Celecoxib in Treating Patients With Early-Stage Head and Neck Cancer or Non-Small Cell Lung Cancer

OBJECTIVES:

• Compare the rate of new malignancies (recurrences and second primary tumors) in patients with early-stage head and neck cancer or non-small cell lung cancer treated with celecoxib vs placebo.
• Compare the event-free and overall survival of patients treated with this drug vs placebo.
• Determine the toxic effects associated with long-term use of celecoxib in these patients.
• Correlate cyclooxygenase-2 and transforming growth factor (TGF)-beta expression and CYP2C9 and TGF-beta genotypes with the rate of new malignancies and survival of patients treated with this drug vs placebo.

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to smoking history (active smokers [including those who quit within 1 year of diagnosis] vs former smokers vs non-smokers), tumor type (lung cancer vs head and neck cancer), and stage (I vs II for head and neck cancer or T1 vs T2 for lung cancer). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral celecoxib twice daily.
• Arm II: Patients receive oral placebo twice daily. In both arms, treatment continues for 24 months in the absence of disease recurrence or unacceptable toxicity.

Patients are followed every 6 months for 5 years or until disease recurrence.

PROJECTED ACCRUAL: A total of 121 patients (approximately 60 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• One of the following histologically confirmed diagnoses:

• Stage I non-small cell lung cancer (NSCLC)

• No small cell component
• Stage I-II squamous cell cancer of the head and neck

• No WHO type II or III nasopharyngeal cancer
• No sinonasal undifferentiated carcinoma
• No evidence of disease
• Must have undergone surgery or radiotherapy with curative intent within the past 4-24 weeks

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Platelet count at least 50,000/mm^3

Hepatic

• Bilirubin normal
• AST/ALT no greater than 2 times upper limit of normal

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• No uncontrolled hypertension
• No severe congestive heart failure

Pulmonary

• No history of asthma caused by cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, or sulfonamides

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• No other prior malignancy (including skin cancer and in situ malignancies)
• No diagnosis of peptic ulcer disease or gastritis/esophagitis within the past 60 days
• No prior hypersensitivity reaction to COX-2 inhibitors, NSAIDs, salicylates, or sulfonamides
• No other concurrent medical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• No cumulative oral or IV corticosteroid use totalling more than 2 weeks within the past 3 months
• No concurrent oral steroids for more than 2 consecutive weeks
• Concurrent inhaled steroids allowed

Radiotherapy

• See Disease Characteristics
• No prior definitive radiotherapy for stage I NSCLC

Surgery

• See Disease Characteristics
• Prior pneumonectomy or lobectomy with mediastinal lymph node sampling or dissection for stage I NSCLC allowed
• No prior segmentectomies or wedge resections for stage I NSCLC

Other

• More than 60 days since prior treatment for peptic ulcer disease or gastritis/esophagitis
• No prior NSAID use within the past 30 days at a frequency of 3 or more times a week for more than 2 weeks
• No concurrent NSAIDs (including low-dose aspirin)
• No other concurrent COX-2 inhibitors
• No concurrent fluconazole
• No concurrent lithium