A phase I study of nelfinavir....pdf

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1、JNeurooncolDOI10.1007/s11060-013-1303-3CLINICALSTUDYAphaseIstudyofnelfinavirconcurrentwithtemozolomideandradiotherapyinpatientswithglioblastomamultiformeMichelleAlonso-Basanta•PennyFang•AmitMaity•StephenM.Hahn•RobertA.Lustig•JayF.DorseyReceived:10May2013/Accepted:21October2013ÓSpring

2、erScience+BusinessMediaNewYork2013AbstractWeconductedaphaseItrialtoexaminethe1,250mgbiddoselevel,patientsshouldbemonitoredformaximallytolerateddose(MTD)oftheoralproteasehepatotoxicityandGIsideeffects.inhibitornelfinavir(NFV)incombinationwithtemozolo-mideandconcurrentradiotherapyinpat

3、ientswithglio-KeywordsNelfinavir
Glioblastoma
Malignantblastomaandtogatherpreliminarydataforresponse.Theglioma
Radiationtherapy
Radiosensitizerstudywasconductedinpatientswithnewlydiagnosedglioblastomaaftersurgicalresection.Patientsweretreatedwithstandardradiotherapy(6,000cGytothegros

4、stumorIntroduction2volume),temozolomide(75mg/mdaily)togetherwithdailyoralNFVstarting7–10dayspriortochemoradio-Glioblastomamultiforme(GBM)isthemostfrequentpri-therapycontinuingforthedurationofchemoradiationformarymalignantbraintumorinadults.Thestandardofcare26weeks.Temozolomide(150–2

5、00mg/m)wasresumedofnewlydiagnosedglioblastomafollowingsurgical4weeksaftercompletionofchemoradiotherapy.Twodoseresectiontotheextentsafelyfeasibleisconcurrenttem-levelsofNFVwereinvestigated:625mgtwicedaily(bid)ozolomidewithradiotherapyfollowedbymonthlytem-and1,250mgbidinacohortescalat

6、iondesign.Atotalofozolomidefor5dayseachmonthforatleast6cycles[1].21patientswereenrolled.Atthemaximumtolerateddose,Thiscourseoftherapyresultsinamediansurvivalof18subjectswereenrolledtofurtherevaluatetoxicityand14.6monthsandaprogression-freesurvivalofaboutforpreliminaryestimateofeffica

7、cyforfurtherphaseII6.9monthsascomparedwithmediansurvivalofstudy.Nodose-limitingtoxicitywasnotedat625mgbid.12.1monthswithradiotherapyalone[1].However,thisAt1,250mgbid,3dose-limitingepisodesofhepatotox-standardtherapystillonlyresultsinamodestsurvivalicitywerenotedandonedose-limitingep

8、isodeofdiarrhea.ben