Phase II study of celecoxib and weekly paclitaxel in the treatment of pretreated advanced non-small cell lung cancer (NSCLC)

Abstract

7337 Background: Cyclooxigenase-2 (COX-2) is overexpressed in about 70% of NSCLC. Selective inhibitors of COX-2 have antitumor activity by blocking angiogenesis and apoptosis. The different mechanisms of action and the non-overlapping side effects suggest their association with cytotoxic agents. This Phase II study was designed to evaluate the activity and tolerability of weekly paclitaxel (PCT) plus celecoxib (CEL), and possible clinical correlations with biomarkers. Methods: PCT was administered at the dose of 80 mg/m2 IV weekly for six weeks followed by two-week rest, and CEL 400 mg p.o. bid continuously. A cycle consisted of 8 weeks. Serum/CTADplasma VEGF and IL-6 analysis was performed at baseline and every two cycles. Results: 53 patients (pts), previously treated with front-line platinum-based chemotherapy, entered the trial since January 2002. None of them had previously received taxanes. Pts characteristics: median (m) age 60 yrs (range 30–77); male/female= 43/10; PS 0/1/2= 31/20/2; 30 adenocarcinomas, 14 epidermoid, 1 bronchioloalveolar, 8 undifferentiated NSCLC; most pts had ≥ 2 sites of disease. 43/53 pts completed at least one course of treatment and are assessable for response: 1/43 CR (2.3%), 10/43 PR (23.3%) have been observed, with m duration of 3 mos (range 2–19+); 18/43 pts (41.9%) had stable disease with m duration of 4 mos (range 2–13); m time to progression (TTP) and m overall survival (OS) are 4+ mos and 7+ mos (range 2–23+), respectively. Among the unevaluable pts, six dropped out during the first cycle and the others are too early. Over 100 administered courses, the following toxicity was recorded in all the 53 pts: G4 neutropenia (2); G3 neutropenia (4); G3 anemia (1); G3 neuropathy (3); G3 fatigue (1); G3 alopecia (2). Preliminary results do not suggest any correlation of baseline values of VEGF (m value= 554 and 29.5 pg/mL in serum and CTADplasma, respectively), IL-6 (m value= 3.6 pg/mL) and clinical parameters. Possible modifications of biomarkers after therapy are under evaluation. Conclusions: The combination of CEL and weekly PCT is promising in terms of response rate, TTP and OS in platinum-pretreated NSCLC. No significant financial relationships to disclose.