NCCN胃癌臨床實(shí)踐指南PPT課件(PPT 69頁(yè))

1、NCCN胃癌臨床實(shí)踐胃 癌第1頁(yè)，共69頁(yè)。Copyright 2005 American Cancer SocietyAge-standardized Incidence Rates for Stomach Cancer in world.From Parkin, D. M. et al. CA Cancer J Clin 2005;55:74-108.世界胃癌年齡調(diào)整發(fā)病率第2頁(yè)，共69頁(yè)。對(duì)1990-1992年中國(guó)的1/10萬(wàn)人口死因抽樣調(diào)查資料中胃癌死亡情況進(jìn)行分析胃癌粗死亡率(crude mortality rate) 25.2/10 萬(wàn)（M：32.8/10 萬(wàn)，F(xiàn)：17.0/10

2、萬(wàn)），占全部惡性腫瘤死亡的23.2%，惡性腫瘤死亡中第一位。（男性是女性1.9倍）中國(guó)胃癌世界人口調(diào)整死亡率(mortality rates adjusted by the world population)男性：40.8/10 萬(wàn)，女性：18.6/10 萬(wàn)，分別是歐美發(fā)達(dá)國(guó)家的4.2-7.9 倍，3.8-8.0 倍有明顯的地區(qū)差異和城鄉(xiāng)差別。全國(guó)抽樣調(diào)查263個(gè)點(diǎn)，胃癌調(diào)整死亡率在2.5-153.0 /10萬(wàn)之間，Urban areas:15.3/10 萬(wàn); Rural areas:24.4/10萬(wàn)，是城市的1.6 倍第3頁(yè)，共69頁(yè)。NCCN共識(shí)分類1類：基于高水平的證據(jù)，NCCN達(dá)成共識(shí)

3、，推薦應(yīng)用2A類：基于包括臨床經(jīng)驗(yàn)在內(nèi)的稍低水平證據(jù)，NCCN達(dá)成共識(shí)，推薦應(yīng)用。2B類：基于包括臨床經(jīng)驗(yàn)在內(nèi)的稍低水平證據(jù)，NCCN未達(dá)成統(tǒng)一共識(shí)（但無(wú)較大分歧）。3類：NCCN對(duì)該建議的適宜性存在較大分歧。除非特別說(shuō)明，本指南中所有的建議均達(dá)成2A類共識(shí)。第4頁(yè)，共69頁(yè)。NCCN 胃癌臨床實(shí)踐指南 2008第1版指南更新主要變化總結(jié)（GAST-1）：workup：PET/CT掃描和EUS作為可選的檢查項(xiàng)目。（GAST 2）： 要求多學(xué)科會(huì)議討論患者所有三個(gè)治療途徑的抉擇 T2以上分期患者將術(shù)前化療作為一類推薦首選治療手段。術(shù)前放化療作為2B類的首選治療手段。（GAST3）： R0術(shù)后分期

4、T2 N0M0及以上者，如術(shù)前采用ECF方案化療，術(shù)后可選擇ECF繼續(xù)（1類）（GAST5）： follow up：近端胃大部或全胃切除者，應(yīng)監(jiān)測(cè)并補(bǔ)充Vit B12（GASTA）：增加綜合治療模式原則新頁(yè)（GASTB、C）： 更新外科及系統(tǒng)化療原則（GASTA）： 新增放療原則新頁(yè)NCCN guidelines -Gastric Cancer Chinese version 1. 2008在整個(gè)治療指南中將chemotherapy/RT 更改為 chemoradiation將salvage 改為palliative第5頁(yè)，共69頁(yè)。與2007版類似注意： 除了特別指出的情況，所有推薦的治療都

5、是2A證據(jù)的。 臨床試驗(yàn)：NCCN認(rèn)為對(duì)于任何一個(gè)腫瘤病人參加臨床實(shí)驗(yàn)都獲得最佳治療. 要特別鼓勵(lì)參與臨床試驗(yàn)。第6頁(yè)，共69頁(yè)。強(qiáng)調(diào)多學(xué)科評(píng)估和協(xié)作！第7頁(yè)，共69頁(yè)。多學(xué)科綜合治療模式有益于局部進(jìn)展期胃癌患者（1類證據(jù)）NCCN專家組基本觀點(diǎn)：不鼓勵(lì)單一學(xué)科成員單方面進(jìn)行治療決策。具備以下條件，可能給局部進(jìn)展期胃癌患者以最佳的綜合治療：例會(huì)形勢(shì)實(shí)用（一周或2周一次），相關(guān)學(xué)科的機(jī)構(gòu)和個(gè)人定期來(lái)共同回顧患者的詳細(xì)資料。每次例會(huì)，各相關(guān)學(xué)科都要積極參與，包括腫瘤外科，腫瘤內(nèi)科，消化科，放射科，病理科。 此外，最好還能包括營(yíng)養(yǎng)科，社工，護(hù)理以及其他支持學(xué)科。所有長(zhǎng)期的治療策略要在全面分期檢查完成

6、后再進(jìn)行，最好在所有治療開(kāi)始之前。決策前共同回顧原始的醫(yī)學(xué)數(shù)據(jù)而非單純閱讀報(bào)告。多學(xué)科團(tuán)隊(duì)做出共識(shí)推薦并摘要記錄在案，對(duì)每位患者是有益的。特定患者的主要治療小組或醫(yī)生應(yīng)尊重以及考慮多學(xué)科團(tuán)隊(duì)所做出的共識(shí)推薦。反饋部分患者的治療隨訪結(jié)果，對(duì)整個(gè)多學(xué)科團(tuán)隊(duì)是有效的實(shí)例教育方式。在例會(huì)期間，正式的定期復(fù)習(xí)相關(guān)文獻(xiàn)，對(duì)整個(gè)多學(xué)科團(tuán)隊(duì)是高效的教育方式。第8頁(yè)，共69頁(yè)。第9頁(yè)，共69頁(yè)。分期CT掃描EUS判斷病灶范圍腹腔鏡有助于部分患者的分期不能根治性切除標(biāo)準(zhǔn)局部進(jìn)展期:3/4站淋巴結(jié)轉(zhuǎn)移, 大血管受侵或被包繞遠(yuǎn)處轉(zhuǎn)移或腹膜種植(包括腹腔脫落細(xì)胞學(xué)陽(yáng)性可切除腫瘤T1者在有經(jīng)驗(yàn)者可采用內(nèi)鏡下胃粘膜切除T1

7、-T3合適的腫瘤切緣4 cm（5 cm）, 鏡下陰性推薦D1/D2淋巴結(jié)清掃, 應(yīng)至少檢查15個(gè)淋巴結(jié)，并結(jié)合位置清掃到2站淋巴結(jié) T4應(yīng)切除受累部位不做常規(guī)脾切除, 除非脾臟受累或脾門(mén)受侵可考慮留置空腸營(yíng)養(yǎng)管姑息手術(shù)可以接受切緣陽(yáng)性，淋巴結(jié)不強(qiáng)求清掃胃腸短路或營(yíng)養(yǎng)管外科治療原則NCCN v.1.2008 Gastric Cancer第10頁(yè)，共69頁(yè)。結(jié)合淋巴結(jié)數(shù)目以及累及區(qū)域分期第11頁(yè)，共69頁(yè)。Japanese Gastric cancer associati（JGCA)腹腔細(xì)胞學(xué)（CY）CY0 腹腔細(xì)胞學(xué)良性或無(wú)法確定CY1 腹腔細(xì)胞學(xué)未見(jiàn)癌細(xì)胞CYx 未作其它遠(yuǎn)處轉(zhuǎn)移（M）M0 腹

8、膜、肝、腹腔細(xì)胞學(xué)外無(wú)遠(yuǎn)處轉(zhuǎn)移M1 腹膜、肝、腹腔細(xì)胞學(xué)外有遠(yuǎn)處轉(zhuǎn)移Mx 不清楚 分期表2 日本胃癌學(xué)會(huì)（JGCA）分期（1998年第13版*）原發(fā)腫瘤（T）T1 腫瘤侵犯粘膜層和/或粘膜肌層(M)和/或粘膜下層(SM)T2 腫瘤侵犯固有肌層(MP)或漿膜下層(SS) T3 腫瘤穿透漿膜(SE) T4 腫瘤侵犯鄰近結(jié)構(gòu)(SI) Nx 不明局部淋巴結(jié)（N）淋巴結(jié)分站分組（見(jiàn)ST-3）淋巴結(jié)轉(zhuǎn)移程度N0 無(wú)淋巴結(jié)轉(zhuǎn)移證據(jù)N1 第一站淋巴結(jié)有轉(zhuǎn)移，第二、三站淋巴結(jié)無(wú)轉(zhuǎn)移N2 第二站淋巴結(jié)有轉(zhuǎn)移，第三站淋巴結(jié)無(wú)轉(zhuǎn)移N3 第三站淋巴結(jié)有轉(zhuǎn)移Nx 區(qū)域淋巴結(jié)無(wú)法評(píng)估肝轉(zhuǎn)移（H）H0 無(wú)肝轉(zhuǎn)移H1 有肝轉(zhuǎn)移

9、Hx 不清楚腹膜轉(zhuǎn)移（P）P0 無(wú)腹膜轉(zhuǎn)移P1 有腹膜轉(zhuǎn)移*本分期源自 Japanese Gastric Cancer Association. Japanese Classification of Gastric Carcinoma - 2nd English Edition. Gastric Cancer (1998) 1: 1024腫瘤可以穿透固有肌層達(dá)胃結(jié)腸韌帶或肝胃韌帶或大小網(wǎng)膜，但沒(méi)有穿透這些結(jié)構(gòu)的臟層腹膜。在這種情況下，原發(fā)腫瘤的分期為T(mén)2。如果穿透覆蓋胃韌帶或網(wǎng)膜的臟層腹膜，則應(yīng)當(dāng)被分為T(mén)3期。腫瘤侵犯大、小網(wǎng)膜、食管和十二指腸不作為T(mén)4,經(jīng)胃壁內(nèi)擴(kuò)展至十二指腸或食管的腫瘤分期

10、取決于包括胃在內(nèi)的這些部位的最大浸潤(rùn)深度。M1的種類應(yīng)注明：LYM: 淋巴結(jié)；PLE: 胸膜；MAR: 骨髓；OSS: 骨；BRA:腦；MEN: 腦膜；SKI: 皮膚；OTH: 其它N0N1N2N3T1IAIBIIIIIAT2IBIIIIIAT3IIIIIAIIIBT4IIIAIIIBIVH1, P1,CY1,M1第12頁(yè)，共69頁(yè)。Regional LN Group According to Location of TumorD14d4d4d653D211p12a14v1998a97LD/L第13頁(yè)，共69頁(yè)。Sasako et al : the long-term outcome of s

11、urvival ：D2 vs D2+, no statistically significant difference69% 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

12、Clin Oncol 2006.24(18S):LBA4015.擴(kuò)大根治 or D2 ? 循證醫(yī)學(xué)證據(jù)第14頁(yè)，共69頁(yè)。A prospective randomized controlled clinical trialin 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 wit

13、h gastric cancer: A randomized controlled trial. Lancet Oncol 2006;7:309-315進(jìn)一步的臨床試驗(yàn)，特別是觀察手術(shù)前后的輔助治療應(yīng)該基于D2式手術(shù)！ D1 or D2 ? 循證醫(yī)學(xué)證據(jù)第15頁(yè)，共69頁(yè)。適合于所有胃癌胃切除標(biāo)本原發(fā)性胃癌胃切除標(biāo)本的檢查原發(fā)性腫瘤*外科切緣評(píng)估淋巴結(jié)評(píng)估原發(fā)性胃癌的組織學(xué)類型Lauren分類，1965日本胃癌研究協(xié)會(huì)（JRSGC）分類，1981WHO分類，2000病理學(xué)分期（pTNM）應(yīng)包括下列參數(shù)：腫瘤的惡性程度（分級(jí)）浸潤(rùn)的深度淋巴結(jié)的部位、數(shù)目及陽(yáng)性數(shù)遠(yuǎn)端及近端外科切緣狀況注釋胃癌原發(fā)

14、腫瘤檢查應(yīng)包括：腫瘤在胃粘膜確切位置及腫瘤范圍；腫瘤距近端和遠(yuǎn)端外科切緣的距離；腫瘤大體形態(tài)，包括腫瘤大小、早期胃癌的形態(tài)類型；腫瘤切面，浸潤(rùn)胃壁情況。 外科切緣評(píng)估：胃切除標(biāo)本有遠(yuǎn)端及近端切緣：部分切除標(biāo)本，遠(yuǎn)端切緣是十二指腸，近端切緣是胃體；全胃切除標(biāo)本，遠(yuǎn)端切緣是十二指腸，近端切緣是食管。外科切緣有3種情況：R0：外科切緣干凈；R1：外科切緣鏡下陽(yáng)性；R2：外科切緣肉眼陽(yáng)性。建議切除的近端切緣應(yīng)距腫瘤邊緣5cm，同時(shí)應(yīng)常規(guī)術(shù)中切緣冰凍檢查。 淋巴結(jié)評(píng)估：見(jiàn)ST-1/2/3。根據(jù)胃切除時(shí)淋巴結(jié)清掃的范圍分為：D0：淋巴結(jié)清掃的范圍不包括所有N1淋巴結(jié)；D1：淋巴結(jié)清掃的范圍不包括所有N2淋

15、巴結(jié)；D2：淋巴結(jié)清掃的范圍不包括所有N3淋巴結(jié)。按照AJCC標(biāo)準(zhǔn)，因?yàn)楸粰z查淋巴結(jié)的數(shù)量和淋巴結(jié)陽(yáng)性率之間有正相關(guān)，應(yīng)檢查至少15個(gè)淋巴結(jié)。 胃癌組織學(xué)類型Lanren分類（1965）：腸型；彌漫型JRSGC分類（1981）： 乳頭狀型 管狀型 低分化型 粘液型 印戒細(xì)胞型WHO分類（2000） 腺癌 腸型 彌漫型 乳頭狀腺癌 管狀腺癌 粘液腺癌 印戒細(xì)胞癌 腺鱗癌 鱗狀細(xì)胞癌 小細(xì)胞癌 未分化癌 其它 胃腺癌組織學(xué)分級(jí)：高分化；中分化；低分化；未分化病理學(xué)分期（pTNM） 病理學(xué)分期與胃癌預(yù)后極其相關(guān)，早期胃癌預(yù)后極好，5年生存率達(dá)90%。建議使用AJCC/UICC分類，在病理報(bào)告中N分期

16、可增加標(biāo)注JRSGC要求的淋巴結(jié)部位。病理診斷原則第16頁(yè)，共69頁(yè)。系統(tǒng)化療原則 NEW遵照原始文獻(xiàn)報(bào)道的藥物劑量/方案, 合理用藥并進(jìn)行適當(dāng)調(diào)整患者合適的器官功能和體力狀況充分考慮化療的毒性和益處, 并始終與患者及家屬討論/交流, 并進(jìn)行患者教育, 警示并防治不良反應(yīng), 避免嚴(yán)重合并癥及縮短持續(xù)時(shí)間患者化療期間仔細(xì)觀察, 及時(shí)治療合并癥, 并適當(dāng)監(jiān)測(cè)患者血液學(xué)改變化療階段及時(shí)評(píng)估療效和長(zhǎng)期合并癥第17頁(yè)，共69頁(yè)。2007.v.22008.v.1Preoperative chemo-therapyECF category 1ECF category 1ECF modification ca

17、tegory 1Preoperative chemo-radiationfluoropyrimidine/leucovorin 2BFluoropyrimidine-based 2BCisplatin-based 2BTaxanes-based 2BIrinotecan-based 2Bpaclitaxel/Docetaxel+fluoropyrimidine (5FU/capecitabine） category 2BUpdate of 2008.v.1 NCCN version第18頁(yè)，共69頁(yè)。可切除胃癌圍手術(shù)期化療-MAGIC trial胃癌（占85%）或低位食管癌（15%）ECF*

18、3cs-手術(shù)-ECF 3cs單一手術(shù)N=2505Y 38%N=2535Y 23%ECF:E 50mg/m2C 60mg/m2FU 200mg/m2/d civD.Cuuningham 2005 ASCO abs 4001Cunningham et al, NEJM 2006第19頁(yè)，共69頁(yè)。Chemo + SurgerySurgeryPatients250253Age6262To Surgery219 (88%)240 (95%)Pts with R0 resection169 (68%)*166 (66%)*No pathologic complete responses可切除胃癌圍手術(shù)期

19、化療-MAGIC trialCunningham et al, NEJM 2006第20頁(yè)，共69頁(yè)。Chemo + SurgerySurgeryPath Size3.1 cm5.0 cm (p = 0.001)T1 / T2T3 / T452%48%38%62% (p= 0.009)N 0/1N 2/384%16%76%24% (p = 0.01)Cunningham et al, NEJM 2006可切除胃癌圍手術(shù)期化療-MAGIC trial第21頁(yè)，共69頁(yè)。Overall SurvivalPatients at riskLogrank p-value = 0.009Hazard Ra

20、tio = 0.75 (95% CI 0.60 - 0.93)CSCS250168111795238272531558050311890.00.10.20.30.40.50.60.70.80.91.0Months from randomization0122436486072149250170253EventsTotalCSCSSurvival rate 第22頁(yè)，共69頁(yè)。可切除胃癌圍手術(shù)期化療 5-FU+DDP in AGC/LE -FFCD 9703 trialFP 23cs（98例）-手術(shù)-FP 2 3cs (RR+SD n+)（54例）單一手術(shù)N=1135Y DFS 34%N=111

21、5Y DFS 21%FP:5-FU 800mg/m2 d1-5 ciDDP 100mg/m2 d1Q4w隨訪 5.7Y賁門(mén)、胃89食管11第23頁(yè)，共69頁(yè)?？汕谐赴﹪中g(shù)期化療 5-FU+DDP in AGC/LE -FFCD 9703 trialSurgeryChemo + SurgerypN111113R084%73%0.043y DFS25%40%5y DFS21%34%0.003HR 0.65V. Boige et al, ASCO 2007 abstr 4510第24頁(yè)，共69頁(yè)?？汕谐赴﹪中g(shù)期化療Patient data-based meta-analysis: CT+S

22、vs S從12隨機(jī)試驗(yàn), 2284 患者中篩選出2102患者,涉及9個(gè)試驗(yàn), 中位隨訪時(shí)間5.3年CT+S vs S HR 0.87 P=0.003 轉(zhuǎn)化為5年絕對(duì)生存率提高4%R0切除率 67% vs 62% p=0.03P.G.Thirion et al, ASCO 2007 abstr 4512第25頁(yè)，共69頁(yè)。GAST-C 1 of 2: preoperative chemoradiation2008.v.1NCCN guideline： Paclitaxel/docetaxel + fluoropyrimidine(5-FU or capecitabine) category 2B

23、；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).？第26頁(yè)，共69頁(yè)。Preoperative chemoradiation: phase IIPhase II Trial of Preoperative Chemoradiation

24、 in Patients With Localized Gastric Adenocarcinoma (RTOG 9904): Quality of Combined Modality Therapy and Pathologic ResponseJaffer A. Ajani JCO 2006：24（24）：3593Phase: IIPatients： 43 cases with localized GC (12% IB; 37% II; 52% III).，20 center Methods: 2cys of 5FU+CF+DDPCRT (infusional 5FU+weekly pac

25、litaxel) 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%）第27頁(yè)，共69頁(yè)。GAST-C 1 of 2: preoperative chemoradiation2008.v.1NCCN guideline： Paclitaxel/docetaxel +

26、 fluoropyrimidine(5-FU+capecitabine) category 2B；Recommendation of Chinese version: Docetaxel might be changed; Category 2B to 3.第28頁(yè)，共69頁(yè)。2007.v.22008.v.1Postoperative chemo-therapyECF category 1（only when preoperative ECF has been administered） ECF category 1ECF modification category 1（only when p

27、reoperative ECF has been administered）Postoperative chemo-radiationfluoropyrimidine/leucovorin 1Fluoropyrimidine-based 1Fluoropyrimidine/cisplatin 2BECF 2BTaxane-based 2BFluoropyrimidine (5FU or capecitabine) category 1Update of 2008.v.1 NCCN versionPostoperative chemotherapy?第29頁(yè)，共69頁(yè)。Stage IB-IV(M

28、0)D0 和 D1占90%第30頁(yè)，共69頁(yè)。第31頁(yè)，共69頁(yè)。第32頁(yè)，共69頁(yè)。GAST-3:T3,T4 or any T,N1 after R0 resection2008.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 noteIf D0/D1 resection

29、: agreed the above;If D2 resection: postoperative chemotherapy recommended.Evidence：D0/D1 operation consists more than 90% in INT0116；2 Meta analysis about adjuvant chemotherapyGASC-study第33頁(yè)，共69頁(yè)。Patients: 23 trials， 4919 ptsMethods: Adjuvant chemotherapy arm(Arm A): 2441 Observation arm(Arm B): 24

30、78 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. Conclus

31、ion: 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 1An updated meta-analysis of adjuvant chemotherapy after curative resection for gastric cancerEurop

32、ean Journal of Surgical Oncology (EJSO) 2008.02.002 第34頁(yè)，共69頁(yè)。META analysis of Adjuvant chemotherapy 2The role of postoperative adjuvant chemotherapy following curative resection for gastric cancer: a meta-analysisShu-Liang Zhao; Jing-Yuan Fang. Renji Hospital, Shanghai, China.Cancer Investigation,

33、May2008, Vol. 26 Issue 3, p317-325,Patients: 15 trials， 3212 pts，Methods: Surgery+adjuvant chemotherapy vs Surgery onlyResults: 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 eit

34、her. Conclusion: Postoperative adjuvant chemotherapy for gastric cancer confers slightly significant benefits compared to the surgery only group. 第35頁(yè)，共69頁(yè)。Postoperative adjuvant chemotherapy S1 monotherapyAdjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. Sakuramoto, S N E

35、ngl J Med，2007，357：1810-1820 1004 cases(stage II/III ，D2,3 years follow up*S-1 monotherapy529 casesOS: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). 2007Gastrointesti

36、nal cancer symposium, sasako MSurgery alone530 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

37、treatment for stage II/III gastric cancer pts after curative D2 dissection. ACTS-GC study JCOG第36頁(yè)，共69頁(yè)。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,

38、 especially after D2 resection for patients with stage II or higher.Postoperative adjuvant chemotherapy Conclusion:第37頁(yè)，共69頁(yè)。GAST-3：after R1 resection2008.v.1NCCN guideline：RT,45-50.4Gy+concurrent 5-FU-based radiosensitization (preferred) +5-FUleucovorinRecommendation of Chinese version: To add “Cli

39、nical 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.第38頁(yè)，共69頁(yè)。2007.v.22008.v.1Metastatic or locally advanced cancerfluoropyrimidine/leucovorin 2B Fluoropyrimidine-bas

40、ed 2BCisplatin-based 2BOxaliplatin-based 2BTaxanes-based 2BIrinotecan-based 2BECF 1DCF 1ECF 1ECF modification 1Irinotecan+cisplatin 2BOxaliplatin+fluoropyrimidine (5-FU or capecitabine) 2BDCF modification 2BIrinotecan+fluoropyrimidine(5-FU or capecitabine) 2BUpdate of 2008.v.1 NCCN versionNo DDP+flu

41、oropyrimidine (5-FU or capecitabine or S1 ) 2BNo paclitaxel-based regimens；第39頁(yè)，共69頁(yè)。V325 研究結(jié)果TCF(多西紫杉醇、順鉑、5FU)是用于預(yù)后較好的患者的一項(xiàng)新的治療選擇Moiseyenko et al, JCO 2007, 例數(shù)總體緩解疾病進(jìn)展時(shí)間（月）總生存期（月）34級(jí)毒性TCF221/22737%5.69.2腹瀉，感染，中性粒細(xì)胞減少癥*p=0.01p=0.0004p=0.02CF#4002224/23025%3.78.6胃炎，腎毒性*34級(jí)毒性包括：81的非血液學(xué)毒性反應(yīng)，75的血液學(xué)毒性反應(yīng)中

42、30伴有中性粒細(xì)胞減少性發(fā)熱第40頁(yè)，共69頁(yè)。CPT-11 for AGC期多中心臨床研究（2003 ASCO）FFCD 9803 法國(guó)Bouche O et al. J Clin Oncol2004;22:431927例 數(shù)RRmTTPmOSLV5FU2 4513%3.2m6.8mLV5FU2-DDP4427%4.9m9.5mLV5FU2-CPT-114540%6.7m11.3m第41頁(yè)，共69頁(yè)。CPT-11聯(lián)合5-FU治療AGC-III期臨床試驗(yàn)（2005 ASCO）N=170CPT-11 80mg/m2CF 500mg/m25FU 2000mg/m2 civ1/W x 6w N=16

43、3CDDP 100mg/m2 d15FU 1000mg/m2/d d1-5Q4WN=333 AGCRR 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 p0.53M. Dank 2005 ASCO abs 4003第42頁(yè)，共69頁(yè)。REAL-2: 療效（Efficacy）EfficacyECFN=263ECXN=250EOFN=245EOXN=244P: ECF vs EOXRR (%)41464248 1 year OS (%) 37.740.840.446.8OS (mo)9.99

44、.99.311.20.025Cunningham et al. ASCO 2006 LBA 4017第43頁(yè)，共69頁(yè)。ECFEOFECXEOXGrade 3/4 non-haematological toxicity, %36423345Grade 3/4 neutropenia, %42305128p-value 0.0080.00430.001REAL 2: 安全性 safety outcomes第44頁(yè)，共69頁(yè)。Oxaliplatin聯(lián)合EPI、5-FU/CF治療晚期胃癌的臨床多中心研究 china用藥方法樂(lè)沙定 100mg/m2 d1EPI 50mg/m2 d1CF 200mg/m

45、2 d1-35-FU 500mg/m2 CIV d1-3每3周重復(fù)，治療至少3個(gè)周期評(píng)價(jià)療效及毒性反應(yīng)CR 2例（5.6%）PR 13例（36.1%）SD 17例（47.2%） 總有效率41.7%。其中初治患者9/20（45%）復(fù)治患者6/16（37.5%）主要不良反應(yīng)：骨髓抑制： -OANC7/36（19.4%）， OPLT3/36（8.3%），O Hb4/36（11.1%），O神經(jīng)末梢毒性 4/36（11.1%），以EPI為基礎(chǔ)的三藥聯(lián)合可行！EOX有明顯生存優(yōu)勢(shì)！第45頁(yè)，共69頁(yè)。ML17032 : CAPE vs 5-FU in AGCtrial designFPCisplatin8

46、0 mg/m2 3-hour i.v. infusion5-FU c.i. 800 mg/m2/day; d15 q3wXPCisplatin80 mg/m2 3-hour i.v. infusionCapecitabine 1000 mg/m2 twice daily; d114 q3wKPS 70%1875 yearsAdvanced and/ormetastatic gastric cancer (AGC)1 measurable lesionNo prior treatment for AGCRANDO MIZATION第46頁(yè)，共69頁(yè)。Superior response rate

47、with XP vs. FPConfirmed response% (95% CI)XP(n=160)FP(n=156)p-valueOverall response41 (3349)29 (2237)0.030Complete response230.668Partial response39260.019Progressive disease10180.041第47頁(yè)，共69頁(yè)。ML17032 : XP vs FPprogression-free survival.HR 0.81 Estimated probabilityHR=0.81 (95% CI: 0.631.04)Compared

48、 to HR upper limit 1.25, p=0.00080Months24681012141618202224261.00.80.60.40.20.0Per protocol analysisXP (n=139) FP (n=137)Median PFSmonths (95% CI)5.6 (4.97.3)5.0 (4.26.3)第48頁(yè)，共69頁(yè)。相似的血液學(xué)不良發(fā)應(yīng) XP vs. FP % of patientsXP(n=156)FP(n=155)Neutropenia3330Leukopenia 1417Anemia125Thrombocytopenia66第49頁(yè)，共69頁(yè)。

49、A Phase II Trial of Capecitabine plus DDP in AGCChina2002.6-2003.5, N=145, Cape 1000mg/m2 Bid d1-14 DDP 20mg/m2 iv d1-5 q3W130pts evaluable : 98M/32F Age: 53.7ysResultsCR 10 (8%)PR 48(37%)SD 51(39%)PD 21(16%)OS 12mSafety：grade 3-4 adverse event 5% -2005,2006 ASCO第50頁(yè)，共69頁(yè)。first-line chemotherapy wit

50、h fluorouracil, leucovorin and oxaliplatin (FLO) versus fluorouracil, leucovorin and cisplatin (FLP)FLOF 2600mg/m2 24h infusion, L 200mg/m2, oxaliplatin 85mg/m2 q2wFLPF 2000mg/m2 24h infusion, qwL 200mg/m2, qw cisplatin 50mg/m2, q2w. Total 220 pts Median age 64 yrs Advanced and/ormetastatic gastric

51、cancer (AGC)RANDO MIZATIONS. Al-Batran, J. Hartmann, ASCO 2006The primary end point was TTP第51頁(yè)，共69頁(yè)。Superior Performance with FLO vs. FLPConfirmed response% (95% CI)FLO(N=98)FLP(n=102)p-valueOverall response34%27%0.012 TTP5.73.80.081TTF5.33.10.028S. Al-Batran, J. Hartmann, ASCO 2006第52頁(yè)，共69頁(yè)。Phase

52、II Study of S-1 DDP vs 5-FU+DDP for Gastric Cancer (PI:ML Jin)C:5-FU+DDPA:S-1B:S-1+DDPrandomizationAssumed 180 cases，60 cases per arm，enrollment completedObjective：RR, TTPPathologically confirmed，unrectable，measurable leasionsEvidence ：SC-101 study 2008 ASCO meeting第53頁(yè)，共69頁(yè)。ArmNCR+PRTTF(d)OS(d)N%A:

53、S1771924.7*126 267 B:S-1/CDDP742837.8159433C:5-FU/CDDP731419.285 309 : 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 , P0.05Evidence ：SC-101 study 2008 ASCO meeting第54頁(yè)，共69頁(yè)。Elderly chemo-nave pts (= 65 years) with measurable metastatic o

54、r 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) randomly10/2004-4/2006 A randomized multi-center phase II trial：capecitabine (X) versus S-1 (S) as first-line tr

55、eatment in elderly patients with mAGCY. Kang, D. Shin 2007 ASCO Annual Meeting第55頁(yè)，共69頁(yè)。A randomized study: the activity and safety of capecitabine vs S-1 in elderly pts with AGC phase II Y. Kang, JCO, 2007 ASCO Meetings Proceedings Part I.Vol 25, No. 18S: 4546) Evidence ：capecitabine vs S-1 Phase I

56、IXeloda (n=44) S-1 (n=45)Regimen1250mg/ bid d1-14/3W40-60mg/ bid d1-28/6W CR (%) 01(2.2%) PR (%) 13 (29.5) 12 (26.7) mOS (mo)10.07.9mTTP(mo)4.84.2mTTF(mo)4.43第56頁(yè)，共69頁(yè)。Xeloda (n=44) S-1 (n=45)Grade 3/4 (%)1250mg/ bid d1-14/3W40-60mg/ bid d1-28/6W Leukopenia6.84.8Asthenia07.2Anorexia6.89.5Diarrhea2.3

57、0HFS6.80Evidence ：capecitabine vs S-1 toxity 第57頁(yè)，共69頁(yè)。2007.v.22008.v.1Metastatic or locally advanced cancerfluoropyrimidine/leucovorin 2B Fluoropyrimidine-based 2BCisplatin-based 2BOxaliplatin-based 2BTaxanes-based 2BIrinotecan-based 2BECF 1DCF 1ECF 1ECF modification 1Irinotecan+cisplatin 2BOxalipl

58、atin+fluoropyrimidine (5-FU or capecitabine) 2BDCF modification 2BIrinotecan+fluoropyrimidine(5-FU or capecitabine) 2BUpdate of 2008.v.1 NCCN versionDDP+fluoropyrimidine (5-FU or capecitabine or S1 ) 2B第58頁(yè)，共69頁(yè)。a randomized phase II trial of the Swiss Group for Clinical Cancer Research.Chemotherapy

59、-naive patientsECF vs DC vs DCFEvidence 1: docetaxelRoth AD, Fazio N, et al, J Clin Oncol. 2007 Aug 1;25(22):3217-23. n=119ECFDCDCFORR25.0% 18.5% 36.6% Median OS8.3 11.010.4neutropenia G 3/4 34%49 %57%QOLsimilar第59頁(yè)，共69頁(yè)。a randomized phase II study in Germanypatients with untreated, advanced gastric

60、 adenocarcinoma.Evidence 2: docetaxelThuss-Patience PC, Kretzschmar A, et al ：J Clin Oncol. 2005 Jan 20;23(3):494-501. n=90ECFDFORR35.6% 37.8% Median OS9.7m9.5mTTP 5.3m5.5m第60頁(yè)，共69頁(yè)。a randomized phase II trial106 patients includedwDCF vs wDXwDCF :DOC 30mg/m2 d1 d8; DDP 60mg/m2; 5-Fu 200mg/m2 civ wDX