结直肠癌新辅助治疗(含肝转移)PPT课件VIP

.,1,结直肠癌患者新辅助治疗,北京大学肿瘤医院消化肿瘤内科,.,2,直肠癌术前放化疗,3,.,新辅助治疗的目的,提高手术切除率提高保肛率降低局部复发延长患者无病生存期,4,.,推荐,T3和/或N+的可切除直肠癌患者，推荐术前新辅助放化疗。直肠癌术前化疗推荐以氟尿嘧啶类药物为基础的化疗方案,5,.,6,.,7,.,8,.,9,.,10,.,11,.,12,.,13,.,14,.,.,15,结肠癌肝转移术前化疗,16,.,推荐,结直肠癌患者合并肝转移，可切除或者潜在可切除，推荐术前化疗或化疗联合靶向药物治疗：西妥昔单抗（推荐用于K-ras基因状态野生型患者），或联合贝伐珠单抗化疗方案推荐FOLFOX，或者FOLFIRI，或者CapeOx，,17,.,livermetastases,Notresectable,resectable,chemotherapy,85%,15%+,otherlocationsofmetastases,chemotherapy,50%,50%,Patientswithmetastaticcolorectalcancer,5ySurvival:5%,5ysurvival:5%,Metastaticcolorectalcancer,5ysurvival:20-40%,18,.,Resectionrateofmetastasesandtumorresponse,Studiesincl.selectedpats.(livermetastasesonly,noextrahepat.disease)r=.96,p=.002,Studiesincl.allpatientswithmetastaticCRC(solidline)r=.74,p.001PhaseIIIstudiesinmetastaticCRC(dashedline)r=.67,p=.024,p=.024,FolprechtKhneetal,AnnOncol2005,19,.,新辅助化疗优势,患者体内化疗药物的药敏试验清除微小转移灶观察甄别出快速进展病例提高R0切除率？并减少切除的正常肝组织延长生存期？,20,.,Adjuvant,neoadjuvant,conversiontherapyforCRClivermetastases,Resectableadjuvantneo-adjuvantUnresectableConversionchemotherapy,21,.,ColorectalCaR0ResectionofMetastases,Controversy:AdjuvantTherapy?,USAYes(KemenyNEJM1999),EuropaNo(LorenzNEJM2000),22,.,KemenyetalNEJM1999and2005,Livermetastases:adjuvantHAI+i.v.CTX,p=0.02,23,.,LV5FUvs.FOLFIRIasadjuvanttherapyfollowingresectionofCLM-DFS,1-yearDFS:63%vs.77%2-yearDFS:46%vs.51%,Ychouetal.ASCO2008,24,.,AdjuvantChemotherapyforCRClivermetastases,YES！Whichpatients?高复发风险whichregimen?化疗？HAI？方案？FU、OXA？Target？,25,.,EORTCphaseIIIstudy40983研究设计,Randomize,Surgery,FOLFOX4,FOLFOX4,Surgery,6cycles(3months),6cycles(3months),364例潜在可切除肝转移(metachronousorsynchronous)，4个以上病灶，无肝外转移,26,.,EORTCStudy40983,CTSP3-yFPS%42.433.20.025,27,.,乐沙定，伊立替康和持续滴注5-FULV(FOLFOXIRI)两周方案和Folfiri相比一线治疗转移性结直肠癌：III期临床结果（GONO）,A.Falcone,etalASCOGI2006,#227,不能切除的结直肠癌肝转移新辅助化疗,28,.,伊立替康，乐沙定和持续滴注5-FULV(FOLFOXIRI)两周方案和Folfiri相比一线治疗转移性结直肠癌：III期临床结果（GONO）,*DouillardLancet2000*MasiAnnOncol2004,临床设计,FOLFIRI*,R,CPT-11180mg/m21-hd.1L-LV100mg/m22-hd.1,25FU400mg/m2bolusd.1,25FU600mg/m222-hd.1,2q.2wksx12个周期,FOLFOXIRI*,CPT-11165mg/m21-hd.1LOHP85mg/m22-hd.1L-LV200mg/m22-hd.15FU3200mg/m248-hCId.1q.2wksx12个周期,分层中心PS0/1-2辅助化疗,FOLFIRI方案进展后，推荐含乐沙定的方案,29,.,A.Falcone,ASCOGI2006,#227,*p0.001,有效率(ITT分析),化疗后手术切除率(所有病人),*p0.033,疗效结果,主要目标：RR次要目标：PFS,OS,postsurgicalresectionsn,safetyQOL,30,.,RescueSurgeryforUnresectableColorectalLiverMetastasesDownstagedbyChemotherapyAModeltoPredictLong-termSurvival,Retrospectivestudy1104caseswithunresectablelivermetastasesChemotherapyregimens：5-FU/LV/OXAorIRIorboth138(12.5%)achievedsecondarycurativehepaticresectionSurvivalrate:5-year33%10-year23%,AdamRetal,Annsurg.2004;240:644-657,31,.,Resectionoflivermetastases:non-selectedpatientstreatedwithtargeted/cytotoxicagents,FirstauthorNRegimenRRResectionrateFolprecht21Cetuximab/irinotecan67%19%/AIO(24%)*DiazRubio43Cetuximab/FOLFOX479%19%Rougier42Cetuximab/FOLFIRI45%21%Fisher27Gefitinib/FOLFOX478%22%Hurwitz411IFL35%（2%412IFL/bevacizumab45%resection)Hoff21FOLFIRI/bevacizumab70%19%*Onepatientdeclinedofferedresection,UpdatedinformationbasedonFolprechtetal.AnnOncol,2005,32,.,Liver-limiteddiseasePFSandRRinKRASwild-type,aCochran-Mantel-Haenszel(CMH)test,VanCutsem,Khneinpress,33,.,RandomizedmulticenterstudyofcetuximabplusFOLFOXorcetuximabplusFOLFIRIinneoadjuvanttreatmentofnon-resectablecolorectallivermetastases(CELIMstudy),G.Folprecht,1T.Gruenberger,2J.T.etal,Patientswithnon-resectablecolorectallivermetastasesNoextrahepaticdisease,34,.,Efficacy:ConfirmedResponse,Responsesconfirmedby2ndCTscanaccordingtoRECISTorbyresection,ChisquaretestforcomparisonbetweenFOLFOX6+CetvsFOLFIRI+Cetwouldbe0.23,35,.,Resections,ComparisonofR0resectionsbetweenstratatechnicallynon-resectableand5livermets:p=0.14,36,.,手术前化疗时限,化疗时间,最佳选择时间？,37,.,Morethan6cyclesofneoadjuvantsystemicchemotherapyincreas