Results of a phase I/II trial of carboplatin/gemcitabine plus celecoxib for first-line treatment of stage IIIB/IV non-small cell lung cancer (NSCLC)

Abstract

7250 Background: This phase I/II trial evaluated the safety and initial efficacy of this novel regimen of celecoxib plus chemotherapy for advanced NSCLC. Celecoxib shows significant inhibitory activity in preclinical models of NSCLC. Since NSCLC often overexpresses COX-2, and chemotherapy and celecoxib have non-overlapping toxicity, this trial was undertaken. Methods: Phase I used a modified Fibonacci design. For phase I and II, chemotherapy was fixed (gemcitabine, 1100 mg/m2 [d 1 & 8]; carboplatin, AUC=5 [d 8 only], q 4 weeks). Celecoxib was given d 1–12, and all planned dose levels (from 120 up to 600 mg/m2 [∼500 mg BID]) were evaluated. Patients with SD or better could receive up to 8 cycles of Rx. CT scans were done q 2 cycles. Results: 49 patients were enrolled (including 8 PS2 pts and 12 pts >70 y.o.), with 47 evaluable for toxicity and 44 for response. The majority of pts received ≥4 cycles. Celecoxib was escalated to the final dose level (600 mg/m2=500 mg BID x 12 d) without dose-limiting toxicity. 32 patients have been treated at this celecoxib dose level. Overall, 195 cycles of Rx have been given, with 11 episodes of transient grade 4 hematologic toxicity, and 1 episode of febrile neutropenia. 5 patients had one episode each of transient grade 3 hepatic toxicity. There was no grade 3/4 renal, GI or other non-hematologic toxicity. Overall, 9/44 patients had ORs (20.5%; 7 confirmed) and 19 patients had SD for ≥4 months (overall SD=43.2%). At this time, median TTP is 3+ months; 1-yr survival is 31.2% and 2-yr survival is 12.5%. Updated data on response, TTP and OS will be provided from ongoing follow-up. COX-2 staining has been done so far on 13 pts from the phase II cohort. Staining intensity was 1+-3+, with most cases showing >50% COX-2+ tumor cells. Additional cases are being tested. Conclusions: Celecoxib plus platinum-based chemotherapy in the 1st-line for stage IIIB/IV NSCLC is safe (even in PS 2 and elderly pts), and results in acceptable initial outcomes. Phase II accrual is complete and follow-up and correlative studies are ongoing. Supported in part by Eli-Lilly, Inc. No significant financial relationships to disclose.