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: A significant benefit with non-platinum regimens was also observed. CCRT: 5y OS 6% CCRT+adjuvant chemo: 5y OS 19% ? IA-IIA IIB III-IVA 5y OS 10% 7% 3% 　　　　　　　　　J Clin Oncol,2008;26:5802-5811

目前存在的问题 铂类为基础的CCRT与非铂类为基础的CCRT CCRT后辅助化疗的作用 晚期宫颈癌应用CCRT生存获益小

研究设计 药物选择 RTOG 9001 GOG: 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

入组标准 IIB-IIIB期宫颈鳞癌 18-65岁 ECOG 0-2 CT/MRI：主动脉旁淋巴结（－） 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 Primary endpoints: response rate, acute toxicity (NCI-CTC V 2.0) Secondary endpoints: failures, OS, PFS, late toxicity (RTOG criteria) Response rate: RECIST criteria Locoregional failure: in the pelvis or both within and outside pelvis Distant 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) characteristics No. of pts (%) Median age (range) 47(35-64) ECOG 0-1 25(73) 2 9(27) Stage IIB 10(29) IIIA 3(9) IIIB 21(62) Pelvic LNM positive 5(15) negative 29(85) Median baseline Hemoglobin (range) 114g/L(90-146)

患者接受化疗情况 Concurrent chemo: all pts received 6 cycles Adjuvant chemo: 28 pts----4 cycles 3 pts------3 cycles 2 pts------2 cycles 1 pt-------refuse Reasons: 2 pts-----G3 vomiting 1 pt--------severe abdominal pain 3 pts------nonmedical reasons

急性毒性反应 toxicity Concurrent chemo(199 cycles) Consolidation chemo(119 cycles) G0-2 G3-4 hematologic Leukopenia 193(96.9) 6(3.1) 106(89.1) 13(10.9) Neutropenia 199(100) 0(0) 106(90.1) 13(9.9) Thrombocytopenia 119(100) Anemia Nonhematologic Nausea/vomiting 195(98) 4(2) 118(99.2) 1(0.8) GI GU Liver damage neuropathy skin

晚期毒性反应 Site of side effect No. of pts (%) G0 G1 G2 G3 G4 GI 23(67.6) 5(14.7) 4(11.8) 2(5.9) 0(0.0) GU 30(88.2) 3(8.8) 0(0) 1(3.0)

治疗结果 1-month after CCRT: 27 pts(79%) CR; 7 pts(21%) PR 1-month after adjuvant chemo: 30 pts(88%) CR Median follow-up of 23 months(14-30) 28 pts: alive without disease 5 pts: locoregional failure 1 pt: distant metastases

2年无瘤生存率82％ N=34 (Progression 6) 2-yr PFS 82% (95%CI, 68-95%)

2年总生存率93％ N=34 (Death 2) 2-yr OS 93% (95%CI, 83-100%)

Studies on CCRT plus adjuvant chemotherapy in LACC Reference No Stage radiotherapy Concurrent chemo Consolidation chemo CR Median Followup Survival rate 3y PFS OS Wong et al 1999 110 I-III Pelvic EBRT +LDR ICBT Epi 60 mg/m2 q4w 90 mg/m2 q4w×5 92 96 m (16-130) 83 85 Vrdoljak et al 2005 44 IB2 ~IVA DDP75mg/m2d11 IFO2g/m2d11 q3w×2 DDP75mg/m2d1 IFO2g/m2 d1-3 q3w×4 100 34 m (20-54) 84 91 Choi et al 2007 32 +HDR ICBT DDP60mg/m2d1 5-Fu1g/m2 d1-5 q3w×3 87 27 m (6-58) 83 91

结论 本研究治疗方法有效，可以耐受. Paclitaxel+nedaplatin 可以替代 cisplatin. CCRT后辅助化疗可以降低局部复发率，提高生存率. 有必要与标准治疗方案进行对比研究，得出肯定结论。

谢　谢 !