BACKGROUND:Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has demonstrated a response rate of 9%-18% in relapsed non-small cell lung cancer (NSCLC) patients. The probability of response to gefitinib was not influenced by response to previous chemotherapy. Preclinical studies have suggested that celecoxib, a cyclooxygenase-2 inhibitor, has antitumor activity in NSCLC and can enhance the activity of EGFR inhibitors. We conducted a phase II study evaluating the combination of gefitinib and celecoxib in platinum-refractory NSCLC patients, defined as patients whose disease had progressed on platinum-based chemotherapy or within 3 months of completing such therapy. METHODS:Platinum-refractory NSCLC patients with performance status of 0-2 and adequate organ function were included. Patients should not have been on a NSAID for 30 continuous days before study enrollment. Patients were treated with gefitinib 250 mg daily and celecoxib 400 mg twice daily. Disease assessment was performed every 8 weeks. RESULTS:Twenty-seven patients were enrolled. The response rate was 7% (2/27). The median time to progression was 2.2 months, and the median survival was 4.6 months. One female, nonsmoking patient is progression free more than 3 years after study enrollment. The drug combination was well tolerated, with the most common adverse effects being skin rash and diarrhea. CONCLUSION:In unselected platinum-refractory NSCLC patients, the response rate to the combination of celecoxib and gefitinib was similar to that observed with gefitinib alone.