胰腺癌癥最新進(jìn)展 王晰程

UpdatesonPancreaticCancerXichengWangGIMedicalOncologyPekingUniversityCancerHospitalGEM

(n=277)1000mg/m2IVDay1,8,15EveryfourweekS-1

(n=280)40,50,60mg*BIDDay1-28EverysixweekGEM+S-1(n=277)GEM:1000mg/m2IVDay1,8S-1:30,40,50mg*BIDDay1-14EverythreeweekRn=834RandomizedPhaseIIIstudyofgemcitabineplusS-1(GS)versusS-1versusgemcitabine(Gem)inunresectableadvancedpancreaticcancer:GESTstudyPrimaryEndPoint：

OverallSurvivalSecondaryEndPoint：ProgressionFreeSurvival（PFS）ResponseRate（RR）GESTstudy:OSandPFSControlArm:GEM8.84.1Superiority：GEM+S-1(GS)10.15.7Non-inferiority：S-19.73.8OSPFSGESTstudy:ObjectiveResponseRateGESTstudy:SafetyProfileConclusions

TheOSofS-1isnon-inferiortoGEM.

S-1iswelltoleratedwithminorGItoxicity.

GCsignificantlyincreasedPFSwithoutprolongingOSandshowedhighobjectiveresponserate.ASCO2011#4007FOLFIRINOXversusGemcitabineforMetastaticPancreaticCancerGEM

1,000mg/m2IVweekly×7,1weekrest,

thenweekly×3q4woxaliplatin85mg/m2day1,irinotecan180mg/m2day1,LV400mg/m2day1followedby5-FU400mg/m2bolusday1and2,400mg/m246hcontinuousinfusionbiweeklyRPS0-1n=342FOLFIRINOX11.1mon6.8mon6.4mon3.7monFOLFIRINOX:ResponseRateandAdverseEventSummaryGEMS1GEM+S1GEMFOLFIRINOXGEMGEM+nab-PTXPFS(mon)4.13.85.73.36.43.75.5OS(mon)8.89.710.16.811.16.78.5RR(%)132129931.6829GESTFrenchStudyMPACTNCCNGuidelinesforPancreaticCancer2013K.Uesaka,A.Fukutomi,N.Kanemoto,M.Konishi,Matsumoto,Y.Kaneoka,Y.Shimizu,S.Nakamori,H.Sakamoto,S.Morinaga,O.Kainuma,K.Imai,N.Sata,S.Hishinuma,T.Nakamura,M.Kanai,S.Hirano,Y.Yoshikawa,Y.OhashiJapanAdjuvantStudyGroupofPancreaticCancer(JASPAC)RandomizedphaseIIItrialofadjuvantchemotherapywithgemcitabinevs.S-1forresectedpancreaticcancerpatients

(JASPAC01study)JASPAC01背景(1)CONKO-001試驗(yàn)

(JAMA2007)

術(shù)后輔助化療（吉西他濱:GEM）可延長(zhǎng)胰腺癌（PC）術(shù)后患者的DFSGEST試驗(yàn)(ASCO2011)

對(duì)于無法手術(shù)切除的胰腺癌患者，口服S-1單藥治療的療效不劣于GEM在日本，S-1是晚期胰腺癌患者標(biāo)準(zhǔn)治療的選擇之一

GEM是胰腺癌術(shù)后患者的標(biāo)準(zhǔn)療法JASPAC01目的目的本研究旨在比較S-1與吉西他濱單藥作為胰腺癌術(shù)后輔助化療在總生存（OS）方面的非劣效性。研究終點(diǎn)主要終點(diǎn)

總生存期次要終點(diǎn)

無復(fù)發(fā)生存期

不良反應(yīng)

健康相關(guān)的QOLJASPAC01試驗(yàn)設(shè)計(jì)隨機(jī)、III期、開放、多中心研究可手術(shù)治療的胰腺癌患者隨機(jī)分組GEM1000mg/m2第1、8和15天給藥，每4周重復(fù)，6個(gè)周期（24周）

S-140-60mg，每日2次,連續(xù)口服4周，每6周重復(fù)，4個(gè)周期（24周）分層因素研究中心R0/R1N0/N1手術(shù)后10周內(nèi)JASPAC01患者處置全分析集：378例患者385例患者入組2007年4月

-2010年6月GEM組193例患者192例患者符合GEM組入組標(biāo)準(zhǔn)191例患者分至GEM組（99%）S-1組192例患者191例患者符合S-1組入組標(biāo)準(zhǔn)187例患者分至S-1組（97%）1例患者：入組當(dāng)天復(fù)發(fā)1例患者術(shù)中發(fā)現(xiàn)腹主動(dòng)脈旁淋巴結(jié)轉(zhuǎn)移1例患者：未治療4例患者：未治療JASPAC01患者基線特征(1)患者基線特征GEM(n=191)S-1(n=187)年齡*，歲65.7[8.6]65.9[9.5]性別男/女104(54%)/87(46%)106(57%)/81(43%)ECOGPS0/1128(67%)/63(33%)131(70%)/56(30%)白細(xì)胞*/mm35599[1496]5646[1677]血紅蛋白*g/dL11.7[1.2]11.9[1.1]血小板*×104/mm326.6[8.4]28.0[10.4]ALT*IU/L29.9[19.2]32.1[19.6]AST*IU/L29.8[15.9]29.4[14.5]總膽紅素*mg/dL0.6[0.2]0.6[0.2]肌酐*mg/dL0.6[0.2]0.6[0.2]*平均[SD]JASPAC01總生存—S-182例患者（44%）死亡—GEM123例患者（64%）死亡共計(jì)死亡：205例患者非劣效性p<0.0001優(yōu)效性p<0.0001（log-ranktest）S-1HR=0.56[99.8%CI,0.36-0.87]S-1:2yrsOS70%[95%CI,63-76]MSTN/AGEM:2yrsOS53%[95%CI,46-60]MST25.5月年危險(xiǎn)病例數(shù)S-1

18717212768281GEM1911519551163JASPAC01無復(fù)發(fā)生存年危險(xiǎn)病例數(shù)S-1

1871268945261GEM191905330101Logrank:

p<0.0001—S-1中位23.2個(gè)月[95%CI17.5-32]—GEM中位11.2個(gè)月[95%CI9.7-13.5]S-1HR=0.56[95%CI0.43-0.71]S-1:2yrsRFS49%[95%CI42-57]GEM:2yrsRFS29%[95%CI22-35]JASPAC01治療依從性GEM(n=191)S-1(n=187)完成研究n(%)110

(58%)135(72%)

中斷研究n(%)81(42%)52(28%)（中止治療原因）

復(fù)發(fā)n(%)26(14%)9(5%)

毒副作用n(%)48(25%)40(21%)

患者拒絕n53

其他n20JASPAC01不良事件(1)實(shí)驗(yàn)室檢查結(jié)果GEM(n=191)S-1(n=187)3級(jí)4級(jí)3級(jí)4級(jí)白細(xì)胞減少32%7%4%5%血紅蛋白減少9%8%9%5%血小板減少2%7%0%4%膽紅素升高0%0.5%1%0%AST升高5%0%1%0%ALT升高4%0%0.5%0%肌酐0%0.5%0.5%0%（CTCAE3.0版）JASPAC01不良事件(2)臨床癥狀GEM(n=191)S-1(n=187)

3級(jí)4級(jí)3級(jí)4級(jí)口腔炎0%0%3%0%厭食

5%0.5%8%0%惡心2%1%4%0%嘔吐0.5%0.5%2%0%腹瀉0%