Meloxicam (M) in combination with paclitaxel (P) and carboplatin (C) in patients with advanced non-small cell lung cancer (NSCLC)

Abstract

7115 Background: Cyclooxygenase-2 (COX-2) is overexpressed in NSCLC, and COX-2 promotes tumor growth through the production of prostaglandins. P is known to induce COX-2, and induction of COX-2 will decrease the efficacy of P itself. M is a selective COX-2 inhibitor, and shown to inhibit the growth of COX-2 positive lung cancer cells in vitro (Anticancer Res. 20:2867, 2000). Neuropathy is a serious problem after P administration, and COX-2 in infiltrating inflammatory cells in injured nerve plays an important role in the maintenance of neuropathic pain (Neuroscience. 121:691, 2003). We conducted this study to evaluate the hypothesis that the addition of M to P/C will enhance the response and reduce the severity of P induced neuropathy through the inhibition of COX-2. Methods: Eligibility criteria included histologically or cytologically confirmed stage IIIB or IV NSCLC, no previous chemotherapy, adequate organ function, and ECOG PS 0–2. Current use of steroid was not allowed. P(200 mg/m2) and C(AUC 6) was administered on day 1 every 3 weeks, and M (10mg/day) was administered orally once a day from day 0. Primary endpoint was response rate and secondary endpoint were toxicity profile and overall suvial. Results: From June 2003 to May 2004, 49 eligible patients(pts) were treated: gender M/F; 38/11, median age; 63yrs (43–74), stage IIIB/IV; 18/31, PS 0/1/2; 22/23/4, histology AD/SQ/LA;36/11/2, number of treatment cycles 1/2/3/4/5; 2/3/21/21/2. The overall response rate was 49% (24/49; 95%CI35 ∼ 63%) and 20 of 49 had stable disease. Median survival time and median progression free survival were 455 days and 152 days. Grade(G) 3/4 neutropenia, anemia, thrombocytopenia occurred in 42 pts (86%), 7pts (14%), 6pts (12%), respectively. Only 3 (6%) developed neutropenic fever. G2 peripheral neuropathy occurred in only 3 pts (6%). G2/3 skin rash, nausea/vomititng occurred in 7 pts(14%) 18pts(37%), respectively. Conclusions: M will enhance the reponse to P/C in patients with advanced NSCLC, and reduce the severity of P-induced neuropathy, without increasing problematic severe toxicities. No significant financial relationships to disclose.