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Early Sorafenib-Induced Toxicity Is Associated with Drug Exposure and UGTIA9 Genetic Polymorphism in Patients with Solid Tumors A Preliminary Study 英文参考文献.docVIP

Early Sorafenib-Induced Toxicity Is Associated with Drug Exposure and UGTIA9 Genetic Polymorphism in Patients with Solid Tumors A Preliminary Study 英文参考文献.doc

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Early Sorafenib-Induced Toxicity Is Associated with Drug Exposure and UGTIA9 Genetic Polymorphism in Patients with Solid Tumors A Preliminary Study 英文参考文献

EarlySorafenib-InducedToxicityIsAssociatedwithDrug ExposureandUGTIA9GeneticPolymorphisminPatients withSolidTumors:APreliminaryStudy PascalineBoudou-Rouquette1,2,3.,Ce′lineNarjoz4,5.,JeanLouisGolmard6,AudreyThomas- Schoemann1,7,8,OlivierMir1,2,3,FabriceTaieb7,Jean-PhilippeDurand1,2,RomainCoriat1,2,3 AlainDauphin7,MichelVidal7,8,MichelTod9,10,Marie-AnneLoriot4,5,Franc?oisGoldwasser1,2,3 BenoitBlanchet1,7 , , * 1Centred’e′tudeetderecourssurlesinhibiteursdel’angioge′ne`se,Paris,France,2AssistancePubliqueHo?pitauxdeParis,Ho?pitalCochin,Unite′deCance′rologieme′dicale, Paris,France,3Universite′ ParisDescartes,SorbonneParisCite′,Paris,France,4AssistancePubliqueHo?pitauxdeParis,Ho?pitalEurope′enGeorgesPompidou,Servicede Biochimie,Unite′FonctionnelledePharmacoge′ne′tiqueetOncologieMole′culaire,Paris,France,5Universite′ParisDescartes,INSERMUMR-S775,Paris,France,6Assistance Publique Ho?pitaux de Paris, Ho?pital Pitie′-Salpe?trie`re, De′partement de Biostatistiques, Paris, France, 7Assistance Publique Ho?pitaux de Paris, Ho?pital Cochin, Unite′ FonctionnelledePharmacocine′tiqueetPharmacochimie,Paris,France,8UMR8638CNRS,UFRdePharmacie,Universite′ParisDescartes,SorbonneParisCite′,Paris,France, 9Pharmacie,Ho?pitaldelaCroix-Rousse,HospicescivilsdeLyon,Lyon,France,10EMR3738,Universite′ deLyon,Lyon,France Abstract Background:Identifyingpredictivebiomarkersofdrugresponseisofkeyimportancetoimprovetherapymanagementand drug selection in cancer therapy. To date, the influence of drug exposure and pharmacogenetic variants on sorafenib- induced toxicity remains poorly documented. The aim of this pharmacokinetic/pharmacodynamic (PK/PD) study was to investigate the relationship between early toxicity and drug exposure or pharmacogenetic variants in unselected adult outpatientstreatedwithsingle-agentsorafenibforadvancedsolidtumors. Methods: Toxicity wasrecorded in54 patients on days 15 and30 after treatmentinitiationand sorafenib exposure was assessedin51patients.Theinfluenceofpolymor

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