Sarcopenia Predicts Early Dose-Limiting Toxicities and Pharmacokinetics of Sorafenib in Patients with Hepatocellular Carcinoma 英文参考文献.docVIP

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Sarcopenia Predicts Early Dose-Limiting Toxicities and Pharmacokinetics of Sorafenib in Patients with Hepatocellular Carcinoma 英文参考文献.doc

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Sarcopenia Predicts Early Dose-Limiting Toxicities and Pharmacokinetics of Sorafenib in Patients with Hepatocellular Carcinoma 英文参考文献

SarcopeniaPredictsEarlyDose-LimitingToxicitiesand PharmacokineticsofSorafenibinPatientswith HepatocellularCarcinoma OlivierMir1,2*,RomainCoriat1,3,BenoitBlanchet1,4,Jean-PhilippeDurand1,PascalineBoudou- Rouquette1,JudithMichels1,StanislasRopert1,MichelVidal4,StanislasPol5,StanislasChaussade3, Franc?oisGoldwasser1 1CentreforResearchonAngiogenesisInhibitors(CERIA),DepartmentofMedicalOncology,CochinTeachingHospital,AP-HP,Universite′ ParisDescartes,SorbonneParis Cite′,Paris,France,2DepartmentofClinicalPharmacology,CochinTeachingHospital,AP-HP,Universite′ParisDescartes,SorbonneParisCite′,Paris,France,3Departmentof Gastro-Enterology,CochinTeachingHospital,AP-HP,Universite′ ParisDescartes,SorbonneParisCite′,Paris,France,4LaboratoryofPharmacologyandToxicology,Cochin TeachingHospital,AP-HP,Universite′ParisDescartes,SorbonneParisCite′,Paris,France,5DepartmentofHepatologyandINSERMU1016,CochinTeachingHospital,AP-HP, Universite′ ParisDescartes,SorbonneParisCite′, Paris,France Abstract Background:Sorafenibinducesfrequentdoselimitingtoxicities(DLT)inpatientswithadvancedhepatocellularcarcinoma (HCC).Sarcopeniahasbeenassociatedwithpoorperformancestatusandshortenedsurvivalincancerpatients. PatientsandMethods:ThecharacteristicsofChildPughAcirrhoticpatientswithHCCreceivingsorafenibinourinstitution were retrospectively analyzed. Sorafenib plasma concentrations were determined at each visit. Toxicities were recorded duringthefirstmonthoftreatment,andsarcopeniawasdeterminedfrombaselineCT-scans. Results:Fortypatients(30males)wereincluded.Eleven(27.5%)weresarcopenic.Eighteenpatients(45%)experienceda DLT during the first month of treatment. Sarcopenic patients experienced significantly more DLTs than non-sarcopenic patientsdid(82%versus31%,p=0.005).Grade3diarrheawassignificantlymorefrequentinsarcopenicpatientsthanin non-sarcopenic patients (45.5% versus 6.9%, p=0.01), but not grade 3 hand foot syndrome reaction (9% versus 17.2%, p=1). On day 28, median sorafenib AUC (n=17) was sig