金锋(英文)：乳腺癌症化疗与骨髓安全管理

关爱•诚信•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级4级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天做初级预防，骨髓抑制降低骨髓抑制是主要的不良反应，G-CSF初级预防能很好控制这些不良反应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