RandyW Posted June 4, 2006 Share Posted June 4, 2006 Celecoxib May Increase Benefit of Erlotinib for Lung Cancer NEW YORK JUN 01, 2006 (Reuters Health) - The addition of celecoxib (Celebrex) to treatment with erlotinib (Tarceva) for advanced non-small cell lung cancer (NSCLC) appears to be safe, and to increase the proportion of patients who respond to erlotinib, results of a phase I trial suggest. Previous research has demonstrated that the cyclooxygenase 2 (COX-2) and epidermal growth factor receptor tyrosine kinase (EGFR-TK) are overexpressed in some cancers, including NSCLC. Erlotinib is a highly specific EGFR-TK inhibitor, and celecoxib is a COX-2 inhibitor, Dr. Karen L. Reckamp and her colleagues note in their report, published in the June 1st issue of Clinical Cancer Research. Only about 10% of patients with NSCLC respond to erlotinib, the researchers point out, and COX-2 expression promotes resistance to erlotinib. The investigators theorized that inhibiting both pathways would inhibit tumor angiogenesis, invasion, and growth. To investigate these interactions, Dr. Reckamp, from the David Geffen School of Medicine at UCLA in Los Angeles, and her associates conducted a dose-escalation trial involving 21 patients with stage IIIB or IV NSCLC. The patients took oral erlotinib 150 mg for two 4-week cycles. Then, in groups of three, patients were consecutively treated with doses of celecoxib escalating from 200 mg twice daily to 800 mg twice daily. Dose escalation was considered when all three subjects in a given group did not experience any dose-limiting toxicity after 28 days of treatment. The optimal biological dose (OBD) was defined as the lowest dose level showing optimal biological activity -- maximal decrease in urinary levels of PGE-M (the major urinary metabolite of prostaglandin E2) with no dose-limiting toxicity. Patients were treated until their disease progressed or unacceptable toxicity occurred. After 12 months, the celecoxib was stopped, but treatment with erlotinib was continued. The combination did not cause any additional toxicity, the investigators report, of which the most common were rash and diarrhea. The OBD was 600 mg twice daily. Dr. Reckamp's team observed that seven patients experienced partial response and five maintained stable disease (disease control rate of 57%). According to a UCLA press release, the longest duration of response so far is 93 weeks, which Dr. Reckamp said is about three to four times longer than the average duration of response for patients with advanced NSCLC. At the time of analysis, the authors note, eight patients had died secondary to progressive disease. Based on these findings, the investigators are planning a phase II trial of celecoxib 600 mg twice daily plus erlotinib versus erlotinib plus placebo for treatment of advanced NSCLC. SOURCE: Clin Cancer Res 2006;12. Quote Link to comment Share on other sites More sharing options...
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