胃癌英文Gastric-Cancer.ppt
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1、 Chemotherapy in Gastric CancerGASTRICCANCERWorldwideincidence*Incidenceper100,000population.ParkinDM,etal.CA Cancer J Clin.1999;49:33-64.MaleMale16.416.4FemaleFemale8.28.2MaleMale36.336.3FemaleFemale16.916.9MaleMale77.977.9FemaleFemale33.333.3MaleMale10.810.8FemaleFemale4.94.9MaleMale43.643.6Female
2、Female19.019.0MaleMale5.95.9FemaleFemale2.62.6MaleMale11.511.5FemaleFemale4.34.3MaleMale18.618.6FemaleFemale13.313.3MaleMale8.48.4FemaleFemale4.04.0EasternEasternEuropeEuropeJapanJapanAustralia/Australia/NewZealandNewZealandChinaNorthernNorthernAfricaAfricaSouthernSouthernAfricaAfricaCentralCentralA
3、mericaAmericaWesternWesternEuropeEuropeNorthNorthAmericaAmerica2ndmostcommoncancerintheworld,558400newcasesand405200deaths.Almost40%ofcasesoccurinChina.PazdurRetal.Cancer management:A multidisciplinary approach.6thedition,2002CountriesinwhichtheincidenceofgastriccarcinomaisextremelyhighincludeJapan,
4、CostaRica,Peru,Brazil,China,Korea,Chile,Taiwan,andthecountriesoftheformerSovietUnion.Atdiagnosis,approximately50%ofpatientshavegastriccarcinomathatextendsbeyondthelocoregionalconfines.Approximately50%ofpatientswithlocoregionalgastriccarcinomacannotundergoacurativeresection(R0).IncountriesintheWester
5、nHemisphere,gastriccarcinomahasmigratedproximally,occurringmostfrequentlyalongtheproximallessercurvature,inthecardia,andinvolvingthegastroesophagealjunction.ItispossiblethatinthecomingdecadesthesechangingtrendswillalsooccurinSouthAmericaandAsia.Nearly70%to80%ofresectedgastriccarcinomaspecimenshaveme
6、tastasesintheregionallymphnodes.Thus,itiscommontoencounterpatientswithadvancedgastriccarcinomaattheoutset.IntheWesternHemisphere,R0resectionispossibleinapproximately50%to80%ofpatients.ThemediansurvivalofpatientswhoundergoanR0resectionisapproximately25months,and5-yearsurvivalratesrangefrom30%to37%.NC
7、NNGuidelinesTheworkuppermitsclassificationofpatientsinto1of2groups:(1)patientswithapparentlocoregionalcarcinoma(stagesItoIIIorM0),and(2)thosewithobviousmetastaticcarcinoma(stageIVorM1).Patientswithapparentlocoregionaldiseasecanbefurtherclassified:(1)thosewhoaremedicallyfitandwhosecancerisresectable,
8、(2)thosewhoaremedicallyfitbutwhosecancerisunresectable,and(3)thosewhoareinoperable(medicallyunfit).Global ConsensusGoodlocalcontrolisessentialtocuregastriccarcinomaTheonlypotentiallycurativetreatmentforlocalizedgastriccancerissurgery.Mostgastriccancersarediagnosedatanadvancedstage.The5-yearsurvivalr
9、ateafter“curativeresection”forgastriccancerisonlybetween30%and40%.Theefficacyofchemotherapywithpalliativeintentisnowwidelyaccepted.Chemotherapy of Gastric CancerKohneCH,WilsJA,WilkeHJ:DevelopmentsinthetreatmentofgastriccancerinEurope.Oncology(Huntingt)14:22-25,2000Chemotherapy of Gastric CancerFluor
10、ouracil(5-FU)isoneofthemosteffectiveandwidelyuseddrugsinthetreatmentofadvancedgastriccancer(AGC),producing a response rate of approximately 20%,with manageable toxicity.Overallsurvivalofbetween5and7monthshasbeenreportedfor5-FUmonotherapyinphaseIIIrandomizedstudies.CoombesR,ChilversCE,AmadoriD,etal:A
11、nInternationalCollaborativeCancerGroup(ICCG)study.AnnOncol5:33-36,19946.Chemotherapy of Gastric Cancer5-FUmodulationbyfolinicacid(FA)hasgenerallyresultedinenhancedantitumorefficacy(22%to48%overallresponserate)andhasledtosomecompleteresponses(5%to9%).AllcurrentreferencecombinationregimensinAGCcontain
12、5-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
13、);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-FUpl
14、uscisplatinhavebeenreportedinthepastseveralyears.Noonestandardtherapyhasemergedfromthesetrials.Outsideofclinicaltrials,therecommendedchemotherapyforadvancedgastriccarcinomaiseithercisplatin-basedor5-FU-basedcombinationchemotherapy.Chemotherapy of Gastric CancerThenewagentsincludepaclitaxel,docetaxel
15、,irinotecan,UFT,oraletoposide,andS-1.Severalreportsofnewercombinationchemotherapyregimenshavealsoappeared.Anumberofneweroralagentsalsoholdpromiseinthetreatmentofgastriccarcinoma.Agentsthathavenotbeenextensivelystudiedincludecapecitabine,oxaliplatin.Inaddition,anumberofnewcategoriesofagentsareofinter
16、est.Theseincludevaccines,antireceptoragents,andantiangiogenicagents.AnumberofchemotherapycombinationsarecurrentlyinphaseIIItrials,andweanticipatethatawidelyacceptedfront-linestandardforpatientswithadvancedgastriccarcinomamightemergeinthenearfuture.NCNNGuidelinesThelandmarktrialistheIntergrouptrialIN
17、T-0116.EligibilityincludedpatientswithT3andorN+adenocarcinomaofthestomachorgastroesophagealjunction.Afteraresectionwithnegativemargins,603patientswererandomlyassignedtoeitherobservationaloneorpostoperativecombinedmodalitytherapyconsistingof5monthlycyclesofboluschemotherapywith45Gyconcurrentwithcycle
18、s2and3.Therewasasignificantdecreaseinlocalfailureasthefirstsiteoffailure(19%versus29%)aswellasanincreaseinmediansurvival(36versus27months),3-yearrelapse-freesurvival(48%versus31%),andoverallsurvival(50%versus41%,=.005)withcombinedmodalitytherapy.NCNNGuidelinesApatientwhosesurgicalpathologicstageisT1
19、,N0,M0maybeobservedandnottreatedwithadjuvanttherapy.AllpatientswithanR0resectionwhohaveT2,N0alongwithadversefeatures(ie,poorlydifferentiatedorhighergradecancer,lymphovascularinvasion,neuralinvasion,orageyoungerthan50years)shouldreceiveadjuvantchemoradiotherapy;thosepatientswithoutadversefeaturesmayb
20、eobserved.NCNNGuidelinesPatientswithR1resectionsshouldbeofferedradiotherapy(45to50.4Gy)withconcurrent5-FU-basedradiosensitizationplus5-FUwithorwithoutleucovorin.NCNNGuidelinesAllpatientswithanR0resectionwhohaveT3,T4oranyT,N+cancershouldbeofferedadjuvantchemoradiotherapy(ie,radiotherapy45Gywithconcur
21、rent5-FU/leucovorin).Itshouldalsobenotedthat20%ofpatientsintheIntergroup-0116trialhadcancersthatinvolvedthegastroesophagealjunction;therefore,adjuvantchemoradiotherapyshouldalsoberecommendedforpatientswithsimilarcancers(again,patientswithT1,N0,M0tumorsmaybeobservedascanpatientswithT2,N0withoutadvers
22、efeatures).NCNNGuidelinesAspreviouslydiscussed,itisrecommendedthatpatientswithnegativemargins(R0resection)andnoevidenceofmetastaticcarcinomaaftergastrectomymaybeconsideredforadjuvantchemoradiationbasedontheresultsoftheIntergrouptrial(INT-0116).NCNNGuidelinesIntheabsenceofM1carcinoma,patientswithR2re
23、sectionsmaybeoffered(1)radiationtherapy(45to50.4Gy)withconcurrent5-FU-basedradiosensitization;(2)5-FU-based,cisplatin-oroxaliplatin-based,taxane-based,oririnotecan-basedchemotherapy;(3)bestsupportivecare,ifperformancestatusispoor;(4)enrollmentinaclinicaltrial.Inoperablepatientsshouldundergorestaging
24、aftercompletionofchemoradiotherapy.Ifacompleteresponseofthecarcinomaisdetermined,thesepatientsshouldbeobservedorhavesurgeryifitisdeemedappropriate.IfthereisevidenceofresidualorM1disease,patientsmaybeofferedsalvagetherapyDocetaxel,cisplatin,UFTandleucovorincombinationchemotherapyinadvancedgastriccanc
25、er.AbstractNo:4231S.C.Oh,KoreaUniversity,Seoul,RepublicofKoreaMethods:Withoutconsideringprevioustreatment,Seventy-twopatientswereenrolledinthisstudyatKoreaUniversityHospitalfromSeptember2001toApril2003.Docetaxel60mg/m2wasgivenasintravenousinfusionfor1houratday1andcisplatin75mg/m2wasintravenousinfusi
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