同步放化疗及辅助化疗治疗局部晚期宫颈癌II期临床研究

同步放化疗及辅助化疗治疗局部晚期宫颈癌II期临床研究第1页/共20页同步放化疗及辅助化疗治疗局部晚期宫颈癌：II期临床研究报告第2页/共20页IB2-IVA期宫颈癌的标准治疗5PhaseIIIRCTs+2largemetaanalysesCisplatin-basedconcurrentchemoradiotherapy(CCRT)第3页/共20页最近meta分析结果:Asignificantbenefitwithnon-platinumregimenswasalsoobserved.CCRT:5yOS6%CCRT+adjuvantchemo:5yOS19%?IA-IIAIIBIII-IVA5yOS10%7%3%

JClinOncol,2008;26:5802-5811第4页/共20页目前存在的问题铂类为基础的CCRT与非铂类为基础的CCRTCCRT后辅助化疗的作用晚期宫颈癌应用CCRT生存获益小铂类为基础的CCRT胃肠道反应大第5页/共20页研究设计药物选择RTOG9001GOG:

II、III期宫颈癌隐匿性主动脉旁淋巴结转移率为16％，25％Choi等：CCRT后辅助化疗可以增强放疗的延迟效应第6页/共20页入组标准IIB-IIIB期宫颈鳞癌18-65岁ECOG0-2CT/MRI：主动脉旁淋巴结（－）血生化指标、EKG、胸片正常第7页/共20页治疗计划HDRintracavitarybrachytherapyExternalbeamradiationtherapyDay18152229364350AfterCCRTDay30517293TN1TN1TN1TN1TN1TN1TN2TN2TN2TN2TN1:TXL35mg/m2+NDP20mg/m2TN2:TXL135mg/m2+NDP60mg/m2第8页/共20页研究终点和治疗评估Primaryendpoints:responserate,acutetoxicity(NCI-CTCV2.0)Secondaryendpoints:failures,OS,PFS,latetoxicity(RTOGcriteria)Responserate:RECISTcriteriaLocoregionalfailure:inthepelvisorbothwithinandoutsidepelvisDistantfailure:onlyoutsidepelvis第9页/共20页入组病例数II期临床研究Simon二阶段法：第一阶段：13例第二阶段：30例第10页/共20页患者特征(n=34)characteristicsNo.ofpts(%)Medianage(range)47(35-64)ECOG0-125(73)29(27)StageIIB10(29)IIIA3(9)IIIB21(62)PelvicLNMpositive5(15)negative29(85)MedianbaselineHemoglobin(range)114g/L(90-146)第11页/共20页患者接受化疗情况Concurrentchemo:allptsreceived6cyclesAdjuvantchemo:28pts----4cycles3pts------3cycles2pts------2cycles1pt-------refuseReasons:2pts-----G3vomiting1pt--------severeabdominalpain3pts------nonmedicalreasons第12页/共20页急性毒性反应toxicityConcurrentchemo(199cycles)Consolidationchemo(119cycles)G0-2G3-4G0-2G3-4hematologicLeukopenia193(96.9)6(3.1)106(89.1)13(10.9)Neutropenia199(100)0(0)106(90.1)13(9.9)Thrombocytopenia199(100)0(0)119(100)0(0)Anemia199(100)0(0)119(100)0(0)NonhematologicNausea/vomiting195(98)4(2)118(99.2)1(0.8)GI199(100)0(0)119(100)0(0)GU199(100)0(0)119(100)0(0)Liverdamage199(100)0(0)119(100)0(0)neuropathy199(100)0(0)119(100)0(0)skin199(100)0(0)119(100)0(0)第13页/共20页晚期毒性反应SiteofsideeffectNo.ofpts(%)G0G1G2G3G4GI23(67.6)5(14.7)4(11.8)2(5.9)0(0.0)GU30(88.2)3(8.8)0(0)1(3.0)0(0)第14页/共20页治疗结果1-monthafterCCRT:27pts(79%)CR;7pts(21%)PR1-monthafteradjuvantchemo:30pts(88%)CRMedianfollow-upof23months(14-30)28pts:alivewithoutdisease5pts:locoregionalfailure1pt:distantmetastases第15页/共20页N=34(Progression6)2-yrPFS82%(95%CI,68-95%)2年无瘤生存率82％第16页/共20页N=34(Death2)2-yrOS93%(95%CI,83-100%)2年总生存率93％第17页/共20页StudiesonCCRTplusadjuvantchemotherapyinLACCReferenceNoStageradiotherapyConcurrentchemoConsolidationchemoCRMedianFollowupSurvivalrate3yPFSOSWongetal1999110I-IIIPelvicEBRT+LDRICBTEpi60mg/m2

q4w90mg/m2q4w×59296m(16-130)8385Vrdoljaketal200544IB2~IVAPelvicEBRT+LDRICBTDDP75mg/m2d11IFO2g/m2d11

q3w×2DDP75mg/m2d1IFO2g/m2d1-3q3w×410034m(20-54)8491Choietal200732IB2~IVAPelvicEBRT+HDRICBTDDP60mg/m2d15-Fu1g/m2d1-5q3w×3DDP60mg/m2d15-Fu1g/m2d1-5