Gefitinib plus celecoxib in chemotherapy-naïve patients with stage IIIB/IV non-small cell lung cancer: A phase II study from the hoosier oncology group

BACKGROUND: Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) pathway, has single agent activity in non-small cell lung cancer (NSCLC). Preclinical studies demonstrate significant interactions between the EGFR and cyclooxygenase 2 (COX-2) pathways and that simultaneous inhibition may have benefits over EGFR inhibitors alone. METHODS: Eligibility criteria: chemotherapy-naive, stage IIIb (with pleural effusion) or IV NSCLC, Eastern Cooperative Oncology Group Performance Status (PS) 0-1. Patients were treated with gefitinib 250 mg po daily plus celecoxib 400 mg po every 12 hours. Cycles consisted of 21-day treatment and continued until unacceptable toxicity or progression of disease. The primary objective was to evaluate the overall response rate; secondary objectives included estimation of progression free survival, overall survival, and to assess the toxicity of this regimen. RESULTS: From January 2004 to November 2004, 31 patients were enrolled: male/female 13/18; median age 70 years (range, 19-93); 68% had adenocarcinoma; Eastern Cooperative Oncology Group PS 0/1 13/18; stage IIIb/IV 2/29. Two patients died of interstitial lung disease due to treatment. There were three additional deaths during treatment that were not considered treatment related. Two additional patients discontinued treatment due to adverse events (elevated liver enzymes). Select grade 3/4 toxicities included: pneumonitis (3%), hepatic (7%), diarrhea (7%), and skin (3%). Response rate was 16% (95% CI, 5-34%), median progression free survival and overall survival were 3.2 (95% CI, 2.7-5.7 months) and 7.0 months (95% CI, 3.7-14.2 months), respectively. All responders were females with adenocarcinoma, two were remote or never smokers and three were former smokers. CONCLUSION: Gefitinib plus celecoxib in an unselected population of chemotherapy naive patients with advanced NSCLC and a PS of 0-1 has a lower response rate and overall efficacy compared with historical controls of combination chemotherapy.