精品张美琴子宫颈癌筛查方法学研究以人群为基础的18项筛查研究的课件

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 analyses Cisplatin-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-IVA 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 CCRT nCCRT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 9001 nGOG: II、III期宫颈癌隐匿性主动脉旁 淋巴结转移率为16，25 nChoi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 0-2 nCT/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 brachytherapy External beam radiation therapy Day 1 8 15 22 29 36 43 50 After CCRT Day 30 51 72 93 TN1 TN1 TN1 TN1 TN1 TN1 TN2 TN2 TN2 TN2 TN1: 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, late toxicity (RTOG criteria) nResponse rate: RECIST criteria nLocoregional failure: in the pelvis or both within and outside pelvis nDistant 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(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 cycles nAdjuvant chemo: 28 pts-4 cycles 3 pts-3 cycles 2 pts-2 cycles 1 pt-refuse nReasons: 2 pts-G3 vomiting 1 pt-severe abdominal pain 3 pts-nonmedical reasons 急性毒性反应 toxicityConcurrent chemo(199 cycles)Consolidation chemo(119 cycles) G0-2G3-4G0-2G3-4 hematologic Leukopenia193(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) Nonhematologic Nausea/vomiting195(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 G4 GI23(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 n1-month after CCRT: 27 pts(79%) CR; 7 pts(21%) PR n1-month after adjuvant chemo: 30 pts(88%) CR nMedian follow-up of 23 months(14-30) n28 pts: alive without disease n5 pts: locoregional failure n1 pt: distant metastases N=34 (Progression 6) 2-yr PFS 82% (95%CI, 68-95%) 2年无瘤生存率82 N=34 (Death 2) 2-yr OS 93% (95%CI, 83-100%) 2年总生存率93 Studies on CCRT plus adjuvant chemotherapy in LACC ReferenceNoStageradiotherapyConcurrent chemo Consolidation chemo CR Median Followup Survival rate 3y PFS OS Wong et al 1999 110I-IIIPelvic EBRT +LDR ICBT Epi 60 mg/m2 q4w 90 mg/m2 q4w59296 m (16-130) 83 85 Vrdoljak et al 2005 44IB2 IVA Pelvic EBRT +LDR ICBT DDP75mg/m2d11 IFO2g/m2d11 q3w2 DDP75mg/m2d1 IFO2g/m2 d1-3 q3w4 10034 m (20-54) 84 91 Choi et al 2007 32IB2 IVA Pelvic EBRT +HDR ICBT DDP60mg/m2d1 5-Fu1g/m2 d1-5 q3w3 DDP60mg/m2d1 5-Fu1g/m2 d1-5 q3w3 8727 m (6-58) 83 91 结论 n本研究治疗方法有效，可以耐受. nPaclitaxel+nedaplatin 可以替代 cisplatin. nCCRT后辅助化疗可以降低局部复发率，提高 生存率. n有必要与标准治疗方案进行对比研究，得出肯 定结论。 谢 谢 ! 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