This randomized phase II trial studies the effects of aspirin and zileuton on genes related
to tobacco use in current smokers. Smokers are at increased risk for developing lung and
other cancers. Aspirin and zileuton may interfere with genes related to tobacco use and may
be useful in preventing lung cancer in current smokers.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Inclusion Criteria:
- Male or female current tobacco smokers with >= 20 pack years of self-reported smoking
exposure and an average use of >= 10 cigarettes/day
- Karnofsky >= 70%
- Leukocytes >= 3,000/microliter
- Absolute neutrophil count >= 1,500/microliter
- Hematocrit within normal institutional limits
- Platelets >= 150,000/microliter
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
within normal institutional limits
- Creatinine within normal institutional limits
- Prothrombin time (PT)/partial thromboplastin time (PTT) within normal institutional
limits
- Fertile subjects must use adequate contraception (abstinence, barrier methods, or
birth control pills) prior to study entry and for the duration of study
participation; women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation; should a woman become
pregnant or suspect she is pregnant while participating in this study, she should
inform her study physician immediately
- Participants may have a history of indeterminate pulmonary nodule(s) by chest imaging
if nodule follow-up has been completed or the study procedures would not interfere
with nodule follow-up
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- History of allergic reaction to aspirin or attributed to compounds of similar
chemical or biologic composition to aspirin, including other nonsteroidal
anti-inflammatory drugs (NSAIDs)
- Gastric intolerance attributable to ASA or NSAIDs
- History of gastric ulcer (with or without bleeding)
- Use of ASA or NSAIDs for more than 5 days per month within 3 months of enrollment
- Not willing or are unable to refrain from use of any non-study ASA, NSAIDs and
leukotriene antagonists during the study period
- Require chronic anticoagulation or anti-platelet therapy
- History of bleeding disorder or hemorrhagic stroke
- Chronic, current or recent (within the past three months) use of leukotriene
antagonists
- Chronic, current or recent (within the past three months) use of glucocorticoids
(systemic, topical and/or nasal sprays)
- History of chronic sinusitis or recent nasal polyps
- History of, or current, active or chronic liver disease even if transaminases have
normalized
- History of allergic reaction to zileuton or attributed to compounds of similar
chemical or biologic composition to zileuton
- Are taking drugs known to interact with zileuton, including theophylline, warfarin,
and propranolol
- Not willing or are unable to limit alcohol consumption to =< 2 alcoholic beverages a
day during the study period
- Pregnant or lactating women; breastfeeding should be discontinued if the mother is
treated with aspirin; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her study physician immediately
- Participants may not be receiving any other investigational agents
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Have a known history of inability to absorb an oral agent
- Invasive cancer within the past five years except non-melanoma skin cancer