Phase I/II Trial Of Weekly Irinotecan And Docetaxel With The Addition Of Celecoxib In 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.