celecoxib in preventing head and neck cancer in patients with oral leukoplakia

Conditions: Head and Neck Cancer; Precancerous Condition

Summary: rationale: chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. the use of celecoxib may prevent or treat head and neck cancer. purpose: this randomized phase ii trial is studying celecoxib to see how well it works compared to placebo in preventing head and neck cancer in patients with oral leukoplakia.

objectives: primary * compare the clinical efficacy of celecoxib vs placebo, in terms of inducing regression of oral leukoplakia lesions, in patients with hyperplastic or dysplastic oral leukoplakia. secondary * determine the effect of this drug in modulating multiple intermediate biomarkers (e.g., cox-2, pparγ, or pparδ) in normal and hyperplastic or dysplastic oral epithelia of these patients. * determine the safety of this drug in these patients. * determine the cost-effectiveness of this drug as a chemopreventative agent in these patients. outline: this is a randomized, double-blind, placebo-controlled, cross-over study. patients are stratified according to the pathology of the leukoplakia lesion (dysplasia vs hyperplasia). patients are randomized to 1 of 2 arms. * arm i: patients receive oral celecoxib twice daily for 3 months. * arm ii: patients receive oral placebo twice daily for 3 months. all patients undergo biopsy. patients then cross-over to the opposite treatment arm for 3 months. in both arms, treatment continues in the absence of unacceptable toxicity or disease progression. patients are followed at 1 month. projected accrual: a total of 27-60 patients (18-40 for study drug, 9-20 for placebo before cross-over) will be accrued for this study.

Eligibility criteria:
disease characteristics: * diagnosis of oral leukoplakia with hyperplasia or dysplasia * documented by baseline biopsy of oral lesions suspicious for leukoplakia * for patients using dentures over the past 6 months, only lesions located on the ventral-lateral tongue or floor of the mouth are allowed * no leukoplakia/hyperplasia secondary to mechanical irritation * no carcinoma in situ of the oral cavity patient characteristics: age * 18 and over performance status * not specified life expectancy * at least 1 year hematopoietic * hemoglobin ≥ 10 g/dl (women) or ≥ 11 g/dl (men) hepatic * ast or alt normal * bilirubin normal renal * creatinine normal or * creatinine clearance ≥ 60 ml/min cardiovascular * no myocardial infarction within the past 12 months * no known active ischemic cardiac disease by stress test or echocardiogram gastrointestinal * no history of gastrointestinal hemorrhage * no known gastrointestinal ulcers within the past 2 years unless there is documentation of healed lesions by upper endoscopy * no active or suspected peptic ulcer disease * negative stool guaiac test other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception during and for 2 months after study treatment * no use of snuff or chewing tobacco within the past 2 months * no active invasive malignancy within the past 3 years except nonmelanoma skin cancer or in situ carcinomas * no clinical evidence of chronic infectious disease * no clinical evidence of connective tissue disease * no known hypersensitivity (asthma, urticaria, or acute rhinitis induced by nsaids) to aspirin or other nsaids * no known hypersensitivity to sulfonamides prior concurrent therapy: biologic therapy * not specified chemotherapy * not specified endocrine therapy * at least 6 months since prior chronic or frequent use of systemic glucocorticoids * no concurrent chronic or frequent use of systemic glucocorticoids radiotherapy * not specified surgery * not specified other * no prior chronic or frequent (\> 100 mg per day aspirin equivalent) use of nonsteroidal anti-inflammatory drugs (nsaids) for 7 of the past 14 days * at least 3 months since prior experimental therapy * no concurrent chronic or frequent use of nsaids * cardioprotective doses of aspirin ≤ 100 mg daily are allowed

Keywords: hypopharyngeal cancer lip and oral cavity cancer nasopharyngeal cancer oropharyngeal cancer tongue cancer oral leukoplakia