乳腺癌的化療進(jìn)展

乳腺癌的化療進(jìn)展1整理課件乳腺癌化療的歷史回憶70年代：CMF80年代：蒽環(huán)類〔anthracyclines〕90年代：紫杉類〔taxanes)21世紀(jì)：化療＋生物靶向治療常規(guī)－－－劑量密集

2整理課件TX方案與AC方案比較docetaxel/capecitabine(TX)ADM/CTX(AC)目的：無蒽環(huán)類方案與含蒽環(huán)類方案比較。3期單中心隨機(jī)試驗(yàn)。LeeKS,etal.BreastCancerResTreat.2007

3整理課件TX方案與AC方案比較209例腋窩淋巴結(jié)陽性，II/III期BC行4周期TXorAC.TX與AC比,增加了pCR(21%/10%,P=0.024)，RR(84%/65%,P=0.003).TX惡心、嘔吐少，但口腔炎、腹瀉,肌肉痛，皮膚及指甲改變比AC明顯。DFS無差異(P=0.932).pCR者復(fù)發(fā)少(P=0.025;hazardratio,0.189;95%CI,0.044-0.815).

LeeKS,etal.BreastCancerResTreat.2007

4整理課件PhaseIIItrialcomparingACwithTCdoxorubicinandcyclophosphamide(AC)docetaxelandcyclophosphamide(TC)1016例AC(n=510)TC(n=506),every3weeks.完成化療后給予放療，受體陽性者給予tamoxifen,

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

5整理課件PhaseIIItrialcomparingACwithTC結(jié)果:TC的5年DFS明顯高于AC(86%v80%,P=0.015).ORR:TC/AC90%/87%,P=0.13.肌肉痛、關(guān)節(jié)痛、水腫、粒細(xì)胞減少在TC組多見。惡心、嘔吐，充血性心衰在AC組多見。

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

6整理課件AphaseIItrialofdocetaxelassecond-linechemotherapyinpatientswithMBCdocetaxel100mg/m(2)every3weeksRR:35%MS:12MMTTP:4Mdocetaxel是治療MBC的有效2線藥物，特別是對anthracycline耐藥的病人。

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

Nab-paclitaxelforbreastcancer:anewformulationwithanimprovedsafetyprofileandgreaterefficacy

8整理課件Nab-paclitaxelforbreastcancer:anewformulationwithanimprovedsafetyprofileandgreaterefficacy

隨機(jī)II期臨床試驗(yàn)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的優(yōu)勢在于平安性提高，可以增加劑量，且進(jìn)入腫瘤細(xì)胞內(nèi)的藥物比例更高。

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

9整理課件Thetrastuzumabandvinorelbineortaxanestudy.

此為一項(xiàng)前瞻性、多中心、隨機(jī)對照研究。方法:HER2過度表達(dá)的MBC，未進(jìn)行過化療的病人隨機(jī)分為trastuzumab＋vinorelbine每周一次。trastuzumab＋taxane每周一次。結(jié)論:vinorelbine/trastuzumab和taxane/trastuzumab一線治療HER2陽性的MBC療效無差異。

BursteinHJ,etal.Cancer.2007

10整理課件Aphase-IIItrialofdoxorubicinanddocetaxelversusdoxorubicinandpaclitaxelinmetastaticbreastcancer:resultsoftheERASME3study.MBC患者隨機(jī)分為AD組或AP組，每3周一次。AD×4-----docetaxel×4AP×4------paclitaxel×4CassierPA,etal.BreastCancerResTreat.2007

11整理課件Aphase-IIItrialofdoxorubicinanddocetaxelversusdoxorubicinandpaclitaxelinmetastaticbreastcancer:resultsoftheERASME3study.結(jié)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的血液學(xué)毒性比AP重(p＝0.0000〕3-4度疲勞AD重(p=0.03).而神經(jīng)病變在AP組多見(p=0.03)。CassierPA,etal.BreastCancerResTreat.2007

12整理課件Aphase-IIItrialofdoxorubicinanddocetaxelversusdoxorubicinandpaclitaxelinmetastaticbreastcancer:resultsoftheERASME3study.結(jié)論：AD與AP在生活質(zhì)量和有效率無差異，但在副作用方面有差異。CassierPA,etal.BreastCancerResTreat.2007

13整理課件Evidence-baseduseoftaxanesintheadjuvantsettingofbreastcancer.AreviewofrandomizedphaseIIItrials.6個大型臨床試驗(yàn)。驗(yàn)證taxanes在乳腺癌輔助治療中的作用。各種不同的以anthracycline為主的方案作為對照組。有充分證據(jù)支持常規(guī)使用taxanes治療乳腺癌是有益的，包括激素受體陽性和Her-2陽性的病人。EstévezLG,etal.CancerTreatRev.2007

14整理課件Combiningchemotherapyandlow-molecular-weightheparinforthetreatmentofadvancedbreastcancer:

凝血激活在腫瘤進(jìn)展中起作用，低分子肝素可影響腫瘤生長，顯示低分子肝素可影響化療療效。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整理課件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整理課件AphaseIIclinicaltrialofZD1839(Iressatrademark)incombinationwithdocetaxelasfirst-linetreatmentinpatientswithadvancedbreastcancer.gefitinib250mg，oncedaily

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

17整理課件AphaseIIclinicaltrialofZD1839(Iressatrademark)incombinationwithdocetaxelasfirst-linetreatmentinpatientswithadvancedbreastcancer.33例，中位治療周期為5周期。臨床受益率為51.5%。CR:1;PR:12;SD:4;ORR:39.4%。DennisonSK,etal.InvestNewDrugs.2007

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

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

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

20整理課件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整理課件MulticenterphaseIItrialofneoadjuvanttherapywithtrastuzumab,docetaxel,andcarboplatinforhumanepidermalgrowthfactorreceptor-2-overexpressingstageIIorIIIbreastcancer:resultsoftheGETN(A)-1trial.CONCLUSION:TrastuzumabplusdocetaxelandcarboplatinachievedagoodpCRrateandfavorabletolerabilityinstageIIorIIIHER-2-positivebreastcancer.

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

22整理課件Pathologiccompleteresponsewithsixcomparedwiththreecyclesofneoadjuvantepirubicinplusdocetaxelandgranulocytecolony-stimulatingfactorinoperablebreastcancer:resultsofABCSG-14.epirubicin75mg/m2docetaxel75mg/m2onday1granulocytecolony-stimulatingfactorondays3through10,ED+Gevery21days,threeorsixcycles.StegerGG,etal.JClinOncol.2007;25(15):2021-2021.23整理課件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整理課件PhaseIIstudyofneoadjuvantdocetaxel/vinorelbinefollowedbysurgeryandadjuvantdoxorubicin/cyclophosphamideinwomenwithstageII/IIIbreastcancer.beforesurgerywith6cyclesofdocetaxel60mg/m2andvinorelbine45mg/m2,repeatedevery2weekswithgranulocytecolony-stimulatingfactorandquinoloneprophylaxis.LimentaniSA,etal.ClinBreastCancer.2006;6(6):511-517.

.

25整理課件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.

.

26整理課件Dosageofcapecitabineandcyclophosphamidecombinationtherapyinpatientswithmetastaticbreastcancer

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

CONCLUSION:Thecapecitabine/cyclophosphamidecombinationregimeniswelltoleratedandactiveinMBC,andisbeingevaluatedinaphaseIIstudyinanthracycline-pretreatedMBC.OhnoS,etal.AnticancerRes.2007;27(2):1009-1013.28整理課件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整理課件PhaseI/IItrialofadjuvantdose-densedocetaxel/epirubicin/cyclophosphamide(TEC)instageIIandIIIbreastcancer.結(jié)論:劑量密度TEC化療是可行的。與TAC等劑量時(docetaxel75mg/m(2),epirubicin75mg/m(2),cyclophosphamide600mg/m(2),毒性反響中等。Burdette-RadouxS,etal.BreastJ.2007;13(3):274-280.

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

31整理課件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整理課件Gemcitabineinthemanagementofmetastaticbreastcancer:asystematicreview.共83個試驗(yàn)，包括4個III期隨機(jī)臨床試驗(yàn)，全部III期臨床試驗(yàn)均為一線用藥。結(jié)果：其中2個III期試驗(yàn)證明含gemcitabine方案治療MBC療效高，副作用小。而另外2個III期試驗(yàn)卻認(rèn)為沒有臨床受益，而副作用大。結(jié)論:Gemcitabine＋taxane一線或二線治療MBC療效顯著。DentS,etal.BreastCancerResTreat.2007

33整理課件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整理課件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整理課件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整理課件LowdoseGemcitabinepluscisplatininaweekly-basedregimenassalvagetherapyforrelapsedbreastcanceraftertaxane-anthracycline-containingregimens.結(jié)論:曾進(jìn)行過屢次化療的，PS較好的MBC.每周一次的cisplatin-gemcitabine是平安有效的挽救治療方案。Sánchez-EscribanoMorcuendeR,etal.ClinTranslOncol.2007;9(7):459-464.

37整理課件Dose-findingstudyofcapecitabineincombinationwithweeklypaclitaxelforpatientswithanthracycline-pretreatedmetastaticbreastcancer.CONCLUSION:capecitabine1,000mg/m(2)twicedaily,days1-14,paclitaxel60mg/m(2)/week.paclitaxel劑量大于60mg/m(2)/week是不適宜的，因出現(xiàn)嚴(yán)重的皮膚毒性。SusnjarS,etal.JBUON.2007;12(2):189-196.

38整理課件AphaseIIstudyoftrastuzumabandcapecitabine

forpatientswithHER2-overexpressingmetastaticbreastcancer:JapanBreastCancerResearchNetwork(JBCRN)00Trial.59例病人由6個中心提供。進(jìn)行trastuzumab＋capecitabine治療乳腺癌的研究。86％接受過化療。CMF(7.1%),anthracyclines(28.6%),taxanes(25.0%),或兩種方案化療(25.0%)。YamamotoD,etal.CancerChemotherPharmacol.2007

.

39整理課件AphaseIIstudyoftrastuzumabandcapecitabine

forpatientswithHER2-overexpressingmetastaticbreastcancer:JapanBreastCancerResearchNetwork(JBCRN)00Trial.RR：65.0%(trastuzumab+capecitabine作為MBC的一線治療)，有效者62.5%在HER2+3的患者中,二線或三線治療者也有許多有效。trastuzumab＋capecitabine作為一線治療比作為二、三線治療有更長的TTP和OS。YamamotoD,etal.CancerChemotherPharmacol.2007

.

40整理課件PhaseIIstudyofcapecitabineplustrastuzumabinhumanepidermalgrowthfactorreceptor2overexpressingmetastaticbreastcancerpretreatedwithanthracyclinesortaxanes.27例HER-2-過度表達(dá)的MBC，曾用anthracyclinesand/ortaxanes治療，給予口服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整理課件Vinorelbineandcisplatinformetastaticbreastcancer:asalvageregimeninpatientsprogressingafterdocetaxelandanthracyclinetreatment.Cisplatin:75mg/m2onday1VNR:25mg/m2ondays1,8every3weeks.CR:5.6%;PR:41.6%;OR:47.2%neutropeniagrade?:47%.Thrombocytopeniagrade3/4:11%.Therewerenotreatment-relateddeaths.VassilomanolakisM,etal.CancerInvest.2003;21(4):497-504.

42整理課件Vinorelbineandcisplatinformetastaticbreastcancer:asalvageregimeninpatientsprogressingafterdocetaxelandanthracyclinetreatment.結(jié)論:DDP/VNR耐受好，且對anthracyclines和docetaxel耐藥的病人有效。.VassilomanolakisM,etal.CancerInvest.2003;21(4):497-504.

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

44整理課件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整理課件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整理課件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整理課件Docetaxel-ifosfamidecombinationinpatientswithHER2-non-overexpressingadvancedbreastcancerfailingprioranthracyclines.RR:58%;medianTTP6MmedianOS12MKosmasC,etal.InvestNewDrugs.2007;25(5):463-470.

48整理課件Arandomized,double-blind,phaseIIstudyoftwodosesofpemetrexedasfirst-linechemotherapyforadvancedbreastcancer.新診斷的MBC病人，pemetrexed600mg/m(2)(P600arm)or900mg/m(2)(P900arm)ofonday1，21天一個周期。結(jié)果:P600(47patients)和P900(45patients)組RR分別為17.0%和15.6%。每組的SD約50%。Llombart-CussacA,etal.ClinCancerRes.2007;13(12):3652-3659.

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

50整理課件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整理課件Weeklypaclitaxelinwomenwithheavilypretreatedmetastaticbreastcancer:aretrospectiveanalysisofcasestreatedattheChangGungMemorialHospital.Paclitaxel80mg/m2,每周一次，連用3周，4周為一個周期。ORR：21.7%(無CR),SD：43.5%。LuCH,etal.ChangGungMedJ.2007;30(1):33-40.

52整理課件Epothilones:mechanismofactionandbiologicactivity.Epothilones是一種新的抗癌藥.臨床前研究提示，epothilones與微管結(jié)合，但又與paclitaxel的作用機(jī)理不同，故對耐paclitaxel的實(shí)體瘤仍有效。GoodinS,etal.JClinOncol.2004;22(10):2021-2025.53整理課件Targetingthemicrotubulesinbreastcancerbeyondtaxanes:theepothilones.epothilones及其類似物是一類新的微管穩(wěn)定劑，其與微管蛋白結(jié)合致細(xì)胞凋亡而死亡。此類化合物有patupilone,ixabepilone,BMS-310705,ZK-EPO和KOS-862等。此類藥不易出現(xiàn)多種耐藥機(jī)制〔MRP-1和P-gp溢出泵，βⅢ微管蛋白過表達(dá)，β微管蛋白突變〕。CortesJ,etal.Oncologist.2007;12(3):271-80.

54整理課件ixabepilone(BMS-247550)

Ixabepilone(40mg/m(2)asa3-hourinfusionevery3weeks.ORR:18.3%;12%;41.5%Grade3/4外周神經(jīng)病變(14%),疲勞(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整理課件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整理課件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整理課件PhaseI/IIstudyofcapecitabineandvinorelbineinpretreatedpatientswithmetastaticbreastcancer.Capecitabine:1000mg/m(2),Bid,d1-14.停1周，再重復(fù)，6周為一個周期。Vinorelbine25mg/m(2)或30mg/m(2)days1,8,22,29.ORR:55%.WeltA,etal.AnnOncol.2005;16(1):64-69.

58整理課件[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整理課件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整理課件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整理課件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整理課件Gemcitabineandoxaliplatininpatientswithmetastaticbreastcancerresistanttoorpretreatedwithbothanthracyclinesandtaxanes:clinicalandpharmacokineticdata.Gemcitabine1000mg/m2ondays1,8followedbyoxaliplatinat100mg/m2ivonday2every2weeks.PR:25%,SD40%,PD:35%AiroldiM,etal.AmJClinOncol.2006;29(5):490-494.63整理課件LapatinibpluscapecitabineforHER2-positiveadvancedbreastcancer.HER2陽性,局部晚期或MBCanthracycline和taxane及trastuzumab治療后進(jìn)展。給予lapatinib1250mg，每天1次，capecitabine2000mg/m2/d,d1-14,21天1周期?；騿嗡巆apecitabine2500mgm2/d,d1-14.GeyerCE,etal.NEnglJMed.2007;356(14):1471;authorreply1471-1472.NatClinPractOncol.2007;4(7):398-399.

64整理課件LapatinibpluscapecitabineforHER2-positiveadvancedbreastcancer.結(jié)論:Lapatinib＋capecitabine治療anthracycline,taxane,trastuzumab治療后進(jìn)展的晚期HER2陽性的乳腺癌，療效明顯好于單用capecitabine。GeyerCE,etal.NEnglJMed.2007;356(14):1471;authorreply1471-1472.NatClinPractOncol.2007;4(7):398-399.

65整理課件小結(jié)方案ORR(%)注備TC(DOC+CTX)