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關(guān)愛?誠信?求真?探索FengJinProfessorChinamedicaluniversityhospitaldirectorofbreastsurgeryBreastcancerchemotherapyandbonemarrowsecuritymanagementEarlydisease:chemotherapytoreducetheriskofrecurrence;Terminalillness:controltumorgrowth,relievesymptomsHer-2positivebreastcancer:combinedwithTrastuzumabcanimprovetheHER2-positivebreastcancerprognosisTNBC:Chemotherapyisthemaintreatment.ERpositivebreastcancer:EndocrineresistanceChemotherapyisimportantmeansoftreatmentofbreastcancer1980s1990s2000s1970sCMFantharcyclineTaxanesContaininganthracycline-basedschemeincreaseyewchemotherapycansignificantlyimprovecurativeeffect2011chemotherapy1940sAnthracycline-basedchemotherapycansignificantlyreducetheriskofrecurrenceanddeathAevaluationof123randomizedstudy,100000casesofearlybreastcancerwomenbetweendifferentmulti-drugchemotherapycurativeeffectoflong-termresultsofmeta-analysisAdjuvantchemotherapycanreducetheriskofbreastcancerrecurrenceanddeathchlormethine

classificationandtreatmentOtherthananthracycline-basedchemotherapyscheme

CMForTCGiveprioritytowithanthracycline-basedsolution

A(E)C、CAF、FE100CAnthracycline-basedandyewjointscheme

TAC

Anthracycline-basedandyewsequentialscheme

AC→T/P3Wor2WFEC→TTheguidelinesrecommendadjuvantchemotherapyarecommonlyusedTheindividualizationofearlybreastcanceradjuvantchemotherapystrategyLuminalAER+/HER2-/Ki67-Anthracycline:

LuminalB(HER2-)ER+/HER2-/Ki67+Anthracycline:

Taxanes:?LuminalB(HER2+)ER+/HER2+Anthracycline:

Taxanes:HER2+ER-/HER2+Anthracycline:

Taxanes:TNBCER-/HER2-Anthracycline:

Taxanes:Anthracycline-baseddrugsintheadjuvanttreatmentofbreastcancer1、>15000

treatmentofpatientsandmorethan15yearsfollowing-updata2、Isthebasisofthebreastcanceradjuvantchemotherapydrugs3、

standard-doseandthecourseoftreatmentisoneoftheimportantfactorstobenefitAC—T(doxorubicin+cyclophosphamideanddocetaxelsequentialscheme)StandarddosesdrugdosepathwayTimeandprogramdoxorubicin60mg/m2IVD1;q21d×4cyclophosphamide600mg/m2IVD1;q21d×4docetaxelsequentialscheme75mg/m2IVD1;q21d×4Doseintensity——EnsurethatbreastcancerchemotherapycurativeeffectProbabilityof

Relapse-FreeSurvival(%)5101520020406080100Probabilityof

OverallSurvival(%)5101520020406080100YearsAfterMastectomy00

>85(n=42) 65-84(n=94)

65(n=71) Control(n=179)RFSOSOptimalDose(%)Morethan85%,curativeeffectisgood;Lessthan65%andalmostwithoutchemotherapyRetrospectiveanalysisFrom1980to2000patientswithearlybreastcancerOnthebasisofanthracycline-baseddrugswithoutataxaneadjuvantchemotherapy793patientsundergoingchemotherapy

Delayonthenumberofcycles(

2vs.>2)(n=793)Thenumberofdaysdelay(<15vs.

15)(n=793)

relativedoseintensity(RDI)(>85%vs.<85%)(n=791)DelaytreatmentandcurativeeffectDelaydaysweresignificantlyassociatedwithDFSandOSP<0.0001Time(inyears)02468100.00.20.40.60.81.0DFS<15天≥15天DFSP=0.0115Time(inyears)02468100.00.20.40.60.81.0OSOS<15天≥15天ChirivellaI,etal.BreastCancerResTreat2009;114:479-484.RDIissignificantlyassociatedwithDFSandOSP=0.0029Time(inyears)02468100.00.20.40.60.81.0DFS<85%

85%DFSP=0.0055Time(inyears)02468100.00.20.40.60.81.0OSOS<85%

85%ChirivellaI,etal.BreastCancerResTreat2009;114:479-484.Guidelinesrecommendstandarddoses,isbasedontheclinicalefficacyandsafetydata,sotheadviceshouldchoosestandarddosesanddon'treducedosecameintouse。ChinaassociationofprofessionalcommitteeofbreastcancerAdjuvantchemotherapyforstandarddosesThemostcommonsideeffectsofbonemarrowsuppression,chemotherapychemotherapymyelosuppressionleukopenia●Morethan60%ofpatientswithchemotherapydelayandreducingprimarycauseis:neutropenia●Adosechangemorethan60%ofthepatientswithneutropeniaappearsagainTheleadingcauseofchemotherapydelayandreduction—myelosuppression

LinkBK,etal.Cancer.2001;92:1354-1367

adverseevent4×TCq3wdocetaxel(75mg/m2)cyclophosphamide(600mg/m2)4×ACq3wDoxorubicin

(60mg/m2)cyclophosphamide(600mg/m2)<65(n=428)≥65(n=78)<65(n=428)≥65(n=78)anemia<1%<1%1%5%neutropenia60%52%54%59%thrombocytopenia<1%01%<1%4%febrileneutropenia4%8%2%4%US9735adverseevent-myelosuppression3/4adverseeventAC-T:A(60mg/m2)C(600mg/m2)q3wx4→T(100mg/m2)q3wx4(N=1749)AT:A(50mg/m2)T(75mg/m2)q3wx4(N=1750)TAC:A(50mg/m2)C(500mg/m2)T(75mg/m2)q3wx4(N=1749)P-Valuefebrileneutropenia22%13%16%<.0001emesis8%5%7%.003infection8%6%6%.0036diarrhea5%4%6%.0012stomatitis5%1%2%<.0001deathrelatedtotherapy5(0.3%)7(0.4%)12(0.7%)-NSABPB-30:adverseevent-myelosuppressionCALGB9741:adverseevent-myelosuppressionGradeofToxicity3級4級N%N%TotalNO.WBCArm1(A→C→Tq3weeks)2-41479Arm2(A→C→Tq2weeks)001-490Arm3(AC→Tq3weeks)315711500Arm4(AC→Tq2weeks)1-286493InfectionArm1(A→C→Tq3weeks)1431-479Arm2(A→C→Tq2weeks)19400490Arm3(AC→Tq3weeks)27500500Arm4(AC→Tq2weeks)1332-4932W方案使用G-CSF3-10天做初級預(yù)防,骨髓抑制降低骨髓抑制是主要的不良反應(yīng),G-CSF初級預(yù)防能很好控制這些不良反應(yīng)ThedangersofbonemarrowinhibitionofneutropeniaChemotherapymyelosuppressionneutropeniaNeutrophilsreducefever(FN)Ⅲ,ⅣneutropeniaComplexrefractoryinfectionsDosereduction,longercycleToextendthelengthofhospitalstay,increasethecostoftreatmentreductionofeffectofchemotherapydeathreductionofoverallsurvivalMorethan60%FNpatientsappearobviousinfectionorlatentinfectionMorethan20%bacteremiaFNfatalityrateisashighas14%Grainoffever(FN)ofseriousconsequencessolidtumorlymph-glandtumourleukemiaFNfatalityrate8.0%8.9%14.3%Normativewhiteprotection-preventionneutropeniaBonemarrowgrowthfactorguidelinesrecommend:Thereasonableapplicationofcolonystimulatingfactor(CSF)notonlycanreducetheoccurrenceofFN,stillcanreducethecomplicationsandmortalityofFN,ensureadequatechemotherapyandontime.primaryprevention(EORTC

guideline)AaproMS,etal.EurJCancer2011;47:8BC:chemotherapyregimensofhighriskFN(>20%)NCCNGuidelinesASCOGuidelinesdocetaxel+Trastuzumab(Metastaticorrecurrent)dosedenseAC→T*(Doxorubicin、cyclophosphamideandpaclitaxel)TAC(Docetaxel,doxorubicinandcyclophosphamide)TAC(Cyclophosphamide,doxorubicin,docetaxel)AT(Doxorubicin、paclitaxel)(Metastaticorrecurrent,first-line)Doc(docetaxel)(Metastatic,second-line)MGF-ASecondaryPrevention(NCCNguideline)Asecondorsubsequentchemotherapyregimenforpatientsbeforeevaluationpreventiveapplication:G-CSF/PEG-G-CSFNoG-CSF/PEG-G-CSFNoFNOrdoselimitingneutropeniaFNordoselimitingneutropeniaConsideringlowerdoseOrchangechemotherapyregimensConsideringG-CSF/PEG-G-CSFInthefollowingrepeatedassessmentaftereachcourseMGF-2ThemethodofapplicationPEG-rhG-CSFfromNCCNguidelinepurpose:TheincidenceofFNPrimaryendpoint:TheincidenceofFNSecondaryefficacyendpoint:hospitalizationrate

andutilizationrateofantibioticsduetoFNAmulticenter,double-blind,placebo-controlledphaseIIIclinicalstudyStudydesignJClinOncol200523:1178-1184TheconditionofpatientsInallthecycle,TheincidencerateofFNofPEG-G-CSFislower.(1%V17%,P<.001)TheincidencerateofFNInallthecycle,ThehospitalizationrateofPEG-G-CSFislower(1%V14%,P<.001)ThehospitalizationrateInallthecycle,utilizationrateofantibioticsofPEG-G-CSFislower(2%V10%,P<.001)utilizationrateofantibioticsAfterchemotherapyPEG-G-CSFcontinuousprotectioncansignificantlyreducetheoccurrenceofFN,FNrelatedrateandantibioticsusageinhospital.ConclusionAretrospectivestudy:BCchemotherapyTCsolutionCyclophosphamide600mg/m2Docetaxel75mg/m2PEG-rhG-CSF(6mg),d3repeatcycleEndthetreamentStudydesignthefirstday2-21days21daysinacycle,for4cyclesMedOncol(2012)29:1495–1501AdverseeventTCn=506<65(n=428)≥65(n=78)febrileneutropenia4%8%neutropenia60%52%Nopreventiveuseofantibiotics,AndonlyonecaseofuseofantibioticstherapyprophylacticantibioticsPEG-G-CSFcanreducetheincidenceofFN,supporttheadequateandtimelycompletionofstandardchemotherapyandensurethe

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