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

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 TN1: TXL35mg/m2+NDP20mg/m2
TN2 TN2 TN2 TN2 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
2年无瘤生存率82％
N=34 (Progression 6) 2-yr PFS 82% (95%CI, 68-95%)
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
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:
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 铂类为基础的CCRT胃肠道反应大
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
晚期毒性反应
Site of side effect GI GU No. of pts (%) G0 23(67.6) 30(88.2) G1 5(14.7) 3(8.8) G2 4(11.8) 0(0) G3 2(5.9) 1(3.0) G4 0(0.0) 0(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
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 Median age (range) ECOG 0-1 2 No. of pts (%) 47(35-64) 25(73) 9(27)
Stage IIB
IIIA IIIB Pelvic LNM
急性毒性反应
toxicity Concurrent chemo(199 cycles) G0-2 G3-4 6(3.1) 0(0) 0(0) 0(0) 4(2) 0(0) 0(0) 0(0) 0(0) 0(0) Consolidation chemo(119 cycles) G0-2 106(89.1) 106(90.1) 119(100) 119(100) 118(99.2) 119(100) 119(100) 119(100) 119(100) 119(100) G3-4 13(10.9) 13(9.9) 0(0) 0(0) 1(0.8) 0(0) 0(0) 0(0) 0(0) 0(0)
10(29)
3(9) 21(62)
positive
negative Median baseline Hemoglobin (range)
ቤተ መጻሕፍቲ ባይዱ5(15)
29(85) 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
hematologic
Leukopenia Neutropenia Thrombocytopenia Anemia Nonhematologic Nausea/vomiting GI GU Liver damage neuropathy skin 195(98) 199(100) 199(100) 199(100) 199(100) 199(100) 193(96.9) 199(100) 199(100) 199(100)



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%