摘要
Objective:Therecurrenceorprogressionunderendocrinetherapyinhormonereceptor-positive(HR+)advancedbreastcancer(ABC)remainedacriticalclinicalchallenge.Chidamideisanoralsubtype-selectivehistonedeacetylase(HDAC)inhibitorwithmultiplefunctionsintumorgrowthinhibitionandmicroenvironmentmodulationviaepigeneticreprogramming.Thepurposeofthisstudywastoevaluatethesafety,pharmacokinetics(PK),andpreliminaryefficacyofchidamideincombinationwithexemestaneinHR+ABCpatients.Methods:EligiblepatientswerepostmenopausalwomenwithHR+ABCrecurrentorprogressedtoatleastoneendocrinetherapy.Bloodsampleswereobtainedintherun-inperiodandthefirstdayofcombinationtreatmentforPKanalysis.Incombinationtreatment,patientsweregivenexemestane25mgdailyandchidamide30mgtwiceaweek(BIW)untilprogressionofdiseaseorintolerabletoxicities.Atreatmentcyclewasdefinedas4weeks.Safety,PKparameters,andpreliminaryefficacywereevaluated.Results:Atotalof20patientswereenrolledbetweenJulyandDecember,2015.Themediannumberoftreatmentscyclewas5.2(20.8weeks)with2patientsstillontreatmentatthedatacut-offdateofOctober,2017.Thetreatment-relatedadverseevents(AE)≥grade3inmorethan2patientswereneutropenia(35%),thrombocytopenia(30%),andleucopenia(20%).Theplasmaexposureofexemestanewasconsistentinthepresenceorabsenceofchidamide.Aslightincreaseinchidamideexposurewasnotedinthepresenceofexemestane,probablyduetotheinter-andintra-patientvariations.Thebestresponsein16evaluablepatientswasassessedbyResponseEvaluationCriteriainSolidTumors(RECIST),including4patientswithpartialresponse,10patientswithstabledisease.Themedianprogression-freesurvival(PFS)was7.6months.Conclusions:ThecombinationofchidamidewithexemestanewasgenerallywelltoleratedwithpromisingpreliminaryefficacyinHR+ABCpatients.Theoverallresultsfromthisstudyencouragefurtherpivotaltrialinthispatie
出版日期
2018年06月16日（中国期刊网平台首次上网日期，不代表论文的发表时间）
