Combination Chemotherapy and Celecoxib in Treating Patients With Advanced Non-Small Cell Lung Cancer

OBJECTIVES:

• Determine the recommended phase II dose of docetaxel and irinotecan in combination with celecoxib in patients with advanced non-small cell lung cancer.
• Determine the toxic effects of this regimen in these patients.
• Determine the response rate of patients treated with this regimen.
• Determine the progression-free and overall survival of patients treated with this regimen.
• Determine the pharmacokinetics of this regimen in these patients.
• Correlate angiogenesis markers (intratumoral microvessel density and vascular endothelial growth factor [VEGF] expression and serum VEGF) and cyclooxygenase-2 expression with response and survival in patients treated with this regimen.
• Correlate UGT1A1 genotype and CYP3A4 activity with the toxic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study of docetaxel and irinotecan.

• Phase I: Patients receive docetaxel IV over 60 minutes and irinotecan IV over 30 minutes on days 1 and 8. Patients also receive oral celecoxib twice daily beginning on day 2. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity Cohorts of 3-6 patients receive escalating doses of docetaxel and irinotecan until the recommended phase II dose is determined. The recommended phase II dose is defined as the highest dose at which 0 of 3 or 1 of 6 patients experience dose-limiting toxicity.
• Phase II: Patients receive treatment as in phase I at the recommended phase II dose.

Patients are followed every 3 months until disease progression.

PROJECTED ACCRUAL: A total of 3-70 patients (3-36 for phase I and 16-34 for phase II) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of non-small cell lung cancer (NSCLC) meeting 1 of the following criteria:

• Stage IV
• Stage IIIB with a malignant pleural effusion
• Locally recurrent and/or persistent disease after locoregional therapy with or without systemic chemotherapy
• Unidimensionally measurable disease

• If the only site of measurable disease is in a previously irradiated area must have documented progression of disease in that area
• No CNS metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin normal
• AST and ALT less than 2.5 times upper limit of normal (ULN) (if alkaline phosphatase is normal)
• Alkaline phosphatase less than 4 times ULN (if AST and ALT are normal)

Renal

• Creatinine less than 2.0 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study treatment
• No other malignancy within the past 5 years except curatively treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
• No diagnosis of peptic ulcer disease or gastritis/esophagitis within the past 60 days
• No prior hypersensitivity to cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, sulfonamides, or drugs formulated with polysorbate 80
• No pre-existing grade 2 or greater peripheral neuropathy
• No concurrent medical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 1 week since prior biologic therapy
• Phase I patients:

• Any number of prior biologic therapies allowed (e.g., chimeric antibodies or kinase inhibitors)
• Phase II patients:

• No prior biologic therapy for recurrent/metastatic disease
• No concurrent filgrastim (G-CSF)

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• No prior irinotecan or docetaxel
• Phase I patients:

• Up to 2 prior chemotherapy regimens for recurrent/metastatic disease allowed (chemonaïve patients are also eligible)
• Phase II patients:

• At least 1 year since prior adjuvant or neoadjuvant chemotherapy for stage I-IIIA disease
• No prior chemotherapy for recurrent/metastatic disease

Endocrine therapy

• Less than 2 weeks of cumulative oral/IV corticosteroid use within the past 3 months

Radiotherapy

• See Disease Characteristics
• Recovered from prior radiotherapy
• At least 3 weeks since prior extensive-field radiotherapy for recurrent/metastatic disease

Surgery

• Recovered from prior surgery

Other

• More than 60 days since prior treatment for peptic ulcer disease or gastritis/esophagitis
• No prior NSAIDs at a frequency of more than 3 times per week for a cumulative period of more than 2 weeks within the past 30 days
• No concurrent antiepileptics, cyclosporine, aspirin, or fluconazole
• No concurrent NSAIDs
• No other concurrent COX-2 inhibitors