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Oral Diseases (2010) 16, 445–452 Objective: To investigate the therapeutic effect of herpes simplex virus thymidine kinase (HSV-TK) gene mediated by synthetic radiation-inducible promoters in the treatment of oral squamous cell carcinoma (OSCC) in vitro and in vivo. Methods: The plasmids pcDNA3.1(+)E6-HSV-TK were constructed, in which the HSV-TK genes were mediated by synthetic radiation-inducible promoters. The recombined plasmids were transfected into the Tca8113 cells and golden hamster buccal carcinoma, respectively. Low-dose radiotherapy was used to upregulate the HSV-TK genes expression. HSV-TK mRNA was assayed by RT-PCR. Apoptosis and proliferating cell nuclear antigen were detected respectively by in situ end-labeling and immunohistochemical method. Results: Compared with control group, the comparative survival rate of Tca8113 cells in HSV-TK/GCV/IR group was markedly decreased and the golden hamster buccal carcinoma in HSV-TK/GCV/IR group was obviously suppressed. Up-regulation of HSV-TK gene expression was found in the Tca8113 cells and in the golden hamster buccal carcinoma resulting from exposure to low-dose irradiation. The apoptosis indexes in Tca8113 cells or golden hamster buccal carcinoma with irradiation were markedly higher than those without irradiation. At the same time, the proliferation indexes in Tca8113 cells or golden hamster buccal carcinoma with irradiation were markedly lower than those without irradiation. Conclusion: The results indicate that the synthetic radiation-inducible promoters can serve as a molecular switch to adjust the expression of HSV-TK gene in the treatment of OSCC, and low-dose induction radiation can significantly improve therapeutic efficiency. [ABSTRACT FROM AUTHOR]

Background: Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second-or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. Patients and methods: Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety. Results: Between January 2013 and August 2014, 296 patients were randomized and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P=0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%) and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P<0.001) and treatment-related AEs (54.1% versus 90.5%; P<0.001) were significantly fewer in the icotinib group than in the chemotherapy group. Conclusions: First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population. [ABSTRACT FROM AUTHOR]

Background: The OPTIMAL study was the first study to compare efficacy and tolerability of the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) erlotinib, versus standard chemotherapy in first-line treatment of patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). Findings from final overall survival (OS) analysis and assessment of post-study treatment impact are presented. Patients and methods: Of 165 randomised patients, 82 received erlotinib and 72 gemcitabine plus carboplatin. Final OS analyses were conducted when 70% of deaths had occurred in the intent-to-treat population. Subgroup OS was analysed by Cox proportional hazards model and included randomisation stratification factors and post-study treatments. Results: Median OS was similar between the erlotinib (22.8 months) and chemotherapy (27.2 months) arms with no significant between-group differences in the overall population [hazard ratio (HR), 1.19; 95% confidence interval (CI) 0.83- 1.71; P = 0.2663], the exon 19 deletion subpopulation (HR, 1.52; 95% CI 0.91-2.52; P = 0.1037) or the exon 21 L858 mutation subpopulation (HR, 0.92; 95% CI 0.55-1.54; P = 0.7392). More patients in the erlotinib arm versus the chemotherapy arm did not receive any post-study treatment (36.6% versus 22.2%). Patients who received sequential combination of EGFR-TKI and chemotherapy had significantly improved OS compared with those who received EGFR-TKI or chemotherapy only (29.7 versus 20.7 or 11.2 months, respectively; P < 0.0001). OS was significantly shorter in patients who did not receive post-study treatments compared with those who received subsequent treatments in both arms. Conclusion: The significant OS benefit observed in patients treated with EGFR-TKI emphasises its contribution to improving survival of EGFR mutant NSCLC patients, suggesting that erlotinib should be considered standard first-line treatment of EGFR mutant patients and EGFR-TKI treatment following first-line therapy also brings significant benefits to those patients. [ABSTRACT FROM AUTHOR]