胃癌英文Gastric-Cancer.ppt

Chemotherapy in Gastric CancerGASTRICCANCERWorldwideincidence*Incidenceper100,000population.ParkinDM,etal.CA Cancer J Clin.1999;49:33-64.MaleMale16.416.4FemaleFemale8.28.2MaleMale36.336.3FemaleFemale16.916.9MaleMale77.977.9FemaleFemale33.333.3MaleMale10.810.8FemaleFemale4.94.9MaleMale43.643.6FemaleFemale19.019.0MaleMale5.95.9FemaleFemale2.62.6MaleMale11.511.5FemaleFemale4.34.3MaleMale18.618.6FemaleFemale13.313.3MaleMale8.48.4FemaleFemale4.04.0EasternEasternEuropeEuropeJapanJapanAustralia/Australia/NewZealandNewZealandChinaNorthernNorthernAfricaAfricaSouthernSouthernAfricaAfricaCentralCentralAmericaAmericaWesternWesternEuropeEuropeNorthNorthAmericaAmerica2ndmostcommoncancerintheworld,558400newcasesand405200deaths.Almost40%ofcasesoccurinChina.PazdurRetal.Cancer management:A multidisciplinary approach.6thedition,2002CountriesinwhichtheincidenceofgastriccarcinomaisextremelyhighincludeJapan,CostaRica,Peru,Brazil,China,Korea,Chile,Taiwan,andthecountriesoftheformerSovietUnion.Atdiagnosis,approximately50%ofpatientshavegastriccarcinomathatextendsbeyondthelocoregionalconfines.Approximately50%ofpatientswithlocoregionalgastriccarcinomacannotundergoacurativeresection(R0).IncountriesintheWesternHemisphere,gastriccarcinomahasmigratedproximally,occurringmostfrequentlyalongtheproximallessercurvature,inthecardia,andinvolvingthegastroesophagealjunction.ItispossiblethatinthecomingdecadesthesechangingtrendswillalsooccurinSouthAmericaandAsia.Nearly70%to80%ofresectedgastriccarcinomaspecimenshavemetastasesintheregionallymphnodes.Thus,itiscommontoencounterpatientswithadvancedgastriccarcinomaattheoutset.IntheWesternHemisphere,R0resectionispossibleinapproximately50%to80%ofpatients.ThemediansurvivalofpatientswhoundergoanR0resectionisapproximately25months,and5-yearsurvivalratesrangefrom30%to37%.NCNNGuidelinesTheworkuppermitsclassificationofpatientsinto1of2groups:(1)patientswithapparentlocoregionalcarcinoma(stagesItoIIIorM0),and(2)thosewithobviousmetastaticcarcinoma(stageIVorM1).Patientswithapparentlocoregionaldiseasecanbefurtherclassified:(1)thosewhoaremedicallyfitandwhosecancerisresectable,(2)thosewhoaremedicallyfitbutwhosecancerisunresectable,and(3)thosewhoareinoperable(medicallyunfit).Global ConsensusGoodlocalcontrolisessentialtocuregastriccarcinomaTheonlypotentiallycurativetreatmentforlocalizedgastriccancerissurgery.Mostgastriccancersarediagnosedatanadvancedstage.The5-yearsurvivalrateafter“curativeresection”forgastriccancerisonlybetween30%and40%.Theefficacyofchemotherapywithpalliativeintentisnowwidelyaccepted.Chemotherapy of Gastric CancerKohneCH,WilsJA,WilkeHJ:DevelopmentsinthetreatmentofgastriccancerinEurope.Oncology(Huntingt)14:22-25,2000Chemotherapy of Gastric CancerFluorouracil(5-FU)isoneofthemosteffectiveandwidelyuseddrugsinthetreatmentofadvancedgastriccancer(AGC),producing a response rate of approximately 20%,with manageable toxicity.Overallsurvivalofbetween5and7monthshasbeenreportedfor5-FUmonotherapyinphaseIIIrandomizedstudies.CoombesR,ChilversCE,AmadoriD,etal:AnInternationalCollaborativeCancerGroup(ICCG)study.AnnOncol5:33-36,19946.Chemotherapy of Gastric Cancer5-FUmodulationbyfolinicacid(FA)hasgenerallyresultedinenhancedantitumorefficacy(22%to48%overallresponserate)andhasledtosomecompleteresponses(5%to9%).AllcurrentreferencecombinationregimensinAGCcontain5-FU.LouvetC,DeGramontA,DemuynckB,etal:.AnnOncol2:229-230,1991Chemotherapy of Gastric Cancer5-FU,doxorubicin,andmitomycin(FAM);5-FU,doxorubicin,andhigh-dosemethotrexate(FAMTX);etoposide,doxorubicin,andcisplatin(EAP);etoposide,leucovorin,and5-FU(ELF);epirubicin,cisplatin,and5-FUcontinuousinfusion(ECF);cisplatin,epirubicin,leucovorin,and5-FU(PELF);cisplatinand5-FU.Chemotherapy of Gastric CancerSeveralrandomizedstudiescomparingFAMversusFAMTX(5-FU,adriamycin,andmethotrexatewithleucovorinrescue),FAMTXversusECF(epirubicin,cisplatin,and5-FU),andFAMTXversusELF(etoposide,leucovorin,and5-FU)versus5-FUpluscisplatinhavebeenreportedinthepastseveralyears.Noonestandardtherapyhasemergedfromthesetrials.Outsideofclinicaltrials,therecommendedchemotherapyforadvancedgastriccarcinomaiseithercisplatin-basedor5-FU-basedcombinationchemotherapy.Chemotherapy of Gastric CancerThenewagentsincludepaclitaxel,docetaxel,irinotecan,UFT,oraletoposide,andS-1.Severalreportsofnewercombinationchemotherapyregimenshavealsoappeared.Anumberofneweroralagentsalsoholdpromiseinthetreatmentofgastriccarcinoma.Agentsthathavenotbeenextensivelystudiedincludecapecitabine,oxaliplatin.Inaddition,anumberofnewcategoriesofagentsareofinterest.Theseincludevaccines,antireceptoragents,andantiangiogenicagents.AnumberofchemotherapycombinationsarecurrentlyinphaseIIItrials,andweanticipatethatawidelyacceptedfront-linestandardforpatientswithadvancedgastriccarcinomamightemergeinthenearfuture.NCNNGuidelinesThelandmarktrialistheIntergrouptrialINT-0116.EligibilityincludedpatientswithT3andorN+adenocarcinomaofthestomachorgastroesophagealjunction.Afteraresectionwithnegativemargins,603patientswererandomlyassignedtoeitherobservationaloneorpostoperativecombinedmodalitytherapyconsistingof5monthlycyclesofboluschemotherapywith45Gyconcurrentwithcycles2and3.Therewasasignificantdecreaseinlocalfailureasthefirstsiteoffailure(19%versus29%)aswellasanincreaseinmediansurvival(36versus27months),3-yearrelapse-freesurvival(48%versus31%),andoverallsurvival(50%versus41%,=.005)withcombinedmodalitytherapy.NCNNGuidelinesApatientwhosesurgicalpathologicstageisT1,N0,M0maybeobservedandnottreatedwithadjuvanttherapy.AllpatientswithanR0resectionwhohaveT2,N0alongwithadversefeatures(ie,poorlydifferentiatedorhighergradecancer,lymphovascularinvasion,neuralinvasion,orageyoungerthan50years)shouldreceiveadjuvantchemoradiotherapy;thosepatientswithoutadversefeaturesmaybeobserved.NCNNGuidelinesPatientswithR1resectionsshouldbeofferedradiotherapy(45to50.4Gy)withconcurrent5-FU-basedradiosensitizationplus5-FUwithorwithoutleucovorin.NCNNGuidelinesAllpatientswithanR0resectionwhohaveT3,T4oranyT,N+cancershouldbeofferedadjuvantchemoradiotherapy(ie,radiotherapy45Gywithconcurrent5-FU/leucovorin).Itshouldalsobenotedthat20%ofpatientsintheIntergroup-0116trialhadcancersthatinvolvedthegastroesophagealjunction;therefore,adjuvantchemoradiotherapyshouldalsoberecommendedforpatientswithsimilarcancers(again,patientswithT1,N0,M0tumorsmaybeobservedascanpatientswithT2,N0withoutadversefeatures).NCNNGuidelinesAspreviouslydiscussed,itisrecommendedthatpatientswithnegativemargins(R0resection)andnoevidenceofmetastaticcarcinomaaftergastrectomymaybeconsideredforadjuvantchemoradiationbasedontheresultsoftheIntergrouptrial(INT-0116).NCNNGuidelinesIntheabsenceofM1carcinoma,patientswithR2resectionsmaybeoffered(1)radiationtherapy(45to50.4Gy)withconcurrent5-FU-basedradiosensitization;(2)5-FU-based,cisplatin-oroxaliplatin-based,taxane-based,oririnotecan-basedchemotherapy;(3)bestsupportivecare,ifperformancestatusispoor;(4)enrollmentinaclinicaltrial.Inoperablepatientsshouldundergorestagingaftercompletionofchemoradiotherapy.Ifacompleteresponseofthecarcinomaisdetermined,thesepatientsshouldbeobservedorhavesurgeryifitisdeemedappropriate.IfthereisevidenceofresidualorM1disease,patientsmaybeofferedsalvagetherapyDocetaxel,cisplatin,UFTandleucovorincombinationchemotherapyinadvancedgastriccancer.AbstractNo:4231S.C.Oh,KoreaUniversity,Seoul,RepublicofKoreaMethods:Withoutconsideringprevioustreatment,Seventy-twopatientswereenrolledinthisstudyatKoreaUniversityHospitalfromSeptember2001toApril2003.Docetaxel60mg/m2wasgivenasintravenousinfusionfor1houratday1andcisplatin75mg/m2wasintravenousinfusionafterdocetaxelinfusionatday1.OralUFT360mg/m2andleucovorin45mg/daywereadministeredfor21consecutivedaysfollowedbya7-daydrugfreeinterval.Thisschedulewasrepeatedevery4weeks.Results72patientsreceived267coursesofchemotherapy(4courses).63patientswereevaluatedforresponse.6patientsachievedCR(9.5%)and25patientsPR(39.7%),ORRwasobservedin49.2%(95%confidenceinterval,36.9-61.5%).Themajortoxicitywasneutropeniawhichreachedgrade3-4in65.2%.However,mostofthepatientsexceptthreepatientswhodiedduetosepsis,recoveredfromneutropeniawithoutcomplicationwithsupportofgranulocyteorgranulocyte-macrophagecolonystimulatingfactor.Non-hematologictoxicitieswereusuallymild.Grad3-4nauseaandvomitingwereobservedin17.9%.Themediantimetoprogressionwas27weeks(range,1to88weeks),Medianresponsedurationwas26weeks(range,2to72weeks).ConclusionsTheseresultssuggeststhatthecombinationofdocetaxel,cisplatin,oralUFTandleucovoriniseffectiveandtolerableregimenforthetreatmentofadvancedgastriccancerwithsupportedofagranulocyteorgranulocyte-macrophagecolonystimulatingfactor.Oxaliplatin-basedregimenasneoadjuvantchemotherapyforChinesepatientswithadvancedgastriccancer:PreliminaryresultsofaphaseIIstudy.AbstractNo:4184J.-F.Ji;UniversitySchoolofOncology,BeijingCancerHospital,Beijing,China;BeijingCancerHospital,Beijing,ChinaMethods:15pts(StageIIIborIV)havebeenenrolledbynow.Allptshadhistologicallyprovengastricadenocarcinomaandnopreviouspalliativechemotherapy.Medianage:59years(33-69years),male/femaleratio:10/5,performancestatus:0-2.PtsreceivedOXA130mg/m23H-infusionday1,leucovorin(LV)200mg/m2(2H-infusion)followedby5FU400mg/m2(bolus)and5FU2.5g/m(22h-continuousinfusion)day1,repeatedevery3weeks.Efficacywasevaluatedafter2cycles.ResultsAllptsareevaluableforresponsewithamorethan50%tumorreductionin7of15(46.7%)pts,SDwasobservedin6pts(40.0%)andPDin2(13.3%).14of15ptsreceivedatotal6cycles(pre-op+or-post-op)ofchemotherapyandall15ptscametosurgeryafterreceiving2-6cycles.OXA-5FU/LVwasgeneralwelltolerated.ThemostcommontoxicitywasGrade(Gr)2or3neutropeniaanddiarrheaorGr2nausea/vomiting,NopatientsexperiencedGr4toxicity.Neutropenicfeverwasnotobserved.AnR0curativeresectionwaspossiblein7pts.Therewerenopostoperativemortalitiesandnotreatmentrelateddeaths;14of15ptsaresurviving(2to24months)andonePDptdiedofdisease2monthsaftersurgery.Pathologicexaminationsofoperativesamplesshowedsignificantchemotherapy-inducedchangesin6pts.Thetrialisstillopenandmorematuredatawillbeavailableatthemeeting.Conclusions:Inviewofthefavorableresponserateandtoxicityprofile,thisprotocolwillbefurtherassessedinamulticenterphaseIItrial.PhaseIIstudyofweeklypaclitaxelinpatientswithadvancedgastriccancerinJapan.AbstractNo:4226:H.Baba;KyushuUniversity,Fukuoka,Japan;HiroshimaRedCrossHospital,Hiroshima,JapanMethods:Theeligibilitycriteriawereasfollows;1)histologicallyprovengastriccancerwithmeasurablelesion,2)PS0-2,3)age75,4)adequatebonemarrow,liver,renalfunctions,5)lifeexpectancyofmorethan3months.Fifty-ninepatientsweretreatedwithweekly1h-infusionpaclitaxelof80mg/m2withashortpremedicationforconsecutive3weekswithoneweekrestasonecourse.ResultsPatientscharacteristicswereasfollows:male/female;44/15,meanageof64,PS0/1/2;27/20/12,previoustreatment(-)/(+);11/48.Mediantreatmentcyclewas3.Overallresponseratewas22.2%andmediansurvivaltimeof263days.Therewerenotreatmwnt-relateddeaths.Hematologicandnonhematologictoxicitiesmorethangrade3includedleucopenia(15.3%),neutopenia(20.3%),fatigue(1.7%),andarthralgia(1.7%).AnimprovementinPS,foodintake,pain,andascitesaccumulationwasrecognizedin17.3%,16.4%,23.1%,and47.6%,respectivelyConclusionsWeeklypaclitaxelwasactiveforbothpreviouslyuntreatedandtreatedpatientswithadvancedgastriccancerwithaminimumtoxicityprofile,andcanbeusefultoimproveQOLandprolongsurvivaltimeofpatients.Docetaxel-cisplatin-5FU(TCF)versusdocetaxel-cisplatin(TC)versusepirubicin-cisplatin-5FU(ECF)assystemictreatmentforadvancedgastriccarcinoma(AGC):ArandomizedphaseIItrialoftheSwissGroupforClinicalCancerResearch(SAKK).AbstractNo:4020:A.D.Roth,Oncosurgery,GenevaUniversityHospital,Geneva,Switzerland;Methods:Patients(pts)withAGC,withoutpriorpalliativechemotherapy,withbidimentionallymeasurabledisease,PS1,normalbloodcounts,hepaticandrenalfunctions,wererandomizedtoreceiveupto8cyclesq3wofTC(docetaxel85mg/m2,ciplatine75mg/m2),TCF(likeTC+5-FUcontinuousinfusion(CI)300mg/m2/dfor2w)orECF(epirubicin50mg/m2,cisplatin60mg/m2,5-FUCI200mg/m2/dfor3w).Results:Among121ptsenrolled,119weretreatedandincludedintheanalysis.5ptsarestillontreatment(3ECFand2TCF).Preliminaryresultsaresummarizedbelow.Atotalof554treatmentcyclesaredocumenteduptonow.Amedianof5,4.5and4cyclesofECF,TCandTCFweregiven,respectively.Hematotoxicitywasthemaintoxicityinall3armswithgrade3granulopeniain73%,76%and58%oftheptsforTC,TCFandECF,respectively.Febrileneutropenia(FN)occurencein10ofthefirst21ptsenrolledindocetaxelbasedregimensledtodecreasedocetaxelfrom85to75mg/m2inTCandTCF,resultinginlesserFNoccurence.Grade3non-hematologictoxicitywasinfrequent(=12weeks;adequatehepatic,renal,andbonemarrowfunction.notreceivedchemotherapyorradiotherapyinrecent4weeks;signedinformedconsentwasobtainedfromallpatients.PatientPopulation-excludedcriteriaPatientswereexperiencingsymptomaticperipheralneuropathyofNationalCancerInstitute(NCI)commontoxicitycriteria(CTC)grade=2;pregnantorbreast-feeding;hadactivenoncontrolledinfectionordisease;showedclinicalevidenceofmajororganfailure;hadCNSmetastases;hadbonemetastasesasthesolediseasesite;werereceivingconcurrenttreatmentwithanyotherdrugsthatcouldpotentiallyinterferewiththestudyevaluation.StudyEvaluationstheweekprecedingtreatment,patientsunderwentacompletemedicalhistory,aphysicalexamination.ECG,chestX-ray,CTscanoftheabdominalareaandofallmeasurable/assessablesites,Baselinebiologicanalyses(CBC,AST,ALT,bilirubin,lactatedehydrogenase,alkalinephosphatase,serumcreatinine,)weremeasuredatbaselineandbeforeeachcycle.ThetumormarkersCEAandCA19-9weremeasuredatbaselineandeverytwocycles.RESULTSPatientCharacteristics45patientswereinitiallyenrolledintothisstudyin3centersinZhejiangProvincebetweenDec20,2001,andSept11,2003.Themedianpatientagewas44years(range,28to72years);21patientsweremale(46.7%)and24werefemale(53.3%)RESULTSPatientCharacteristicsmostpatientsbeingingoodgeneralcondition(89%withaperformancestatusKPS=80).Allpatientshadhistologicallyconfirmedadenocarcinoma82%,ofwhichweremoderately,poorlyorwelldifferentiated(48%or26%,respectively),andsignetringcell18%.RESULTSPatientCharacteristicsofthe45patients,39patientswereconsideredassessableforantitumoralactivity.6patientsreceivedfewerthan3cycleswereconsideredineligibleandwerenotevaluatedinthecurrentanalysis.FourofthePRswerenotformallyconfirmed:onepatientunderwentsurgeryafter3cyclesofstudytreatment,3patientsleftthestudyfourcyclesaftertheinitialPRassessment,responseratesofpatientsResponseResponserate(%)Completeresponse7/39(17.9)Partialresponse13/39(33.3)Stabledisease11/39(28.2)Progressivedisease8/39(20.6)Givinganoverall best response rate of 51.3%(95%confidenceinterval,35.6%to62.1%)EfficacyThemediantimetoprogressionwas5.8monthsandmedianoverallsurvivalwas8.2months.Itisalsoimportanttonotethat2patientswereabletoundergofurthercomplementarylocoregionaltreatment(2CR).2patientsliverlesionunderwentradiofrequencyablationTheincidenceofhematologicalandnon-hematologicaltoxicitiesTypeoftoxicitytoxicitygrade(%)(%)(%)(%)Hematological toxicityLeukopenia35.68.98.9Thrombocytopenia13.36.72.2Anemia15.68.9Non-hematological toxicityNausea/vomiting33.38.96.7Peripheralneuropathy26.711.16.7ConclusionThisELF+Oxaliplatinregimenshowsgoodefficacyan