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1、TooMuch,TooLittle,TooLatetoStartAgain?AssessingtheEfficacyofBisphosphonatesinPatientswithBoneMetastasesfromBreastCancer LEARNINGOBJECTIVES Afterpletingthiscourse,thereaderetastasisinthesettingofadvancedbreastcancer. Describetheroleofbisphosphonatesinmanagingbonemetasta
2、sesinthesettingofbreastcancer. Discussclinicalendpointsusedtodetermineetastasescanbeadevastatingoccurrenceforanyanetastasescanresultinskeletal-relatedevents(SREs)suchaspathologicfracture,spinalcordpression,andhypercalcemia.Severaltrialshaveconfirmedtheabilityofbisphospho
3、natestoreduceordelaytheseskeletalplications,andtheyshouldnoen. TheanalysisofSREsisthetypicalprimaryendpointinbisphosphonatestudies.oststudiesdependonthenumberandtimingofSREstoparethetreatmentandplaceboarms.ThedefinitionofanSREdoesnotincludeendpointsthatareimportanttopati
4、ents:pain,immobility,analgesicuse,andnonhospitalcostssuchasthoseofphysiotherapy[5].Inaddition,manystudiesuseserialplainradiographsintheformofskeletalsurveystodetectasymptomaticfractures,therebydetectingSREsbutignoringpain.Painscores,analgesicconsumption,andqualityoflife(Q
5、oL)scoresareallsubjecttoobserverbiasandaredifficulttopareamongdifferentpatientpopulations.Toalloationofanalgesicandpalliativebenefitsofbisphosphonates,easurementandQoLinstrumentthatincludesdomainsthatareimportanttothepatient.Thispaperrevieeasuresusedinbisphosphonatetrials
6、anddiscussestheirlimitations. ENDPOINTSINBISPHOSPHONATETRIALS TheU.S.FoodandDrugAdministration’s"regularapproval"isbasedonendpointsthatdemonstratethatadrugprovidesalongerorbetterlifeorthatithasafavorableeffectonanestablishedsurrogate[14].Regulatoryapprovalsforcurrentlya
7、vailablebisphosphonatesostfrequentlyusedprimaryendpointsinbisphosphonatetrials(Table1)[2,8,1527],manydifferentSREscoresareavailable,makingparisonsamongtrialsdifficult. First-eventanalysesconsiderinformationforfirstSREsonly.Thistypeofanalysishasbeenusedastheprimaryendpoin
8、tinvariouszoledronicacidandpamidronatestudiesandincludestheproportionofpatientsetofirsteventasse