Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers

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PRIMARY OBJECTIVES: I. To analyze the impact of combined treatment of acetylsalicylic acid (ASA) (aspirin) and zileuton on smoking-related gene expression signature in the nasal epithelium in current smokers and to analyze any difference between the ASA and zileuton intervention and placebo control....

PRIMARY OBJECTIVES: I. To analyze the impact of combined treatment of acetylsalicylic acid (ASA) (aspirin) and zileuton on smoking-related gene expression signature in the nasal epithelium in current smokers and to analyze any difference between the ASA and zileuton intervention and placebo control. SECONDARY OBJECTIVES: I. To assess the impact of ASA and zileuton on three lung cancer gene signatures (an 80-gene bronchial signature, a phosphatidylinositol 3-kinase [PI3K] pathway gene signature and a nasal diagnostic gene signature) and to compare this to placebo control. II. To determine whether the change in the smoking-related gene expression signature and the three lung cancer gene signatures of nasal epithelium persists 10-14 days off agent intervention. III. To measure urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE[4]) levels in current smokers after ASA and zileuton. IV. To assess the safety in current smokers of 12 week exposure to ASA and zileuton. V. To evaluate a gender effect in the modulatory effects of ASA and zileuton on smoking related-gene expression signature. VI. To explore the effect of ASA and zileuton on the metabolomics profile of the arachidonic acid pathway. VII. To explore, in a discovery-driven fashion, the effect of ASA and zileuton on whole-genome gene expression. VIII. To analyze the impact of ASA and zileuton on karyometric analysis of buccal cells. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive aspirin orally (PO) once daily (QD) and zileuton PO twice daily (BID) for 12 weeks in the absence of unacceptable toxicity. ARM II: Patients receive aspirin placebo PO QD and zileuton placebo PO BID for 12 weeks. After completion of study treatment, patients are followed up for 2 weeks.

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