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Background and Objective: Epidermal growth factor receptor (EGFR)-activating mutation predicts excellent response to EGFR tyrosine kinase inhibitors (TKIs). However, lung cancer patients are often with unknown EGFR mutation status because there are little tumor specimen to determine. TKIs induce tumor cell apoptosis which associates with several apoptosis-related genes. To explore the association between GNAS1 T393C polymorphism and therapeutic efficacy of TKI in pretreated advanced non-small cell lung cancer (NCSLC) with unknown EGFR mutation status., Methods: A total of 116 patients were recruited for the study from Zhejiang Cancer Hospital, all of whom were treated with gefitinib or erlotinib after failure to prior chemotherapy. We detected the genotype of peripheral blood lymphocytes of patients with GNAS1 T393C polymorphism through polymerase chain reaction (PCR). Statistical analysis was performed by SPSS version 18.0., Results: The overall response rate was 29.3%. No significant associations were found among GNAS1 T393C polymorphism and the objective response rate. The disease control rate of patients with GNAS1 T393C CC genotype was lower than that of patients with variant genotype (TT or CT) (46.2% vs 73.8%, P=0.039). Univariate analysis identified gender, smoking history, histology and GNAS1 T393C polymorphism as predictive marker of PFS (P=0.04, P<0.001, P<0.001 and P=0.005). Multivariate analysis of factors, including smoking history, performance status score, histology, GNAS1 T393C polymorphism demonstrated that GNAS1 T393C polymorphism was correlated independently with PFS (P=0.007)., Conclusions: Our data suggest the role of GNAS1 T393C CC genotype as a poor predictive marker both of DCR and PFS in advanced NSCLC patients treated with tyrosine kinase inhibitor.

Background and Objective: BIM gene is a member of the BCL-2 family, is involved in cell death. The aim of this study is to explore the relationship between BIM gene polymorphism and therapeutic efficacy in the retreatment advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitor (EGFR-TKI)., Methods: In the study, there were 123 patients who were diagnosed with advanced NSCLC in Zhejiang Province Cancer Hospital between January 2009 to October 2012, all of who were received gefitinib and erlotinib therapy after failure to chemotherapy. We detected the genotype of peripheral blood leukocytes of patients with BIM gene polymorphism though polymerase chain reaction (PCR). Statistical analysis was performed by SPSS version 13.0., Results: On the disease control rates, BIM gene with no polymorphism type was slightly better trend than polymorphism types in disease control rate DCR (75.5% vs 57.1%, χ²=2.931, P=0.087). Univariate analysis the median PFS, women were longer than men (6.9 months vs 4.5 months, χ² =7.077, P=0.008). Non-smokers were longer than smokers (8.0 months vs 2.5 months, χ² =15.277, P<0.001). Adenocarcinoma were longer than others pathological type (7.0 months vs 2.0 months, χ² =14.978, P<0.001). The median PFS in BIM gene with no polymorphism type were longer than with polymorphism type (6.0 months vs 3.5 months, χ²=7.035, P=0.008). Multi-factor analysis showed that smoking, pathological type, the BIM gene polymorphism were the independent prognostic factors for PFS., Conclusions: The patients with the BIM gene no polymorphism have longer the median progression-free time than the polymorphism types in retreatment advanced non-small cell lung cancer patients with tyrosine kinase inhibitor.

Background and Objective: As the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in China, icotinib shows promising anticancer activity in vitro and vivo. The phase III clinical study (ICOGEN) showed that icotinib has a good efficacy and tolerability in Chinese patients with advanced non-small cell lung cancer (NSCLC) compared with gefitinib. This retrospective study aims to evaluate the efficacy and tolerability of icotinib monotherapy for advanced NSCLC patients with EGFR mutation and wild-type patients in our hospital., Methods: Patients with advanced NSCLC who were treated with icotinib in Zhejiang Cancer Hospital were retrospectively analyzed from August, 2011 to August, 2012. Survival was estimated using Kaplan-Meier analysis and Log-rank tests., Results: The clinical data of 49 patients (13 with wild-type and 36 with EGFR mutation) with NSCLC were enrolled in the current study. The patients' overall objective response rate (ORR) was 58.3% and the disease control rate (DCR) in 36 EGFR mutation patients was 88.9%. The ORR was 7.7% and DCR was 53.8% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 9.5 months and 2.2 months in wild-type patients (P<0.001). Nineteen patients with EGFR mutation received icotinib as first-line and 17 in further-line treatment. The PFS was 9.5 months in the first-line and 8.5 months for second-line or further-line patients (P=0.41). Median overall survival (OS) in EGFR mutation patients was not reached, but was 12.6 months in wild-type patients. Most of the drug-related adverse events were mild (grade I or II) and reversible with no grade IV toxicity., Conclusions: Icotinib monotherapy showed significant antitumor activity in advanced NSCLC EGFR mutation patients. The toxicity was well tolerated and acceptable.

Background and Objective: The appearance of highly effective and low toxic drugs enables an increasing number of advanced non-small cell lung cancer (NSCLC) patients to receive third-line therapy. No other standard choice for third-line therapy aside from erlotinib is possible. This study respectively explores the efficacy and safety of single chemotherapy, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and doublet chemotherapy in advanced NSCLC third-line treatment., Methods: This study included 115 NSCLC patients in the stage IIIb or IV who were retrospectively reviewed to investigate the differences of survival time between different treatments. Univariate and multivariate analyses were conducted based on the Kaplan-Meier method and Cox proportional-hazards model., Results: The median progression free survival (PFS) values in the single agent, EGFR-TKIs and doublet groups were 2.30, 3.17 and 2.37 months, respectively (P=0.045). The median overall survival from the initiation of the third-line treatment were 8.00, 10.40 and 7.87 months in the three groups (P=0.110). The rates of stage III-IV toxicities were 33.3%, 18.2% and 68.8% (P<0.001), respectively. After the third-line treatment, the PFS was significantly increased in patients with a performance status (PS) of 0 to 1 (P<0.001), and the survival time was prolonged in patients who never smoke (P=0.011), have good PS (P<0.001), and have disease control after both first- and second-line treatments (P=0.044) using multivariate analysis., Conclusion: Advanced NSCLC patients who never smoke, have good PS scores, and have good disease control from the first- and second-line therapies could benefit more in third-line treatment. EGFR-TKIs therapy showed increased PFS compared with single and doublet agents.