乳腺癌的化疗进展

乳腺癌的化疗进展1整理课件乳腺癌化疗的历史回忆70年代：CMF80年代：蒽环类〔anthracyclines〕90年代：紫杉类〔taxanes)21世纪：化疗＋生物靶向治疗常规－－－剂量密集

2整理课件TX方案与AC方案比较docetaxel/capecitabine(TX)ADM/CTX(AC)目的：无蒽环类方案与含蒽环类方案比较。3期单中心随机试验。LeeKS,etal.BreastCancerResTreat.2007

3整理课件TX方案与AC方案比较209例腋窝淋巴结阳性，II/III期BC行4周期TXorAC.TX与AC比,增加了pCR(21%/10%,P=0.024)，RR(84%/65%,P=0.003).TX恶心、呕吐少，但口腔炎、腹泻,肌肉痛，皮肤及指甲改变比AC明显。DFS无差异(P=0.932).pCR者复发少(P=0.025;hazardratio,0.189;95%CI,0.044-0.815).

LeeKS,etal.BreastCancerResTreat.2007

4整理课件PhaseIIItrialcomparingACwithTCdoxorubicinandcyclophosphamide(AC)docetaxelandcyclophosphamide(TC)1016例AC(n=510)TC(n=506),every3weeks.完成化疗后给予放疗，受体阳性者给予tamoxifen,

JonesSE,etal.JClinOncol.2006;24(34):5381-5387.

5整理课件PhaseIIItrialcomparingACwithTC结果:TC的5年DFS明显高于AC(86%v80%,P=0.015).ORR:TC/AC90%/87%,P=0.13.肌肉痛、关节痛、水肿、粒细胞减少在TC组多见。恶心、呕吐，充血性心衰在AC组多见。

JonesSE,etal.JClinOncol.2006;24(34):5381-5387.

6整理课件AphaseIItrialofdocetaxelassecond-linechemotherapyinpatientswithMBCdocetaxel100mg/m(2)every3weeksRR:35%MS:12MMTTP:4Mdocetaxel是治疗MBC的有效2线药物，特别是对anthracycline耐药的病人。

BaurM,etal.JCancerResClinOncol.20077整理课件Nab-paclitaxel(ABI-007,Abraxane)是将paclitaxel包裹在白蛋白里。HendersonIC,etal.ExpertRevAnticancerTher.2007;7(7):919-943.

Nab-paclitaxelforbreastcancer:anewformulationwithanimprovedsafetyprofileandgreaterefficacy

8整理课件Nab-paclitaxelforbreastcancer:anewformulationwithanimprovedsafetyprofileandgreaterefficacy

随机II期临床试验提示每周一次nab-paclitaxel比每3周一次nab-paclitaxel或docetaxel更有效、更平安。nab-paclitaxel的优势在于平安性提高，可以增加剂量，且进入肿瘤细胞内的药物比例更高。

HendersonIC,etal.ExpertRevAnticancerTher.2007;7(7):919-943.

9整理课件Thetrastuzumabandvinorelbineortaxanestudy.

此为一项前瞻性、多中心、随机对照研究。方法:HER2过度表达的MBC，未进行过化疗的病人随机分为trastuzumab＋vinorelbine每周一次。trastuzumab＋taxane每周一次。结论:vinorelbine/trastuzumab和taxane/trastuzumab一线治疗HER2阳性的MBC疗效无差异。

BursteinHJ,etal.Cancer.2007

10整理课件Aphase-IIItrialofdoxorubicinanddocetaxelversusdoxorubicinandpaclitaxelinmetastaticbreastcancer:resultsoftheERASME3study.MBC患者随机分为AD组或AP组，每3周一次。AD×4-----docetaxel×4AP×4------paclitaxel×4CassierPA,etal.BreastCancerResTreat.2007

11整理课件Aphase-IIItrialofdoxorubicinanddocetaxelversusdoxorubicinandpaclitaxelinmetastaticbreastcancer:resultsoftheERASME3study.结果:RR:39.6%forADand41.8%forAP.medianPFS和medianOS：8.7M和21.4M(AD)；8.0M和27.3M(AP)(p=0.977and0.081),AD的血液学毒性比AP重(p＝0.0000〕3-4度疲劳AD重(p=0.03).而神经病变在AP组多见(p=0.03)。CassierPA,etal.BreastCancerResTreat.2007

12整理课件Aphase-IIItrialofdoxorubicinanddocetaxelversusdoxorubicinandpaclitaxelinmetastaticbreastcancer:resultsoftheERASME3study.结论：AD与AP在生活质量和有效率无差异，但在副作用方面有差异。CassierPA,etal.BreastCancerResTreat.2007

13整理课件Evidence-baseduseoftaxanesintheadjuvantsettingofbreastcancer.AreviewofrandomizedphaseIIItrials.6个大型临床试验。验证taxanes在乳腺癌辅助治疗中的作用。各种不同的以anthracycline为主的方案作为对照组。有充分证据支持常规使用taxanes治疗乳腺癌是有益的，包括激素受体阳性和Her-2阳性的病人。EstévezLG,etal.CancerTreatRev.2007

14整理课件Combiningchemotherapyandlow-molecular-weightheparinforthetreatmentofadvancedbreastcancer:

凝血激活在肿瘤进展中起作用，低分子肝素可影响肿瘤生长，显示低分子肝素可影响化疗疗效。Enoxaparin,0,5or1.0mg/kg，每天一次。Docetaxel35-45mg/m(2)，每周一次。PR:36%;SD:36SeeholzerN,etal.BloodCoagulFibrinolysis.2007;18(5):415-423.

15整理课件Vinorelbine/docetaxelcombinationtreatmentofmetastaticbreastcancer:aphaseIstudy

方法:DOC:60or70mg/m2,day1NVB:20to25mg/m2fori.v.onday1,60mg/m2onday8orday15fororal,every3weeks.BonneterreJ,etal.CancerChemotherPharmacol.2007;60(3):365-373.

16整理课件AphaseIIclinicaltrialofZD1839(Iressatrademark)incombinationwithdocetaxelasfirst-linetreatmentinpatientswithadvancedbreastcancer.gefitinib250mg，oncedaily

docetaxel75mg/m(2)，every3weeks,untiltumorprogression,toxicityorotherreasonsfordiscontinuation.DennisonSK,etal.InvestNewDrugs.2007

17整理课件AphaseIIclinicaltrialofZD1839(Iressatrademark)incombinationwithdocetaxelasfirst-linetreatmentinpatientswithadvancedbreastcancer.33例，中位治疗周期为5周期。临床受益率为51.5%。CR:1;PR:12;SD:4;ORR:39.4%。DennisonSK,etal.InvestNewDrugs.2007

18整理课件AphaseIIclinicaltrialofZD1839(Iressatrademark)incombinationwithdocetaxelasfirst-linetreatmentinpatientswithadvancedbreastcancer.CONCLUSION:ThecombinationofgefitinibanddocetaxelisanactiveregimeninpatientswithpreviouslyuntreatedMBC.DennisonSK,etal.InvestNewDrugs.2007

19整理课件MulticenterphaseIItrialofneoadjuvanttherapywithtrastuzumab,docetaxel,andcarboplatinforhumanepidermalgrowthfactorreceptor-2-overexpressingstageIIorIIIbreastcancer:resultsoftheGETN(A)-1trial.方法:HER-2-阳性患者。trastuzumab4mg/kg(day1),followedby2mg/kgweekly,docetaxel75mg/m2，every3weeks,carboplatin(areaundercurve,6)forsixcycles

CoudertBP,etal.JClinOncol.2007;25(19):2678-2684.

20整理课件MulticenterphaseIItrialofneoadjuvanttherapywithtrastuzumab,docetaxel,andcarboplatinforhumanepidermalgrowthfactorreceptor-2-overexpressingstageIIorIIIbreastcancer:resultsoftheGETN(A)-1trial.RESULTS:Sixty-sevenpatients,HER-2-positive,completedsixcyclesoftherapy.

CRandPR:95%(85%and10%).Grade3/4neutropeniaandfebrileneutropeniawere2%.Nosymptomaticcardiacdysfunctionoccurred.

CoudertBP,etal.JClinOncol.2007;25(19):2678-2684.

21整理课件MulticenterphaseIItrialofneoadjuvanttherapywithtrastuzumab,docetaxel,andcarboplatinforhumanepidermalgrowthfactorreceptor-2-overexpressingstageIIorIIIbreastcancer:resultsoftheGETN(A)-1trial.CONCLUSION:TrastuzumabplusdocetaxelandcarboplatinachievedagoodpCRrateandfavorabletolerabilityinstageIIorIIIHER-2-positivebreastcancer.

CoudertBP,etal.JClinOncol.2007;25(19):2678-2684.

22整理课件Pathologiccompleteresponsewithsixcomparedwiththreecyclesofneoadjuvantepirubicinplusdocetaxelandgranulocytecolony-stimulatingfactorinoperablebreastcancer:resultsofABCSG-14.epirubicin75mg/m2docetaxel75mg/m2onday1granulocytecolony-stimulatingfactorondays3through10,ED+Gevery21days,threeorsixcycles.StegerGG,etal.JClinOncol.2007;25(15):2021-2021.23整理课件Pathologiccompleteresponsewithsixcomparedwiththreecyclesofneoadjuvantepirubicinplusdocetaxelandgranulocytecolony-stimulatingfactorinoperablebreastcancer:resultsofABCSG-14.SixcyclesofED+G,comparedwiththreecycles,resultedinasignificantlyhigherpCRrate(18.6%v7.7%,P=.0045),ahigherpercentageofpatientswithnegativeaxillarystatus(56.6%v42.8%,P=.02).Ratesofadverseeventsweresimilar,andnopatientsdiedontreatment.StegerGG,etal.JClinOncol.2007;25(15):2021-2021.24整理课件PhaseIIstudyofneoadjuvantdocetaxel/vinorelbinefollowedbysurgeryandadjuvantdoxorubicin/cyclophosphamideinwomenwithstageII/IIIbreastcancer.beforesurgerywith6cyclesofdocetaxel60mg/m2andvinorelbine45mg/m2,repeatedevery2weekswithgranulocytecolony-stimulatingfactorandquinoloneprophylaxis.LimentaniSA,etal.ClinBreastCancer.2006;6(6):511-517.

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25整理课件PhaseIIstudyofneoadjuvantdocetaxel/vinorelbinefollowedbysurgeryandadjuvantdoxorubicin/cyclophosphamideinwomenwithstageII/IIIbreastcancer.RESULTS:59patients,

RR:98%,CR:63%.Grade3/4neutropenia(95%),neutropenicfever(22%),mucositis(5%),andpulmonarytoxicity(5%).LimentaniSA,etal.ClinBreastCancer.2006;6(6):511-517.

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26整理课件Dosageofcapecitabineandcyclophosphamidecombinationtherapyinpatientswithmetastaticbreastcancer

oralcapecitabine628to829mg/m2twicedaily(bid)oralcyclophosphamide33to50mg/m2bid,ondays1to14acycleevery21days.OhnoS,etal.AnticancerRes.2007;27(2):1009-1013.27整理课件Dosageofcapecitabineandcyclophosphamidecombinationtherapyinpatientswithmetastaticbreastcancer

CONCLUSION:Thecapecitabine/cyclophosphamidecombinationregimeniswelltoleratedandactiveinMBC,andisbeingevaluatedinaphaseIIstudyinanthracycline-pretreatedMBC.OhnoS,etal.AnticancerRes.2007;27(2):1009-1013.28整理课件PhaseI/IItrialofadjuvantdose-densedocetaxel/epirubicin/cyclophosphamide(TEC)instageIIandIIIbreastcancer.docetaxel(T)75mg/m(2),epirubicin(E)75mg/m(2)(cohort1,n=3)or100mg/m(2)(cohort2,n=12),cyclophosphamide(C)500mg/m(2)day1,withpegfilgrastim6mgsubcutaneouslyonday2,

every2weeksforsixcycles.Burdette-RadouxS,etal.BreastJ.2007;13(3):274-280.

29整理课件PhaseI/IItrialofadjuvantdose-densedocetaxel/epirubicin/cyclophosphamide(TEC)instageIIandIIIbreastcancer.结论:剂量密度TEC化疗是可行的。与TAC等剂量时(docetaxel75mg/m(2),epirubicin75mg/m(2),cyclophosphamide600mg/m(2),毒性反响中等。Burdette-RadouxS,etal.BreastJ.2007;13(3):274-280.

30整理课件GemcitabinePlusDoxorubicinasFirst-LineTreatmentinAdvancedorMetastaticBreastCancer(MBC),APhaseIIStudy.gemcitabine1250mg/m2IVondays1,8doxorubicin60mg/m2IVonday1every21days,for6cycles.ElSerafiMM,etal.JEgyptNatlCancInst.2006;18(3):209-215.

31整理课件GemcitabinePlusDoxorubicinasFirst-LineTreatmentinAdvancedorMetastaticBreastCancer(MBC),APhaseIIStudy.RESULTS:CR:17.1%PR40%SD:22.9%ORR:57.1%.MTTP:7monthsTheoverallsurvivalat1and2yearswas74.2%and34.2%;ElSerafiMM,etal.JEgyptNatlCancInst.2006;18(3):209-215.

32整理课件Gemcitabineinthemanagementofmetastaticbreastcancer:asystematicreview.共83个试验，包括4个III期随机临床试验，全部III期临床试验均为一线用药。结果：其中2个III期试验证明含gemcitabine方案治疗MBC疗效高，副作用小。而另外2个III期试验却认为没有临床受益，而副作用大。结论:Gemcitabine＋taxane一线或二线治疗MBC疗效显著。DentS,etal.BreastCancerResTreat.2007

33整理课件LowdoseGemcitabinepluscisplatininaweekly-basedregimenassalvagetherapyforrelapsedbreastcanceraftertaxane-anthracycline-containingregimens.gemcitabine(G)(initialdose750mg/m(2),or600mg/m(2)ifthepatienthadreceivedmorethantwopreviousCTlines)pluscisplatin(P)(initialdose30mg/m(2),or20mg/m(2)incaseof>/=3priorCTlines)ondays1and8ofa21-daycycle.Treatmentwaspostponedtoday15ifitcouldnotbegivenonday8,withoutdosereduction.Iftreatmentcouldnotbegivenonday15,a20%dosereductionwasallowedandtreatmentgiventhenextweek.Sánchez-EscribanoMorcuendeR,etal.ClinTranslOncol.2007;9(7):459-464.

34整理课件LowdoseGemcitabinepluscisplatininaweekly-basedregimenassalvagetherapyforrelapsedbreastcanceraftertaxane-anthracycline-containingregimens.Allhadprioranthracyclinesandtaxanes.Otheragentsusedincluded5-FU/eniluracil,MTX,RPR109881A,trastuzumab,cisplatin,VP16,vinorelbine,capecitabineandirinotecan.72.7%hadreceivedradiotherapy68.1%hormonaltherapy.Sánchez-EscribanoMorcuendeR,etal.ClinTranslOncol.2007;9(7):459-464.

35整理课件LowdoseGemcitabinepluscisplatininaweekly-basedregimenassalvagetherapyforrelapsedbreastcanceraftertaxane-anthracycline-containingregimens.Results:PR:9.1%,SD:36.4%.ClinicalBenefitRate(PR+SD):45.5%MTTP:4monthsMediansurvival:8monthsToxicitiesgrade>3wereneutropenia35%andthrombocytopenia15%.Sánchez-EscribanoMorcuendeR,etal.ClinTranslOncol.2007;9(7):459-464.

36整理课件LowdoseGemcitabinepluscisplatininaweekly-basedregimenassalvagetherapyforrelapsedbreastcanceraftertaxane-anthracycline-containingregimens.结论:曾进行过屡次化疗的，PS较好的MBC.每周一次的cisplatin-gemcitabine是平安有效的挽救治疗方案。Sánchez-EscribanoMorcuendeR,etal.ClinTranslOncol.2007;9(7):459-464.

37整理课件Dose-findingstudyofcapecitabineincombinationwithweeklypaclitaxelforpatientswithanthracycline-pretreatedmetastaticbreastcancer.CONCLUSION:capecitabine1,000mg/m(2)twicedaily,days1-14,paclitaxel60mg/m(2)/week.paclitaxel剂量大于60mg/m(2)/week是不适宜的，因出现严重的皮肤毒性。SusnjarS,etal.JBUON.2007;12(2):189-196.

38整理课件AphaseIIstudyoftrastuzumabandcapecitabine

forpatientswithHER2-overexpressingmetastaticbreastcancer:JapanBreastCancerResearchNetwork(JBCRN)00Trial.59例病人由6个中心提供。进行trastuzumab＋capecitabine治疗乳腺癌的研究。86％接受过化疗。CMF(7.1%),anthracyclines(28.6%),taxanes(25.0%),或两种方案化疗(25.0%)。YamamotoD,etal.CancerChemotherPharmacol.2007

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39整理课件AphaseIIstudyoftrastuzumabandcapecitabine

forpatientswithHER2-overexpressingmetastaticbreastcancer:JapanBreastCancerResearchNetwork(JBCRN)00Trial.RR：65.0%(trastuzumab+capecitabine作为MBC的一线治疗)，有效者62.5%在HER2+3的患者中,二线或三线治疗者也有许多有效。trastuzumab＋capecitabine作为一线治疗比作为二、三线治疗有更长的TTP和OS。YamamotoD,etal.CancerChemotherPharmacol.2007

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40整理课件PhaseIIstudyofcapecitabineplustrastuzumabinhumanepidermalgrowthfactorreceptor2overexpressingmetastaticbreastcancerpretreatedwithanthracyclinesortaxanes.27例HER-2-过度表达的MBC，曾用anthracyclinesand/ortaxanes治疗，给予口服capecitabine1,250mg/m(2)，bid，1－14天。trastuzumab4mg/kg，第1天，以后每周2mg/kg。RR:45%,CR:15%,PR:30%.SD:33%.MOS:28M.MPFS:6.7M.SchallerG,etal.JClinOncol.2007;25(22):3246-50.

41整理课件Vinorelbineandcisplatinformetastaticbreastcancer:asalvageregimeninpatientsprogressingafterdocetaxelandanthracyclinetreatment.Cisplatin:75mg/m2onday1VNR:25mg/m2ondays1,8every3weeks.CR:5.6%;PR:41.6%;OR:47.2%neutropeniagrade¾:47%.Thrombocytopeniagrade3/4:11%.Therewerenotreatment-relateddeaths.VassilomanolakisM,etal.CancerInvest.2003;21(4):497-504.

42整理课件Vinorelbineandcisplatinformetastaticbreastcancer:asalvageregimeninpatientsprogressingafterdocetaxelandanthracyclinetreatment.结论:DDP/VNR耐受好，且对anthracyclines和docetaxel耐药的病人有效。.VassilomanolakisM,etal.CancerInvest.2003;21(4):497-504.

43整理课件TrastuzumabplusvinorelbineortaxanechemotherapyforHER2-overexpressingmetastaticbreastcancer:Thetrastuzumabandvinorelbineortaxanestudy.trastuzumabwithweeklyvinorelbinetherapyorweeklytaxanetherapy(paclitaxelordocetaxelattheinvestigator'schoice).BursteinHJ,etal.Cancer.2007

44整理课件TrastuzumabplusvinorelbineortaxanechemotherapyforHER2-overexpressingmetastaticbreastcancer:Thetrastuzumabandvinorelbineortaxanestudy.RESULTS.:RR:vinorelbine/trastuzumab51%taxane/trastuzumab40%(P=0.37).MTTP:vinorelbine8.5months,taxane6.0months(P=0.09)BursteinHJ,etal.Cancer.2007

45整理课件Docetaxel-ifosfamidecombinationinpatientswithadvancedbreastcancerfailingprioranthracycline-basedregimens:resultsofaphaseI-IIstudy.docetaxel70-100mg/m(2)over1honday1followedbyifosfamide5-6g/m(2)dividedoverdays1+2(2.5-3.0g/m(2)/dayover1h),every21days.KosmasC,etal.JChemother.2007;19(3):322-331.

46整理课件Docetaxel-ifosfamidecombinationinpatientswithadvancedbreastcancerfailingprioranthracycline-basedregimens:resultsofaphaseI-IIstudy.RR:56%;medianTTP6.5MmedianOS13MGrade3/4toxicitiesincluded:neutropeniain72%ofpatients,with60%developinggrade4neutropenia(<or=7days)andin10%ofthesefebrileneutropenia,Othertoxicitiesincludedperipheralneuropathygrade2onlyin10%,grade2myalgiasin8%,grade3diarrheain8%,skin/nailtoxicityin14%,KosmasC,etal.JChemother.2007;19(3):322-331.

47整理课件Docetaxel-ifosfamidecombinationinpatientswithHER2-non-overexpressingadvancedbreastcancerfailingprioranthracyclines.RR:58%;medianTTP6MmedianOS12MKosmasC,etal.InvestNewDrugs.2007;25(5):463-470.

48整理课件Arandomized,double-blind,phaseIIstudyoftwodosesofpemetrexedasfirst-linechemotherapyforadvancedbreastcancer.新诊断的MBC病人，pemetrexed600mg/m(2)(P600arm)or900mg/m(2)(P900arm)ofonday1，21天一个周期。结果:P600(47patients)和P900(45patients)组RR分别为17.0%和15.6%。每组的SD约50%。Llombart-CussacA,etal.ClinCancerRes.2007;13(12):3652-3659.

49整理课件Pemetrexedinpatientswithlocallyadvancedormetastaticbreastcancerwhohadreceivedpreviousanthracyclineandtaxanetreatment:phaseIIstudy.Pemetrexed500mg/m2wasadministeredasa10-minuteintravenousinfusiononday1,every21days.RESULTS:ORR:9%.Llombart-CussacA,etal.ClinBreastCancer.2006Dec;7(5):380-385.

50整理课件Gemcitabineplusdocetaxeladministeredeveryotherweekasfirst-linetreatmentofmetastaticbreastcancer:preliminaryresultsfromaphaseIItrial.

docetaxel65mg/m(2)followedbygemcitabine2,500mg/m(2),bothonday1ofa14-daycycle,ORR:66%,SD:22%.Grade3/4neutropenia:46%.PelegríA,etal.SeminOncol.2004;31(2Suppl5):20-24.

51整理课件Weeklypaclitaxelinwomenwithheavilypretreatedmetastaticbreastcancer:aretrospectiveanalysisofcasestreatedattheChangGungMemorialHospital.Paclitaxel80mg/m2,每周一次，连用3周，4周为一个周期。ORR：21.7%(无CR),SD：43.5%。LuCH,etal.ChangGungMedJ.2007;30(1):33-40.

52整理课件Epothilones:mechanismofactionandbiologicactivity.Epothilones是一种新的抗癌药.临床前研究提示，epothilones与微管结合，但又与paclitaxel的作用机理不同，故对耐paclitaxel的实体瘤仍有效。GoodinS,etal.JClinOncol.2004;22(10):2021-2025.53整理课件Targetingthemicrotubulesinbreastcancerbeyondtaxanes:theepothilones.epothilones及其类似物是一类新的微管稳定剂，其与微管蛋白结合致细胞凋亡而死亡。此类化合物有patupilone,ixabepilone,BMS-310705,ZK-EPO和KOS-862等。此类药不易出现多种耐药机制〔MRP-1和P-gp溢出泵，βⅢ微管蛋白过表达，β微管蛋白突变〕。CortesJ,etal.Oncologist.2007;12(3):271-80.

54整理课件ixabepilone(BMS-247550)

Ixabepilone(40mg/m(2)asa3-hourinfusionevery3weeks.ORR:18.3%;12%;41.5%Grade3/4外周神经病变(14%),疲劳(13%),肌肉痛(8%),口腔炎(6%).PerezEA,etal.JClinOncol.2007;25(23):3407-3414.USAThomasE,etal.JClinOncol.2007;25(23):3399-3406.USARochéH,etal.JClinOncol.2007;25(23):3415-3420.France

55整理课件AphaseIIstudyofepirubicin,cisplatinandcapecitabineasneoadjuvantchemotherapyinlocallyadvancedorinflammatorybreastcancer.epirubicin60mg/m(2)day1;capecitabine1000mg/m(2)bid,days1-14;cisplatin60mg/m(2)day1,every3-weeks.ORR:74%;CR:13%.

VillmanK,etal.EurJCancer.2007;43(7):1153-1160.56整理课件Clinicalefficacyofcapecitabineasfirst-linechemotherapyinmetastaticbreastcancer-Howlowcanyougo?63例，capecitabine1000mg/m(2)twicedaily，days1-14,every21days.RR:29%.TTP:4.5M(11%TTPof>1y),YapYS,etal.Breast.2007;16(4):420-424.57整理课件PhaseI/IIstudyofcapecitabineandvinorelbineinpretreatedpatientswithmetastaticbreastcancer.Capecitabine:1000mg/m(2),Bid,d1-14.停1周，再重复，6周为一个周期。Vinorelbine25mg/m(2)或30mg/m(2)days1,8,22,29.ORR:55%.WeltA,etal.AnnOncol.2005;16(1):64-69.

58整理课件[Pilotstudyofprimarysystemicchemotherapywithdocetaxel(DOC),epirubicin(EPI)andcapecitabine(Xeloda)inpatientswithadvancedbreastcancer]XLD(2,400or3,000mg/day)d1-14DOC(60or70mg/m2),d8EPI(50or60mg/m2),d8.every3weeks.RR:77.8%.TagayaN,etal.GanToKagakuRyoho.2006;33(1):39-42.59整理课件Dose-denseadjuvantchemotherapyinnode-positivebreastcancer:docetaxelfollowedbyepirubicin/cyclophosphamide(T/EC),orthereversesequence(EC/T),every2weeks,versusdocetaxel,epirubicinandcyclophosphamide(TEC)every3weeks.AEROB03randomizedphaseIIstudy.docetaxel75mg/m2,epirubicin75mg/m2cyclophosphamide(C)500mg/m2(TEC)x6,every3weeks;E100mg/m2,C600mg/m2x4,thenT100mg/m2x4(EC-->T)or(T-->EC),every2weeks,PiedboisP,etal.AnnOncol.2007;18(1):52-7.60整理课件Dose-denseadjuvantchemotherapyinnode-positivebreastcancer:docetaxelfollowedbyepirubicin/cyclophosphamide(T/EC),orthereversesequence(EC/T),every2weeks,versusdocetaxel,epirubicinandcyclophosphamide(TEC)every3weeks.AEROB03randomizedphaseIIstudy.CONCLUSIONS:Dose-denseregimensyieldmorefrequentandseverenonhematologicaltoxiceffectsthanstandarddoseTECregimen.PiedboisP,etal.AnnOncol.2007;18(1):52-7.61整理课件Gemcitabine-oxaliplatincombinationinheavilypretreatedmetastaticbreastcancer:apilotstudyon43patients.gemcitabine1,000or2,000mg/m(2)of(D1D2orD1D8schedule,respectively)oxaliplatin100mg/m(2).overallresponserateof7.5%and11demonstratedstabledisease,grades3and4neutropenia,thrombocytopenia,andanemiain42%,19%,and14%CarubaT,etal.BreastJ.2007;13(2):165-171.

62整理课件Gemcitabineandoxaliplatininpatientswithmetastaticbreastcancerresistanttoorpretreatedwithbothanthracyclinesandtaxanes:clinicalandpharmacokineticdata.Gemcitabine1000mg/m2ondays1,8followedbyoxaliplatinat100mg/m2ivonday2every2weeks.PR:25%,SD40%,PD:35%AiroldiM,etal.AmJClinOncol.2006;29(5):490-494.63整理课件LapatinibpluscapecitabineforHER2-positiveadvancedbreastcancer.HER2阳性,局部晚期或MBCanthracycline和taxane及trastuzumab治疗后进展。给予lapatinib1250mg，每天1次，capecitabine2000mg/m2/d,d1-14,21天1周期。或单药capecitabine2500mgm2/d,d1-14.GeyerCE,etal.NEnglJMed.2007;356(14):1471;authorreply1471-1472.NatClinPractOncol.2007;4(7):398-399.

64整理课件LapatinibpluscapecitabineforHER2-positiveadvancedbreastcancer.结论:Lapatinib＋capecitabine治疗anthracycline,taxane,trastuzumab治疗后进展的晚期HER2阳性的乳腺癌，疗效明显好于单用capecitabine。GeyerCE,etal.NEnglJMed.2007;356(14):1471;authorreply1471-1472.NatClinPractOncol.2007;4(7):398-399.

65整理课件小结方案ORR(%)注备TC(DOC+CTX)