Phase II trial of celecoxib in combination with paclitaxel and carboplatin in advanced non-small cell lung cancer

ABSTRACT

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. Thirty-seven patients were enrolled in this trial. The inclusion criteria were chemotherapy-na‹ve 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/m[2]] and carboplatin [AUC 6] on day 1, every 21 days and celecoxib [400 mg] daily. 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. 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