidine triad protein is an enzyme involved in purine metabolism and had been demonstrated to be a tumor suppressor), apoptotic index, and microvessel density, in these patients. * determine the genes whose expression is altered by this drug in these patients. outline: this is a randomized, double-blind, placebo-controlled, multicenter study. patients are stratified according to smoking status (current vs former) and participating center. patients are randomized to 1 of 2 treatment arms. * arm i: patients receive oral iloprost twice daily. * arm ii: patients receive oral placebo twice daily. in both arms, treatment continues for 6 months in the absence of unacceptable toxicity. patients are followed at 1 month and then annually thereafter. projected accrual: a total of 152 patients (76 \[38 current smokers and 38 former smokers\] per treatment arm) will be accrued for this study within 2 years.

Eligibility criteria:
inclusion criteria: * current or former smoker with ≥ 20 pack-year history of smoking with no tobacco use within the past 6 months * mild atypia or worse on sputum cytology, or * bronchial biopsy with mild or worse dysplasia within the past 12 months * age 18 and over * swog (southwest oncology group)0-2 * life expectancy at least 6 months * granulocyte count \> 1,500/mm\^3 * platelet count \> 100,000/mm\^3 * alkaline phosphatase ≤ 2.5 times upper limit of normal (uln) * transaminases ≤ 2.5 times uln * bilirubin ≤ 2.0 mg/dl * albumin ≥ 2.5 g/dl * creatinine ≤ 1.5 mg/dl * well-controlled atrial fibrillation or rare (\< 2 minutes) premature ventricular contractions allowed * negative pregnancy test * fertile patients must use effective contraception * able and willing to undergo bronchoscopy exclusion criteria * clinically apparent bleeding diathesis * ventricular tachycardia * multifocal premature ventricular contractions or supraventricular tachycardias with rapid ventricular response * pneumonia or acute bronchitis within the past 2 weeks * hypoxemia (\< 90% saturation with supplemental oxygen) * pregnant or nursing * malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * serious medical condition that would preclude bronchoscopy or study participation * clinically active coronary artery disease * myocardial infarction within the past 6 weeks * chest pain * congestive heart failure * cardiac dysrhythmia that is potentially life-threatening exclusion for prior concurrent therapy: * biologic therapy (not specified) * more than 5 years since prior chemotherapy * more than 6 weeks since prior inhaled steroids * more than 5 years since prior thoracic radiotherapy * surgery (not specified) * no prior prostacyclin

Keywords: non-small cell lung cancer squamous lung dysplasia