胃癌课件英文Gastric Cancer.ppt

ChemotherapyinGastricCancer GASTRICCANCERWorldwideincidence Incidenceper100 000population ParkinDM etal CACancerJClin 1999 49 33 64 2ndmostcommoncancerintheworld 558400newcasesand405200deaths Almost40 ofcasesoccurinChina PazdurRetal Cancermanagement Amultidisciplinaryapproach 6thedition 2002 CountriesinwhichtheincidenceofgastriccarcinomaisextremelyhighincludeJapan 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 NCNNGuidelines Theworkuppermitsclassificationofpatientsinto1of2groups 1 patientswithapparentlocoregionalcarcinoma stagesItoIIIorM0 and 2 thosewithobviousmetastaticcarcinoma stageIVorM1 Patientswithapparentlocoregionaldiseasecanbefurtherclassified 1 thosewhoaremedicallyfitandwhosecancerisresectable 2 thosewhoaremedicallyfitbutwhosecancerisunresectable and 3 thosewhoareinoperable medicallyunfit GlobalConsensus GoodlocalcontrolisessentialtocuregastriccarcinomaTheonlypotentiallycurativetreatmentforlocalizedgastriccancerissurgery Mostgastriccancersarediagnosedatanadvancedstage The5 yearsurvivalrateafter curativeresection forgastriccancerisonlybetween30 and40 Theefficacyofchemotherapywithpalliativeintentisnowwidelyaccepted ChemotherapyofGastricCancer KohneCH WilsJA WilkeHJ DevelopmentsinthetreatmentofgastriccancerinEurope Oncology Huntingt 14 22 25 2000 ChemotherapyofGastricCancer Fluorouracil 5 FU isoneofthemosteffectiveandwidelyuseddrugsinthetreatmentofadvancedgastriccancer AGC producingaresponserateofapproximately20 withmanageabletoxicity Overallsurvivalofbetween5and7monthshasbeenreportedfor5 FUmonotherapyinphaseIIIrandomizedstudies CoombesR ChilversCE AmadoriD etal AnInternationalCollaborativeCancerGroup ICCG study AnnOncol5 33 36 19946 ChemotherapyofGastricCancer 5 FUmodulationbyfolinicacid FA hasgenerallyresultedinenhancedantitumorefficacy 22 to48 overallresponserate andhasledtosomecompleteresponses 5 to9 AllcurrentreferencecombinationregimensinAGCcontain5 FU LouvetC DeGramontA DemuynckB etal AnnOncol2 229 230 1991 ChemotherapyofGastricCancer 5 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 ChemotherapyofGastricCancer SeveralrandomizedstudiescomparingFAMversusFAMTX 5 FU adriamycin andmethotrexate withleucovorinrescue FAMTXversusECF epirubicin cisplatin and5 FU andFAMTXversusELF etoposide leucovorin and5 FU versus5 FUpluscisplatinhavebeenreportedinthepastseveralyears Noonestandardtherapyhasemergedfromthesetrials Outsideofclinicaltrials therecommendedchemotherapyforadvancedgastriccarcinomaiseithercisplatin basedor5 FU basedcombinationchemotherapy ChemotherapyofGastricCancer Thenewagentsincludepaclitaxel docetaxel irinotecan UFT oraletoposide andS 1 Severalreportsofnewercombinationchemotherapyregimenshavealsoappeared Anumberofneweroralagentsalsoholdpromiseinthetreatmentofgastriccarcinoma Agentsthathavenotbeenextensivelystudiedincludecapecitabine oxaliplatin Inaddition anumberofnewcategoriesofagentsareofinterest Theseincludevaccines antireceptoragents andantiangiogenicagents AnumberofchemotherapycombinationsarecurrentlyinphaseIIItrials andweanticipatethatawidelyacceptedfront linestandardforpatientswithadvancedgastriccarcinomamightemergeinthenearfuture NCNNGuidelines ThelandmarktrialistheIntergrouptrialINT 0116 EligibilityincludedpatientswithT3andorN adenocarcinomaofthestomachorgastroesophagealjunction Afteraresectionwithnegativemargins 603patientswererandomlyassignedtoeitherobservationaloneorpostoperativecombinedmodalitytherapyconsistingof5monthlycyclesofboluschemotherapywith45Gyconcurrentwithcycles2and3 Therewasasignificantdecreaseinlocalfailureasthefirstsiteoffailure 19 versus29 aswellasanincreaseinmediansurvival 36versus27months 3 yearrelapse freesurvival 48 versus31 andoverallsurvival 50 versus41 005 withcombinedmodalitytherapy NCNNGuidelines ApatientwhosesurgicalpathologicstageisT1 N0 M0maybeobservedandnottreatedwithadjuvanttherapy AllpatientswithanR0resectionwhohaveT2 N0alongwithadversefeatures ie poorlydifferentiatedorhighergradecancer lymphovascularinvasion neuralinvasion orageyoungerthan50years shouldreceiveadjuvantchemoradiotherapy thosepatientswithoutadversefeaturesmaybeobserved NCNNGuidelines PatientswithR1resectionsshouldbeofferedradiotherapy 45to50 4Gy withconcurrent5 FU basedradiosensitizationplus5 FUwithorwithoutleucovorin NCNNGuidelines AllpatientswithanR0resectionwhohaveT3 T4oranyT N cancershouldbeofferedadjuvantchemoradiotherapy ie radiotherapy 45Gy withconcurrent5 FU leucovorin Itshouldalsobenotedthat20 ofpatientsintheIntergroup 0116trialhadcancersthatinvolvedthegastroesophagealjunction therefore adjuvantchemoradiotherapyshouldalsoberecommendedforpatientswithsimilarcancers again patientswithT1 N0 M0tumorsmaybeobservedascanpatientswithT2 N0withoutadversefeatures NCNNGuidelines Aspreviouslydiscussed itisrecommendedthatpatientswithnegativemargins R0resection andnoevidenceofmetastaticcarcinomaaftergastrectomymaybeconsideredforadjuvantchemoradiationbasedontheresultsoftheIntergrouptrial INT 0116 NCNNGuidelines IntheabsenceofM1carcinoma 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 Docetaxel cisplatin UFTandleucovorincombinationchemotherapyinadvancedgastriccancer AbstractNo 4231S C Oh KoreaUniversity Seoul RepublicofKorea Methods Withoutconsideringprevioustreatment Seventy twopatientswereenrolledinthisstudyatKoreaUniversityHospitalfromSeptember2001toApril2003 Docetaxel60mg m2wasgivenasintravenousinfusionfor1houratday1andcisplatin75mg m2wasintravenousinfusionafterdocetaxelinfusionatday1 OralUFT360mg m2andleucovorin45mg daywereadministeredfor21consecutivedaysfollowedbya7 daydrugfreeinterval Thisschedulewasrepeatedevery4weeks Results 72patientsreceived267coursesofchemotherapy 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 Conclusions Theseresultssuggeststhatthecombinationofdocetaxel cisplatin oralUFTandleucovoriniseffectiveandtolerableregimenforthetreatmentofadvancedgastriccancerwithsupportedofagranulocyteorgranulocyte macrophagecolonystimulatingfactor Oxaliplatin basedregimenasneoadjuvantchemotherapyforChinesepatientswithadvancedgastriccancer PreliminaryresultsofaphaseIIstudy AbstractNo 4184J F Ji UniversitySchoolofOncology BeijingCancerHospital Beijing China BeijingCancerHospital Beijing China Methods 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 Results Allptsareevaluableforresponsewithamorethan50 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 Japan Methods Theeligibilitycriteriawereasfollows 1 histologicallyprovengastriccancerwithmeasurablelesion 2 PS0 2 3 age 75 4 adequatebonemarrow liver renalfunctions 5 lifeexpectancyofmorethan3months Fifty ninepatientsweretreatedwithweekly1h infusionpaclitaxelof80mg m2withashortpremedicationforconsecutive3weekswithoneweekrestasonecourse Results Patientscharacteristicswereasfollows 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 Conclusions Weeklypaclitaxelwasactiveforbothpreviouslyuntreatedandtreatedpatientswithadvancedgastriccancerwithaminimumtoxicityprofile 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 PS 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 Results 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 Conclusions Despiteanincreasedtoxicity docetaxelbasedregimensseemtobemoreefficaciousthanECF IntermsofRRandTTP TCFisthemorepromisingregimenandshouldbechosenforformalcomparisonwithECF ThistrialissupportedinpartbyAventis MulticentricphaseIIstudyofepirubicinanddocetaxelasfirstlinetreatmentforpatientswithadvancedgastriccancer AGERCORstudy AbstractNo 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 Results 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 Conclusions First lineefficacyofEPITAXcombinationisinthesamerangeasthatobservedinsecond line withanacceptabletoxicity 1 yroverallsurvivalmayberelatedtothetherapeuticstrategyincludingearlyevaluationandactivesecond linetherapy AphaseIIstudyofOxaliplatinwithELFregimeninpatientswithadvancedgastriccancerAbstractNo 4206 Hong MingPan1 NongXu2 FangLou1 YongGuo3 WeiJin1 Hai ZhouLou1 YuZheng1 Wei jiaFang21 MedicalOncology SirRunRunShawHospital ZhejiangUniversity 2 ChemotherapyDepartment the1sthospitalaffliatedtoZhejiangUniversity 3 Oncologydepartment ZhejiangtraditionalChineseHospital Hangzhou 310016 ZhejiangProvince China Louvet C Andr T Tigaud J M etal PhaseIIStudyofOxaliplatin Fluorouracil andFolinicAcidinLocallyAdvancedorMetastaticGastricCancerPatients JournalofClinicalOncology20 23 4543 4548 2002 Bestresponsesinthe49assessablepatientsweretwocompleteresponsesand20partialresponses givinganoverallbestresponserateof44 9 Eightpatientsunderwentcomplementarytreatmentwithcurativeintent sixwithsurgeryandtwowithchemoradiotherapy Medianfollow up18 6months TTP6 2months andoverallsurvival8 6months KimDY KimJH LeeSHetal PhaseIIstudyofoxaliplatin 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 OurStudyDesign AphaseIIstudywasconductedtoevaluatetheefficacyandsafetyofthecombinationofOxaliplatinandELFregimeninthetreatmentofpatientswithadvancedgastriccancer thisisamulticenter nonrandomized open label phaseIItrial PatientsreceivedOxaliplatin100mg m 2hronday1 calciumfolinate200mg m 1 2hronday1 3 5 FU500mg m 2hronday1 3andetoposide100mg m 3hronday1 3 OurStudyDesign Cycleswererepeatedevery21days Treatmentwascontinuedforatleast3cyclesexceptintheeventofdiseaseprogression unacceptabletoxicity patientrefusal Efficacyandsafetywereevaluatedevery3cyclesandresponseswerere confirmed4weekslater Antiemetictreatment Ondansetron GranisetronwithorwithoutDexamethasone wasalwaysadministeredbeforetheoxaliplatininfusion PatientPopulation eligiblecriteria Tobeeligibleforthisstudy patientshadtohavepathologicallyconfirmednonresectablelocallyadvancedormetastaticgastriccancer atleastonemeasurablelesioninanonirradiatedarea performancestatus KPS Karnofskyscale 60 PatientPopulation eligiblecriteria agedbetween18and75years alifeexpectancy 12weeks adequatehepatic renal andbonemarrowfunction notreceivedchemotherapyorradiotherapyinrecent4weeks signedinformedconsentwasobtainedfromallpatients PatientPopulation excludedcriteria PatientswereexperiencingsymptomaticperipheralneuropathyofNationalCancerInstitute NCI commontoxicitycriteria CTC grade 2 pregnantorbreast feeding hadactivenoncontrolledinfectionordisease showedclinicalevidenceofmajororganfailure hadCNSmetastases hadbonemetastasesasthesolediseasesite werereceivingconcurrenttreatmentwithanyotherdrugsthatcouldpotentiallyinterferewiththestudyevaluation StudyEvaluations theweekprecedingtreatment patientsunderwentacompletemedicalhistory aphysicalexamination ECG chestX ray CTscanoftheabdominalareaandofallmeasurable assessablesites Baselinebiologica