Background We have developed a tridirectional regimen combining intraperitoneal,intravenous,and oral chemotherapy as a treatment for patients with advanced gastric cancer and individualized these chemotherapeutics acc...Background We have developed a tridirectional regimen combining intraperitoneal,intravenous,and oral chemotherapy as a treatment for patients with advanced gastric cancer and individualized these chemotherapeutics according to mRNA expression.This multicenter Phase Ⅲ umbrella study compared the efficacy and safety of individualized tridirectional intraperitoneal and systemic chemotherapy with that of standard systemic chemotherapy.Methods BRCA1/TOPO1 mRNA expression was examined in all enrolled patients.The patients were then randomized in a ratio of 3:1 to an individualized arm and a control arm.Patients in the control arm received systemic intravenous/oral chemotherapy,whereas those in the individualized arm received sensitive chemotherapeutics selected from oxaliplatin/cisplatin/docetaxel/irinotecan/S-1 according to their BRCA1/TOPO1 mRNA expression and received individualized tridirectional intraperitoneal/intravenous/oral chemotherapy.The primary endpoint was progressionfree survival and the secondary endpoints were response rate,overall survival,and safety.Results Overall,233 of 240 patients enrolled between August 2014 and December 2016 were included in the efficacy analysis.Baseline patient characteristics were balanced between the two arms.The objective response rate was 33.9%in the control arm and 49.1%in the individualized arm(P=0.039).In the control and individualized arms,median progression-free survival was 5.9 months and 8.0 months,respectively(hazard ratio 0.521,95%confidence interval 0.362-0.750,P=0.0005)and median overall survival was 13.5 months and 16.4 months,respectively(hazard ratio 0.684,95%confidence interval 0.474-0.988,P=0.0430).Both regimens were tolerable.Conclusion The primary analysis demonstrated the statistical superiority of this tridirectional individualized regimen and suggests that this regimen has clinical efficacy in patients with advanced gastric cancer.Trial registration Chinese Clinical Trial Registry(chictr.org.cn)Identifier:ChiCTR-IPR-15006201.展开更多
文摘目的:分析胃癌石蜡组织BRCA1、hENT1、Topo1 mRNA水平与新鲜胃癌组织多西紫杉醇、吉西他滨、伊立替康体外药物敏感性的关系。方法:收集36例经病理确诊的新鲜胃癌标本,采用三维微组织块培养法(HDRA)行三种药物的体外药物敏感试验。实时荧光定量PCR检测对应胃癌石蜡组织中BRCA1、hENT1、To-po1 mRNA水平。结果:新鲜胃癌组织对三种药物的敏感性均与临床特征无明显相关性。对应胃癌石蜡组织中BRCA1、hENT1、Topo1 mRNA水平与临床特征无明显相关性。在胃癌组织中,hENT1 mRNA水平最高,BRCA1 mRNA水平最低。胃癌石蜡组织BRCA1 mRNA水平与新鲜胃癌组织的多西紫杉醇敏感性正相关(7.927 vs 3.464,P=0.001);hENT1 mRNA水平在吉西他滨敏感组高于耐药组(15.710 vs 10.145,P=0.243),Topo1 mRNA水平在伊立替康敏感组高于耐药组(10.024 vs 6.038,P=0.124),但均未达统计学差异。结论:胃癌石蜡组织BRCA1mRNA水平与新鲜胃癌组织对多西紫杉醇的敏感性呈正相关。
基金funded by grants from the National Key Research and Development Program of China(grant numbers 2017YFC1308900 and SQ2018ZX090301)the National Natural Science Foundation of China(grant numbers 81370064 and 81672367).
文摘Background We have developed a tridirectional regimen combining intraperitoneal,intravenous,and oral chemotherapy as a treatment for patients with advanced gastric cancer and individualized these chemotherapeutics according to mRNA expression.This multicenter Phase Ⅲ umbrella study compared the efficacy and safety of individualized tridirectional intraperitoneal and systemic chemotherapy with that of standard systemic chemotherapy.Methods BRCA1/TOPO1 mRNA expression was examined in all enrolled patients.The patients were then randomized in a ratio of 3:1 to an individualized arm and a control arm.Patients in the control arm received systemic intravenous/oral chemotherapy,whereas those in the individualized arm received sensitive chemotherapeutics selected from oxaliplatin/cisplatin/docetaxel/irinotecan/S-1 according to their BRCA1/TOPO1 mRNA expression and received individualized tridirectional intraperitoneal/intravenous/oral chemotherapy.The primary endpoint was progressionfree survival and the secondary endpoints were response rate,overall survival,and safety.Results Overall,233 of 240 patients enrolled between August 2014 and December 2016 were included in the efficacy analysis.Baseline patient characteristics were balanced between the two arms.The objective response rate was 33.9%in the control arm and 49.1%in the individualized arm(P=0.039).In the control and individualized arms,median progression-free survival was 5.9 months and 8.0 months,respectively(hazard ratio 0.521,95%confidence interval 0.362-0.750,P=0.0005)and median overall survival was 13.5 months and 16.4 months,respectively(hazard ratio 0.684,95%confidence interval 0.474-0.988,P=0.0430).Both regimens were tolerable.Conclusion The primary analysis demonstrated the statistical superiority of this tridirectional individualized regimen and suggests that this regimen has clinical efficacy in patients with advanced gastric cancer.Trial registration Chinese Clinical Trial Registry(chictr.org.cn)Identifier:ChiCTR-IPR-15006201.
