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Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 16003
© 2008 American Society of Clinical Oncology
Phase II trial of meloxicam, a COX-2 inhibitor, and interferon alfa in patients with metastatic renal cell carcinoma
N. Shinohara,
T. Abe,
A. Sazawa,
K. Nonomura and
Hokkaido Immunotherapy Research Group
Hokkaido University Graduate School of Medicine, Sapporo, Japan
16003
Background: Cyclooxygenase (COX)-2 plays a major role in the development of cancer through numerous mechanisms. We have previously confirmed that COX-2 has an important role in tumorigenesis and angiogenesis of renal cell carcinoma (RCC) (Int J Cancer 2004). Some preclinical studies suggest that a selective COX-2 inhibitor may augment the antitumor effects of immunotherapeutic agents. In view of potential additive or synergistic effects of COX-2 inhibitor and interferon (IFN)-alfa, we conducted a phase II trial to characterize the efficacy and toxicity of the combination of meloxicam, an oral COX-2 inhibitor, and IFN-alfa 2a for the treatment of patients with metastatic RCC. Methods: Eligible patients had metastatic RCC, no prior systemic therapy, performance status 0–2, measurable disease. Patients received IFN 3–5MIU 3x/week and meloxicam 10mg orally once daily continuously. Primary end point was RECIST response rate. Secondary endpoints were time to progression, overall survival and toxicity. Results: Patients characteristics of 43 patients entered included: median age 63 years (44–78), male/female: 34/9, PS 0/1/2: 26/12/5, prior nephrectomy: 32 (74%). Evaluable lesions were lung only in 19 patients and others in 24. MSKCC prognostic categories were good/intermediate/poor: 11(26%)/22 (51%)/10 (23%). A median follow-up was 14 months (range 3–41+). Based on the RECIST criteria, complete response (CR) was observed in 3 patients (7%) and partial response (PR) in 10 (23%), yielding an overall response rate of 30%. An additional 17 patients (40%) had stable disease. Response rates were 7 of 33 patients (21%) in good- or intermediate-risk group and 6 of 10 (60%) in poor-risk group. Median time to progression for 43 patients was 13.7 months (1–41+). Overall survival at 2 years was 71.7%. Fatigue, depression, anorexia were the most common toxicities. Grade 3 toxicities were uncommon but included liver dysfunction, duodenal ulcer, arthralgia and fatigue. Conclusions: In patients with metastatic RCC, the combination of meloxicam and IFN-alfa has enhanced antitumor activity in comparison with IFN alone reported previously, and displays an acceptable safety profile. Further investigation with this combination is warranted.
No significant financial relationships to disclose.
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