晚期胃癌化疗策略.pptx

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,*,晚期胃癌化疗策略,北京大学临床肿瘤学院,消化内科 沈 琳,8,晚期胃癌化疗策略,第1页,晚期胃癌治疗现实状况,局部进展期治愈：手术与化疗结合,复发或转移不能治愈：化疗为主综合治疗，但手术或其它局部治疗伎俩作用加强,化疗：新药、新方案高效低毒，近期疗效增加而生存期延长不满意，但近3年进展快速,晚期胃癌化疗策略,第2页,胃癌化疗,新辅助化疗,辅助化疗,晚期胃癌化疗,生存目标,新辅化,辅化,根治、延长PFS,手术,姑息化疗,手术,化,疗,化,疗,延长生存期,改进生活质量,化疗,手术,局部治疗,晚期胃癌化疗策略,第3页,晚期胃癌化疗临床问题,药品、方案选择,疗程及后续治疗,化疗与手术或局部治疗合理应用,（新辅助化疗）,手术后辅助化疗,晚期胃癌化疗策略,第4页,药品、方案选择,全部选择:,5FU,/,CAPE,/,S-1,DDP+5FU,ECF/LFEP,多西紫杉醇/紫杉醇CAPE/,DDP+5FU,OXA,+,CAPE,/5FU,CPT-11,+,5FU/,CAPE/S-1,分子靶点药品,晚期胃癌化疗策略,第5页,Randomized Phase III Study:1990-,Study,Regimen,N,RR(%),p-value,MST,p-value,EORTC,1991,FAM,FAMTX,103,105,9,41,5%)inPrior 3 Months,Centers,Response assessment every 8 weeks independent of treatment schedule,Cisplatin 100 mg/m,2,IV D1,Cycles repeated every 4 weeks,Docetaxel 75 mg/m,2,IV D1,Cisplatin 75 mg/m,2,IV D1,5-,FU 750 mg/m,2,CIV D1-5,Cycles repeated every 3 weeks,5-,FU 1000 mg/m,2,CIV D1-5,vs,晚期胃癌化疗策略,第11页,胃癌III期临床-TAX 325随访结果,TCF vs CF p,N 227 230,RR 37%25%0.0106,TTP 5.6m 3.7m 0.0004,2Y 18%9%0.0201,G3/4 81%75%,ASCO，abs 4002,晚期胃癌化疗策略,第12页,TAX325:increased febrile neutropenia with TCF,%patients with grade 3/4,Neutropenia,Anemia,Platelets,Febrile neutro-penia,infection,0,20,40,60,80,100,TCF,FP,Moiseyenko VM et al.Proc Am Soc Clin Oncol;(Abst 4002).,82,57,30,14,晚期胃癌化疗策略,第13页,TAX 325 研究结果,TCF(多西紫杉醇、顺铂、5FU)是用于预后很好患者一项新治疗选择,Moiseyenko et al,ASCO,Abstract 4002,例数,总体缓解,疾病进展时间（月）,总生存期（月）,34级毒性,TCF,221/227,37%,5.6,9.2,腹泻，感染，中性粒细胞降低症*,p=0.01,p=0.0004,p=0.02,CF,224/230,25%,3.7,8.6,胃炎，肾毒性,*34级毒性包含：81非血液学毒性反应，,75血液学毒性反应中30伴有中性粒细胞降低性发烧,晚期胃癌化疗策略,第14页,CPT-11 for AGC,期多中心临床研究,（ASCO）FFCD 9803 法国,Bouche O et al.J Clin Oncol;22:431927,例 数,RR,mTTP,mOS,LV5FU2,45,13%,3.2m,6.8m,LV5FU2-DDP,44,27%,4.9m,9.5m,LV5FU2-CPT-11,45,40%,6.7m,11.3m,晚期胃癌化疗策略,第15页,CPT-11联合5-FU治疗AGC,-III期临床试验（ASCO）,N=170,CPT-11 80mg/m2,CF 500mg/m2,5FU mg/m2 civ,1/W x 6w,N=163,CDDP 100mg/m2 d1,5FU 1000mg/m2/d d1-5,Q4W,N=333 AGC,RR,54（31.8%）42（25.8%）,TTP 5.0m 4.2m (p=0.088),TTF 4.0m 3.4m (p=0.002),OS 9.0m 8.7m p0.53,M.Dank ASCO abs 4003,晚期胃癌化疗策略,第16页,新世纪初选择：问题！,多西紫杉醇（,Docetaxel）联合DDP/5-FU：,高效！生存期延长！不良反应性大！,CPT-11联合5-FU/CF:RR改进、安全性提升、TTF延长,OS无延长,怎样改变？更合理选择？,晚期胃癌化疗策略,第17页,新探索和循证医学证据,OXA DDP,CAPE5-FU,重新设定剂量强度或改变剂量密度,增、减药品联合,续惯。,晚期胃癌化疗策略,第18页,REAL 2,randomised multicentre phase III study,comparing,capecitabine,with,5-FU,and,oxaliplatin,with cisplatin in patients with advanced oesophagogastric cancer,D Cunningham,et al.,ASCO,Abstract LBA 4017,晚期胃癌化疗策略,第19页,REAL-2:randomized,phase III trial in gastric and GEJ cancer,E,pirubicin,C,isplatin,5-,F,U,E,pirubicin,C,isplatin,X,eloda,E,pirubicin,E,loxatin,5-,F,U,E,pirubicin,E,loxatin,X,eloda,21-day cycle,Planned duration of treatment:24 weeks(8 cycles),Target randomization,n=600,Eloxatin,130mg/m,2,day 1,CAPE,625 mg/m,2,twice daily days 121,Eprirubucin,50mg/m,2,day 1;Cisplatin 60 mg/m,2,day1;5-FU 200 mg/m,2,/day,晚期胃癌化疗策略,第20页,REAL 2:,研究目标,Primary endpoint of non-inferiority in overall survival,Xeloda vs.5-FU,oxaliplatin vs.cisplatin,Secondary endpoints,ORR and response duration,PFS,safety,QoL,Sumpter K et al.Br J Cancer;92:197683.,晚期胃癌化疗策略,第21页,REAL 2 interim analysis:good response with,oxali-,vs.cisplatin,%,Cisplatin armsECF&ECX(n=94),Oxaliplatin armsEOF&EOX(n=102),ORR,33,43,CR,5,4,PR,28,39,SD,33,30,D.Cunningham Md ASCO,200,6,晚期胃癌化疗策略,第22页,1-year S,(%),Median OS,(months),HR,2x2 comparisons,5-FU:ECF+EOF,39.4,9.6,1,Capecitabine:ECX+EOX,44.6,10.9,0.86,Cisplatin:ECF+ECX,40.1,10.1,1,Oxaliplatin:EOX+EOF,43.9,10.4,0.92,REAL 2:,survival outcomes,晚期胃癌化疗策略,第23页,Updated results for four regimens,1 year OS(95%CI),Median OS,HR(95%CI),ECF n=263,37.7%(31.8-43.6),9.9 mths,1,EOF n=245,40.4%(34.2-46.5),9.3 mths,0.95(0.79-1.15),ECX n=250,40.8%(34.7-46.9),9.9 mths,0.92(0.76-1.11),EOX n=244,46.8%(40.4-52.9),11.2 mths,0.80(0.65-0.97),D.Cunningham Md ASCO,200,6,晚期胃癌化疗策略,第24页,ECF,EOF,ECX,EOX,Grade 3/4 non-haematological toxicity,%,36,42,33,45,Grade 3/4 neutropenia,%,42,30,51,28,p-value,0.008,0.008,0.0043,0.001,REAL 2:safety outcomes,There was less neutropenia in the Eloxatin-containing arms compared with the cisplatin-containing arms,晚期胃癌化疗策略,第25页,REAL 2:conclusions,The primary objective of the trial was met:,Capecitabine is not inferior to 5-FU,Oxaliplatin is not inferior to cisplatin,In these triplet regimens,Capecitabine could replace 5-FU,Oxaliplatin could replace cisplatin,The use of,EOX,is associated with improved efficacy over ECF,以EPI为基础三药联合可行！,EOX有显著生存优势！,晚期胃癌化疗策略,第26页,Oxaliplatin联合EPI、5-FU/CF治疗晚期胃癌临床多中心研究,china,用药方法,乐沙定,100mg/m,2,d,1,EPI 50mg/m,2,d,1,CF 200mg/m,2,d,1-3,5-FU 500mg/m,2,CIV d,1-3,每3周重复，治疗最少3个周期评价疗效及毒性反应,CR 2例（5.6%）,PR 13例（36.1%）,SD 17例（47.2%）,总有效率41.7%,。,其中初治患者9/20（45%）,复治患者6/16（37.5%）,主要不良反应,：,骨髓抑制：,-,O,ANC7/36（19.4%），,O,PLT3/36（8.3%），,O,Hb,4/36（11.1%），,O,神经末梢毒性,4/36（11.1%），,晚期胃癌化疗策略,第27页,first-line chemotherapy with fluorouracil,leucovorin and,oxaliplatin(FLO),versus fluorouracil,leucovorin and cisplatin(FLP),FLO,F 2600mg/m2 24h infusion,L 200mg/m2,oxaliplatin 85mg/m2 q2w,FLP,F mg/m2 24h infusion,qw,L 200mg/m2,qw,cisplatin 50mg/m2,q2w.,Total 220 pts,Median age 64 yrs,Advanced and/ormetastatic gastric cancer(AGC),RANDO MIZ,ATION,S.Al-Batran,J.Hartmann,ASCO,晚期胃癌化疗策略,第28页,Superior Performance with FLO vs.FLP,Confirmed response%(95%CI),FLO,(N=98),FLP(n=102),p-value,Overall response,34%,27%,0.012,TTP,5.7,3.8,0.081,TTF,5.3,3.1,0.028,S.Al-Batran,J.Hartmann,ASCO,晚期胃癌化疗策略,第29页,奥沙利铂5FU作为一线治疗,1.De Vita et al.,Br J Cancer,;,92,:164449.2.Al-Batran et al.,J Clin Oncol,;,22,:65863.,3.Al-Batram et al,ASCO,Abstract 4014.,方案,例数,缓解率,疾病进展时间/总生存期,3-4度神经病变,FOLFOX4,1,61,38%,7.1/11.2,5%,FOLFOX6,2,41,43%,-/9.6,0,改良FOLFOX6 vs,5-Fu(AIO)顺铂3,105,（80例可评价）,39.1%,24.2%,-,54.5%,19.4%,晚期胃癌化疗策略,第30页,Oxaliplatin/CF/5-FU vs paclitaxel/CF/5-FU in pats with advanced gastric cancer,A phase II clinical trial,T.Lin,ASCO Abstr 14014,armA FOLFOX6,armB FOLFPa,PTX 80 mg/m2,病例数,46,43,CR+PR,37.0%,47.2%,CR+PR+SD,76.1%,69.4%,TTP,6.0 m,3.2 m,?,OS,13.4 m,13.8 m,晚期胃癌化疗策略,第31页,Phase II multicenter trial of docetaxel+oxaliplatin in stage IV gastroesophageal and/or stomach cancer,PATIENT PROFILE:,Median age=59.4 years,72%male patients,76%white,ECOG PS scores:0(45%);1(49%);2(6%),32.8%of patients had distal gastric cancer,N=71,Eligibility:,Patients with metastatic(Stage IV)AGEJ/S,ENDPOINTS:,Primary:ORR,Secondary:time to response,duration of response,TTP,toxicity,1-and 2-year survival,Docetaxel,60 mg/m,2,1h IV D1;q3w,Oxaliplatin,130 mg/m,2,2h IV D1;q3w,+,Richards DA,et al.,ASCO,Abstract 4071,晚期胃癌化疗策略,第32页,Results:efficacy,N,%,Best response,Partial response,25,38,Stable disease(SD 6 months;3 patients),34,52,Progressive disease,7,11,Clinical benefit rate,28,42,Time to response(months),Median,1.3,Range,1.14.4,Duration of response(months),Median,4.6,Range,2.718.3,Estimated overall survival rate,Media survival time 95%CI,9.2 months 6.511.2,RR of 38%,similar to TAX 325;OS of 9.2 months similar to TAX 325,晚期胃癌化疗策略,第33页,Adverse events(Grade 3/4),Total(%),Haematological,Leukopenia,Neutropenia,Thrombocytopenia,Febrile neutropenia,17,70,7,7,Non-haematological,Dehydration,Diarrhoea,Fatigue,Nausea,Vomiting,13,13,13,16,17,Results:toxicity,晚期胃癌化疗策略,第34页,ML17032:CAPE vs 5-FU trial design,FP,Cisplatin,80 mg/m,2,3-hour i.v.infusion,5-FU c.i.,800 mg/m,2,/day;d15 q3w,XP,Cisplatin,80 mg/m,2,3-hour i.v.infusion,Capecitabine,1000 mg/m,2,twice daily;d114 q3w,KPS,70%,1875 years,Advanced and/ormetastatic gastric cancer(AGC),1 measurable lesion,No prior treatment for AGC,RANDO MIZ,ATION,晚期胃癌化疗策略,第35页,Superior response rate with XP vs.FP,Confirmed response%(95%CI),XP(n=160),FP(n=156),p-value,Overall response,41,(33,49),29,(2237),0.030,Complete response,2,3,0.668,Partial response,39,26,0.019,Progressive disease,10,18,0.041,晚期胃癌化疗策略,第36页,ML17032:XP vs FPprogression-free survival HR 0.81,Estimated probability,HR=0.81(95%CI:0.631.04),Compared to HR upper limit 1.25,p=0.0008,0,Months,2,4,6,8,10,12,14,16,18,20,22,24,26,1.0,0.8,0.6,0.4,0.2,0.0,Per protocol analysis,XP(n=139),FP(n=137),Median PFSmonths(95%CI),5.6(4.97.3),5.0(4.26.3),晚期胃癌化疗策略,第37页,Similar all-grades hematologic adverse events:,XP vs.FP,%of patients,XP(n=1,56,),FP(n=,155,),Neutropenia,33,30,Leukopenia,14,17,Anemia,12,5,Thrombocytopenia,6,6,晚期胃癌化疗策略,第38页,A Phase II Trial of Capecitabine and DDP in AGCChina,.6-.5,N=145,Cape 1000mg/m2 Bid d1-14,DDP 20mg/m2 iv d1-5,q3W,130pts evaluable:98M/32F,Age:53.7ys,Results,CR 10(8%),PR 48(37%),SD 51(39%),PD 21(16%),OS 12m,Safety：,grade 3-4 adverse event 5%,-,ASCO,晚期胃癌化疗策略,第39页,Summary of Combination Chemotherapy with CAPE in AGC,Regimen,X,XP,TX,DX,DX(weekly,),ECX,DXP,N,44,42,45,42,55,54,40,RR(%),34,55,49,60,40,59,68,TTP,(mo),3.2,6.3,5.7,5.2,4.5,6.0,7.8,OS,(mo),9.5,10.1,11.4,10.5,12.0,9.6,16.9,Neut,(%)G3/4,0,32,47,15*,36,60,63,Neut,Fever(%),0,0,0,7,9,19,10,Tx,Death,-,-,-,-,-,1,1,X;Xeloda,P;Cisplatin,T;Taxol,D;Docetaxel,E;Epirubicin,C;Cisplatin,*not based on weekly CBC,晚期胃癌化疗策略,第40页,CAPE vs,5-FU in doublet regimens for AGC,Studies,n,RR(%),PFS/TTPmonths,OSmonths,Oxaliplatin+5-FU,1,Oxaliplatin+X,2,44,20,40,65,5.8,7.5,9.3,too early,Irinotecan+5-FU,3,Irinotecan+X,4,172,38,32,46,5.0,5.1,9.0,8.6,Paclitaxel+5-FU,5,Paclitaxel+X,6,38,40,42,50,4.3,6.8,9.9,13.6,Docetaxel+5-FU,7,Docetaxel+X,8,43,38,38,60,5.5,5.2,9.5,10.5,1.Al-Batran S Proc Am Soc Clin Oncol;(Abst 4015);2.Park Y Br J Cancer;94:95963;,3.Dank M Proc Am Soc Clin Oncol;(Abst 4003);4.Baek J Br J Cancer Apr 25;5.Park S.Anticancer Drugs;17:2259;6.Kang.H.Proc Am Soc Clin Oncol;(Abst 4051,poster update);7.Thuss-Patience P J Clin Oncol;23:494501;8.,Park Y Br J Cancer;90:132933,晚期胃癌化疗策略,第41页,新探索和循证医学证据,CAPE5-FU,OXA DDP,重新设定剂量强度或改变剂量密度,增、减药品联合,续惯。,晚期胃癌化疗策略,第42页,伊立替康联合5-FU/LV、,CDDP,治疗胃癌,方法,n,RR(%),中位生存期（月）,研究者,CPT-11:80mg/m2,5-FU:mg/m2,FA：500mg/m2,CDDP：20-50mg/m2,每2周1次,17,70,NA,Schleucher et al（）,降低5FU剂量强度,改变给药间隔,增加DDP,晚期胃癌化疗策略,第43页,伊立替康联合奥沙利铂治疗胃癌,CR(%),PR(%),RR(%),中位使用期（月）,中位进展期（月）,中位存活时间（月）,3.1,46.9,50.0,5,5.5,8.5,中性粒细胞降低症,贫血,3级腹泻,神经毒性,3级虚弱,发烧性中性粒细胞降低症,不良反应发生率,Souglakos J,et al.,Ann Oncol.;15(8):1204-9,N=32,CPT:200mg/m2 iv 30m d1,OXA:85mg/m2 iv 2h d1 Q3W,有效率提升！,生存期延长不满意！,晚期胃癌化疗策略,第44页,irinotecan plus capecitabine in patients with AGC,N=38/40/41，,Cape 1000 mg/m2 BID day 1-14,irinotecan 100 mg/m2 d 1，8,Q3W,RR 46.3%.TTP 5.1,OS 8.6 m,Grade 3/4 neutropenia in 4 pats,grade 3 febrile neutropenia in 2 pats.,grade 3 diarrhea,grade 2 HFS in 6 patients,J.Baek ASCO，ABSTR14037,Iri 80 mg/m2 on d1,8,and 15,cape 625 mg/m2 BID D1-14;Q 4 w,29/31 pts were evaluable for response,PR 38.5%.SD29%,TTP 5.8 months,OS 10.5 months,no grade III-IV toxicity,F.Farhat ASCO Abstr 14030,晚期胃癌化疗策略,第45页,S-1 80 mgm2 d1-14 q28d,CPT-11 70-100 mgm2 d1,8,q 4 weeks,phase I:,MTD:CPT-11 90 mg/m2,RD 80 mg/m2.,phase II:,42 pats,The median treatment course was 5(range:113).,RR 62%,(95%confidence interval:47.276.6%),The median survival time was,444 days,.,grade 34haematological 19%;nonhaematological toxicities 10%,伊立替康联合S1治疗胃癌临床I/II期试验,M Inokuch British J Cancer()94,1130 1135,晚期胃癌化疗策略,第46页,N=45/48,irinotecan 150 mg/m2 d1,oxaliplatin 85 mg/m2 d1,lv 100 mg/m2/d,5-FU mg/m2 48-h ci d1,Q 2 w,RR 73.3%,（2 CRs and 31 PR）.SD 9%PD 18%,estimated,mOS 14.0 m estimated mTTP 8.9 m,grade 3/4 toxicities were neutropenia(11%of all cycles)and emesis(12%),FOLFOXIRI combination chemotherapy in metastatic or recurrent gastric cancer,J.Lee,ASCO Abstr 4076,晚期胃癌化疗策略,第47页,Aphase I study of S-1 plus weekly docetaxel in patients with mGC,MTD for this regimen was S-1 90 mg/m2/d+docetaxel 35 mg/m2 d1,8,RD was S-1 80 mg/m2/d(D1-14)+docetaxel 35 mg/m2(D1,8).,DLT:diarrhea and febrile neutropenia,S.R.Park,H.K.Kim ASCO Abst 14005；,T.Ozaki,ASCO Abst 14108,MTD S1:80 mg/m2 d1-21+docetaxel 25mg/m2 D1,8,15,RD S1 80 mg/m2 d1-21 and docetaxel:20 mg/m2 day1,8 and 15,DLT:febrile neutropenia,Grade3 stomatitis and continuous Grade 4 neutropenia.,3周方案,5周方案,晚期胃癌化疗策略,第48页,Capecitabine and docetaxel for advanced gastric cancer,part I：Docetaxel 75 mg/m2 d1,capecitabine mg/m2 d1-14,q3w.,CR 2.6%,PR 52.6%,NC 36.8%,PD 7.9%,RR:55.3%,In part II：further improve tolerability：reduced the dose of docetaxel to,60 mg/m2,and capecitabine to,1600 mg/m2,to,P.C.Thuss-Patience,ASCO Abstr:4068,晚期胃癌化疗策略,第49页,Taxanes+5-FU,或CDDP二联治疗AGC,方法：PCT 175mg/m,2,/3w,DCT 75-85mg/m,2,/3w,5-FU 750mg/m,2,civ,d1-5/3w,或 200-300mg/m,2,/3w civ2w/3w,CDDP 20mg/m,2,I.V.d1-5/3w或75mg/m,2,I.V./d1/3w,晚期胃癌化疗策略,第50页,A phase I/II study of oxaliplatin,docetaxel,and capecitabine in advanced carcinoma of the esophagus and stomach.,DLT：Grade 3/4 diarrhea,nausea,and febrile neutropenia,RD：Oxaliplatin 50 mg/m2 and docetaxel 35 mg/m2 day 1 and 8,capecitabine 750mg/m2 BID 10 days Q21 day,D.L.Evans,ASCO Abstr 14046,晚期胃癌化疗策略,第51页,A phase II study of alternating chemotherapy with CDDP/5FU/FA and epirubicin(E)/docetaxel(T)(CF-ET regimen)as first line therapy for pts with MGC,N=34,CDDP 35 mg/m2 d1,2,15 and 16,5FU mg/m2 ci d 1,8,15 and 22,FA 200 mg/m2 iv d 1,8,15 and 22,E 60 mg/m2 d 29 and 43,T 60 mg/m2 d 29 and 43 q 8W,RR 64.5%.The median response duration was 6.1 months.OS 11.4 months。,Grade 3/4 toxicities：leukopenia 41/37.5%,neutropenia 16/82%,thrombocytopenia 23.2/0%,H.H.Kirchner ASCO Abstr 14021,续贯,晚期胃癌化疗策略,第52页,靶向治疗,靶点,期,Her-2,Herceptin,VEGF,Bevacizumab(Avastin),EGFR,西妥昔单抗（C225）,多靶点,Sutent(Sunitinib),晚期胃癌化疗策略,第53页,EGFR,EGFR在66胃癌中过表示（Roid）,吉非替尼（酪氨酸激酶抑制剂）,胃癌：缓解率为1，N75（ASCO）,食管腺/鳞细胞癌：缓解率为1012，N=56（ASCO）,Erlotinib（Tarceva）,食管腺/鳞细胞癌：缓解率为16，N=17（ASCO）,胃或胃食管交接部癌：N2644，缓解率为012（1例完全缓解）（ASCO）,晚期胃癌化疗策略,第54页,VEGFR,Bevacizumab抑制VEGFR,在转移性病变中顺铂和伊立替康（MSKCC）,辅助ECF方案（MAGIC-2试验）,晚期胃癌化疗策略,第55页,胃癌靶向治疗,Bevacizumab（BEV）联合PT-11+DDP,一线治疗AGC,-II期临床试验,（ASCO）,BEV 15mg/kg d1,CPT 65mg/m2 d1，8,DDP 30mg/m2 d1，8,q3w,N=24,3m PFS 89%,6m PFS 76%,16例可评价近期疗效,PR（12/16）75%,MR 3，SD 1,不良反应（24例）：,级白细胞降低、恶心呕吐、腹泻 8%,血栓（4肺和2深静脉）：6例（20%）；,2例胃穿孔，2例几近穿孔（肿瘤部位）,M.A.ShAh et al:ASCO abstr 4025,晚期胃癌化疗策略,第56页,CPT-11、DDPBevacizumabin AGC,仅进行了初步治探索,正在进行或准备之中,早期效果令人鼓舞,但需要注意一些确定潜在毒性（如血栓形成、穿孔）,Shah MA et al,ASCO.,晚期胃癌化疗策略,第57页,新药新方案选择小结,新世纪选择趋向,紫杉烷类(DOC),顺铂+5-Fu,/,CAPE/S-1,CAPEOXA/DDP,OXAEPI+CAPE,/5-Fu,伊立替康,5-Fu/,CAPE/S-1,/DDP,分子靶点药品,晚期胃癌化疗策略,第58页,OXA治疗胃癌：,与5FU联合高效、安全！生存期延长尚不理想,CAPE替换5FU与之联合有望延长生存期,作为三药联合取代DDP，疗效、安全性及生存期改进,或CPT/TAX+CAPE/FU，以期深入提升疗效延长生存,XELOX;EOF vs FOLFOX;DOX vs DCF,-需深入临床试验证实！,有前景的药物,晚期胃癌化疗策略,第59页,Taxanes在胃癌中应用关键减毒经过,改变,剂量或方案,疗效不减低,不良反应降低,疗效明确,从三药联合改为两药：减去DDP,CAPE 5-FU,OXA DDP,DOC改为周给药方法,DOC降低剂量强度：5060mg/m2,是可行的！,不过还需要临床循证医学证据！,晚期胃癌化疗策略,第60页,CAPE/,S-1,在胃癌治疗中作用,安全，方便，疗效可靠,可与当前证实对胃癌有效任一药品联合，尤其是与DOC/PTX/OXA/DDP,且有协同作用，有取代5-FU成为联合方案基本用药趋势,应用灵活，可依据联合药品以及患者体质合理改变给药方式,符合胃癌生物学特点,晚期胃癌化疗策略,第61页,CPT-11在胃癌治疗中关键,深入提升疗效，延长生存期，降低不良反应,合理用药：FOLFIRI，5FU剂量强度、使用方法,三药联合：FOLFOXIRI、CPT-11+DDP5-FU,CAPE5FU+CPT-11,任重道远,需要临床循证医学证据！,晚期胃癌化疗策略,第62页,胃癌靶向治疗,刚才开始,胃癌患者特质,胃内病灶影响,晚期胃癌化疗策略,第63页,晚期胃癌化疗临床问题,药品、方案选择,疗程及后续治疗,化疗与手术或局部治疗合理应用,（新辅助化疗）,手术后辅助化疗,晚期胃癌化疗策略,第64页,疗程及后续治疗,疗程？,后续治疗？,一线？二线？维持？停药？,尚无定论,晚期胃癌对化疗耐受性和TTF/TTP预计,晚期胃癌化疗策略,第65页,晚期胃癌化疗临床问题,药品、方案选择,疗程及后续治疗,化疗与手术或局部治疗合理应用（新辅助化疗）,手术后辅助化疗,晚期胃癌化疗策略,第66页,化疗与手术或局部治疗合理应用,新辅助化疗,目标：,提升手术根治性切除率！,选择：晚期胃癌化疗近期有效率最高、最安全药品及方案，能够强强联合！,姑息手术切除，局部治疗：放疗、射频等,晚期胃癌化疗策略,第67页,小 结,当前，在转移性胃癌治疗中没有一个标准方案各项指标显著优于其它方案。需要更多研究来优化最正确方案。,合理综合治疗能够让患者取得最大利益,真正个体化治疗尚难以确定,靶向药品应用值得探索,晚期胃癌化疗策略,第68页,谢