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
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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:
1 pt--------severe abdominal pain 3 pts------nonmedical reasons
急性毒性反应
toxicity
hematologic Leukopenia
Concurrent chemo(199 cycles)
G0-2
G3-4
Consolidation chemo(119 cycles)
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
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 TN1 TN1 TN1 TN1 TN1 TN1 TN1: TXL35mg/m2+NDP20mg/m2
After CCRT Day 30 51 72 93 TN2 TN2 TN2 TN2
TN2: TXL135mg/m2+NDP60mg/m2
研究终点和治疗评估
Primary endpoints: response rate, acute toxicity (NCICTC V 2.0)
Secondary endpoints: failures, OS, PFS, late toxicity (RTOG criteria)
DDP60mg/m2d1 5-Fu1g/m2 d1-5
q3w×3
q3w×3
Median Survival rate CR Followup
3y PFS OS
92 96 m
83 85
(16-130)
100 34 m (20-54)
84 91
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
G0-2
G3-4
193(96.9) 6(3.1)
106(89.1)
13(10.9)
Neutropenia
199(100)
0(0)
Thrombocytopenia 199(100)
0(0)
Anemia
199(100)
0(0)
Nonhematologic
Nausea/vomiting 195(98)
4(2)
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!
2005
IB2 ~IVA
Pelvic EBRT +LDR ICBT
DDP75mg/m2d11 IFO2g/m2d11 q3w×2
DDP75mg/m2d1 IFO2g/m2 d1-3 q3w×4
Choi et al 2007
32
IB2 ~IVA
Pelvic EBRT +HDR ICBTຫໍສະໝຸດ Baidu
DDP60mg/m2d1 5-Fu1g/m2 d1-5
Reference
No
Stage radiotherapy
Concurrent chemo
Consolidation chemo
Wong et al 110 I-III Pelvic EBRT Epi 60 mg/m2
1999
+LDR ICBT q4w
90 mg/m2 q4w×5
Vrdoljak et 44 al
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
13(9.9) 0(0) 0(0)
1(0.8) 0(0) 0(0) 0(0) 0(0) 0(0)
晚期毒性反应
Site of side effect
GI GU
G0
G1
23(67.6) 5(14.7)
30(88.2) 3(8.8)
No. of pts (%)
G2 4(11.8) 0(0)
G3 2(5.9) 1(3.0)
5(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
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
患者特征(n=34)
characteristics Median age (range) ECOG 0-1
2 Stage IIB
IIIA IIIB Pelvic LNM positive negative Median baseline Hemoglobin (range)
No. of pts (%) 47(35-64) 25(73) 9(27) 10(29) 3(9) 21(62)
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
GI
199(100)
0(0)
GU
199(100)
0(0)
Liver damage
199(100)
0(0)
neuropathy
199(100)
0(0)
skin
199(100)
0(0)
106(90.1) 119(100) 119(100)
118(99.2) 119(100) 119(100) 119(100) 119(100) 119(100)
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
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:
1 pt--------severe abdominal pain 3 pts------nonmedical reasons
急性毒性反应
toxicity
hematologic Leukopenia
Concurrent chemo(199 cycles)
G0-2
G3-4
Consolidation chemo(119 cycles)
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
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 TN1 TN1 TN1 TN1 TN1 TN1 TN1: TXL35mg/m2+NDP20mg/m2
After CCRT Day 30 51 72 93 TN2 TN2 TN2 TN2
TN2: TXL135mg/m2+NDP60mg/m2
研究终点和治疗评估
Primary endpoints: response rate, acute toxicity (NCICTC V 2.0)
Secondary endpoints: failures, OS, PFS, late toxicity (RTOG criteria)
DDP60mg/m2d1 5-Fu1g/m2 d1-5
q3w×3
q3w×3
Median Survival rate CR Followup
3y PFS OS
92 96 m
83 85
(16-130)
100 34 m (20-54)
84 91
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
G0-2
G3-4
193(96.9) 6(3.1)
106(89.1)
13(10.9)
Neutropenia
199(100)
0(0)
Thrombocytopenia 199(100)
0(0)
Anemia
199(100)
0(0)
Nonhematologic
Nausea/vomiting 195(98)
4(2)
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!
2005
IB2 ~IVA
Pelvic EBRT +LDR ICBT
DDP75mg/m2d11 IFO2g/m2d11 q3w×2
DDP75mg/m2d1 IFO2g/m2 d1-3 q3w×4
Choi et al 2007
32
IB2 ~IVA
Pelvic EBRT +HDR ICBTຫໍສະໝຸດ Baidu
DDP60mg/m2d1 5-Fu1g/m2 d1-5
Reference
No
Stage radiotherapy
Concurrent chemo
Consolidation chemo
Wong et al 110 I-III Pelvic EBRT Epi 60 mg/m2
1999
+LDR ICBT q4w
90 mg/m2 q4w×5
Vrdoljak et 44 al
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
13(9.9) 0(0) 0(0)
1(0.8) 0(0) 0(0) 0(0) 0(0) 0(0)
晚期毒性反应
Site of side effect
GI GU
G0
G1
23(67.6) 5(14.7)
30(88.2) 3(8.8)
No. of pts (%)
G2 4(11.8) 0(0)
G3 2(5.9) 1(3.0)
5(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
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
患者特征(n=34)
characteristics Median age (range) ECOG 0-1
2 Stage IIB
IIIA IIIB Pelvic LNM positive negative Median baseline Hemoglobin (range)
No. of pts (%) 47(35-64) 25(73) 9(27) 10(29) 3(9) 21(62)
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
GI
199(100)
0(0)
GU
199(100)
0(0)
Liver damage
199(100)
0(0)
neuropathy
199(100)
0(0)
skin
199(100)
0(0)
106(90.1) 119(100) 119(100)
118(99.2) 119(100) 119(100) 119(100) 119(100) 119(100)
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