Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,表阿霉素联奥沙利铂、卡培他滨,(EOX),一线治疗晚期胃癌的临床研究分析,南昌大学一附院肿瘤科,项晓军,背景,资料与方法,结果与讨论,结论,概要,Chemotheray,VS,BSC,Wagner AD,et al.J Clin Oncol 2006;24,combination,vs,single agent,Wagner AD,et al.J Clin Oncol 2006;24,Drug combinations,FAM FU,doxorubicin,mitomycins,FAMTX FU,doxorubicin,methotrexate(high dose),EAP etopside,doxorubicin,cisplatin,PELF epirubicin,cisplatin,leucovorin,FU(bolus),ECF epirubicin,cisplatin,FU(infusional),CF cisplatin,FU,IC irinotecan,FU,leucovorin,TC docetaxel,cisplatin,TCF docetaxel,cisplatin,FU,ECF(epirubicin,cisplatin,infusional 5-FU)is widely used particularly in Europe on the basis of the results of two randomized phase 3 trials and a recent meta-analysis,ECF,vs,FAMTX,Waters JS,et al,Br J Cancer 1999,Waters JS,et al,Br J Cancer 1999,ECF vs FAMTX,2.ECF vs MCF,Ross P,et al,J Clin Oncol,2002,3.ECF vs CF,(a meta-analysis),Wagner AD,et al.J Clin Oncol 2006;24,But the a drawback of ECF is the 5-FU infusion requires,a central venous indwelling catheter,which is associated with significant morbidity,particularly venous thrombosis and infections.,EOX vs ECF,oxaliplatin,cumulative sensory,neurotoxicity,capecitabine,orally,simplifies the administration,and preclude the complication possibility.,cisplatin,venous hydration,renal toxicity,、,ototoxicity and severe emesis,5-FU,needs a central venous catheter,associated with significant morbidity,particularly venous thrombosis and infections.,Sumpter,et al.,confirmed,:(EOX),epirubicin(50mg/m2,day1),oxaliplatin(130mg/m2,day1),capecitabine(500-625 mg/m2 bid.day 1-14),overall response rate:48%,grade 3/4 netropenia:40%,EOX regimen,Sumpter,et al.British Journal of Cancer 2005;92,基于以上结果，我们开展了一项,2,期临床研究，采用,EOX,方案，用于治疗晚期胃癌患者，观察其疗效及毒性。,背景,资料与方法,结果与讨论,结论,概要,患者入选标准,获得知情同意,年龄,18-70,岁,病理学或细胞学确诊为胃癌,为局部晚期或发生转移,距末次手术、放、化疗、生物治疗时间,4,周,ECOG,评分,2,分,预计生存期,3,个月,有一个以上可测量的肿瘤病灶,血常规、肝肾功能、心、肺功能正常,无其他恶性肿瘤病史,患者特点,对照组,(N),性别 男,35,女,21,年龄,54,（,30-68,）,病理诊断,低分化腺癌,40,中分化腺癌,5,印戒细胞癌,7,粘液腺癌,4,PS,评分,0,分,15,1,分,30,2,分,11,原发部位 胃,46,连接部,10,转移部位 淋巴结,27,肝脏,18,腹膜,14,其他部位,16,转移部位个数,0,或,1,38,2,18,给药方案,epirubicin50mg/,oxaliplatin 85mg/,capecitabine 625mg/,2h infusion,d1,bid,orally,d1-14,iv,d1,每,3,周重复,剂量调整,当中性粒细胞低于1500/mm3，血小板低于100 000/mm3,化疗延迟,最长至多2周。,出现4度粒细胞减少性发热，那么所有药物减量25%。,出现3-4度神经毒性，奥沙利铂减量25%。,卡培他滨：2度手足综合症第1次出现，剂量不调整；第2次出现，减量25%；第3次那么减量50%，第4次出现后不再使用。3度手足综合症第1次出现，减量25%；第2次出现，减量50%；第3次出现后不再使用。4度的腹泻，口腔炎，或恶心/呕吐，那么不再使用或减量50%。出现手足综合症者给予维生素B6.,评估指标,治疗前1周内完成肿瘤影像学检查,治疗过程监测血常规、尿常规、血生化、心电图,用药第2周期末就同一病灶使用同一检查方法复查,在首次评价CR、PR、SD之后4 周再次复查确认疗效,疗效评价依据WHO实体瘤疗效评价标准评定,不良反响按NCI 抗癌药物常见毒副反响分级标准,统计方法,TTP,为治疗开始至肿瘤进展时间。,OS,为治疗开始至死亡或末次随访时间。,TTP,和,OS,根据,KaplanMeier,方法分析。统计软件为,SPSS(version 10.0).(SPSS,Chicago,Illinois,USA).,背景,资料与方法,结果与讨论,结论,概要,从,2005,年,5,月,2007,年,5,月，入组,56,例晚期胃癌患者，一共接受,242,周期化疗，每名者至少接受,2,周期化疗，最多者达,8,周期，中位为,4,周期。所有患者均可评价疗效和毒性。,剂量强度：,epirubicin 97%,oxaliplatin 95%,capecitabine 93%,化疗周期与剂量强度,疗效及生存期,n,CR,PR,SD,PD,RR,TTP,MST,1-y SR,56,2(3.6),25(44.6),21(37.5),8(14.4),27(48.2),6.5m,10.6m,44%,TTP,OS,疗效讨论,:,1.Oxaliplatin,奥沙利铂是第三代铂类化疗药，其化学结构不同于顺铂。奥沙利铂在体内与,DNA,结合的速率较顺铂快,10,倍以上，结合牢固，有更强的细胞毒作用。与顺铂相比，奥沙利铂有更广谱的抗癌活性且无交叉耐药性,.,联合,5-FU,而组成的,FOLFOX,方案,已是晚期大肠癌治疗的首选方案。,Oxaliplatin,联合,5-FU,用于胃癌,Zaniboni A,et al.J Chemother,2005;17,Al-Batran S,et al.J Clin Oncol 2021;26,Oxaliplatin+LV/5-FU vs cisplatin+,LV/5-FU,FLO vs FLP,Al-Batran S,et al.J Clin Oncol 2021;26,TTF,PFS,OS,疗效讨论,:,2.capecitabine,Ajani,et al.Cancer,2006;107,Authors,Regimens,ORR,TTP,OS,Hoff PM,(650 pats),X vs bolus 5-FU/LV,24.8 vs 15.5%,（,p=0.005,）,4.3 vs 4.7m,(p=0.72),12.5 vs 13.3m,(p=0.974),Van Cutsem E,(602 pats),X vs bolus 5-FU/LV,18.9 vs 15.0%,5.2 vs 4.7m,(p=0.65),13.2 vs 12.1m,(p=0.33),Porschen R,(474 pats),X+O vs FUFOX,48 vs 54%,7.1 vs 8.0m,(0.117),16.8 vs 18.8m,(p=0.26),Daz-Rubio E,(348 pats),X+O vs FUFOX,37 vs 46%,(p=0.54),8.9 vs 9.5m,(0.153),18.1 vs 20.8m,(0.145),Cassidy J,(2034 pats),X+O vs FOLFOX,47 vs 48%,8.0 vs 8.5m,19.8 vs 19.6m,Capecitabine alone or in combination in advanced CRC,Capecitabine in combination in advanced GC,Authors,Regimens,ORR,TTP,OS,Kim TW,(42 pats,，,phase 2),XP,54.7%,6.3m,10.1m,Kang Y,(316 pats phase 3),XP vs FP,41 vs 29%,（,p=0.03,）,5.6 vs 5.0m,10.5 vs 9.3m,Kim TW,et al.Ann Oncol 2002;13,Kang Y,et al.JClin Oncol 2006;24,疗效讨论,:,3.EOX,方案的疗效,Sumpter K,et al.British Journal of Cancer 2005;92,REAL-2 trial,Cunningham D,et al.N Engl J Med 2021;358,Survival benefit with EOX vs ECF,11.2 vs 9.9 months;,p,=0.02,Cunningham D,et al.N Engl J Med 2021;358,Toxicity,Grade,1(%),Grade,2(%),Grade,3(%),Grade,4(%),Grade,3,4(%),Neutropenia,10(17.9),15(26.8),8(14.3),4(7.2),12(21.4),Febrile neutro-,0,0,2(3.6),2(3.6),4(7.2),Anemia,16(28.6),12(21.4),4(7.2),0,4(7.2),Throbocytopenia,7(14.3),3(5.4),2(3.6),0,2(3.6),nausea/vomiting,21(37.5),13(23.2),4(7.2),2(3.6),6(10.7),Diarrhea,13(23.2),9(16.1),5(8.9