NCCN胃癌臨床實踐指南PPT課件(PPT 69頁)

1、NCCN胃癌臨床實踐胃 癌第1頁，共69頁。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，共69頁。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：32.8/10 萬，F(xiàn)：17.0/10

2、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 倍第3頁，共69頁。NCCN共識分類1類：基于高水平的證據(jù)，NCCN達成共識

3、，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。第4頁，共69頁。NCCN 胃癌臨床實踐指南 2008第1版指南更新主要變化總結（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患者所有三個治療途徑的抉擇 T2以上分期患者將術前化療作為一類推薦首選治療手段。術前放化療作為2B類的首選治療手段。（GAST3）： R0術后分期

4、T2 N0M0及以上者，如術前采用ECF方案化療，術后可選擇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 chemoradiation將salvage 改為palliative第5頁，共69頁。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：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。第6頁，共69頁。強調(diào)多學科評估和協(xié)作！第7頁，共69頁。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），相關學科的機構和個人定期來共同回顧患者的詳細資料。每次例會，各相關學科都要積極參與，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

6、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文獻，對整個多學科團隊是高效的教育方式。第8頁，共69頁。第9頁，共69頁。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站淋巴結轉移, 大血管受侵或被包繞遠處轉移或腹膜種植(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

7、-T3合適的腫瘤切緣4 cm（5 cm）, 鏡下陰性推薦D1/D2淋巴結清掃, 應至少檢查15個淋巴結，并結合位置清掃到2站淋巴結 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)管姑息手術可以接受切緣陽性，淋巴結不強求清掃胃腸短路或營養(yǎng)管外科治療原則NCCN v.1.2008 Gastric Cancer第10頁，共69頁。結合淋巴結數(shù)目以及累及區(qū)域分期第11頁，共69頁。Japanese 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 未作其它遠處轉移（M）M0 腹

8、膜、肝、腹腔細胞學外無遠處轉移M1 腹膜、肝、腹腔細胞學外有遠處轉移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 腫瘤侵犯鄰近結構(SI) Nx 不明局部淋巴結（N）淋巴結分站分組（見ST-3）淋巴結轉移程度N0 無淋巴結轉移證據(jù)N1 第一站淋巴結有轉移，第二、三站淋巴結無轉移N2 第二站淋巴結有轉移，第三站淋巴結無轉移N3 第三站淋巴結有轉移Nx 區(qū)域淋巴結無法評估肝轉移（H）H0 無肝轉移H1 有肝轉移

9、Hx 不清楚腹膜轉移（P）P0 無腹膜轉移P1 有腹膜轉移*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胃結腸韌帶或肝胃韌帶或大小網(wǎng)膜，但沒有穿透這些結構的臟層腹膜。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

10、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；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，共69頁。Regional LN Group According to Location of TumorD14d4d4d653D211p12a14v1998a97LD/L第13頁，共69頁。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.擴大根治 or D2 ? 循證醫(yī)學證據(jù)第14頁，共69頁。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進一步的臨床試驗，特別是觀察手術前后的輔助治療應該基于D2式手術！ D1 or D2 ? 循證醫(yī)學證據(jù)第15頁，共69頁。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)

14、腫瘤檢查應包括：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)術中切緣冰凍檢查。 淋巴結評估：見ST-1/2/3。根據(jù)胃切除時淋巴結清掃的范圍分為：D0：淋巴結清掃的范圍不包括所有N1淋巴結；D1：淋巴結清掃的范圍不包括所有N2淋

15、巴結；D2：淋巴結清掃的范圍不包括所有N3淋巴結。按照AJCC標準，因為被檢查淋巴結的數(shù)量和淋巴結陽性率之間有正相關，應檢查至少15個淋巴結。 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，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

16、可增加標注JRSGC要求的淋巴結部位。病理診斷原則第16頁，共69頁。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第17頁，共69頁。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，共69頁?？汕谐赴﹪中g期化療-MAGIC trial胃癌（占85%）或低位食管癌（15%）ECF*

18、3cs-手術-ECF 3cs單一手術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，共69頁。Chemo + SurgerySurgeryPatients250253Age6262To Surgery219 (88%)240 (95%)Pts with R0 resection169 (68%)*166 (66%)*No pathologic complete responses可切除胃癌圍手術期

19、化療-MAGIC trialCunningham et al, NEJM 2006第20頁，共69頁。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可切除胃癌圍手術期化療-MAGIC trial第21頁，共69頁。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，共69頁?？汕谐赴﹪中g期化療 5-FU+DDP in AGC/LE -FFCD 9703 trialFP 23cs（98例）-手術-FP 2 3cs (RR+SD n+)（54例）單一手術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、胃89食管11第23頁，共69頁。可切除胃癌圍手術期化療 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，共69頁?？汕谐赴﹪中g期化療Patient data-based meta-analysis: CT+S

22、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 HR 0.87 P=0.003 轉化為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第25頁，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。Stage IB-IV(M

28、0)D0 和 D1占90%第30頁，共69頁。第31頁，共69頁。第32頁，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。V325 研究結果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的血液學毒性反應中

42、30伴有中性粒細胞減少性發(fā)熱第40頁，共69頁。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第41頁，共69頁。CPT-11聯(lián)合5-FU治療AGC-III期臨床試驗（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，共69頁。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，共69頁。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，共69頁。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，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%）， OPLT3/36（8.3%），O Hb4/36（11.1%），O神經(jīng)末梢毒性 4/36（11.1%），以EPI為基礎的三藥聯(lián)合可行！EOX有明顯生存優(yōu)勢！第45頁，共69頁。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，共69頁。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，共69頁。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，共69頁。相似的血液學不良發(fā)應 XP vs. FP % of patientsXP(n=156)FP(n=155)Neutropenia3330Leukopenia 1417Anemia125Thrombocytopenia66第49頁，共69頁。

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，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。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，共69頁。a randomized phase II trial106 patients includedwDCF vs wDXwDCF :DOC 30mg/m2 d1 d8; DDP 60mg/m2; 5-Fu 200mg/m2 civ wDX