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

1、同步放化疗及辅助化疗治疗局部晚期宫颈癌：II期临床研究报告复旦大学附属肿瘤医院妇科张美琴IB2-IVA期宫颈癌的标准治疗 5 Phase III RCTs + 2 large meta analysesCisplatin-based concurrent chemoradiotherapy ( CCRT )最近meta分析结果:nA significant benefit with non-platinum regimens was also observed.nCCRT: 5y OS 6% CCRT+adjuvant chemo: 5y OS 19% ?n IA-IIA IIB III-IV

2、A 5y OS 10% 7% 3%J Clin Oncol,2008;26:5802-5811目前存在的问题n铂类为基础的CCRT与非铂类为基础的CCRTnCCRT后辅助化疗的作用n晚期宫颈癌应用CCRT生存获益小n铂类为基础的CCRT胃肠道反应大研究设计n药物选择nRTOG 9001nGOG:II、III期宫颈癌隐匿性主动脉旁淋巴结转移率为16，25nChoi等：CCRT后辅助化疗可以增强放疗的延迟效应入组标准nIIB-IIIB期宫颈鳞癌n18-65岁nECOG 0-2nCT/MRI：主动脉旁淋巴结（）n血生化指标、EKG、胸片正常治疗计划HDR intracavitary brachyth

3、erapyExternal beam radiation therapyDay 1 8 15 22 29 36 43 50 After CCRT Day 30 51 72 93 TN1 TN1 TN1 TN1 TN1 TN1 TN2 TN2 TN2 TN2TN1: TXL35mg/m2+NDP20mg/m2 TN2: TXL135mg/m2+NDP60mg/m2研究终点和治疗评估nPrimary endpoints: response rate, acute toxicity (NCI-CTC V 2.0)nSecondary endpoints: failures, OS, PFS, lat

4、e toxicity (RTOG criteria)nResponse rate: RECIST criterianLocoregional failure: in the pelvis or both within and outside pelvisnDistant failure: only outside pelvis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例患者特征(n=34)characteristicsNo. of pts (%)Median age (range)47(35-64)ECOG 0-125(73) 29(27)Stage IIB10

5、(29) IIIA3(9) IIIB21(62)Pelvic LNM positive 5(15) negative29(85)Median baseline Hemoglobin (range)114g/L(90-146)患者接受化疗情况nConcurrent chemo: all pts received 6 cyclesnAdjuvant chemo: 28 pts-4 cycles 3 pts-3 cycles 2 pts-2 cycles 1 pt-refusenReasons: 2 pts-G3 vomiting 1 pt-severe abdominal pain 3 pts-n

6、onmedical reasons急性毒性反应toxicityConcurrent chemo(199 cycles)Consolidation chemo(119 cycles)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

7、(98)4(2)118(99.2)1(0.8)GI199(100)0(0)119(100)0(0)GU 199(100)0(0)119(100)0(0)Liver damage199(100)0(0)119(100)0(0)neuropathy199(100)0(0)119(100)0(0)skin199(100)0(0)119(100)0(0)晚期毒性反应Site of side effect No. of pts (%) G0 G1 G2 G3 G4GI23(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)治疗结果n

8、1-month after CCRT: 27 pts(79%) CR; 7 pts(21%) PRn1-month after adjuvant chemo: 30 pts(88%) CRnMedian follow-up of 23 months(14-30)n28 pts: alive without diseasen5 pts: locoregional failuren1 pt: distant metastasesN=34 (Progression 6)2-yr PFS 82% (95%CI, 68-95%)2年无瘤生存率82N=34 (Death 2)2-yr OS 93% (95

9、%CI, 83-100%)2年总生存率93 Studies on CCRT plus adjuvant chemotherapy in LACC ReferenceNoStageradiotherapyConcurrent chemoConsolidation chemoCR MedianFollowupSurvival rate3y PFS OSWong et al1999110I-IIIPelvic EBRT+LDR ICBTEpi 60 mg/m2 q4w90 mg/m2 q4w59296 m(16-130) 83 85Vrdoljak et al200544IB2IVAPelvic EBRT+LDR ICBTDDP75mg/m2d11IFO2g/m2d11 q3w2DDP75mg/m2d1IFO2g/m2 d1-3 q3w410034 m(20-54) 84 91Choi et al200732IB2IVAPelvic EBRT+HDR ICBTDDP60mg/m2d15-Fu1g/m2 d1-5q3w3DDP60mg/m2