NCCN胃癌臨床實(shí)踐指南中國版解讀-沈琳

NCCN胃癌臨床實(shí)踐指南中國版

解讀北京大學(xué)臨床腫瘤學(xué)院北京腫瘤醫(yī)院消化內(nèi)科沈琳2008腫瘤學(xué)臨床實(shí)踐指南（中國版）2008年第一版胃癌Copyright?2005AmericanCancerSocietyAge-standardizedIncidenceRatesforStomachCancerinworld.FromParkin,D.M.etal.CACancerJClin2005;55:74-108.世界胃癌年齡調(diào)整發(fā)病率對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(jìn)行分析胃癌粗死亡率(crudemortalityrate)25.2/10萬（M：32.8/10萬，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(mortalityratesadjustedbytheworldpopulation)男性：40.8/10萬，女性：18.6/10萬，分別是歐美發(fā)達(dá)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(diǎn)，胃癌調(diào)整死亡率在2.5-153.0/10萬之間，Urbanareas:15.3/10萬;Ruralareas:24.4/10萬，是城市的1.6倍NCCN共識分類1類：基于高水平的證據(jù)，NCCN達(dá)成共識，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，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（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(dá)成2A類共識。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)NCCNguidelines----GastricCancerChineseversion1.2008在整個治療指南中將chemotherapy/RT更改為chemoradiation將salvage改為palliative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(yàn)：NCCN認(rèn)為對于任何一個腫瘤病人參加臨床實(shí)驗(yàn)都獲得最佳治療.要特別鼓勵參與臨床試驗(yàn)。強(qiáng)調(diào)多學(xué)科評估和協(xié)作！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：例會形勢實(shí)用（一周或2周一次），相關(guān)學(xué)科的機(jī)構(gòu)和個人定期來共同回顧患者的詳細(xì)資料。每次例會，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，最好還能包括營養(yǎng)科，社工，護(hù)理以及其他支持學(xué)科。所有長期的治療策略要在全面分期檢查完成后再進(jìn)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(xué)數(shù)據(jù)而非單純閱讀報告。多學(xué)科團(tuán)隊(duì)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(yīng)尊重以及考慮多學(xué)科團(tuán)隊(duì)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(xué)科團(tuán)隊(duì)是有效的實(shí)例教育方式。在例會期間，正式的定期復(fù)習(xí)相關(guān)文獻(xiàn)，對整個多學(xué)科團(tuán)隊(duì)是高效的教育方式。外科治療原則NCCNv.1.2008GastricCancer結(jié)合淋巴結(jié)數(shù)目以及累及區(qū)域分期JapaneseGastriccancerassociati（JGCA)腹腔細(xì)胞學(xué)（CY）CY0腹腔細(xì)胞學(xué)良性或無法確定CY1腹腔細(xì)胞學(xué)未見癌細(xì)胞CYx未作其它遠(yuǎn)處轉(zhuǎn)移（M）§M0腹膜、肝、腹腔細(xì)胞學(xué)外無遠(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

N0N1N2N3T1IAIBIIIIIAT2IBIIIIIAT3IIIIIAIIIBT4IIIAIIIBIVH1,P1,CY1,M1RegionalLNGroupAccordingtoLocationofTumorD14d4d4d653D211p12a14v1998a97LD/LSasakoetal:thelong-termoutcomeofsurvival：D2vsD2+,

nostatisticallysignificantdifference69%vs70%,p=0.57,HR:1.03,(95%CI:0.77-1.37).

SasakoM,SanoT,YamamotoS,etal.RandomizedphaseIIItrialofstandardD2versusD2+para-aorticlymphnode(PAN)dissection(D)forclinicallyM0advancedgastriccancer:JCOG9501.JClinOncol2006.24(18S):LBA4015.擴(kuò)大根治orD2?——循證醫(yī)學(xué)證據(jù)D1orD2?——循證醫(yī)學(xué)證據(jù)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*外科切緣評估?淋巴結(jié)評估?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（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）ξ浸潤的深度淋巴結(jié)的部位、數(shù)目及陽性數(shù)遠(yuǎn)端及近端外科切緣狀況§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ξ胃腺癌組織學(xué)分級：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，在病理報告中N分期可增加標(biāo)注JRSGC要求的淋巴結(jié)部位。病理診斷原則系統(tǒng)化療原則NEW遵照原始文獻(xiàn)報道的藥物劑量/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)時間患者化療期間仔細(xì)觀察,及時治療合并癥,并適當(dāng)監(jiān)測患者血液學(xué)改變化療階段及時評估療效和長期合并癥2007.v.22008.v.1Preoperativechemo-therapyECFcategory1ECFcategory1ECFmodificationcategory1Preoperativechemo-radiationfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based2BTaxanes-based2BIrinotecan-based2Bpaclitaxel/Docetaxel+fluoropyrimidine(5FU/capecitabine）category2BUpdateof2008.v.1NCCNversion胃癌（占85%）或低位食管癌（15%）N=2505Y38%N=2535Y23%ECF:E50mg/m2C60mg/m2FU200mg/m2/dcivD.Cuuningham2005ASCOabs4001Cunninghametal,NEJM2006Chemo+SurgerySurgeryPatients250253Age6262ToSurgery219(88%)240(95%)PtswithR0resection169(68%)*166(66%)*NopathologiccompleteresponsesCunninghametal,NEJM2006Chemo+SurgerySurgeryPathSize3.1cm5.0cm(p=0.001)T1/T2T3/T452%48%38%62%(p=0.009)N0/1N2/384%16%76%24%(p=0.01)Cunninghametal,NEJM2006OverallSurvivalPatientsatriskLogrankp-value=0.009HazardRatio=0.75

(95%CI0.60-0.93)CSCS250168111795238272531558050311890.00.10.20.30.40.50.60.70.80.91.0Monthsfromrandomization0122436486072149250170253EventsTotalCSCSSurvivalrateN=1135YDFS34%N=1115YDFS21%FP:5-FU800mg/m2d1-5ciDDP100mg/m2d1Q4w隨訪5.7Y賁門、胃89％食管11％SurgeryChemo+SurgerypN111113R084%73%0.043yDFS25%40%5yDFS21%34%0.003HR0.65V.Boigeetal,ASCO2007abstr4510從12隨機(jī)試驗(yàn),2284患者中篩選出2102患者,涉及9個試驗(yàn),中位隨訪時間5.3年CT+SvsSHR0.87P=0.003轉(zhuǎn)化為5年絕對生存率提高4%R0切除率67%vs62%p=0.03etal,ASCO2007abstr4512GAST-C1of2:preoperativechemoradiation2008.v.1NCCNguideline：

Paclitaxel/docetaxel+fluoropyrimidine(5-FUorcapecitabine)category2B；RecommendationofChineseversion:Docetaxelmightbechanged;Category2Bto3.Reason:StudyaboutPaclitaxel/5FU+RTisonlyphaseII.Noprospectivestudieshasbeensearchedondocetaxel/5-FU+RT(medline).？Preoperativechemoradiation:phaseIIPhaseIITrialofPreoperativeChemoradiationinPatientsWithLocalizedGastricAdenocarcinoma(RTOG9904):QualityofCombinedModalityTherapyandPathologicResponse——JafferA.AjaniJCO2006：24（24）：3593Phase:IIPatients：43caseswithlocalizedGC(12%IB;37%II;52%III).，20centerMethods:2cysof5FU+CF+DDP——CRT(infusional5FU+weeklypaclitaxel)Resection（5to6weeksafterchemoradiotherapywascompleted.）Result：pathCR：26%R0resection：77%,1year：morepatientswithpathCR(82%)arelivingthanthosewithlessthanpathCR(69%）GAST-C1of2:preoperativechemoradiation2008.v.1NCCNguideline：

Paclitaxel/docetaxel+fluoropyrimidine(5-FU+capecitabine)category2B；RecommendationofChineseversion:Docetaxelmightbechanged;

Category2Bto3.2007.v.22008.v.1Postoperativechemo-therapyECFcategory1（onlywhenpreoperativeECFhasbeenadministered）ECFcategory1ECFmodificationcategory1（onlywhenpreoperativeECFhasbeenadministered）Postoperativechemo-radiationfluoropyrimidine/leucovorin1Fluoropyrimidine-based1Fluoropyrimidine/cisplatin2BECF2BTaxane-based2BFluoropyrimidine(5FUorcapecitabine)category1Updateof2008.v.1NCCNversionPostoperativechemotherapy?StageIB-IV(M0)D0和D1占90%GAST-3:T3,T4oranyT,N1afterR0resection2008.v.1NCCNguideline：RT,45-50.4Gy+concurrent5-FUbasedradiosensitization(preferred)+5-FU±leucovorinorECFifreceivedpreoperatively（category1）RecommendationofChineseversion:AddfootnoteIfD0/D1resection:agreedtheabove;IfD2resection:postoperativechemotherapyrecommended.Evidence：D0/D1operationconsistsmorethan90%inINT0116；2MetaanalysisaboutadjuvantchemotherapyGASC-studyPatients:23trials，4919ptsMethods:Adjuvantchemotherapyarm(ArmA):2441Observationarm(ArmB):2478Results:3ySurvivalrate:60.6%inArmA,53.4%inArmB(RR:0.85,95%CI:0.80–0.90)DFS:ArmBhadashorterDFS(RR:0.88,95%CI:0.77–0.99)Recurrencerate:ArmAhadalowerrecurrencerate(RR:0.78,95%CI:0.710.86)Grade3/4ofAE(myelosuppressionandGI):morefrequentlyinArmA.Conclusion:Adjuvantchemotherapycouldimprovethesurvivalrateanddisease-freesurvivalrateingastriccanceraftercurativeresectionandreducetherelapserate.METAanalysisofAdjuvantchemotherapy1Anupdatedmeta-analysisofadjuvantchemotherapyaftercurativeresectionforgastriccancer——EuropeanJournalofSurgicalOncology(EJSO)

METAanalysisofAdjuvantchemotherapy2Theroleofpostoperativeadjuvantchemotherapyfollowingcurativeresectionforgastriccancer:ameta-analysisShu-LiangZhao;Jing-YuanFang.RenjiHospital,Shanghai,China.CancerInvestigation,May2008,Vol.26Issue3,p317-325,Patients:15trials，3212pts，Methods:Surgery+adjuvantchemotherapyvsSurgeryonlyResults:RRfordeathinthetreatedgroupwas0.90(P=0.0010).

Littleornosignificantbenefitsweresuggestedinsubgroupanalysesbetweendifferentpopulationandregimenseither.Conclusion:Postoperativeadjuvantchemotherapyforgastriccancerconfersslightlysignificantbenefitscomparedtothesurgeryonlygroup.

Postoperativeadjuvantchemotherapy——S1monotherapyAdjuvantchemotherapyforgastriccancerwithS-1,anoralfluoropyrimidine.——Sakuramoto,SNEnglJMed，2007，357：1810-1820

1004cases(stageII/III，D2,3yearsfollowup*S-1monotherapy529casesOS:80.5%OS:70.5%RandomizedphaseIIItrialcomparingS-1monotherapyversussurgeryaloneforstageII/IIIgastriccancerpatients(pts)aftercurativeD2gastrectomy(ACTS-GCstudy).2007Gastrointestinalcancersymposium,sasakoMSurgeryalone530cases*12/2005showedthatHRofdeathforS-1toCwas0.57,trialwasrecommendedtostop.09/2006HRofdeathforS-1was0.68.Conclusions:AdjuvantchemotherapywithS-1forgastriccancerisfeasibleandeffective.ThisregimencanbethestandardtreatmentforstageII/IIIgastriccancerptsaftercurativeD2dissection.ACTS-GCstudyJCOGPostoperativechemoradiationmightbeagoodoptiontocompensatetheinsufficiencyofthesurgerysuchasD0/D1resection.Adjuvantchemotherapyshowssurvivalbenefitcomparedwithsurgeryalone,especiallyafterD2resectionforpatientswithstageIIorhigher.Postoperativeadjuvantchemotherapy

Conclusion:GAST-3：afterR1resection2008.v.1NCCNguideline：RT,45-50.4Gy+concurrent5-FU-basedradiosensitization(preferred)+5-FU±leucovorinRecommendationofChineseversion:

Toadd“Clinicaltrials”asanotheroption.Reason：R1resectionisnotradical,tillnow,nostandardtherapyhasbeenaccepted,itshouldbebettertofindtheappropriateonesbyclinicalstudies.2007.v.22008.v.1Metastaticorlocallyadvancedcancerfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based2BOxaliplatin-based2BTaxanes-based2BIrinotecan-based2BECF1DCF1ECF1ECFmodification1Irinotecan+cisplatin2BOxaliplatin+fluoropyrimidine(5-FUorcapecitabine)2BDCFmodification2BIrinotecan+fluoropyrimidine(5-FUorcapecitabine)2BUpdateof2008.v.1NCCNversionNoDDP+fluoropyrimidine(5-FUorcapecitabineorS－1)2BNopaclitaxel-basedregimens；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Moiseyenkoetal,JCO2007,例數(shù)總體緩解疾病進(jìn)展時間（月）總生存期（月）3—4級毒性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*3－4級毒性包括：81％的非血液學(xué)毒性反應(yīng)，75％的血液學(xué)毒性反應(yīng)中30％伴有中性粒細(xì)胞減少性發(fā)熱CPT-11forAGC——Ⅱ期多中心臨床研究

（2003ASCO）FFCD9803法國BoucheOetal.JClinOncol2004;22:4319–27例數(shù)RRmTTPmOSLV5FU24513%3.2m6.8mLV5FU2-DDP4427%4.9m9.5mLV5FU2-CPT-114540%6.7m11.3mCPT-11聯(lián)合5-FU治療AGC

----III期臨床試驗(yàn)（2005ASCO）N=170CPT-1180mg/m2CF500mg/m25FU2000mg/m2civ1/Wx6wN=163CDDP100mg/m2d15FU1000mg/m2/dd1-5Q4WN=333AGCRR54（31.8%）42（25.8%）TTP5.0m4.2m(p=0.088)TTF4.0m3.4m(p=0.002)OS9.0m8.7mp＝0.53M.Dank2005ASCOabs4003REAL-2:療效（Efficacy）EfficacyECF

N=263ECX

N=250EOF

N=245EOX

N=244P:ECFvsEOXRR(%)41464248

1yearOS(%)

37.740.840.446.8OS(mo)9.99.99.311.20.025Cunninghametal.ASCO2006LBA4017ECFEOFECXEOXGrade3/4non-haematologicaltoxicity,%36423345Grade3/4neutropenia,%42305128p-value

0.0080.00430.001REAL2:安全性

safetyoutcomesOxaliplatin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/m2d1EPI50mg/m2d1CF200mg/m2d1-35-FU500mg/m2CIVd1-3每3周重復(fù)，治療至少3個周期評價療效及毒性反應(yīng)CR2例（5.6%）PR13例（36.1%）SD17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：Ⅲ-ⅣOANC7/36（19.4%），ⅢOPLT3/36（8.3%），ⅢO

Hb4/36（11.1%），ⅢO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！ML17032:CAPEvs5-FUinAGC

trialdesignFP

Cisplatin

80mg/m23-houri.v.infusion5-FUc.i.

800mg/m2/day;d1–5q3wXPCisplatin

80mg/m23-houri.v.infusionCapecitabine

1000mg/m2twicedaily;d1–14q3wKPS≥70%18–75yearsAdvancedand/or

metastaticgastriccancer(AGC)≥1measurablelesionNopriortreatmentforAGCR

A

N

D

OM

I

ZA

T

I

O

NSuperiorresponseratewithXPvs.FPConfirmedresponse

%(95%CI)XP

(n=160)FP

(n=156)p-valueOverallresponse41(33–49)29(22–37)0.030Completeresponse230.668Partialresponse39260.019Progressivedisease10180.041ML17032:XPvsFP

progression-freesurvival.HR0.81

EstimatedprobabilityHR=0.81(95%CI:0.63–1.04)ComparedtoHRupperlimit1.25,p=0.00080Months24681012141618202224261.00.80.60.40.20.0PerprotocolanalysisXP(n=139)FP(n=137)MedianPFS

months(95%CI)5.6(4.9–7.3)5.0(4.2–6.3)相似的血液學(xué)不良發(fā)應(yīng)

XPvs.FP

%ofpatientsXP

(n=156)FP

(n=155)

Neutropenia3330Leukopenia1417Anemia125Thrombocytopenia66APhaseIITrialofCapecitabineplusDDPinAGC－－China2002.6-2003.5,N=145,Cape1000mg/m2Bidd1-14DDP20mg/m2ivd1-5q3W130ptsevaluable:98M/32FAge:53.7ysResultsCR10(8%)PR48(37%)SD51(39%)PD21(16%)OS12mSafety：grade3-4adverseevent<5%-----2005,2006ASCOfirst-linechemotherapywithfluorouracil,leucovorinandoxaliplatin(FLO)versusfluorouracil,leucovorinandcisplatin(FLP)FLO

F2600mg/m224hinfusion,L200mg/m2,oxaliplatin85mg/m2q2wFLPF2000mg/m224hinfusion,qwL200mg/m2,qwcisplatin50mg/m2,q2w.Total220

ptsMedianage64yrs

Advancedand/or

metastaticgastriccancer(AGC)R

A

N

D

OM

I

ZA

T

I

O

NS.Al-Batran,J.Hartmann,ASCO2006TheprimaryendpointwasTTPSuperiorPerformancewithFLOvs.FLPConfirmedresponse

%(95%CI)FLO(N=98)FLP

(n=102)p-valueOverallresponse34%27%0.012TTP5.73.80.081TTF5.33.10.028S.Al-Batran,J.Hartmann,ASCO2006PhaseIIStudyofS-1±DDPvs5-FU+DDPforGastricCancer(PI:MLJin)C:5-FU+DDPA:S-1B:S-1+DDPrandomizationAssumed180cases，60casesperarm，enrollmentcompletedObjective：RR,TTPPathologicallyconfirmed，unrectable，measurableleasionsEvidence：SC-101study

——2008ASCOmeetingArmNCR+PRTTF(d)OS(d)N%A:S1771924.7*126★267＃B:S-1/CDDP742837.8159433C:5-FU/CDDP731419.2※85★309?！?ArmBcomparedwithArmC,P<0.05★:ArmBcomparedwithArmAandC,P<0.05＃:ArmBcomparedwithArmAandC,P<0.05*:ArmBcomparedwithArmA,P>0.05Evidence：SC-101study

——2008ASCOmeetingElderlychemo-na?vepts(>=65years)withmeasurablemetastaticorrecurrentgastriccancerarmX(N=46,Medianage=71.0years

)Capecitabine(1,250mg/m2bid,D1-14every3weeks)

armS(N=45,Medianage=70.5years)S-1(40~60mgbidD1-28every6weeks)

randomly10/2004-4/2006

Arandomizedmulti-centerphaseIItrial：

capecitabine(X)versusS-1(S)asfirst-linetreatment

inelderlypatientswithmAGCY.Kang,D.Shin

2007ASCOAnnualMeetingArandomizedstudy:theactivityandsafetyofcapecitabinevsS-1inelderlyptswithAGCphaseII

Y.Kang,

JCO,2007ASCOMeetingsProceedingsPartI.Vol25,No.18S:4546)

Evidence：capecitabinevsS-1

PhaseIIXeloda(n=44)S-1(n=45)Regimen1250mg/㎡bidd1-14/3W40-60mg/㎡bidd1-28/6WCR(%)01(2.2%)PR(%)13(29.5)12(26.7)mOS(mo)10.07.9mTTP(mo)4.84.2mTTF(mo)4.43Xeloda(n=44)S-1(n=45)Grade3/4(%)1250mg/㎡bidd1-14/3W40-60mg/㎡bidd1-28/6WLeukopenia6.84.8Asthenia07.2Anorexia6.89.5Diarrhea2.30HFS6.80Evidence：capecitabinevsS-1toxity2007.v.22008.v.1Metastaticorlocallyadvancedcancerfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based2BOxaliplatin-based2BTaxanes-based2BIrinotecan-based2BECF1DCF1ECF1ECFmodification1Irinotecan+cisplatin2BOxaliplatin+fluoropyrimidine(5-FUorcapecitabine)2BDCFmodification2BIrinotecan+fluoropyrimidine(5-FUorcapecitabine)2BUpdateof2008.v.1NCCNversionDDP+fluoropyrimidine(5-FUorcapecitabineorS－1)2BarandomizedphaseIItrialoftheSwissGroupforClinicalCancerResearch.Chemotherapy-naivepatientsECFvsDCvsDCFEvidence1:docetaxel——RothAD,FazioN,etal,JClinOncol.2007Aug1;25(22):3217-23.n=119ECFDCDCFORR25.0%18.5%36.6%MedianOS8.311.010.4neutropeniaG3/434%49%57%QOLsimilararandomizedphaseIIstudyinGermanypatientswithuntreated,advancedgastricadenocarcinoma.Evidence2:docetaxel——Thuss-PatiencePC,KretzschmarA,etal：JClinOncol.2005Jan20;23(3):494-501.

n=90ECFDFORR35.6%37.8%MedianOS9.7m9.5mTTP5.3m5.5marandomizedphaseIItrial106patientsincludedwDCFvswDXwDCF:DOC30mg/m2d1d8;DDP60mg/m2;5-Fu200mg/m2civwDX

DOC30mg/m2d1d8;CAPE1600mg/m2d1-14Evidence3:docetaxel（Weekly）——N.Tebbutt,etal,Asco2007,4528.

wDCFn=50wDXn=56CR+PR%4926Febrileneutropenia%42Gr?lethargy%104Gr?diarrhea%107Gr?stomatitis%222Gr3hand-footSyn%42OSmonths12.810.1Evidence:paclitaxelvsdocetaxelPaclitaxelversusdocetaxelforadvancedgastriccancer:arandomizedphaseIItrialincombinationwithinfusional5-fluorouracil.

——ParkSHetal,AnticancerDrugs.2006Feb;17(2):225-9Phase:II,randomizedPatients：77caseswithmeasurablemetastaticgastriccancer(PFvsDF).Methods:

PXL+5-FuvsDOC+5-FuResult：responserate(42vs33%,P=0.53)overallsurvival(9.9vs9.3m;P=0.42)grade3/4toxicities(68vs85%;P=0.09)Globalqualityoflife:similarpain,dyspnea,constipationanddiarrheafavoredPFConclusion:

BothPFandDFappeartohaveefficacyagainstmetastaticgastriccancer,withdifferent,butacceptable,safetyprofiles.2007.v.22008.v.1Metastaticorlocallyadvancedcancerfluoropyrimidine/leucovorin2BFluoropyrimidine-based2BCisplatin-based