NCCN胃癌临床实践指南课件

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,*,NCCN,胃癌临床实践,胃 癌,NCCN胃癌临床实践胃 癌,Copyright 2005 American Cancer Society,Age-standardized Incidence Rates for Stomach Cancer in world.,From Parkin, D. M. et al. CA Cancer J Clin 2005;55:74-108.,世界胃癌年龄调整发病率,Copyright 2005 American Cance,对,1990-1992,年中国的,1/10,万人口死因抽样调查资料中胃癌死亡情况进行分析,胃癌粗死亡率,(crude mortality rate) 25.2/10,万（,M,：,32.8/10,万，,F,：,17.0/10,万），占全部恶性肿瘤死亡的,23.2%,，恶性肿瘤死亡中第一位。（男性是女性,1.9,倍）,中国胃癌世界人口调整死亡率,(mortality rates adjusted by the world population),男性：,40.8/10,万，女性：,18.6/10,万，分别是欧美发达国家的,4.2-7.9,倍，,3.8-8.0,倍,有明显的地区差异和城乡差别。全国抽样调查,263,个点，胃癌调整死亡率在,2.5-153.0 /10,万之间，,Urban areas:15.3/10,万,; Rural areas:24.4/10,万，是城市的,1.6,倍,对1990-1992年中国的1/10万人口死因抽样调查资料中,NCCN,共识分类,1,类：基于高水平的证据，,NCCN,达成共识，推荐应用,2A,类：基于包括临床经验在内的稍低水平证据，,NCCN,达成共识，推荐应用。,2B,类：基于包括临床经验在内的稍低水平证据，,NCCN,未达成统一共识（但无较大分歧）。,3,类：,NCCN,对该建议的适宜性存在较大分歧。,除非特别说明，本指南中所有的建议均达成,2A,类共识。,NCCN共识分类1类：基于高水平的证据，NCCN达成共识，推,NCCN,胃癌临床实践指南,2008,第,1,版指南更新,主要变化,总结,（,GAST-1,）：,workup,：,PET/CT,扫描和,EUS,作为可选的检查项目。,（,GAST,2,）：,要求多学科会议讨论患者所有三个治疗途径的抉择,T2,以上分期患者将术前化疗作为一类推荐,首选治疗手段。,术前放化疗作为,2B,类的首选治疗手段。,（,GAST,3,）：,R0,术后分期,T2 N0M0,及以上者，如术前采用,ECF,方案化疗，术后可选择,ECF,继续（,1,类）,（,GAST,5,）：,follow up,：近端胃大部或全胃切除者，应监测并补充,Vit B12,（,GAST,A,）：,增加综合治疗模式原则新页,（,GAST,B,、,C,）：,更新外科及系统化疗原则,（,GAST,A,）：,新增放疗原则新页,NCCN guidelines -Gastric Cancer Chinese version 1. 2008,在整个治疗指南中将,chemotherapy/RT,更改为,chemoradiation,将,salvage,改为,palliative,NCCN 胃癌临床,与,2007,版类似,注意：,除了特别指出的情况，所有推荐的治疗都是,2A,证据的。,临床试验：,NCCN,认为对于任何一个肿瘤病人参加临床实验都获得最佳治疗,.,要特别鼓励参与临床试验。,与2007版类似注意：,强调多学科评估和协作！,强调多学科评估和协作！,多学科综合治疗模式有益于局部进展期胃癌患者,（,1,类证据）,NCCN,专家组基本观点：不鼓励单一学科成员单方面进行治疗决策。,具备以下条件，可能给局部进展期胃癌患者以最佳的综合治疗,：,例会形势实用（一周或,2,周一次），相关学科的机构和个人定期来共同回顾患者的详细资料。,每次例会，各相关学科都要积极参与，包括肿瘤外科，肿瘤内科，消化科，放射科，病理科。 此外，最好还能包括营养科，社工，护理以及其他支持学科。,所有长期的治疗策略要在全面分期检查完成后再进行，最好在所有治疗开始之前。决策前共同回顾原始的医学数据而非单纯阅读报告。,多学科团队做出共识推荐并摘要记录在案，对每位患者是有益的。,特定患者的主要治疗小组或医生应尊重以及考虑多学科团队所做出的共识推荐。,反馈部分患者的治疗随访结果，对整个多学科团队是有效的实例教育方式。,在例会期间，正式的定期复习相关文献，对整个多学科团队是高效的教育方式。,多学科综合治疗模式有益于局部进展期胃癌患者（1类证据）,NCCN胃癌临床实践指南课件,分期,CT,扫描,EUS,判断病灶范围,腹腔镜有助于部分患者的分期,不能根治性切除标准,局部进展期,:3/4,站淋巴结转移,大血管受侵或被包绕,远处转移或腹膜种植,(,包括腹腔脱落细胞学阳性,可切除肿瘤,T1,者在有经验者可采用内镜下胃粘膜切除,T1-T3,合适的肿瘤切缘,4 cm,（,5 cm,）,镜下阴性,推荐,D1,/D2,淋巴结清扫,应至少检查,15,个淋巴结，并结合位置清扫到,2,站淋巴结,T4,应切除受累部位,不做常规脾切除,除非脾脏受累或脾门受侵,可考虑留置空肠营养管,姑息手术,可以接受切缘阳性，淋巴结不强求清扫,胃肠短路或营养管,外科治疗原则,NCCN v.1.2008 Gastric Cancer,分期外科治疗原则NCCN v.1.2008,结合淋巴结数目以及累及区域分期,结合淋巴结数目以及累及区域分期,Japanese Gastric cancer associati,（,JGCA),腹腔细胞学（,CY,）,CY0,腹腔细胞学良性或无法确定,CY1,腹腔细胞学未见癌细胞,CYx,未作,其它远处转移（,M,）,M0,腹膜、肝、腹腔细胞学外无远处转移,M1,腹膜、肝、腹腔细胞学外有远处转移,Mx,不清楚,分期,表,2,日本胃癌学会（,JGCA,）分期,（,1998,年第,13,版*）,原发肿瘤（,T,）,T1,肿瘤侵犯粘膜层和,/,或粘膜肌层,(M),和,/,或粘膜下层,(SM),T2,肿瘤侵犯固有肌层,(MP),或浆膜下层,(SS) ,T3,肿瘤穿透浆膜,(SE) ,T4,肿瘤侵犯邻近结构,(SI) ,Nx,不明,局部淋巴结（,N,）,淋巴结分站分组（见,ST-3,）,淋巴结转移程度,N0,无淋巴结转移证据,N1,第一站淋巴结有转移，第二、三站淋巴结无转移,N2,第二站淋巴结有转移，第三站淋巴结无转移,N3,第三站淋巴结有转移,Nx,区域淋巴结无法评估,肝转移（,H,）,H0,无肝转移,H1,有肝转移,Hx,不清楚,腹膜转移（,P,）,P0,无腹膜转移,P1,有腹膜转移,*,本分期源自,Japanese Gastric Cancer Association. Japanese Classification of Gastric Carcinoma - 2nd English Edition. Gastric Cancer (1998) 1: 1024,肿瘤可以穿透固有肌层达胃结肠韧带或肝胃韧带或大小网膜，但没有穿透这些结构的脏层腹膜。在这种情况下，原发肿瘤的分期为,T2,。如果穿透覆盖胃韧带或网膜的脏层腹膜，则应当被分为,T3,期。,肿瘤侵犯大、小网膜、食管和十二指肠不作为,T4,经胃壁内扩展至十二指肠或食管的肿瘤分期取决于包括胃在内的这些部位的最大浸润深度。,M1,的种类应注明：,LYM:,淋巴结；,PLE:,胸膜；,MAR:,骨髓；,OSS:,骨；,BRA:,脑；,MEN:,脑膜；,SKI:,皮肤；,OTH:,其它,N0,N1,N2,N3,T1,IA,IB,II,IIIA,T2,IB,II,IIIA,T3,II,IIIA,IIIB,T4,IIIA,IIIB,IV,H1, P1,CY1,M1,Japanese Gastric cancer associ,Regional LN,G,roup,A,ccording to Location of,T,umor,D1,4d,4d,4d,6,5,3,D2,11p,12a,14v,1,9,9,8a,9,7,LD/L,Regional LN Group According to,Sasako et al :,the long-term outcome of survival,：,D2 vs D2+,no statistically significant difference,69% vs 70%, p=0.57, HR:1.03, ( 95% CI: 0.77-1.37).,Sasako M, Sano T, Yamamoto S, et al. Randomized phase III trial of standard D2 versus D2 + para-aortic lymph node (PAN) dissection (D) for clinically M0 advanced gastric cancer: JCOG9501.,J Clin Oncol,2006.24(18S):LBA4015.,扩大根治,or D2,?,循证医学证据,Sasako et al :扩大根治 or D2 ? ,A prospective randomized controlled clinical trial,in Taiwan :,D2 vs D1,5-year survival,D2 dissection was superior to D1 dissection,59.5% vs 53.6%, p=0.041; HR: 0.49, p=0.002,Wu CW, Hsiung CA, Lo SS, et al. Nodal dissection for patients with gastric cancer: A randomized controlled trial.,Lancet Oncol,2006;7:309-315,进一步的临床试验，特别是观察手术前后的辅助治疗应该基于,D2,式手术！,D1 or D2,?,循证医学证据,A prospective randomized contr,适合于所有胃癌胃切除标本,原发性胃癌胃切除标本的检查,原发性肿瘤,*,外科切缘评估,淋巴结评估,原发性胃癌的组织学类型,Lauren,分类，,1965,日本胃癌研究协会（,JRSGC,）分类，,1981,WHO,分类，,2000,病理学分期（,pTNM,）,应包括下列参数：,肿瘤的恶性程度（分级）,浸润的深度,淋巴结的部位、数目及阳性数,远端及近端外科切缘状况,注释,胃癌,原发肿瘤,检查应包括：肿瘤在胃粘膜确切位置及肿瘤范围；肿瘤距近端和远端外科切缘的距离；肿瘤大体形态，包括肿瘤大小、早期胃癌的形态类型；肿瘤切面，浸润胃壁情况。,外科,切缘,评估：胃切除标本有远端及近端切缘：部分切除标本，远端切缘是十二指肠，近端切缘是胃体；全胃切除标本，远端切缘是十二指肠，近端切缘是食管。外科切缘有,3,种情况：,R0,：外科切缘干净；,R1,：外科切缘镜下阳性；,R2,：外科切缘肉眼阳性。建议切除的近端切缘应距肿瘤边缘,5cm,，同时应常规术中切缘冰冻检查。,淋巴结,评估,：见,ST-1/2/3,。根据胃切除时淋巴结清扫的范围分为：,D0,：,淋巴结清扫的范围不包括所有,N1,淋巴结；,D1,：淋巴结清扫的范围不包括所有,N2,淋巴结；,D2,：淋巴结清扫的范围不包括所有,N3,淋巴结。按照,AJCC,标准，因为被检查淋巴结的数量和淋巴结阳性率之间有正相关，应检查至少,15,个淋巴结。,胃癌组织学类型,Lanren,分类（,1965,）：肠型；弥漫型,JRSGC,分类（,1981,）：,乳头状型,管状型,低分化型,粘液型,印戒细胞型,WHO,分类（,2000,）,腺癌,肠型,弥漫型,乳头状腺癌,管状腺癌,粘液腺癌,印戒细胞癌,腺鳞癌,鳞状细胞癌,小细胞癌,未分化癌,其它,胃腺癌组织学分级：高分化；中分化；低分化；未分化,病理学分期（,pTNM,）,病理学分期与胃癌预后极其相关，早期胃癌预后极好，,5,年生存率达,90%,。建议使用,AJCC/UICC,分类，在病理报告中,N,分期可增加标注,JRSGC,要求的淋巴结部位。,病理诊断原则,适合于所有胃癌胃切除标本注释 胃癌组织学类型病理诊断原则,系统化疗原则,NEW,遵照原始文献报道的药物剂量,/,方案,合理用药并进行适当调整,患者合适的器官功能和体力状况,充分考虑化疗的毒性和益处,并始终与患者及家属讨论,/,交流,并进行患者教育,警示并防治不良反应,避免严重合并症及缩短持续时间,患者化疗期间仔细观察,及时治疗合并症,并适当监测患者血液学改变,化疗阶段及时评估疗效和长期合并症,系统化疗原则 NEW遵照原始文献报道的药物剂量/方案, 合,2007.v.2,2008.v.1,Preoperative chemo-therapy,ECF category 1,ECF category 1,ECF modification category 1,Preoperative chemo-radiation,fluoropyrimidine/leucovorin 2B,Fluoropyrimidine-based 2B,Cisplatin-based 2B,Taxanes-based 2B,Irinotecan-based 2B,paclitaxel/Docetaxel+fluoropyrimidine (5FU/capecitabine,）,category 2B,Update of 2008.v.1 NCCN version,2007.v.22008.v.1Preoperative c,可切除胃癌围手术期化疗,-MAGIC trial,胃癌（占,85%,）,或低位食管癌（,15%,）,ECF* 3cs-,手术,-ECF 3cs,单一手术,N=250,5Y 38%,N=253,5Y 23%,ECF:,E 50mg/m2,C 60mg/m2,FU 200mg/m2/d civ,D.Cuuningham 2005 ASCO abs 4001,Cunningham et al, NEJM 2006,可切除胃癌围手术期化疗-MAGIC trial胃癌（占,Chemo + Surgery,Surgery,Patients,250,253,Age,62,62,To Surgery,219 (88%),240 (95%),Pts with R0 resection,169 (68%)*,166 (66%),*No pathologic complete responses,可切除胃癌围手术期化疗,-MAGIC trial,Cunningham et al, NEJM 2006,Chemo + SurgerySurgeryPatients,Chemo + Surgery,Surgery,Path Size,3.1 cm,5.0 cm (p = 0.001),T1 / T2,T3 / T4,52%,48%,38%,62% (p= 0.009),N 0/1,N 2/3,84%,16%,76%,24% (p = 0.01),Cunningham et al, NEJM 2006,可切除胃癌围手术期化疗,-MAGIC trial,Chemo + SurgerySurgeryPath Siz,Overall Survival,Patients at risk,Logrank p-value = 0.009,Hazard Ratio = 0.75 (95% CI 0.60 - 0.93),CSC,S,250,168,111,79,52,38,27,253,155,80,50,31,18,9,0.0,0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8,0.9,1.0,Months from randomization,0,12,24,36,48,60,72,149,250,170,253,Events,Total,CSC,S,Survival rate,Overall SurvivalPatients at ri,可切除胃癌围手术期化疗,5-FU+DDP in AGC/LE,-FFCD,9703 trial,FP 2,3cs,（,98,例）,-,手术,-,FP 2,3cs (,RR+SD n+),（,54,例）,单一手术,N=113,5Y DFS 34%,N=111,5Y DFS 21%,FP:,5-FU 800mg/m2 d1-5 ci,DDP 100mg/m2 d1,Q4w,随访,5.7Y,贲门、胃,89,食管,11,可切除胃癌围手术期化疗 5-FU+DDP in AGC/L,可切除胃癌围手术期化疗,5-FU+DDP in AGC/LE,-FFCD,9703 trial,Surgery,Chemo + Surgery,p,N,111,113,R0,84%,73%,0.04,3y DFS,25%,40%,5y DFS,21%,34%,0.003,HR 0.65,V. Boige et al, ASCO 2007 abstr 4510,可切除胃癌围手术期化疗 5-FU+DDP in AGC/L,可切除胃癌围手术期化疗,Patient,data-based meta-analysis: CT+S vs S,从,12,随机试验, 2284,患者中筛选出,2102,患者,涉及,9,个试验,中位随访时间,5.3,年,CT+S vs S HR 0.87 P=0.003,转化为,5,年绝对生存率提高,4%,R0,切除率,67% vs 62% p=0.03,P.G.Thirion et al, ASCO 2007 abstr 4512,可切除胃癌围手术期化疗Patient data-based,GAST-C 1 of 2: preoperative chemoradiation,2008.v.1NCCN guideline,：,Paclitaxel/docetaxel + fluoropyrimidine(5-FU or capecitabine) category 2B,；,Recommendation of Chinese version:,Docetaxel might be changed;,Category 2B to 3.,Reason:,Study about Paclitaxel/5FU+RT is only,phase II,.,No prospective studies has been searched on docetaxel/5-FU +RT(,medline,).,？,GAST-C 1 of 2: preoperative ch,Preoperative chemoradiation: phase II,Phase II Trial of Preoperative Chemoradiation in Patients With Localized Gastric Adenocarcinoma (RTOG 9904): Quality of Combined Modality Therapy and Pathologic Response,Jaffer A. Ajani JCO,2006,：,24,（,24,）：,3593,Phase: II,Patients,：,43 cases with localized GC,(12% IB; 37% II; 52% III).,，,20 center,Methods:,2cys of 5FU+CF+DDP,CRT (infusional 5FU+weekly paclitaxel),Resection,（,5 to 6 weeks after chemoradiotherapy was completed.,）,Result,：,path CR,：,26%,R0 resection,：,77%,1 year,：,more patients with path CR (82%) are living than those with less than path CR (69%,）,Preoperative chemoradiation: p,GAST-C 1 of 2: preoperative chemoradiation,2008.v.1NCCN guideline,：,Paclitaxel/docetaxel + fluoropyrimidine(5-FU+capecitabine) category 2B,；,Recommendation of Chinese version:,Docetaxel might be changed;,Category 2B to 3.,GAST-C 1 of 2: preoperative c,2007.v.2,2008.v.1,Postoperative chemo-therapy,ECF category 1,（,only when preoperative ECF has been administered,）,ECF category 1,ECF modification category 1,（,only when preoperative ECF has been administered,）,Postoperative chemo-radiation,fluoropyrimidine/leucovorin 1,Fluoropyrimidine-based 1,Fluoropyrimidine/cisplatin 2B,ECF 2B,Taxane-based 2B,Fluoropyrimidine (5FU or capecitabine) category 1,Update of 2008.v.1 NCCN version,Postoperative chemotherapy?,2007.v.22008.v.1Postoperative,Stage IB-IV(M0),D0,和,D1,占,90%,Stage IB-IV(M0),NCCN胃癌临床实践指南课件,NCCN胃癌临床实践指南课件,GAST-3:T3,T4 or any T,N1 after R0 resection,2008.v.1NCCN guideline,：,RT,45-50.4Gy+concurrent 5-FU based radiosensitization(preferred)+5-FUleucovorin or ECF if received preoperatively,（,category 1,）,Recommendation of Chinese version: Add foot note,If D0/D1 resection: agreed the above;,If D2 resection: postoperative chemotherapy recommended.,Evidence,：,D0/D1 operation consists more than 90% in INT0116,；,2 Meta analysis about adjuvant chemotherapy,GASC-study,GAST-3:T3,T4 or any T,N1 after,Patients: 23 trials,，,4919 pts,Methods:,Adjuvant chemotherapy arm(Arm A): 2441,Observation arm(Arm B): 2478,Results:,3y Survival rate: 60.6% in Arm A, 53.4% in Arm B,(RR: 0.85,95%CI: 0.800.90 ),DFS: Arm B had a shorter DFS (RR: 0.88, 95%CI: 0.770.99),Recurrence rate: Arm A had a lower recurrence rate,(RR: 0.78, 95%CI: 0.710.86),Grade 3/4 of AE(myelosuppression and GI): more frequently in Arm A.,Conclusion:,Adjuvant chemotherapy could improve the survival rate and disease-free survival rate in gastric cancer after curative resection and reduce the relapse rate.,META analysis of Adjuvant chemotherapy 1,An updated meta-analysis of adjuvant chemotherapy after curative resection for gastric cancer,European Journal of Surgical Oncology (EJSO),2008.02.002,Patients: 23 trials， 4919 ptsM,META analysis of Adjuvant chemotherapy 2,The role of postoperative adjuvant chemotherapy following curative resection for gastric cancer: a meta-analysis,Shu-Liang Zhao; Jing-Yuan Fang. Renji Hospital, Shanghai, China.,Cancer Investigation, May2008, Vol. 26 Issue 3, p317-325,Patients: 15 trials,，,3212 pts,，,Methods: Surgery+adjuvant chemotherapy vs Surgery only,Results:,RR for death in the treated group was 0.90 (P = 0.0010).,Little or no significant benefits were suggested in subgroup analyses between different population and regimens either.,Conclusion:,Postoperative adjuvant chemotherapy for gastric cancer confers slightly significant benefits compared to the surgery only group.,META analysis of Adjuvant chem,Postoperative adjuvant chemotherapy S1 monotherapy,Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine., Sakuramoto, S N Engl J Med,，,2007,，,357,：,1810-1820,1004 cases,(stage II/III,，,D2,3 years follow up*,S-1 monotherapy,529 cases,OS:80.5%,OS:70.5%,Randomized phase III trial comparing S-1 monotherapy versus surgery alone for stage II/III gastric cancer patients (pts) after curative D2 gastrectomy (ACTS-GC study).,2007Gastrointestinal cancer symposium, sasako M,Surgery alone,530 cases,*12/2005 showed that HR of death for S-1 to C was 0.57, trial was recommended to stop.,09/2006 HR of death for S-1 was 0.68.,Conclusions: Adjuvant chemotherapy with S-1 for gastric cancer is feasible and effective. This regimen can be the standard treatment for stage II/III gastric cancer pts after curative D2 dissection.,ACTS-GC study JCOG,Postoperative adjuvant chemoth,Postoperative chemoradiation might be a good option to compensate the insufficiency of the surgery such as D0/D1 resection.,Adjuvant chemotherapy shows survival benefit compared with surgery alone,especially after D2 resection for patients with stage II or higher.,Postoperative adjuvant chemotherapy,Conclusion:,Postoperative chemoradiation m,GAST-3,：,after R1 resection,2008.v.1NCCN guideline,：,RT,45-50.4Gy+concurrent 5-FU-based radiosensitization (preferred) +5-FUleucovorin,Recommendation of Chinese version:,To add “Clinical trials” as another option.,Reason,：,R1 resection is not radical, till now, no standard therapy has been accepted, it should be better to find the appropriate ones by clinical studies.,GAST-3：after R1 resection2008.,2007.v.2,2008.v.1,Metastatic or locally advanced cancer,fluoropyrimidine/leucovorin 2B,Fluoropyrimidine-based 2B,Cisplatin-based 2B,Oxaliplatin-based 2B,Taxanes-based 2B,Irinotecan-based 2B,ECF 1,DCF 1,ECF 1,ECF modification 1,Irinotecan+cisplatin 2B,Oxaliplatin+fluoropyrimidine,(5-FU or capecitabine) 2B,DCF modification 2B,Irinotecan+fluoropyrimidine,(5-FU or capecitabine) 2B,Update of 2008.v.1 NCCN version,No DDP+fluoropyrimidine,(5-FU or capecitabine or S,1 ) 2B,No paclitaxel-based regimens,；,2007.v.22008.v.1Metastatic or,V325,研究结果,TCF(,多西紫杉醇、顺铂、,5FU),是用于预后较好的患者的一项新的治疗选择,Moiseyenko et al, JCO 2007,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，中性粒细胞减少症*,p=0.01,p=0.0004,p=0.02,CF,#,4002,224/230,25%,3.7,8.6,胃炎，肾毒性,*3,4,级毒性包括：,81,的非血液学毒性反应，,75,的血液学毒性反应中,30,伴有中性粒细胞减少性发热,V325 研究结果TCF(多西紫杉醇、顺铂、5FU)是用于预,CPT-11 for AGC,期多中心临床研究,（,2003 ASCO,）,FFCD 9803,法国,Bouche O et al. J Clin Oncol2004;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,CPT-11 for AGC期多中心临床研究（200,CPT-11,联合,5-FU,治疗,AGC,-III,期临床试验（,2005 ASCO,）,N=170,CPT-11 80mg/m2,CF 500mg/m2,5FU 2000mg/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 p,0.53,M. Dank 2005 ASCO abs 4003,CPT-11联合5-FU治疗AGC-III期临床试验,REAL-2:,疗效（,Efficacy,）,Efficacy,ECFN=263,EC,X,N=250,E,O,FN=245,E,O,X,N=244,P:,ECF vs EOX,RR,(%),41,46,42,48,1 year OS,(%),37.7,40.8,40.4,46.8,OS,(mo),9.9,9.9,9.3,11.2,0.025,Cunningham et al. ASCO 2006 LBA 4017,REAL-2: 疗效（Efficacy）EfficacyEC,ECF,EOF,ECX,EOX,Grade 3/4,non-,haematological toxicity, %,36,42,33,45,Grade 3/4 neutropenia, %,42,30,51,28,p-value,0.008,0.0043,0.001,REAL 2:,安全性,safety outcomes,ECFEOFECXEOXGrade 3/4 non-haem,Oxaliplatin,联合,EPI,、,5-FU/CF,治疗晚期胃癌的临床多中心研究, 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，治疗至少,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%,），,以,EPI,为基础的三药联合可行！,EOX,有明显生存优势！,Oxaliplatin联合EPI、5-FU/CF治疗晚期胃,ML17032 : CAPE vs 5-FU in AGCtrial design,FP,Cisplatin,80 mg/m,2,3-hour i.v. infusion,5-FU c.i.,800 mg/m,2,/day; d15 q3w,XP,Cisplatin80 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,ML17032 : CAPE vs 5-FU in AGC,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,Superior response rate with XP,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),ML17032 : XP vs FPprogression,相似的血液学不良发应,XP vs. FP,% of patients,XP(n=1,56,),FP(n=,155,),Neutropenia,33,30,Leukopenia,14,17,Anemia,12,5,Thrombocytopenia,6,6,相似的血液学不良发应 XP vs. FP % of pa,A Phase II Trial of Capecitabine,plus,DDP in AGC,China,2002.6-2003.5,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%,-2005,2006,ASCO,A Phase II Trial of Capecitabi,first-line chemotherapy with fluorouracil, leucovorin and,oxaliplatin (FLO),versus fluorouracil, leucovorin and cisplatin (FLP),F,LO,F 2600mg/m2 24h infusion,L 200mg/m2,oxaliplatin 85mg/m2 q2w,FLP,F 2000mg/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 2006,The primary end point was TTP,first-line chemotherapy with f,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 2006,Superior Performance with FLO,Phase II Study of S-1,DDP vs 5-FU+DDP,for Gastric Cancer,(PI:ML Jin),C:5-FU+DDP,A:S-1,B:S-1+DDP,randomization,Assumed 180 cases,，,60 cases per arm,，,enrollment completed,Objective,：,RR, TTP,Pathologically confirmed,，,unrectable,，,measurable leasions,Evidence,：,SC-101 study, 2008 ASCO meeting,Phase II Study of S-1 DDP vs,Arm,N,CR+PR,TTF(d),OS(d),N,%,A:S1,77,19,24.7*,126,267,B:S-1/CDDP,74,28,37.8,159,433,C:5-FU/CDDP,73,14,19.2,85,309,: Arm B compared with Arm C , P0.05,: Arm B compared with Arm A and C , P0.05,: Arm B compared with Arm A and C , P0.05,Evidence,：,SC-101 study, 2008 ASCO meeting,CR+PRN%A:S1771924.7*126 267 ,Elderly chemo-nave pts (= 65 years) with measurable metastatic or recurrent gastric cancer,armX (N=46, Median age=,71.0 years,),Capecitabine,(1,250 mg/m2 bid, D1-14 every 3 weeks),arm S (N=45,Median age= 70.5 years,),S-1,(4060 mg bid D1-28 every 6 weeks),randomly,10/2004-4/2006,A randomized multi-center phase II trial,：,capecitabine (X) versus S-1 (S) as first-line treatment in elderly patients with mAGC,Y. Kang, D. Shin,2007 ASCO Annual Meeting,Elderly chemo-nave pts (= 65,A randomized study: the activity and safety of capecitabine vs S-1 in elderly pts