胃癌解讀培訓課件

1、沈琳胃癌解讀沈琳胃癌解讀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)病率沈琳胃癌解讀2Copyright 2005 American Cance對1990-1992年中國的1/10萬人口死因抽樣調(diào)查資料中胃癌死亡情況進行分析胃癌粗死亡率(crude mortality rate) 25.2/10 萬（M：32.

2、8/10 萬，F(xiàn)：17.0/10 萬），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，女性：18.6/10 萬，分別是歐美發(fā)達國家的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。全國抽樣調(diào)查263個點，胃癌調(diào)整死亡率在2.5-153.0 /10萬之間，Urban areas:15.3/10 萬; Rural areas:24.4/10萬，是城市的1.6 倍沈琳胃癌解讀3對1990-1992年中國

3、的1/10萬人口死因抽樣調(diào)查資料中NCCN共識分類1類：基于高水平的證據(jù)，NCCN達成共識，推薦應用2A類：基于包括臨床經(jīng)驗在內(nèi)的稍低水平證據(jù)，NCCN達成共識，推薦應用。2B類：基于包括臨床經(jīng)驗在內(nèi)的稍低水平證據(jù)，NCCN未達成統(tǒng)一共識（但無較大分歧）。3類：NCCN對該建議的適宜性存在較大分歧。除非特別說明，本指南中所有的建議均達成2A類共識。沈琳胃癌解讀4NCCN共識分類1類：基于高水平的證據(jù)，NCCN達成共識，推NCCN 胃癌臨床實踐指南 2008第1版指南更新主要變化總結(jié)（GAST-1）：workup：PET/CT掃描和EUS作為可選的檢查項目。（GAST 2）： 要求多學科會議討論

4、患者所有三個治療途徑的抉擇 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，應監(jiān)測并補充Vit B12（GASTA）：增加綜合治療模式原則新頁（GASTB、C）： 更新外科及系統(tǒng)化療原則（GASTA）： 新增放療原則新頁NCCN guidelines -Gastric Cancer Chinese version 1. 2008在整個治療指南中將chemotherapy/RT 更改為 c

5、hemoradiation將salvage 改為palliative沈琳胃癌解讀5NCCN 胃癌臨床與2007版類似注意： 除了特別指出的情況，所有推薦的治療都是2A證據(jù)的。 臨床試驗：NCCN認為對于任何一個腫瘤病人參加臨床實驗都獲得最佳治療. 要特別鼓勵參與臨床試驗。沈琳胃癌解讀6與2007版類似注意：沈琳胃癌解讀6強調(diào)多學科評估和協(xié)作！沈琳胃癌解讀7強調(diào)多學科評估和協(xié)作！沈琳胃癌解讀7多學科綜合治療模式有益于局部進展期胃癌患者（1類證據(jù)）NCCN專家組基本觀點：不鼓勵單一學科成員單方面進行治療決策。具備以下條件，可能給局部進展期胃癌患者以最佳的綜合治療：例會形勢實用（一周或2周一次），相

6、關(guān)學科的機構(gòu)和個人定期來共同回顧患者的詳細資料。每次例會，各相關(guān)學科都要積極參與，包括腫瘤外科，腫瘤內(nèi)科，消化科，放射科，病理科。 此外，最好還能包括營養(yǎng)科，社工，護理以及其他支持學科。所有長期的治療策略要在全面分期檢查完成后再進行，最好在所有治療開始之前。決策前共同回顧原始的醫(yī)學數(shù)據(jù)而非單純閱讀報告。多學科團隊做出共識推薦并摘要記錄在案，對每位患者是有益的。特定患者的主要治療小組或醫(yī)生應尊重以及考慮多學科團隊所做出的共識推薦。反饋部分患者的治療隨訪結(jié)果，對整個多學科團隊是有效的實例教育方式。在例會期間，正式的定期復習相關(guān)文獻，對整個多學科團隊是高效的教育方式。沈琳胃癌解讀8多學科綜合治療模式

7、有益于局部進展期胃癌患者（1類證據(jù)）沈琳胃沈琳胃癌解讀9沈琳胃癌解讀9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準局部進展期:3/4站淋巴結(jié)轉(zhuǎn)移, 大血管受侵或被包繞遠處轉(zhuǎn)移或腹膜種植(包括腹腔脫落細胞學陽性可切除腫瘤T1者在有經(jīng)驗者可采用內(nèi)鏡下胃粘膜切除T1-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, 應至少檢查15個淋巴結(jié)，并結(jié)合位置清掃到2站淋巴結(jié) T4應切除受累部位不做常規(guī)脾切除, 除非脾臟受累或脾門受侵可考慮留置空腸營養(yǎng)管姑息手術(shù)可以接受切緣陽性，淋巴結(jié)不強求清掃胃腸短路或營養(yǎng)管外科治療原則NCCN v.1.2008 G

8、astric Cancer沈琳胃癌解讀10分期外科治療原則NCCN v.1.2008 結(jié)合淋巴結(jié)數(shù)目以及累及區(qū)域分期沈琳胃癌解讀11結(jié)合淋巴結(jié)數(shù)目以及累及區(qū)域分期沈琳胃癌解讀11Japanese Gastric cancer associati（JGCA)腹腔細胞學（CY）CY0 腹腔細胞學良性或無法確定CY1 腹腔細胞學未見癌細胞CYx 未作其它遠處轉(zhuǎn)移（M）M0 腹膜、肝、腹腔細胞學外無遠處轉(zhuǎn)移M1 腹膜、肝、腹腔細胞學外有遠處轉(zhuǎn)移Mx 不清楚 分期表2 日本胃癌學會（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

9、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ST-3）淋巴結(jié)轉(zhuǎn)移程度N0 無淋巴結(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)無轉(zhuǎn)移N2 第二站淋巴結(jié)有轉(zhuǎn)移，第三站淋巴結(jié)無轉(zhuǎn)移N3 第三站淋巴結(jié)有轉(zhuǎn)移Nx 區(qū)域淋巴結(jié)無法評估肝轉(zhuǎn)移（H）H0 無肝轉(zhuǎn)移H1 有肝轉(zhuǎn)移Hx 不清楚腹膜轉(zhuǎn)移（P）P0 無腹膜轉(zhuǎn)移P1 有腹膜轉(zhuǎn)移*本分期源自 Japanese Gastric Cancer Association. Japanese Classification of Gastric Carcin

10、oma - 2nd English Edition. Gastric Cancer (1998) 1: 1024腫瘤可以穿透固有肌層達胃結(jié)腸韌帶或肝胃韌帶或大小網(wǎng)膜，但沒有穿透這些結(jié)構(gòu)的臟層腹膜。在這種情況下，原發(fā)腫瘤的分期為T2。如果穿透覆蓋胃韌帶或網(wǎng)膜的臟層腹膜，則應當被分為T3期。腫瘤侵犯大、小網(wǎng)膜、食管和十二指腸不作為T4,經(jīng)胃壁內(nèi)擴展至十二指腸或食管的腫瘤分期取決于包括胃在內(nèi)的這些部位的最大浸潤深度。M1的種類應注明：LYM: 淋巴結(jié)；PLE: 胸膜；MAR: 骨髓；OSS: 骨；BRA:腦；MEN: 腦膜；SKI: 皮膚；OTH: 其它N0N1N2N3T1IAIBIIIIIAT2I

11、BIIIIIAT3IIIIIAIIIBT4IIIAIIIBIVH1, P1,CY1,M1沈琳胃癌解讀12Japanese Gastric cancer associRegional LN Group According to Location of TumorD14d4d4d653D211p12a14v1998a97LD/L沈琳胃癌解讀13Regional LN Group According toSasako et al : the long-term outcome of survival ：D2 vs D2+, no statistically significant differenc

12、e69% 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.擴大根治 or D2 ? 循證醫(yī)學證據(jù)沈琳胃癌解讀1

13、4Sasako et al :擴大根治 or D2 ? 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 with gastric cancer: A randomized co

14、ntrolled trial. Lancet Oncol 2006;7:309-315進一步的臨床試驗，特別是觀察手術(shù)前后的輔助治療應該基于D2式手術(shù)！ D1 or D2 ? 循證醫(yī)學證據(jù)沈琳胃癌解讀15A prospective randomized contr適合于所有胃癌胃切除標本原發(fā)性胃癌胃切除標本的檢查原發(fā)性腫瘤*外科切緣評估淋巴結(jié)評估原發(fā)性胃癌的組織學類型Lauren分類，1965日本胃癌研究協(xié)會（JRSGC）分類，1981WHO分類，2000病理學分期（pTNM）應包括下列參數(shù)：腫瘤的惡性程度（分級）浸潤的深度淋巴結(jié)的部位、數(shù)目及陽性數(shù)遠端及近端外科切緣狀況注釋胃癌原發(fā)腫瘤檢查應

15、包括：腫瘤在胃粘膜確切位置及腫瘤范圍；腫瘤距近端和遠端外科切緣的距離；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，浸潤胃壁情況。 外科切緣評估：胃切除標本有遠端及近端切緣：部分切除標本，遠端切緣是十二指腸，近端切緣是胃體；全胃切除標本，遠端切緣是十二指腸，近端切緣是食管。外科切緣有3種情況：R0：外科切緣干凈；R1：外科切緣鏡下陽性；R2：外科切緣肉眼陽性。建議切除的近端切緣應距腫瘤邊緣5cm，同時應常規(guī)術(shù)中切緣冰凍檢查。 淋巴結(jié)評估：見ST-1/2/3。根據(jù)胃切除時淋巴結(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淋巴結(jié)；D2

16、：淋巴結(jié)清掃的范圍不包括所有N3淋巴結(jié)。按照AJCC標準，因為被檢查淋巴結(jié)的數(shù)量和淋巴結(jié)陽性率之間有正相關(guān)，應檢查至少15個淋巴結(jié)。 胃癌組織學類型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 印戒細胞癌 腺鱗癌 鱗狀細胞癌 小細胞癌 未分化癌 其它 胃腺癌組織學分級：高分化；中分化；低分化；未分化病理學分期（pTNM） 病理學分期與胃癌預后極其相關(guān)，早期胃癌預后極好，5年生存率達90%。建議使用AJCC/UICC分類，在病理報告中N分期可增加標注

17、JRSGC要求的淋巴結(jié)部位。病理診斷原則沈琳胃癌解讀16適合于所有胃癌胃切除標本注釋 胃癌組織學類型病理診斷原則沈系統(tǒng)化療原則 NEW遵照原始文獻報道的藥物劑量/方案, 合理用藥并進行適當調(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, 并進行患者教育, 警示并防治不良反應, 避免嚴重合并癥及縮短持續(xù)時間患者化療期間仔細觀察, 及時治療合并癥, 并適當監(jiān)測患者血液學改變化療階段及時評估療效和長期合并癥沈琳胃癌解讀17系統(tǒng)化療原則 NEW遵照原始文獻報道的藥物劑量/方案, 合2007.v.22008.v.1Preoperative chemo-thera

18、pyECF category 1ECF category 1ECF modification category 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沈琳胃癌解讀18

19、2007.v.22008.v.1Preoperative c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* 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沈琳胃癌解讀19可切除胃癌圍手術(shù)期化療-MAGIC trial胃癌（占Chemo + SurgerySurgeryPatients250253Age6262To Surge

20、ry219 (88%)240 (95%)Pts with R0 resection169 (68%)*166 (66%)*No pathologic complete responses可切除胃癌圍手術(shù)期化療-MAGIC trialCunningham et al, NEJM 2006沈琳胃癌解讀20Chemo + SurgerySurgeryPatientsChemo + 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 =

21、 0.01)Cunningham et al, NEJM 2006可切除胃癌圍手術(shù)期化療-MAGIC trial沈琳胃癌解讀21Chemo + SurgerySurgeryPath SizOverall SurvivalPatients at riskLogrank p-value = 0.009Hazard Ratio = 0.75 (95% CI 0.60 - 0.93)CSCS250168111795238272531558050311890.00.10.20.30.40.50.60.70.80.91.0Months from randomization01224364860721492

22、50170253EventsTotalCSCSSurvival rate 沈琳胃癌解讀22Overall SurvivalPatients at ri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=1115Y DFS 21%FP:5-FU 800mg/m2 d1-5 ciDDP 100mg/m2 d1Q4w隨訪 5.7Y賁門、胃89食管11沈琳胃癌解讀23可切除胃癌圍手術(shù)期化療 5-FU+DDP in AGC/L可切除胃癌圍手術(shù)

23、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沈琳胃癌解讀24可切除胃癌圍手術(shù)期化療 5-FU+DDP in AGC/L可切除胃癌圍手術(shù)期化療Patient data-based meta-analysis: CT+S vs S從12隨機試驗, 2284 患者中篩選出2102患者,涉及9個試驗, 中位隨訪時間5.3年CT+S vs S H

24、R 0.87 P=0.003 轉(zhuǎn)化為5年絕對生存率提高4%R0切除率 67% vs 62% p=0.03P.G.Thirion et al, ASCO 2007 abstr 4512沈琳胃癌解讀25可切除胃癌圍手術(shù)期化療Patient data-basedGAST-C 1 of 2: preoperative chemoradiation2008.v.1NCCN guideline： Paclitaxel/docetaxel + fluoropyrimidine(5-FU or capecitabine) category 2B；Recommendation of Chinese versio

25、n: 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).？沈琳胃癌解讀26GAST-C 1 of 2: preoperative chPreoperative chemoradiation: phase IIPhase II Trial of Preoperative Chemoradiation in P

26、atients 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 paclitax

27、el) 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%）沈琳胃癌解讀27Preoperative chemoradiation: pGAST-C 1 of 2: preoperative chemoradiation2008.v.1NCCN guideline：

28、 Paclitaxel/docetaxel + fluoropyrimidine(5-FU+capecitabine) category 2B；Recommendation of Chinese version: Docetaxel might be changed; Category 2B to 3.沈琳胃癌解讀28GAST-C 1 of 2: preoperative c2007.v.22008.v.1Postoperative chemo-therapyECF category 1（only when preoperative ECF has been administered） ECF

29、 category 1ECF modification category 1（only when preoperative 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 version

30、Postoperative chemotherapy?沈琳胃癌解讀292007.v.22008.v.1Postoperative Stage IB-IV(M0)D0 和 D1占90%沈琳胃癌解讀30Stage IB-IV(M0)沈琳胃癌解讀30沈琳胃癌解讀31沈琳胃癌解讀31沈琳胃癌解讀32沈琳胃癌解讀32GAST-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

31、or ECF if received preoperatively（category 1）Recommendation of Chinese version: Add foot noteIf 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 chemotherapyGASC-study沈琳

32、胃癌解讀33GAST-3:T3,T4 or any T,N1 afterPatients: 23 trials， 4919 ptsMethods: 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

33、: 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.

34、 META analysis of Adjuvant chemotherapy 1An updated meta-analysis of adjuvant chemotherapy after curative resection for gastric cancerEuropean Journal of Surgical Oncology (EJSO) 2008.02.002 沈琳胃癌解讀34Patients: 23 trials， 4919 ptsMMETA analysis of Adjuvant chemotherapy 2The role of postoperative adjuv

35、ant chemotherapy following curative resection for gastric cancer: a meta-analysisShu-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 onlyResults: RR fo

36、r 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

37、 only group. 沈琳胃癌解讀35META analysis of Adjuvant chemPostoperative adjuvant chemotherapy S1 monotherapyAdjuvant 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 monotherapy529 casesOS:80.

38、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 MSurgery alone530 cases*12/2005 showed that HR of death for S-1 to C was 0.5

39、7, 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沈琳胃癌解讀36Pos

40、toperative adjuvant chemothPostoperative 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.Postopera

41、tive adjuvant chemotherapy Conclusion:沈琳胃癌解讀37Postoperative chemoradiation mGAST-3：after R1 resection2008.v.1NCCN guideline：RT,45-50.4Gy+concurrent 5-FU-based radiosensitization (preferred) +5-FUleucovorinRecommendation of Chinese version: To add “Clinical trials” as another option.Reason：R1 resecti

42、on is not radical, till now, no standard therapy has been accepted, it should be better to find the appropriate ones by clinical studies.沈琳胃癌解讀38GAST-3：after R1 resection2008.2007.v.22008.v.1Metastatic or locally advanced cancerfluoropyrimidine/leucovorin 2B Fluoropyrimidine-based 2BCisplatin-based

43、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+fluoropyrimidine (5-FU o

44、r capecitabine or S1 ) 2BNo paclitaxel-based regimens；沈琳胃癌解讀392007.v.22008.v.1Metastatic or V325 研究結(jié)果TCF(多西紫杉醇、順鉑、5FU)是用于預后較好的患者的一項新的治療選擇Moiseyenko et al, JCO 2007, 例數(shù)總體緩解疾病進展時間（月）總生存期（月）34級毒性TCF221/22737%5.69.2腹瀉，感染，中性粒細胞減少癥*p=0.01p=0.0004p=0.02CF#4002224/23025%3.78.6胃炎，腎毒性*34級毒性包括：81的非血液學毒性反應，75的血

45、液學毒性反應中30伴有中性粒細胞減少性發(fā)熱沈琳胃癌解讀40V325 研究結(jié)果TCF(多西紫杉醇、順鉑、5FU)是用于預CPT-11 for AGC期多中心臨床研究（2003 ASCO）FFCD 9803 法國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沈琳胃癌解讀41CPT-11 for AGC期多中心臨床研究（200CPT-11聯(lián)合5-FU治療AGC-III期臨床試驗（2005 ASCO）N

46、=170CPT-11 80mg/m2CF 500mg/m25FU 2000mg/m2 civ1/W x 6w N=163CDDP 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沈琳胃癌解讀42CPT-11聯(lián)合5-FU治療AGC-III期臨床試驗REAL-2: 療效（Efficacy）EfficacyECFN=263ECXN=250EO

47、FN=245EOXN=244P: ECF vs EOXRR (%)41464248 1 year OS (%) 37.740.840.446.8OS (mo)9.99.99.311.20.025Cunningham et al. ASCO 2006 LBA 4017沈琳胃癌解讀43REAL-2: 療效（Efficacy）EfficacyECECFEOFECXEOXGrade 3/4 non-haematological toxicity, %36423345Grade 3/4 neutropenia, %42305128p-value 0.0080.00430.001REAL 2: 安全性 s

48、afety outcomes沈琳胃癌解讀44ECFEOFECXEOXGrade 3/4 non-haemOxaliplatin聯(lián)合EPI、5-FU/CF治療晚期胃癌的臨床多中心研究 china用藥方法樂沙定 100mg/m2 d1EPI 50mg/m2 d1CF 200mg/m2 d1-35-FU 500mg/m2 CIV d1-3每3周重復，治療至少3個周期評價療效及毒性反應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%）復治患者6/16（37.5%）主要不良反應：骨髓抑制： -OANC7/36（19.4%）， O

49、PLT3/36（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！沈琳胃癌解讀45Oxaliplatin聯(lián)合EPI、5-FU/CF治療晚期胃ML17032 : CAPE vs 5-FU in AGCtrial designFPCisplatin80 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 dail

50、y; d114 q3wKPS 70%1875 yearsAdvanced and/ormetastatic gastric cancer (AGC)1 measurable lesionNo prior treatment for AGCRANDO MIZATION沈琳胃癌解讀46ML17032 : CAPE vs 5-FU in AGCSuperior response rate with XP vs. FPConfirmed response% (95% CI)XP(n=160)FP(n=156)p-valueOverall response41 (3349)29 (2237)0.030C

51、omplete response230.668Partial response39260.019Progressive disease10180.041沈琳胃癌解讀47Superior response rate with XPML17032 : XP vs FPprogression-free survival.HR 0.81 Estimated probabilityHR=0.81 (95% CI: 0.631.04)Compared to HR upper limit 1.25, p=0.00080Months24681012141618202224261.00.80.60.40.20.

52、0Per protocol analysisXP (n=139) FP (n=137)Median PFSmonths (95% CI)5.6 (4.97.3)5.0 (4.26.3)沈琳胃癌解讀48ML17032 : XP vs FPprogression相似的血液學不良發(fā)應 XP vs. FP % of patientsXP(n=156)FP(n=155)Neutropenia3330Leukopenia 1417Anemia125Thrombocytopenia66沈琳胃癌解讀49相似的血液學不良發(fā)應 XP vs. FP % of paA Phase II Trial of Capeci

53、tabine 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 = 65 years) with measurable metastatic or recurrent gastric cancer armX (N=46, Me

54、dian 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 treatment in elderly patients with mAGCY. K

55、ang, D. Shin 2007 ASCO Annual Meeting沈琳胃癌解讀55Elderly chemo-nave pts (= 65A 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 IIXeloda (n=44)

56、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沈琳胃癌解讀56A randomized study: the activiXeloda (n=44) S-1 (n=45)Grade 3/4 (%)1250mg/ bid d1-14/3W40-60mg/ bid d1-28/6W Leukopenia6.84.8Asthenia07.2Anorexia6.89

57、.5Diarrhea2.30HFS6.80Evidence ：capecitabine vs S-1 toxity 沈琳胃癌解讀57Xeloda (n=44) S-1 (n=45)Grade 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 mod

58、ification 1Irinotecan+cisplatin 2BOxaliplatin+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沈琳胃癌解讀582007.v.22008.v.1Metastatic or a randomized phase

59、II trial of the Swiss Group for Clinical Cancer Research.Chemotherapy-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沈琳胃癌解讀59a randomized

60、 phase II trial ofa randomized phase II study in Germanypatients with untreated, advanced gastric 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沈琳胃癌解讀60a randomized phase II s