胃癌的輔助治療新認(rèn)識

1胃癌的輔助治療新認(rèn)識

(第11屆CSCO上海)南昌大學(xué)第一附屬醫(yī)院熊建萍2008年08月29日2流行病學(xué):發(fā)病及死亡位次

NewCases(rank)Deaths(rank)Unitedstates(2007)121,260(﹟13)11,210(﹟13)Worldwide(2002)2

934,000(﹟4)700,000(﹟2)1Jemal,et.al.CACancerJClin2007;57:432Parkin,et.al.CACancerJClin2005;55:753流行病學(xué)：發(fā)病率及部位超勢EpidemiologicTrendsWorldwidedeclineinage-adjustedincidencenowparallelspatternpreviouslyobservedinUnitedStatesDiseasenowappearinganatomicallyinamoreproximalpattern45部分國家胃癌發(fā)生部位Percentage1.YangH,etal.CancerResTreat2001;33:207–15;2.Inoue,etal.IntJCancer1994;56:494–93;

3.HundalhS,etal.Cancer2000;88:921–2;4.SiewertJ,etal.AnnSurg1998;228:449–61;

5.BonenkampJ,etal.NEnglJMed340;908–14125436胃癌5年生存率（中國）

時(shí)期例數(shù)ⅠⅡⅢⅣ總體~197571485.747.827.6023.71976~85261588.762.528.98.035.91986~352090.467.936.78.645.67胃癌的臨床特點(diǎn)8重視早期患者的綜合治療9新輔助化療的目的10新輔助化療的種類1112尚缺少Ш期臨床研究證據(jù)13新輔助化療的種類14CSCn=250Sn=253RCunninghametal,NEnglJMed2006;355:11-20.(MAGIC研究)ECF:E50mg/m2C60mg/m2FU200mg/m2/dciv15

Pre-opECFSurgeryaloneP-valueExtentoftumor(gastriconly)T1/T252%38%0.009T3/T448%62%Nodalstatus(Gastriconly)N0/N184%76%0.01N2/N316%29%16Pre-opECFN=250SurgeryaloneN=253PMediantimetosurgery99days14daysProceededtosurgery219240R0resection169166R0resectionrate79%(169/219)70%(166/240)0.03R0resectionITT169/250166/253R0rateITT68%66%0.6417181920MAGIC:PreoperativeECFvs.Surgeryalone2122FFCD9703:研究方案設(shè)計(jì)23FFCD9703:入選標(biāo)準(zhǔn)24FFCD9703:病人特征252627FFCD9703:5年DFS及OS均有提高2829FFCD9703:結(jié)論30新輔助化療的優(yōu)點(diǎn)31重視早期患者的綜合治療321244316123829191Leeetal2000;2Maruyamaetal1998;

3Landryetal1991;4Macdonaldetal2001Patients(%)D2D254%36%10%D0:D1:D2:LNdissection33Presenter:Dr.F.DeVitaSurgeryplusELFE(epirubicin,leucovorin,5-fluorouracilandetoposide)vssurgeryaloneinradicallyresectedgastriccancer:

FinalresultsofarandomisedphaseIIItrialbytheGruppoOncologicoItaliaMeridionale(GOIM)

2006ASCO34GOIM9602:

研究方案設(shè)計(jì)RadicallyresectedgastriccancerNodalStatus(N-/N+)RSURGERY+ELFESURGERYFOLLOW-UPEVERY12WEEKS

ELFE×6EPI60mg/m2IVD1LV100mg/m2IVD1-55-FU375mg/m2IVD1-5VP-16100mg/m2IVD1-3Every3Weeks35PATIENTPOPULATIONSURGERYPRODCEDURESR0resection(totalorsubtotalgastrectomyandD1lymphoadenectomy)GOIM9602:

Entrycriteria36GOIM9602:DrugdeliveryTotalnumberofcycles638Mediannumber5(1-6)CTSTOP18%61%ofptsfulldoseCT39%ofptsdosereduction37GOIM9602:SurvivalResult5-YearResultLogRankHR(95%CI)Surgery+FLFESurgeryOS48%43.5%p=0.6100.91(0.69,1.21)DFS44%39%p=0.3050.88(0.78,0.91)OS/N+41%34%P=0.0680.84(0.69,1.01)DFS/N+39%31%P=0.0500.86(0.75,1.00)InmultivariateCoxproportionalhazardratioanalysis.Treatmentwasnotasignifinantpredictorforriskofdeath.HR0.91(95%CI0.69,1.21),P=0.61038

GOIM9602:

Toxicity

ofCT(WHO)AdverseeventGrade3(%)

Grade4(%)Neutropenia25(22)5(4)Thrombocytopenia12(11)2(2)Anemia11(10)-Diarrhea22(20)7(6)Mucositis11(10)2(2)Nausea&vomiting20(18)

Cardiac

2(2)

39GOIM9602:

Conclusions4041作者年份研究個(gè)數(shù)病例數(shù)優(yōu)勢比95%可信區(qū)間結(jié)論Hermans等19931120960.880.78-1.08化療無明顯生存益處Earle及Maroun等19991319900.800.66-0.97化療有微小的生存益處，淋巴結(jié)陽性者益處更大Mari等20002036580.820.75-0.89化療有微小的生存益處Janunger等2002213962

全部西方人群東方人群

治療組的異質(zhì)性，如臨床試驗(yàn)有含新輔助化療，腹腔化療；輔助化療有微小的生存益處，亞裔人群有生存益處，西方人群則無，輔助化療不推薦給西方人群。0.840.74-0.960.960.83-1.120.580.44-0.764243S-1(替吉奧膠丸)PhaseII1stlineStudynmgbid

RR

(%)

TTP

(月)OS

(月)Sakata,EJC,1998518049Sugimachi,Onco,19992850-7554Koizumi,Onco20004440-6044Chollet,2000Sympo3035-4026Kobayashi,ASCO2002252840-603936407d215dYoshida,ClinCanRes2006+Doc4840567.314.3Ajani,2006JCO+Cis4125514.810.9Lenz,2007Cancer+Cis64255511.010.4.442007ASCOGlCancersSymposiumAbstr8

ACTS-GC45ACTS-GC:方案設(shè)計(jì)ACTS-GC:方案設(shè)計(jì)46ACTS-GC:病人特征47ACTS-GC:S1完成情況48ACTS-GC:不良反應(yīng)49ACTS-GC:總生存率有差異(P=0.0024)

無復(fù)發(fā)生存率差異明顯(P<0.0001)50ACTS-GC:各亞組分析均有生存優(yōu)勢性別、年齡臨床分期、T分期N分期51ACTS-GC:結(jié)論5253545556韓國的文獻(xiàn)綜述57胃癌輔助治療仍然存在爭論58正在進(jìn)行的PhaseIIIadjuvanttrials

ingastriccancerTrialTestarmControlarmEndpointsAsian

post-operativeXELOX

Observation

1o:DFS

2o:OS,toxicityMAGIC2

peri-operativeECX+AvastinECX

1o:DFS

2o:OS,toxicity59alongwaytogo

TumourtypeMedianTTP