Camptothecin-Based Regimens for Treatment of Ewing Sarcoma sPast Studies and Future Directions英文文献资料.docVIP

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Camptothecin-Based Regimens for Treatment of Ewing Sarcoma sPast Studies and Future Directions英文文献资料.doc

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Camptothecin-Based Regimens for Treatment of Ewing Sarcoma sPast Studies and Future Directions英文文献资料

HindawiPublishingCorporation Sarcoma Volume2011,ArticleID957957,9pages doi:10.1155/2011/957957 ReviewArticle Camptothecin-BasedRegimensforTreatmentofEwingSarcoma: PastStudiesandFutureDirections LarsWagner DivisionofPediatricHematology/Oncology,CincinnatiChildren’sHospitalMedicalCenter, UniversityofCincinnatiCollegeofMedicine,MLC7015,3333BurnetAvenue,Cincinnati,OH45229,USA CorrespondenceshouldbeaddressedtoLarsWagner,lars.wagner@ Received1July2010;Accepted17January2011 AcademicEditor:IreneAndrulis Copyright?2011LarsWagner.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,which permitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. NewtherapiesareneededtoimprovesurvivalforpatientswithEwingsarcoma.Overthepastdecade,camptothecinagentssuch astopotecanandirinotecanhavedemonstratedactivityagainstEwingsarcoma,especiallyincombinationwithalkylatingagents. Previousstudieshaveshowncamptothecin-basedcombinationstobetolerableoutpatientstrategiesthatareattractiveforsalvage therapy.Thispaperhighlightsimportantissuesrelatedtodrugdosing,scheduleofadministration,pharmacokinetics,toxicity, andactivityofcommonlyusedcamptothecin-basedregimens.Alsodiscussedarestrategiesforincorporatingtheseregimensinto therapyfornewlydiagnosedpatients,includingseveralpotentialpossibilitiesforcombinationwithtargetedagents. 1.Introduction additionalimprovementin3-yearevent-freesurvival,which is now up to 76% for nonmetastatic patients [1]. Since furthermodi?cationofthis5-drugregimenseemsunlikely toproduceadditionalbene?ts[5],futureregimenswilllikely needtoincorporatenewdrugsinordertocontinueprogress inthe?eld. Currenttreatmentsusingintervalcompressionofmultiagent chemotherapycombinedwithsurgeryand/orradiationcan now cure the majority of patients with localized Ewing sarcoma[1].However,outcomesaremuchworseforpatients whodevelopdiseaserecurrenceafterinitialtherapy,orwho havemetastasesatdiagnosis.Forexample,fewerthan20%of patientswithre