| Objective: To evaluated the efficacy and safety of Gefitinib in advanced non-small cell lung cancer (NSCLC) in China, and to explore the predictive model in efficacy and prognostic factors of Gefitinib.Methods: From 2002.7 to 2006.12, 262 consecutive patients with advanced NSCLC, who received oral gefitinib 250 mg/day, were reviewed. Expressions of EGFR, Her-2, phosphorylated (p)-Akt and ERCC1 were determined via immunohistochemistry in 70 cases,. EGFR mutation was analyzed by DNA sequencing of exons 18, 19, 20, and 21 in the EGFR tyrosine kinase domain in 55 cases. Efficacy and overall survival were analyzed by SPSS 11.0 software.Results: Gefitinib was well tolerant, with rash and diarrhea as commonly adverse events. The response rate and disease control rate of Gefitinib in advanced NSCLC were 30.1% and 78.6 %. The median progress free survival (PFS) and median overall survival (MS) of all patients were 6.0 and 16.0 months, while one, two and three-year survival were 60.8%,35.6% and 18.3 % respectively. Patients who were less than 65-year-old, adenocarcinoma, never smoker and EGFR mutated showed better response than the opposite population. As second-line treatment, the response rate of gefitinib was significant higher than that of Docetaxel (28.0% vs. 12.2%, p=0.019 ) Moreover, gefitinib ahead (Group A) appeared to have longer TTP than Docetaxol ahead (Group B ) (5.0 vs. 3.0 months, p=0.038), though there was no significant survival difference between two groups. Twenty-four patients (47.3%) harbored EGFR mutations. These mutations include deletions in exon 19 in twelve patients, L858R in eight patients, G719C accompany with S768I in one patient, and three novel mutations(V742I, P741T, T847A) in each patient. Response rate in patients with EGFR mutation was 50.0% (12/24), in contrast to 16.1% (5/31) in patients without mutation (P=0.014). Moreover, these 24 patients with EGFR mutation had significantly prolonged TTP (8.0 vs. 4.0months; P=0.023) compared with the remaining 31 patients without mutation. However, no significant correlation was detected between gefitinib sensitivety/EGFR mutation and expressions of EGFR, Her-2/neu, p-Akt and ERCC1. No survival benefit was seen in patients with mutation. However EGFR overexpression was associated with prolonged TTP in patients with EGFR mutation. Cut-off value was 2 in the predictive model of gefitinib sensitivity which was based on age, histology, smoke statue and mutation,. The response rate in patients with 2 more scores was much higher than in that of less than 2 (34.2% vs. 9.3%, p=0.001). Histology, performance statue and response to Gefitinib were independent prognostic factors in cox proportional regression analysis, though smoke statue could also impact overall survival in mono-variate analysis.Conclusion: (1) Gefitinib was active and safe in advanced NSCLC in China; (2) Gefitinib had superior efficacy compare to Docetaxel in second-line treatment for NSCLC; Prolonged TTP was discovered when Gefitinib treatment prior to Docetaxol; (3) In addition to its predictive role, EGFR mutation confers significant longer TTP on NSCLC patients treated with gefitinib; (4) The established predictive model, which was basesd on age, histology, smoke statue and EGFR mutation, is valuable for selecting appropriated population to receive gefitinib treatment; further prospective randomized study must be conducted to confirm its practice value. (5)Histology, PS and response to gefitinib were prognostic factors in advanced NSCLC.
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