• Tumor response rate as measured by RECIST at 4 weeks after initiation of study treatment and periodically thereafter [ Designated as safety issue: No ]
• Effect of study drugs on biomarkers at 4 weeks after initiation of study treatment [ Designated as safety issue: No ]

• Tumor response rate as measured by RECIST at 4 weeks after initiation of study treatment and periodically thereafter
• Effect of study drugs on biomarkers at 4 weeks after initiation of study treatment

RATIONALE: Celecoxib and erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase I trial is studying the side effects and best dose of celecoxib when given together with erlotinib in treating former smokers with stage IIIB, stage IV, recurrent, or progressive non-small cell lung cancer

OBJECTIVES:

Primary

• Determine the clinical toxicity and tolerability of celecoxib and erlotinib hydrochloride in former smokers with stage IIIB or IV or recurrent or progressive non-small cell lung cancer.

Secondary

• Determine the tumor response rate in patients treated with this regimen.
• Determine the dose of celecoxib that results in maximal induction of apoptosis, maximal inhibition of prostaglandin E_2 (PGE_2) in bronchoalveolar fluid, and maximal inhibition of bronchial cell proliferation in patients treated with this regimen.

OUTLINE: This is an open-label, dose-escalation study of celecoxib.

Patients receive oral erlotinib hydrochloride once daily and oral celecoxib twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of celecoxib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 6 additional patients are treated at the MTD.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 6-45 patients will be accrued for this study.

• Drug: celecoxib
• Drug: erlotinib hydrochloride

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) meeting 1 of the following stage criteria:

  • Stage IIIB with pleural effusion
  • Stage IV disease
  • Recurrent or progressive disease after prior surgery, radiotherapy, and/or chemotherapy

• Meets 1 of the following criteria:

  • Advanced NSCLC with at least stable disease after ≥ 4 courses of platinum-containing chemotherapy

  • Relapsed or refractory disease after treatment with ≥ 1 prior platinum-containing chemotherapy program, including adjuvant or neoadjuvant therapy for NSCLC

    • If the sole prior treatment was in the adjuvant or neoadjuvant setting, tumor progression or recurrence must have occurred within 6 months after completion of prior treatment

• Former smoker, as indicated by the following:

  • At least a 30 pack-year smoking history
  • Smoking duration at least 10 years
  • At least 12 months of self-reported smoking cessation
  • Negative urine cotinine
• No untreated brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• Hemostasis normal

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• PT/PTT within 0.5 seconds of normal

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• No significant cardiovascular disease
• No New York Heart Association class III or IV cardiac disease
• No uncontrolled dysrhythmia
• No unstable angina
• No myocardial infarction within the past 6 months

Pulmonary

• FEV_1 ≥ 1.0 liter OR 40% of predicted within the past 3 months
• Oxygen saturation ≥ 90% on room air

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study treatment
• Willing to undergo bronchoscopy
• No allergy to sulfonamides or hypersensitivity reaction to celecoxib
• No other medical or psychological condition (e.g., acute psychosis) that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin)

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy

Surgery

• See Disease Characteristics
• Prior complete resection allowed provided there is histologic and cytologic documentation of disease recurrence

Other

• More than 3 months since prior chemopreventative agents (e.g., oltipraz, retinoids, or N-acetylcysteine [NAC])
• No prior erlotinib hydrochloride
• No other prior EGFR antagonists

• No concurrent medication known to interact with erlotinib hydrochloride or celecoxib, including the following:

  • Fluconazole
  • Lithium
  • Furosemide
  • Angiotensin-converting enzyme inhibitors
  • Phenytoin
  • Carbamazepine
  • Rifampin
  • Barbiturates
  • Hypericum perforatum (St. John's wort)

• No concurrent non-steroidal anti-inflammatory drugs

  • Concurrent aspirin of up to an average dose of 325 mg/day allowed

    • No aspirin treatment for 7 days prior to any bronchoscopic or skin biopsy
• No other concurrent EGFR inhibitors or cyclo-oxygenase-2 (COX-2) inhibitors