肺癌多學科治療

化療在非小細胞肺癌

多學科治療進展的探討2017幾乎大部分非小細胞肺癌治療方案中

都需采用化療一.輔助化療目的完全性切除后殺死血道、淋巴道中的微轉(zhuǎn) 移灶輔助化療的臨床研究：

1995年輔助化療薈萃分析，結(jié)果為 負性

2003年后輔助化療隨機研究報告較 多有陽 性結(jié)果SurgeryMonths100908070605040302010006121824303642485460Survival(%)Surgery+chemotherapyHazardratio=0.87P=0.08Meta-AnalysisAdjuvantCisplatininNSCLC

Anonymous.BMJ311:899,19951.2003年ASCO，WCLC會議

LeChevalier報告1867例NSCLC術(shù)后化療二代含鉑方案隨機研究★P＜0.03死亡HR0.8695%CI（0.76~0.98）▲P＜0.003死亡HR0.8395%CI（0.74~0.94）IALTTrialDesign

OpenDesignPhaseIIIRANOMIZEEligibility:pStageI-IIINSCLCAge:18-75yrNopriormalignancyInformedconsentNochemotherapyChemotherapy**PE:56%;PVin:27%;PVlb:11%;PVnd:6%IALT–LeChevalieretalPatientcharacteristicsMedianage-59yrsMales-80%Histology-SqCC-47%,AdenoCa-40%Surgery-lobectomy-64%pneumonectomy-35%Stages:37%(pI);25%(pII);39%(pIII)IALT–LeChevalieretalChemotherapycombinedwithcisplatin(N=935)92%complianceinchemotherapyarm74%received>240mg/m2cumulativedosesofcisplatinChemoassociatedlethaltoxicity:0.8%(7pts)ThoracicRTplannedin30%:71%complianceinchemoarm85%complianceinobservationarmIALT–LeChevalieretalMedianf/uof56months

Chemo

Observation

Medsurvival:

50.8m 44.4m2-yearOS: 70% 67%5-yearOS: 45% 40% HR=0.86;p<0.03Wouldprevent7000deathsannuallyworldwideOverallSurvivalControlChemotherapyYears164286432602774935181308450624775932Atrisk2004年ASCOHamada報告

UFT

250mg/M2/天×2年2003例NSCLC

觀察R生存率結(jié)果Hamada.MeetingProceedingASCO#70023.ANITA

NVB+DDP840例按分期類型分層

觀察

RANITA生存率結(jié)果

Overallsurvival

logrankpvalue=0.013

OBS.NVB+CDDPMedianmonths 43.8 65.81-yearsurvival+3.1%80.4%83.5%2-yearsurvival+5.1% 62.8%67.9%5-yearsurvival+8.6%42.6%51.2%7-yearsurvival+8.4%36.8%45.2%Survival:COXUnivariateanalysisImproves00.51NVB+CDDPAge<55yStageIB/IIN0p<0.001p<0.001p=0.006p=0.002Survival:ResultsofCOXMultivariateanalysis4.上海市肺部腫瘤多中心隨機研究

337例化療-手術(shù)-化療（二代含鉑）

NSCLCⅠ—Ⅲ期手術(shù)-化療

R影響累積年生存率的Cox多因素分析Overall,P<0.01

除期別和術(shù)后化療次數(shù)外均無統(tǒng)計學意義5.意大利1209例Ⅰ-Ⅲa期輔助化療研究用MVP×3對生存率、復發(fā)率無差別（ALPI/EORTC）ScogliottiGV,J.Nat1CancerInet2003;95:1453-61AdjuvantChemotherapy

ALPI(AdjuvantLungProjectItaly)

Tonato,PASCO2002abstract1157OverallSurvival

Events/Total CT278/548

Control 288/540HR=0.96(0.81-1.13)p=0.585PROBABILITYYEARSMedianf/upof63months輔助化療評述1.有益報告4篇4921例，無益報告1篇1209例，顯示輔助化療的優(yōu)勢2.化療藥物:95年前為一代、二代或含鉑方案，近年為二代、三代含鉑方案3.其他影響生存率的因素未予計入，如切除范圍、化療開始時間、間期、營養(yǎng)、耐受性等

早期NSCLC（Ⅰ-Ⅱ）輔助化療臨床研究

1.VIN-CISinCompletedresectedstageIBandIINSCLCIntergroupJBR.10.隨機分組入組患者

n=482

完全切除

T2N0:45％

T1N1:15％

T2N1:40%

腺癌:53%觀察

Vinorelbine25mg/m2weekly×12

Cisplatin50mg/m2d1,q4wks×4分層：N0vsN1Ras突變研究終點OSRFS*QOLToxicityVinorelbine最初劑量為30mg/m2

，因毒副反應較大而改為25mg/m2

RFS*:RecurrenceFreeSurvivalT.L.Wintonetal,ASCO2004,#7018

輔助化療組觀察組HRP值OS(月)94730.690.011

RFS(月)notreached46.70.60.00035年生存率69%54%T.L.Wintonetal,ASCO2004,#7018毒副反應血液學毒性常見:7%粒缺性發(fā)熱(多在Vinorelbine

30mg/m2

時)

非血液學毒性:

乏力77%,惡心76%,厭食53％，嘔吐46％，感覺神經(jīng)病變45%,便秘44%

2名患者死于化療毒性:1粒缺性發(fā)熱，1肺纖維化VIN-CISinCompletelyresectedstageIBandIINSCLCIntergroupJBR.10.2.Pacli+CarboinCompletelyresectedstageIBNSCLCCALGB9633G.M.Straussetal,ASCO2004,#7019隨機分組入組患者

n=344

完全切除

T2N0

中位年齡:61

男性：64%

葉切：89%觀察(171人)

Paclitaxel200mg/m2

CarboplatinAUC6

Every3wks×4(173人)術(shù)后4－8wks手術(shù)或縱隔鏡證實無淋巴結(jié)轉(zhuǎn)移

Pacli+CarboinCompletelyresectedstageIBNSCLCCALGB9633G.M.Straussetal,ASCO2004,#7019*FFS:FailureFreeSurvival研究結(jié)果輔助化療組vs

觀察組HR=0.62；95%CI:0.41-0.95P=0.028死亡(所有原因)

36人52人肺癌至死：19人34人4年生存率：71％59％*FFS:HR=0.69;95%CI:0.48-0.98;P=0.035HR=0.51,95%CI=0.29-0.89P=0.018III/IV級毒副反應：中性粒細胞減少：36%3.日本Kato等報告979例（999例ITT）Ⅰ期腺癌術(shù)后口服化療2年（UFT=Tegafur∶Uracil1∶4)的生存率。隨訪中數(shù)值70月按P-stage,gender,age分層。4.ANITA

OverallSurvival-StageI(pT2N0)SurvivalDistributionFunction1.000.750.500.250020406080100120monthsObsNVB+CDDPOverallSurvival-StageII(pT1-2,N1)1.000.750.500.250020406080100120SurvivalDistributionFunctionmonthsObsNVB+CDDPOverallSurvival-StageIIIA(pT1-2N2,pT3N0-3)1.