肺癌多学科治疗

化疗在非小细胞肺癌

多学科治疗进展的探讨2017几乎大部分非小细胞肺癌治疗方案中

都需采用化疗一.辅助化疗目的完全性切除后杀死血道、淋巴道中的微转 移灶辅助化疗的临床研究：

1995年辅助化疗荟萃分析，结果为 负性

2003年后辅助化疗随机研究报告较 多有阳 性结果SurgeryMonths100908070605040302010006121824303642485460Survival(%)Surgery+chemotherapyHazardratio=0.87P=0.08Meta-AnalysisAdjuvantCisplatininNSCLC

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

LeChevalier报告1867例NSCLC术后化疗二代含铂方案随机研究★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报告

UFT

250mg/M2/天×2年2003例NSCLC

观察R生存率结果Hamada.MeetingProceedingASCO#70023.ANITA

NVB+DDP840例按分期类型分层

观察

RANITA生存率结果

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.上海市肺部肿瘤多中心随机研究

337例化疗-手术-化疗（二代含铂）

NSCLCⅠ—Ⅲ期手术-化疗

R影响累积年生存率的Cox多因素分析Overall,P<0.01

除期别和术后化疗次数外均无统计学意义5.意大利1209例Ⅰ-Ⅲa期辅助化疗研究用MVP×3对生存率、复发率无差别（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辅助化疗评述1.有益报告4篇4921例，无益报告1篇1209例，显示辅助化疗的优势2.化疗药物:95年前为一代、二代或含铂方案，近年为二代、三代含铂方案3.其他影响生存率的因素未予计入，如切除范围、化疗开始时间、间期、营养、耐受性等

早期NSCLC（Ⅰ-Ⅱ）辅助化疗临床研究

1.VIN-CISinCompletedresectedstageIBandIINSCLCIntergroupJBR.10.随机分组入组患者

n=482

完全切除

T2N0:45％

T1N1:15％

T2N1:40%

腺癌:53%观察

Vinorelbine25mg/m2weekly×12

Cisplatin50mg/m2d1,q4wks×4分层：N0vsN1Ras突变研究终点OSRFS*QOLToxicityVinorelbine最初剂量为30mg/m2

，因毒副反应较大而改为25mg/m2

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

辅助化疗组观察组HRP值OS(月)94730.690.011

RFS(月)notreached46.70.60.00035年生存率69%54%T.L.Wintonetal,ASCO2004,#7018毒副反应血液学毒性常见:7%粒缺性发热(多在Vinorelbine

30mg/m2

时)

非血液学毒性:

乏力77%,恶心76%,厌食53％，呕吐46％，感觉神经病变45%,便秘44%

2名患者死于化疗毒性:1粒缺性发热，1肺纤维化VIN-CISinCompletelyresectedstageIBandIINSCLCIntergroupJBR.10.2.Pacli+CarboinCompletelyresectedstageIBNSCLCCALGB9633G.M.Straussetal,ASCO2004,#7019随机分组入组患者

n=344

完全切除

T2N0

中位年龄:61

男性：64%

叶切：89%观察(171人)

Paclitaxel200mg/m2

CarboplatinAUC6

Every3wks×4(173人)术后4－8wks手术或纵隔镜证实无淋巴结转移

Pacli+CarboinCompletelyresectedstageIBNSCLCCALGB9633G.M.Straussetal,ASCO2004,#7019*FFS:FailureFreeSurvival研究结果辅助化疗组vs

观察组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级毒副反应：中性粒细胞减少：36%3.日本Kato等报告979例（999例ITT）Ⅰ期腺癌术后口服化疗2年（UFT=Tegafur∶Uracil1∶4)的生存率。随访中数值70月按P-stage,gender,age分层。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.