胃癌英文Gastric Cancer課件

ChemotherapyinGastricCancer胃癌英文GastricCancerGASTRICCANCER

Worldwideincidence**Incidenceper100,000population.ParkinDM,etal.CACancerJClin.1999;49:33-64.Male 16.4Female 8.2Male 36.3Female 16.9Male 77.9Female 33.3Male 10.8Female 4.9Male 43.6Female 19.0Male 5.9Female 2.6Male 11.5Female 4.3Male 18.6Female 13.3Male 8.4Female 4.0EasternEuropeJapanAustralia/NewZealandChinaNorthernAfricaSouthernAfricaCentralAmericaWesternEuropeNorthAmerica2ndmostcommoncancerintheworld,558400newcasesand405200deaths.Almost40%ofcasesoccurinChina.PazdurRetal.Cancermanagement:Amultidisciplinaryapproach.6thedition,2002

胃癌英文GastricCancerCountriesinwhichtheincidenceofgastriccarcinomaisextremelyhighincludeJapan,CostaRica,Peru,Brazil,China,Korea,Chile,Taiwan,andthecountriesoftheformerSovietUnion.Atdiagnosis,approximately50%ofpatientshavegastriccarcinomathatextendsbeyondthelocoregionalconfines.Approximately50%ofpatientswithlocoregionalgastriccarcinomacannotundergoacurativeresection(R0).胃癌英文GastricCancerIncountriesintheWesternHemisphere,gastriccarcinomahasmigratedproximally,occurringmostfrequentlyalongtheproximallessercurvature,inthecardia,andinvolvingthegastroesophagealjunction.ItispossiblethatinthecomingdecadesthesechangingtrendswillalsooccurinSouthAmericaandAsia.胃癌英文GastricCancerNearly70%to80%ofresectedgastriccarcinomaspecimenshavemetastasesintheregionallymphnodes.Thus,itiscommontoencounterpatientswithadvancedgastriccarcinomaattheoutset.IntheWesternHemisphere,R0resectionispossibleinapproximately50%to80%ofpatients.ThemediansurvivalofpatientswhoundergoanR0resectionisapproximately25months,and5-yearsurvivalratesrangefrom30%to37%.胃癌英文GastricCancerNCNNGuidelinesTheworkuppermitsclassificationofpatientsinto1of2groups:(1)patientswithapparentlocoregionalcarcinoma(stagesItoIIIorM0),and(2)thosewithobviousmetastaticcarcinoma(stageIVorM1).Patientswithapparentlocoregionaldiseasecanbefurtherclassified:(1)thosewhoaremedicallyfitandwhosecancerisresectable,(2)thosewhoaremedicallyfitbutwhosecancerisunresectable,and(3)thosewhoareinoperable(medicallyunfit).胃癌英文GastricCancerGlobalConsensusGoodlocalcontrolisessentialtocuregastriccarcinomaTheonlypotentiallycurativetreatmentforlocalizedgastriccancerissurgery.胃癌英文GastricCancerMostgastriccancersarediagnosedatanadvancedstage.The5-yearsurvivalrateafter“curativeresection”forgastriccancerisonlybetween30%and40%.Theefficacyofchemotherapywithpalliativeintentisnowwidelyaccepted.ChemotherapyofGastricCancerKohneCH,WilsJA,WilkeHJ:DevelopmentsinthetreatmentofgastriccancerinEurope.Oncology(Huntingt)14:22-25,2000胃癌英文GastricCancerChemotherapyofGastricCancerFluorouracil(5-FU)isoneofthemosteffectiveandwidelyuseddrugsinthetreatmentofadvancedgastriccancer(AGC),producingaresponserateofapproximately20%,withmanageabletoxicity.

Overallsurvivalofbetween5and7monthshasbeenreportedfor5-FUmonotherapyinphaseIIIrandomizedstudies.CoombesR,ChilversCE,AmadoriD,etal:AnInternationalCollaborativeCancerGroup(ICCG)study.AnnOncol5:33-36,19946.胃癌英文GastricCancerChemotherapyofGastricCancer5-FUmodulationbyfolinicacid(FA)hasgenerallyresultedinenhancedantitumorefficacy(22%to48%overallresponserate)andhasledtosomecompleteresponses(5%to9%).AllcurrentreferencecombinationregimensinAGCcontain5-FU.

LouvetC,DeGramontA,DemuynckB,etal:.AnnOncol2:229-230,1991胃癌英文GastricCancerChemotherapyofGastricCancer5-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.胃癌英文GastricCancerChemotherapyofGastricCancerSeveralrandomizedstudiescomparingFAMversusFAMTX(5-FU,adriamycin,andmethotrexate[withleucovorinrescue),FAMTXversusECF(epirubicin,cisplatin,and5-FU),andFAMTXversusELF(etoposide,leucovorin,and5-FU)versus5-FUpluscisplatinhavebeenreportedinthepastseveralyears.Noonestandardtherapyhasemergedfromthesetrials.Outsideofclinicaltrials,therecommendedchemotherapyforadvancedgastriccarcinomaiseithercisplatin-basedor5-FU--basedcombinationchemotherapy.胃癌英文GastricCancerChemotherapyofGastricCancerThenewagentsincludepaclitaxel,docetaxel,irinotecan,UFT,oraletoposide,andS-1.Severalreportsofnewercombinationchemotherapyregimenshavealsoappeared.Anumberofneweroralagentsalsoholdpromiseinthetreatmentofgastriccarcinoma.Agentsthathavenotbeenextensivelystudiedincludecapecitabine,oxaliplatin.Inaddition,anumberofnewcategoriesofagentsareofinterest.Theseincludevaccines,antireceptoragents,andantiangiogenicagents.AnumberofchemotherapycombinationsarecurrentlyinphaseIIItrials,andweanticipatethatawidelyacceptedfront-linestandardforpatientswithadvancedgastriccarcinomamightemergeinthenearfuture.胃癌英文GastricCancerNCNNGuidelinesThelandmarktrialistheIntergrouptrialINT-0116.EligibilityincludedpatientswithT3andorN+adenocarcinomaofthestomachorgastroesophagealjunction.Afteraresectionwithnegativemargins,603patientswererandomlyassignedtoeitherobservationaloneorpostoperativecombinedmodalitytherapyconsistingof5monthlycyclesofboluschemotherapywith45Gyconcurrentwithcycles2and3.Therewasasignificantdecreaseinlocalfailureasthefirstsiteoffailure(19%versus29%)aswellasanincreaseinmediansurvival(36versus27months),3-yearrelapse-freesurvival(48%versus31%),andoverallsurvival(50%versus41%,=.005)withcombinedmodalitytherapy.胃癌英文GastricCancerNCNNGuidelinesApatientwhosesurgicalpathologicstageisT1,N0,M0maybeobservedandnottreatedwithadjuvanttherapy.AllpatientswithanR0resectionwhohaveT2,N0alongwithadversefeatures(ie,poorlydifferentiatedorhighergradecancer,lymphovascularinvasion,neuralinvasion,orageyoungerthan50years)shouldreceiveadjuvantchemoradiotherapy;thosepatientswithoutadversefeaturesmaybeobserved.胃癌英文GastricCancerNCNNGuidelinesPatientswithR1resectionsshouldbeofferedradiotherapy(45to50.4Gy)withconcurrent5-FU-basedradiosensitizationplus5-FUwithorwithoutleucovorin.胃癌英文GastricCancerNCNNGuidelinesAllpatientswithanR0resectionwhohaveT3,T4oranyT,N+cancershouldbeofferedadjuvantchemoradiotherapy(ie,radiotherapy[45Gy]withconcurrent5-FU/leucovorin).Itshouldalsobenotedthat20%ofpatientsintheIntergroup-0116trialhadcancersthatinvolvedthegastroesophagealjunction;therefore,adjuvantchemoradiotherapyshouldalsoberecommendedforpatientswithsimilarcancers(again,patientswithT1,N0,M0tumorsmaybeobservedascanpatientswithT2,N0withoutadversefeatures).胃癌英文GastricCancerNCNNGuidelinesAspreviouslydiscussed,itisrecommendedthatpatientswithnegativemargins(R0resection)andnoevidenceofmetastaticcarcinomaaftergastrectomymaybeconsideredforadjuvantchemoradiationbasedontheresultsoftheIntergrouptrial(INT-0116).胃癌英文GastricCancerNCNNGuidelinesIntheabsenceofM1carcinoma,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,patientsmaybeofferedsalvagetherapy胃癌英文GastricCancerDocetaxel,cisplatin,UFTandleucovorincombinationchemotherapyinadvancedgastriccancer.Abstract

No:4231S.C.Oh,KoreaUniversity,Seoul,RepublicofKoreaMethods:

Withoutconsideringprevioustreatment,Seventy-twopatientswereenrolledinthisstudyatKoreaUniversityHospitalfromSeptember2001toApril2003.Docetaxel60mg/m2wasgivenasintravenousinfusionfor1houratday1andcisplatin75mg/m2wasintravenousinfusionafterdocetaxelinfusionatday1.OralUFT360mg/m2andleucovorin45mg/daywereadministeredfor21consecutivedaysfollowedbya7-daydrugfreeinterval.Thisschedulewasrepeatedevery4weeks.胃癌英文GastricCancerResults72patientsreceived267coursesofchemotherapy(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).胃癌英文GastricCancerConclusionsTheseresultssuggeststhatthecombinationofdocetaxel,cisplatin,oralUFTandleucovoriniseffectiveandtolerableregimenforthetreatmentofadvancedgastriccancerwithsupportedofagranulocyteorgranulocyte-macrophagecolonystimulatingfactor.胃癌英文GastricCancerOxaliplatin-basedregimenasneoadjuvantchemotherapyforChinesepatientswithadvancedgastriccancer:PreliminaryresultsofaphaseIIstudy.

Abstract

No: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/m2(22h-continuousinfusion)day1,repeatedevery3weeks.Efficacywasevaluatedafter2cycles.胃癌英文GastricCancerResultsAllptsareevaluableforresponsewithamorethan50%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.胃癌英文GastricCancerConclusions:Inviewofthefavorableresponserateandtoxicityprofile,thisprotocolwillbefurtherassessedinamulticenterphaseIItrial.胃癌英文GastricCancerPhaseIIstudyofweeklypaclitaxelinpatientswithadvancedgastriccancerinJapan.

Abstract

No:4226:H.Baba;KyushuUniversity,Fukuoka,Japan;HiroshimaRedCrossHospital,Hiroshima,JapanMethods:Theeligibilitycriteriawereasfollows;1)histologicallyprovengastriccancerwithmeasurablelesion,2)PS0-2,3)age<75,4)adequatebonemarrow,liver,renalfunctions,5)lifeexpectancyofmorethan3months.Fifty-ninepatientsweretreatedwithweekly1h-infusionpaclitaxelof80mg/m2withashortpremedicationforconsecutive3weekswithoneweekrestasonecourse.胃癌英文GastricCancerResultsPatientscharacteristicswereasfollows: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%,respectively胃癌英文GastricCancerConclusionsWeeklypaclitaxelwasactiveforbothpreviouslyuntreatedandtreatedpatientswithadvancedgastriccancerwithaminimumtoxicityprofile,andcanbeusefultoimproveQOLandprolongsurvivaltimeofpatients.胃癌英文GastricCancerDocetaxel-cisplatin-5FU(TCF)versusdocetaxel-cisplatin(TC)versusepirubicin-cisplatin-5FU(ECF)assystemictreatmentforadvancedgastriccarcinoma(AGC):ArandomizedphaseIItrialoftheSwissGroupforClinicalCancerResearch(SAKK).Abstract

No:4020:A.D.Roth,Oncosurgery,GenevaUniversityHospital,Geneva,Switzerland;

Methods:Patients(pts)withAGC,withoutpriorpalliativechemotherapy,withbidimentionallymeasurabledisease,PSa‰¤1,normalbloodcounts,hepaticandrenalfunctions,wererandomizedtoreceiveupto8cyclesq3wofTC(docetaxel85mg/m2,ciplatine75mg/m2),TCF(likeTC+5-FUcontinuousinfusion(CI)300mg/m2/dfor2w)orECF(epirubicin50mg/m2,cisplatin60mg/m2,5-FUCI200mg/m2/dfor3w).胃癌英文GastricCancerResults:Among121ptsenrolled,119weretreatedandincludedintheanalysis.5ptsarestillontreatment(3ECFand2TCF).Preliminaryresultsaresummarizedbelow.Atotalof554treatmentcyclesaredocumenteduptonow.Amedianof5,4.5and4cyclesofECF,TCandTCFweregiven,respectively.Hematotoxicitywasthemaintoxicityinall3armswithgrade≥3granulopeniain73%,76%and58%oftheptsforTC,TCFandECF,respectively.Febrileneutropenia(FN)occurencein10ofthefirst21ptsenrolledindocetaxelbasedregimensledtodecreasedocetaxelfrom85to75mg/m2inTCandTCF,resultinginlesserFNoccurence.Grade≥3non-hematologictoxicitywasinfrequent(<10%ofpts)apartfromalopecia(3arms),nausea(18%inTCandTCFpts)anddiarrhea(15%inTCFpts).胃癌英文GastricCancerConclusions:

Despiteanincreasedtoxicity,docetaxelbasedregimensseemtobemoreefficaciousthanECF.IntermsofRRandTTP,TCFisthemorepromisingregimenandshouldbechosenforformalcomparisonwithECF.ThistrialissupportedinpartbyAventis胃癌英文GastricCancerMulticentricphaseIIstudyofepirubicinanddocetaxelasfirstlinetreatmentforpatientswithadvancedgastriccancer:AGERCORstudy.

Abstract

No:4062:S.Nguyen,CentreHospitalierdeBeauvais,Beauvais,France;

Methods:36patients(7females,29males;performancestatus[PS]0/1/2:12/8/6,LA/M:7/29;meanweight:69,6kg)weretreatedwithepirubicin60mg/m2in30minutes,followed1hlaterbydocetaxel75mg/m2in60minutes,every21days,inanoutpatientbasis.Corticosteroidswereadministeredfromday-1today4,andGCSFrecommendedfromday3today9.Allpatientswereassessablefortoxicity(NCI-CTCcriteria)andefficacy(Recistevalutioncriteria).Patientswereevaluatedevery3cycles(2months),and5FU+platinium-basedsecond-linetreatmentwasrecommendedatprogression胃癌英文GastricCancerResults:174cycleswereadministered(median5,range1-9).Notoxicdeathwasreported.Grade3-4toxicitieswere:neutropeniain41,7%ofpatients,thrombocytopeniain5,6%,anemiain11,1%,nausea-vomitingin13,9%anddiarrheain5,6%.MedianPSandmeanweightremainedunchangedatfirstevaluation.Symptoms(includingpain,anorexiaanddysphagia)wereimprovedatfirstevaluationinone-thirdofpatientswithinitialsymptoms.1completeresponse(CR)(2,7%)and6partialresponse(PR)(16.7%)wereobtained,foranoverallresponse(OR)rateof19,4%(95%CI:0,07-0,32).10patients(27,8%)hadstabledisease,and19patients(52,8%)progressed.Two-thirdofpatientsreceivedsecond-linetherapy.Withamedianfollow-uptimeof100weeks,themedianPFSandOStimeswere18and52weeks,respectively.胃癌英文GastricCancerConclusions:First-lineefficacyofEPITAXcombinationisinthesamerangeasthatobservedinsecond-line,withanacceptabletoxicity.1-yroverallsurvivalmayberelatedtothetherapeuticstrategyincludingearlyevaluationandactivesecond-linetherapy.胃癌英文GastricCancerAphaseIIstudyofOxaliplatinwithELFregimeninpatientswithadvancedgastriccancerAbstract

No:4206

Hong-MingPan1,NongXu2,FangLou1,YongGuo3,WeiJin1,Hai-ZhouLou1,YuZheng1,Wei-jiaFang2

1.MedicalOncology,SirRunRunShawHospital,ZhejiangUniversity;2.ChemotherapyDepartment,the1sthospitalaffliatedtoZhejiangUniversity;3.Oncologydepartment,ZhejiangtraditionalChineseHospital;Hangzhou,310016,ZhejiangProvince,China

胃癌英文GastricCancerLouvet,C.;André,T.;Tigaud,J.M,etal..PhaseIIStudyofOxaliplatin,Fluorouracil,andFolinicAcidinLocallyAdvancedorMetastaticGastricCancerPatients.JournalofClinicalOncology

20(23)

:4543-4548,2002Bestresponsesinthe49assessablepatientsweretwocompleteresponsesand20partialresponses,givinganoverallbestresponserateof44.9%.Eightpatientsunderwentcomplementarytreatmentwithcurativeintent(sixwithsurgeryandtwowithchemoradiotherapy).Medianfollow-up18.6months,TTP6.2months,andoverallsurvival8.6months.

胃癌英文GastricCancerKimDY,KimJH,LeeSHetal.PhaseIIstudyof

oxaliplatin,5-fluorouracilandleucovorininpreviouslyplatinum-treatedpatientswithadvancedgastriccancer.AnnalsofOncology14:383-387,2003

Ofthe23evaluablepatients,thereweresixpartialresponses(responserate26%).Allrespondingpatientswereamongthosewhoenteredintothistrialimmediatelyafterfailureofpreviouschemotherapywith5-FUandcisplatin.ThemedianTTPwas4.3monthsandthemedianoverallsurvivalwas7.3months.Grade1–2anemiain39cycles(39%).Nograde4leukopeniaorthrombocytopeniawereobserved.nausea/vomiting(33%).Peripheralneuropathyofgrade1or2wasnoted(27%),buttherewasnograde3or4neurotoxicity.胃癌英文GastricCancerOurStudyDesignAphaseIIstudy

wasconductedtoevaluatetheefficacyandsafetyofthecombinationofOxaliplatinandELFregimeninthetreatmentofpatientswithadvancedgastriccancer.thisisamulticenter,nonrandomized,open-label,phaseIItrial.PatientsreceivedOxaliplatin100mg/m22hronday1,calciumfolinate200mg/m21/2hronday1-3,5-FU500mg/m22hronday1-3andetoposide100mg/m23hronday1-3.胃癌英文GastricCancerOurStudyDesignCycleswererepeatedevery21days.Treatmentwascontinuedforatleast3cyclesexceptintheeventofdiseaseprogression,unacceptabletoxicity,patientrefusal.Efficacyandsafetywereevaluatedevery3cyclesandresponseswerere-confirmed4weekslater.Antiemetictreatment(Ondansetron/GranisetronwithorwithoutDexamethasone)wasalwaysadministeredbeforetheoxaliplatininfusion.胃癌英文GastricCancerPatientPopulation---eligiblecriteria

Tobeeligibleforthisstudy,patientshadtohavepathologicallyconfirmednonresectablelocallyadvancedormetastaticgastriccancer;atleastonemeasurablelesioninanonirradiatedarea;performancestatus,KPS(Karnofskyscale)≥60胃癌英文GastricCancerPatientPopulation---eligiblecriteria

agedbetween18and75years;alifeexpectancy>=12weeks;adequatehepatic,renal,andbonemarrowfunction.notreceivedchemotherapyorradiotherapyinrecent4weeks;signedinformedconsentwasobtainedfromallpatients.胃癌英文GastricCancerPatientPopulation----

excludedcriteriaPatientswereexperiencingsymptomaticperipheralneuropathyofNationalCancerInstitute(NCI)commontoxicitycriteria(CTC)grade>=2;pregnantorbreast-feeding;hadactivenoncontrolledinfectionordisease;showedclinicalevidenceofmajororganfailure;hadCNSmetastases;hadbonemetastasesasthesolediseasesite;werereceivingconcurrenttreatmentwithanyotherdrugsthatcouldpotentiallyinterferewiththestudyevaluation.胃癌英文GastricCancerStudyEvaluationstheweekprecedingtreatment,patientsunderwentacompletemedicalhistory,aphysicalexamination.ECG,chestX-ray,CTscanoftheabdominalareaandofallmeasurable/assessablesites,Baselinebiologicanalyses(CBC,AST,ALT,bilirubin,lactatedehydrogenase,alkalinephosphatase,serumcreatinine,)weremeasuredatbaselineandbeforeeachcycle.ThetumormarkersCEAandCA19-9weremeasuredatbaselineandeverytwocycles.胃癌英文GastricCancerRESULTS

PatientCharacteristics45patientswereinitiallyenrolledintothisstudyin3centersinZhe