胃癌内科治疗-课件

,ppt课件,*,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,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,*,胃癌内科治疗,1,ppt课件,胃癌内科治疗1ppt课件,内科治疗的几个问题,晚期胃癌的最佳化疗方案,；,化疗获益后如何安排后续治疗；,Alimita,B,ortezomib,Cetuximab,和,bevacizumab,的定位,；,2,ppt课件,内科治疗的几个问题晚期胃癌的最佳化疗方案；2ppt课件,哪个方案更好 ？,90,年代的,III,期临床试验结果,3,ppt课件,哪个方案更好 ？3ppt课件,化疗相对敏感；,临床疗效一般，主要起姑息作用，但比,BSC,好；,ECF、FAMTX、EAP,方案的,PR 30-50%; CR,罕见,缓解期短，,OS 6-10,个月，毒性大；,没有标准方案：,5-FU/ PDD,为基础的方案 如：,ECF、5FU/LV/PDD,或,5FU/ PDD,为“,参 考,” 方案。,90年代的化疗状况,4,ppt课件,化疗相对敏感；90年代的化疗状况4ppt课件,Agent No RR(%) 95% CI,Paclitaxel 212 24 20-28%,Docetaxel 157 22 18-26%,Irinotecan 135 17 12-24%,Capecitabine 69 29 20-38%,S1 94 44 34-54%,单药一线治疗,5,ppt课件,Agent No RR(%,Response rate as per independent review (eligible population & WHO criteria),Gastric Cancer Study,6,ppt课件,Response rate as per independe,months,0,10,20,30,40,50,60,70,80,90,100,0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,%,LV5FU2 (n=45) 3.2 mo.,95% CI (1.8-4.6),LV5FU2-P (n=44) 4.9 mo.,95% CI (3.5-6.3),LV5FU2-I (n=45) 6.9 mo.,95% CI (5.5-9.3),Progression-free survival,Gastric Cancer Study,7,ppt课件,months010203040506070809010001,0,10,20,30,40,50,60,70,80,90,100,0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,months,%,LV5FU2 (n=45) 6.8 mo.,95% CI (2.6-11.1),LV5FU2-P (n=44) 9.5 mo.,95% CI (6.9-12.2),LV5FU2-I (n=45) 11.3 mo.,95% CI (9.3-13.3),Overall survival,Gastric Cancer Study,8,ppt课件,010203040506070809010001234567,Capecitabine and Cisplatin for AGC,Capecitabine 1250 mg/m,2,po bid Day 1-14 Cisplatin 60 mg/m,2,iv Day 1,q 3 weeks,No. of patients 42Response 55 % Time to progression 6.3 mMedian survival time 10.1 m,Asian Medical Center Trial, Korea,9,ppt课件,Capecitabine and Cisplatin for,Paclitaxel 80 mg/m,2,iv (1h) weekly x 6 Cisplatin 50 mg/m,2,iv Day 8, 29 5-FU 2000 mg/m,2,iv (civ) weekly x 6 Lv 500 mg/m,2,iv (2h) weekly x 6,q 7 weeks,No. of patients 29 Response 48 % (4CR) Time to progression 8 m Median survival time 11 m,Paclitaxel, CIFU and Cisplatin (TCF),Honecker, Anticancer Drug 2002,10,ppt课件,Paclitaxel 80 mg/,14.3%,Not Evaluable,DCFn=111,CFn=112,CR,2.7%,2.7%,PR,36.0%,20.5%,Overall RR (CR+PR),38.7%,23.2%,95%,CI,29.6 - 48.5,15.8 - 32.1,P-value Chi Square,p=0.012,NC/SD,30.6%,34.8%,PD,17.1%,27.7%,13.5%,Response Rate V 325 Phase III Interim Analysis,Responses confirmed by External Response Review,11,ppt课件,14.3%Not EvaluableDCFn=111,p-value = .0008,RR = 1.704,Probability,21,20,19,18,17,16,15,14,13,12,11,10,9,8,7,6,5,4,3,2,1,0,1.0,0.9,0.8,0.7,0.6,0.5,0.4,0.3,0.2,0.1,0.0,Duration (Months),1.0,0.9,0.8,0.7,0.6,0.5,0.4,0.3,0.2,0.1,0.0,21,20,19,18,17,16,15,14,13,12,11,10,9,8,7,6,5,4,3,2,1,0,Duration (Months),29,28,27,26,25,24,23,22,30,Results: V 325 Phase III,DCF,CF,DCF,CF,Time to Progression,Overall Survival,12,ppt课件,Probability2120191817161514131,Study Regimen No RR (%) TTP MST,French FOLFOX6 53 44.9 6.2 m 8.6 m,UK EOF, EOX 43 38 - -,Oxaliplatin for AGC,13,ppt课件,Study Regimen No,REAL-2,: Capecitabine vs 5-FU,Oxaliplatin vs Cisplatin,14,ppt课件,REAL-2 : Capecitabine vs 5-FU,REAL-2: overall survival for ECFand EOX (ITT),0,1,3,0,20,40,60,80,100,2,ECF,EOX,Probability (%),Time (years),Cunningham D, et al. ASCO 2006 (Abstract LBA4017).,15,ppt课件,REAL-2: overall survival for E,Conclusions,The REAL-2 study shows that,Oxaliplatin-containing triplets have a favourablesafety profile compared with cisplatin-containing triplets,Capecitabine is not inferior to PVI 5-FU,Oxaliplatin is not inferior to cisplatin,EOX is associated with improved efficacy vs reference ECF,16,ppt课件,ConclusionsThe REAL-2 study sh,EOX,方案疗效优于,ECF,方案；,紫杉类、,CPT-11,为基础方案疗效确切。,小 结,17,ppt课件,EOX方案疗效优于ECF方案；17ppt课件,内科治疗的几个问题,晚期胃癌的最佳化疗方案,；,化疗获益后如何安排后续治疗；,Alimita,B,ortezomib,Cetuximab,和,bevacizumab,的定位,；,18,ppt课件,内科治疗的几个问题晚期胃癌的最佳化疗方案；18ppt课件,Stop,and,Go,concept - OPTIMOX1,Tournigand et al, JCO 2006,6,x,FOLFOX7,- 12x sLV5FU2 - 6x,FOLFOX7,FOLFOX4,620,pts,R,Cum. Oxali,780,1560,(%),FOLFOX4,FOLFOX7,RR58.558.3,PFS9.08.7,DDC9.010.6,OS19.321.2,G3/4 NTox17.913.3,Primary endpoint,19,ppt课件,Stop and Go concept - OPTIMOX1,RANDOMI,ZAT,ION,maintenance therapy,vs chemotherapy-free interval,mFOLFOX7 x 6 cy,sLV5FU2,until baseline progression,mFOLFOX7 reintroduction,mFOLFOX7 x 6 cy,No maintenance,until baseline progression,mFOLFOX7 reintroduction,OPTIMOX,2,Study design,A,B,OPTIMOX2 : chemotherapy-free interval (CFI),OPTIMOX1 : maintenance therapy,Maindrault-Goebel et al., ASCO 2006,20,ppt课件,RANDOMImaintenance therapy vs,OPTIMOX Studies,OPTIMOX-1,FOLFOX 4 until TF,FOLFOX 7,FOLFOX 7,sLV5FU2,OPTIMOX-2,mFOLFOX 7,mFOLFOX 7,sLV5FU2,mFOLFOX 7,mFOLFOX 7,CFI,21,ppt课件,OPTIMOX StudiesOPTIMOX-1FOLFOX,0,1,0,2,0,3,0,4,0,5,0,6,0,7,0,8,0,9,0,1,0,0,0,.,0,0,0,.,2,5,0,.,5,0,0,.,7,5,1,.,0,0,o,p,t,i,m,o,x,1,m,e,d,i,a,n,3,8,w,e,e,k,s,o,p,t,i,m,o,x,2,m,e,d,i,a,n,3,0,w,e,e,k,s,w,e,e,k,s,p,r,o,b,a,b,i,l,i,t,y,p,=,.,0,0,9,Progression-free Survival,8.7 months,6.9 months,Maindrault-Goebel et al., ASCO 2006,22,ppt课件,01020304050607080901000.000.25,0,1,0,2,0,3,0,4,0,5,0,6,0,7,0,8,0,9,0,1,0,0,0,.,0,0,0,.,2,5,0,.,5,0,0,.,7,5,1,.,0,0,o,p,t,i,m,o,x,1,m,e,d,i,a,n,5,6,w,e,e,k,s,o,p,t,i,m,o,x,2,m,e,d,i,a,n,5,1,w,e,e,k,s,w,e,e,k,s,p,r,o,b,a,b,i,l,i,t,y,p,=,.,4,1,Duration of Disease Control,12.9 months,11.7 months,Maindrault-Goebel et al., ASCO 2006,23,ppt课件,01020304050607080901000.000.25,24,ppt课件,24ppt课件,胃癌的联合化疗间隙期是,maintenance,or,Stop,and,Go,?,小 结,25,ppt课件,胃癌的联合化疗间隙期是 maintenance25ppt课,内科治疗的几个问题,晚期胃癌的最佳化疗方案,；,化疗获益后如何安排后续治疗；,Alimita,B,ortezomib,Cetuximab,和,bevacizumab,的定位,；,26,ppt课件,内科治疗的几个问题晚期胃癌的最佳化疗方案；26ppt课件,培美曲塞（,Alimita,）联合顺铂治疗晚期胃癌的多中心,II,期临床研究,27,ppt课件,培美曲塞（Alimita）联合顺铂治疗晚期胃癌的多中心II,常见,3/4,度毒副反应,培美曲塞（,Alimita,）联合顺铂治疗晚期胃癌的多中心,II,期临床研究,28,ppt课件,常见3/4度毒副反应培美曲塞（Alimita）联合顺铂治疗,结 论,培美曲塞（,Alimita,）联合顺铂治疗晚期胃癌的多中心,II,期临床研究,使用以上剂量、方法的,Alimita,联合顺铂方案治疗晚期胃癌，安全，疗效尚可，将进一步研究使用不同剂量、方法用药方案的结果。,29,ppt课件,结 论培美曲塞（Alimita）联合顺铂治疗晚期胃癌的多,Alimita,联合奥沙利铂治疗晚期胃癌的多中心,II,期临床研究,入组患者,：无法手术切除、有可测量病灶,的,IV,期胃癌患者。,用药方法,：,Alimita 500mg/m,2,d,1,L-OHP 120mg/m,2,d,1,21d,同时给予维生素和地塞米松,结 果,：,2004.5-2005.01,，,13,例患者入组。,30,ppt课件,Alimita联合奥沙利铂治疗晚期胃癌的多中心II期临床研,Alimita,联合奥沙利铂治疗晚期胃癌的多中心,II,期临床研究,31,ppt课件,Alimita联合奥沙利铂治疗晚期胃癌的多中心II期临床研,3,度毒副反应包括中性粒细胞减少,(30.8%),，白细胞减少,(7.7%),，呕吐,(7.7%),，肝脏毒性,(7.7%),。,没有出现,4,度毒副反应。,Alimita,联合奥沙利铂治疗晚期胃癌的多中心,II,期临床研究,副作用,32,ppt课件,3度毒副反应包括中性粒细胞减少(30.8%)，白细胞,Alimita,联合奥沙利铂治疗晚期胃癌安全有效，具有良好的应用前景。,Alimita,联合奥沙利铂治疗晚期胃癌的多中心,II,期临床研究,结 论,33,ppt课件,Alimita联合奥沙利铂治疗晚期胃癌安全有效，具有,入组患者,：无法手术切除或复发,/,转移的胃癌患者,初治，,EGFR(+).,用药方法,：,a,C225,单药,(,首次,400mg/m2,，以后每周,250mg/m2,),b,C225,(,用法同前,),FOLFIRI,(2,周方案，最多用,24,周，以后,C225,单药,),结 果,：,2004.11-2005.12,，,38,例患者入组。,C225,联合,FOLFIRI,治疗晚期胃癌,II,期临床研究（,FOLCETUX,）,34,ppt课件,入组患者：无法手术切除或复发/转移的胃癌患者C225联合FO,C225,联合,FOLFIRI,治疗晚期胃癌,II,期临床研究（,FOLCETUX,）,35,ppt课件,C225联合FOLFIRI治疗晚期胃癌II期临床研究（FO,C225,联合,FOLFIRI,治疗晚期胃癌,II,期临床研究（,FOLCETUX,）,3/4,度毒副反应,36,ppt课件,C225联合FOLFIRI治疗晚期胃癌II期临床研究（FO,C225,联合,FOLFIRI,治疗晚期胃癌,II,期临床研究（,FOLCETUX,）,结 论,C225,联合,FOLFIRI,治疗晚期胃癌，有效率高，副作用可以耐受。,37,ppt课件,C225联合FOLFIRI治疗晚期胃癌II期临床研究（FO,PS-341 (bortezomib),联合,CPT-11,治疗晚期胃癌的,II,期临床研究,入组患者,：无法手术切除、有可测量病灶的晚期胃,癌患者。,用药方法,：,A,(,初治患者,),PS-341 1.3mg/m2 d1,、,4,、,8,、,11 / 21d,B,(,化疗失败患者,),PS-341 1.3mg/m2 d1,、,4,、,8,、,11,CPT-11 125mg/m2 d1,、,8 21d,结 果,：,33,例患者入组。,PS-341,（,bortezomib,）,蛋白酶体抑制剂,38,ppt课件,PS-341 (bortezomib) 联合 CPT-11,PS-341 (bortezomib),联合,CPT-11,治疗晚期胃癌的,II,期临床研究,PS-341,（,bortezomib,）,蛋白酶体抑制剂,39,ppt课件,PS-341 (bortezomib) 联合 CPT-11,PS-341 (bortezomib),联合,CPT-11,治疗晚期胃癌的,II,期临床研究,毒副反应,3,度：,恶心,(6),，呕吐,(7),，粒细胞减少,(3),，血小板 减少,(6),，腹泻,(4),，贫血,(6).,4,度：,心搏骤停,(1),，胃穿孔,(1),，白细胞减少,(2),，腹泻,(4),，水肿,(1).,死亡,(3).,40,ppt课件,PS-341 (bortezomib) 联合 CPT-11,PS-341 (bortezomib),联合,CPT-11,治疗晚期胃癌的,II,期临床研究,PS-341,联合非铂类细胞毒药物治疗晚期胃癌疗效可观。,PS-341,单药治疗化疗失败的晚期胃癌的有效率可达,9,。,研究尚在进行中,41,ppt课件,PS-341 (bortezomib) 联合 CPT-11,新的化疗药物和分子靶向药物显现效果；,剂量、方案有待确定。,小 结,42,ppt课件,新的化疗药物和分子靶向药物显现效果；42ppt课件,EOX,方案将动摇,ECF,参考方案；,紫杉类、,CPT-11,为基础方案疗效确切，但还,优待评价；,晚期胃癌联合化疗获益后是,维持治疗,还是,间,隙治疗,，有待确定；,新的化疗药物和分子靶向药物显现效果，剂,量、方案有待确定。,总 结,43,ppt课件,EOX方案将动摇ECF参考方案；43ppt课件,内科治疗的几个问题,晚期胃癌的最佳化疗方案,；,化疗获益后如何安排后续治疗；,Alimita,B,ortezomib,Cetuximab,和,bevacizumab,的定位。,44,ppt课件,内科治疗的几个问题晚期胃癌的最佳化疗方案；44ppt课件,