简介:PURPOSE:ResistancetotemozolomidechemotherapyispartlymediatedbyO^6-methylguanine-DNAmethlytransferase(MGMT).ProtractedtreatmentwithtemozolomidepotentiallyovercomesMGMTresistanceandimprovesoutcome.WeconductedaphaseIIstudyofprotracteddailytemozolomideinadultswithlow-gradegliomas.EXPERIMENTALDESIGN:PatientswithnewlydiagnosedoligodendrogliomaoroligoastrocytomawithaMIB-1indexof〉5%orrecurrentlow-gradegliomasreceivedtemozolomide(75mg/m^2/dayin11-weekcyclesof7weekson/4weeksoff).Treatmentcontinuedforatotalofsixcyclesoruntiltumorprogressionorunacceptabletoxicity.Primaryendpointwasbestoverallresponserate;secondaryendpointswereprogression-freesurvival,overallsurvival,andtoxicity.
简介:BACKGROUND:In2004,arandomisedphaseⅢtrialbytheEuropeanOrganisationforResearchandTreatmentofCancer(EORTC)andNationalCancerInstituteofCanadaClinicalTrialsGroup(NCIC)reportedimprovedmedianand2-yearsurvivalforpatientswithglioblastomatreatedwithconcomitantandadjuvanttemozolomideandradiotherapy.We'reportthefinalresultswithamedianfollow-upofmorethan5years.METHODS:Adultpatientswithnewlydiagnosedglioblastomawererandomlyassignedtoreceiveeitherstandardradiotherapyoridenticalradiotherapywithconcomitanttemozolomidefollowedbyuptosixcyclesofadjuvanttemozolomide.
简介:PURPOSE:Toevaluatethetoxicityandresponserateofbortezomibwithconcurrentradiotherapyandtemozolomideinthetreatmentofpatientswithcentralnervoussystemmalignancies.PATIENTSANDMETHODS:Thisopen-label,dose-escalation,PhaseⅠclinicalstudyevaluatedthesafetyofthreedoselevelsofintravenouslyadministeredbortezomib(0.7,1.0,and1.3mg/m(2)/dose)onDays1,4,8,and11ofa21-daycycle,inadditiontoconcurrentradiotherapyandtemozolomideatadailydoseof75mg/m(2)startingonDay1.Theprimaryendpointwasdose-limitingtoxicity,definedasanyGrade4-5toxicityorGrade3toxicitydirectlyat-tr/butabletoprotocoltreatment,requiringhospitalizationand/orradiotherapyinterruption.
简介:PURPOSE:ThisphaseⅡtrialwasdesignedtodefinetheroleofO^6-benzylguanine(O^6-BG)inrestoringtemozolomidesensitivityinpatientswithrecurrentorprogressive,temozolomidc-resistantmalignantgliomaandtoevaluatethesafetyofadministeringO^6-BGincombinationwithtemozolomide.PATIENTSANDMETHODS:Patientswereaccruedintotwoindependentstrataonthebasisofhistology:glioblastomamultifonne(GBM)andaanaplasticglioma.BothtemozolomideandO6-BGwereadministeredonday1ofa28-daytreatmentcycle.Patientswereadministereda1-hourO^6-BGinfusionatadoseof120mg/m^2followedimmediatelybya48-hourinfusionatadoseof30mg/m^2/d.
简介:PURPOSE:Toevaluatesingle-agentactivityofbevacizumabinpatientswithrecurrentglioblastoma.PATIENTSANDMETH-ODS:Patientswithrecurrentglioblastomaweretreatedwithbevacizumab10mg/kgevery2weeks.Aftertumorprogression,patientswereimmediatelytreatedwithbevacizumabincombinationwithirinotecan340mg/m^2or125mg/m^2every2weeks,dependingonuseofenzyme-inducingantiepilepticdrugs.Completepatientevaluationswererepeatedevery4weeks.RESULTS:Forty-eightheavilypretreatedpatientswereaccruedtothisstudy.Thromboembolicevents(12.5%),hypertension(12.5%),hypophosphatemia(6%),andthrombocytopenia(6%)werethemostcommondrug-associatedadverseevents.Sixpatients(12.5%)wereremovedfromstudyfordrug-associatedtoxicity(fivethromboembolicevents,onebowelperforation).
简介:PURPOSE:Fotemustineisanitrosoureacompoundusedforthetreatmentofmalignantgliomas,especiallyinFrance.Recently,anEORTC-NCICstudyhasshownthataconcomitantcombinationofradiotherapyplustemozolomide(anoralcytotoxicdrug)improvedsurvivalinglioblastomapatients.Wesetouttotestaconcurrentcombinationofradiotherapyandfotemustinefornewlymalignantgliomas.
简介:BACKGROUND:SupratentorialPNET(sPNET)arerareCNStumorsofembryonaloriginarisinginchildrenandadults.Thetreat-mentofsPNETforallagegroupsatourcancercenterhasbeenbasedonthemanagementofmedulloblastoma(MB),involvingneurosurgicaldebulkingfollowedbyeranio-spinalirradiation(CS1)andsystemicchemotherapy.METHODS:MedicalrecordswerereviewedtogatherdemographicandclinicaldataaboutallembryonalCNStumorsinchildrenandadultsfrom2001to2007.Tumorpathology,clinicalmanagementandsurvivaldatawerealsoassessed,particularlyasregardsthosepatientswhoreceivedthePackerchemotherapyregimenforeithersPNETorMB.
简介:Humanglioblastomas(GBM)arethoughttobeinitiatedbygliomastem-likecells(GSLCs).GSLCsalsoparticipateintumorneovascularizationbytransdifferentiatingintovascularendothelialcells.Here,wereportacriticalroleofGSLCsintheformationofvasculogenicmimicry(VM),whichdefineschannelslinedbytumorcellstosupplynutrientstoearlygrowingtumorsandtumor
简介:Glioblastomaisoneofthemostangiogenichumantumorsandcharacterizedbymicrovascularproliferations.Abetterunderstandingofglioblastomavasculatureisneededtooptimizeanti-angiogenictherapythathasshownapromisingbutincompleteefficacy.Thepresentstudyexamined48glioblastomasbyCD34endothelialmarkerperiodicacid-Schiff(PAS)dualstainingandfoundnon-endothelialcell-linedblood
简介:<正>InvitrobiologicaldosimetermodelingoftheglioblastomaresponsetoradiationdeliveredbytheGammaKnife.Laboratoryinvestigation.JNeurosurg.2010Dec;113Suppl:222-7.SmithR,SmithKA,BiggsCA,ScheckAC.Neuro-OncologyandNeurosurgeryResearch,BarrowNeurologicalInstitute,Phoenix,Arizona85013,USA.