Abstract: Objective  To explore the clinical effect of S-1 combined with gefitinib in the treatment of advanced non-small cell lung cancer (NSCLC) with acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI). MethodsA total of 74 patients with advanced NSCLC were selected as the study subjects from January 2016 to August 2017 in Qian′an People′s Hospital of Hebei Province. The patients were divided into control group (n=37) and experimental group (n=37) by random number table method. The control group was given sequential gefitinib with pemetrexed, and the experimental group was given S-1 combined with gefitinib. The clinical efficacy and adverse reactions of the two groups were compared. Results  The effective rates of the control group and the experimental group were 21.62% (8/37) and 27.03% (10/37) respectively, and the difference was not statistically significant (χ²=0.294, P=0.588). The disease control rates were 75.68% (28/37) and 78.38% (29/37) respectively, and the difference was not statistically significant (χ²=0.076, P=0.782). The median progression-free survival of the control group and the experimental group were 8.4 months and 8.2 months, and the median overall survival were 9.8 months and 10.5 months respectively, and the differences were not statistically significant (χ2=0.186, P=0.666; χ2=0.608, P=0.436). The occurrence rate of diarrhea was 56.76% (21/37) in the control group and 62.16% (23/37) in the experimental group, with no significant difference (χ²=0.224，P=0.636). The occurrence rates of rash in the control group and the experimental group were 62.16% (23/37) and 13.51% (5/37), the occurrence rates of leukopenia were 35.14% (13/37) and 5.41% (2/37), the occurrence rates of thrombocytopenia were 27.03% (10/37) and 2.70% (1/37), the occurrence rates of anemia were 40.54% (15/37) and 10.81% (4/37), and the occurrence rates of liver damage were 18.92% (7/37) and 0 (0/37). The occurrence rates of the above adverse reactions in the experimental group were significantly lower than those in the control group, and the differences were statistically significant (χ²=18.615, P＜0.001; χ²=10.118, P=0.001; χ²=8.650, P=0.003; χ²=8.568, P=0.003; χ²=5.680, P=0.017). There were no grade Ⅲ-Ⅳ adverse reactions in the two groups. ConclusionThe combination of S-1 and gefitinib is effective in the treatment of advanced NSCLC with acquired resistance to EGFR-TKI  and well tolerated, with mild adverse reactions, and oral administration is easy for patients to accept. It is an ideal way for clinical treatment of advanced NSCLC with EGFR-TKI acquired resistance.

Key words: Carcinoma, non-small-cell lung, Pemetrexed, Epidermal growth factor receptor-tyrosine kinase inhibitor, Acquired drug resistance, S-1