Background: Prostaglandins (PGs) can enhance tumor growth and metastasis by stimulating angiogenesis and invasiveness, in addition to apoptosis and immune surveillance. Microtubule-interfering agents induce cyclooxygenase-2 (COX-2) and PG biosynthesis and this might reduce the efficacy of paclitaxel. Preclinical studies suggest that treatment with a selective COX-2 inhibitor may augment the antitumoral effects of chemotherapy. Thus, we designed a phase II trial to evaluate the efficacy of the combination of paclitaxel, carboplatin and celecoxib in advanced non-small cell lung cancer. Materials and Methods: Thirty-seven patients were enrolled in this trial. The inclusion criteria were: chemotherapy-naïve advanced NSCLC (non-resectable locally advanced stage IIIA, stage IIIB and IV), age>18 yrs. and performance status (PS) of 0-2 (ECOG). All patients were given paclitaxel (200 mg/m2 ) and carboplatin (AUC 6) on day 1, every 21 days and celecoxib (400 mg) daily. Results: Most of the patients were male and the mean age was 58 yrs. Old. Performance status 0, 1, and 2 were 8.2%, 40.5% and 51.3%, respectively. Four patients were in stage IIIA (10.8%), 12 patients in stage IIIB (32.4%) and 21 (56.8%) in stage IV. The overall response rate was 54%. Time to progression and median overall survival were 5.7 and 9 months, respectively. Only one patient had grade 3 anemia. There was no grade 4 cytotoxicity. Three patients had cytotoxic drug allergy. Conclusion: Based on this study, adding 400 mg celecoxib to the standard regimen (paclitaxel plus carboplatin) does not enhance time to progression and overall survival compared to historical data. Thus, we recommend combining higher dosage of celecoxib with other targeted agents in phase I/II trials. (Tanaffos 2007; 6(1): 37-46)