结肠癌的治疗

1、会计学1结肠癌的治疗结肠癌的治疗II期病人送检淋巴结数目与生存的关系（ I NT-0089的再分析）的再分析）1009080706050403020100生存百分比生存百分比0122436486072849610812020个送检淋巴结个送检淋巴结1120 送检淋巴结送检淋巴结110 送检淋巴结送检淋巴结87%80%73%79%73%59%术后月术后月如果如果 10个送检淋巴结，则诊断效力降低个送检淋巴结，则诊断效力降低Phase III MOSAICFOLFOX4LV5FU2(de Gramont)6 months (12 Cycles)2,236 pts148 Centers20 Coun

2、tries0020406080100无疾病生存无疾病生存 (%) HR 95% CI: 0.77 0.650.906.6%FOLFOX4 279/1123 (24.8%)LV5FU2 345/1123 (30.7%)月612182430364248546066p0.001HR (95% CI): 0.82 (0.601.13) Stage II 0.75 (0.620.89) Stage III1.00.90.80.70.60.50.30.40.20.10.0 0FOLFOX4: LV5FU2:6661218243036424854604-yr: 8.6%4-yr: 3.5%3-yr: 7.2

3、%672 Stage III675 Stage III451 Stage II448 Stage IIFOLFOX4: LV5FU2: 无疾病生存无疾病生存Uncertain IndicationObservation 16175-FU (370 mg/m2) with low dose FA, 1622-Large randomized trial-Pragmatic trial NSABP C-07FU 500+LV 500weekly x 6every 8 weeks x 3FU 500+LV 500weekly x 6every 8 weeks x 3+Oxaliplatin 85 w

4、eeks 1, 3 & 5of each 8 week cycleN = 2492Primary endpoint: 3-year DFSp 0.004HR: 0.79 0.67 0.9321% Risk Reduction0.50.60.70.80.9101234 Ev # 3-yr DFSFLOX 272 76.5%FU/LV 332 71.6%C-07 and MOSAIC 3-yr DFS: Stage II and IIIITT 人群人群5 年年DFS卡培他滨卡培他滨 60.8%5-FU/LV 56.7%HR=0.88 (95% CI: 0.771.01)NI margin 1.20

5、优效性检验优效性检验 p=0.06820123456780.40.60.81.0概率概率年年5年绝对差异年绝对差异 4.1%Twelves C, et al. ASCO GI 2008. Abstract 274.0123456780.40.60.81.0年年概率概率5年绝对差异年绝对差异3.0%HR=0.86 (95% CI: 0.741.01)优效性检验优效性检验 p=0.06 5年年OS卡培他滨卡培他滨(n=1 004) 71.4%5-FU/LV(n=983)68.4%未化未化疗疗或放或放疗疗III 期期结肠结肠癌癌切除切除术术后后8 周周N=1886n=944 n=942随随机机化化推

6、注推注 5-FU/LV (6 月月) Mayo Clinic n=664或或Roswell Park n=278XELOX (6 月月) 希希罗罗达达 1000mg/m2 bid d114奥沙利奥沙利铂铂d1 q3w8 个周期个周期Schmoll et al. JCO 2007Haller et al. ESMO/ECCO 2009XELOX 5-FU/LV 1.00.00.20.40.60.80123456年年ITT人群人群4年差异年差异: 6.1%5年差异年差异: 6.3%3年差异年差异: 4.5%70.9% 68.4%3年年DFS66.5% 62.3%4年年DFS5年年DFS59.8%6

7、6.1%生存概率生存概率Haller et al. Eur J Cancer Suppl 2009;7:4(Abst 5LBA)HR=0.80(95%CI:0.69-0.93)P=0.0045ITT 人群人群1.01.00.00.00.20.20.40.40.60.60.80.80123456XELOX 5-FU/LV 72.1% 69.7%3年年RFS67.5% 63.3%4年年RFS5年年RFS60.9%67.8%HR=0.78 (95% CI: 0.670.92)p=0.00244年差异年差异: 6.4%5年差异年差异: 6.9%3年差异：年差异：4.6%年年生存概率生存概率Haller

8、 et al. Eur J Cancer Suppl 2009;7:4(Abst 5LBA)ITT population1.01.00.00.00.20.20.40.40.60.60.80.80123456XELOX 5-FU/LV 5年差异年差异: 3.4%HR=0.87 (95% CI: 0.721.05)p=0.1486年年77.6%5年年OS74.2%生存概率生存概率Haller et al. Eur J Cancer Suppl 2009;7:4(Abst 5LBA)对于辅助化疗，目对于辅助化疗，目前没有任何证据显前没有任何证据显示可以联合任何分示可以联合任何分子靶向药物。子靶向药物

9、。Progression-free survival time (months)PFS estimate1.00.80.90.00.10.20.30.40.50.60.702468101214161820HR = 0.851; 95% CI = 0.726-0.998Stratified log-rank p-value = 0.04798.9 mo8.0 moFOLFIRI, n=599Cetuximab + FOLFIRI, n=5991-year PFS rate23% vs 34%Subjects at riskFOLFIRI alone 59949240229317883351674

10、1Cetuximab + FOLFIRI59949939229819610358291251 2007.ASCO annual meeting .Abstract No.4000总生存的分层分析(wK-ras)Bokemeyer et al. ECCO-ESMO 2009 (abstract No. 6079) Continuous* XELOX 或或 FOLFOXArm AR一线治疗一线治疗 mCRC( 2445例例)Arm BContinuous XELOX or FOLFOX + 西妥昔西妥昔Arm CIntermittent*XELOX 或或 FOLFOX65% XELOX; 35%

11、FOLFOX(根据患者或医生的选择根据患者或医生的选择)Maughan, et al. ECCO-ESMO 2009 (abstract No. 6LBA)*Odds ratioMaughan, et al. ECCO-ESMO 2009 (abstract No. 6LBA)1.000.750.500.250生存生存时间时间(月月)ITT analysisNo. at riskArm A Arm B0612182430364236736124524992103414218221196610Maughan, et al. ECCO-ESMO 2009 (abstract No. 6LBA)Ar

12、m A (XELOX/FOLFOX)Arm B (XELOX/FOLFOX + 西妥昔西妥昔)HR point estimate = 0.95995% CI 0.841.09p=0.601.000.750.500.250生存概率生存概率Time (months)06121824303642No. at riskArm AArm B36736231630625023815414983804442191713ITT analysisMaughan, et al. ECCO-ESMO 2009 (abstract No. 6LBA)Arm A (XELOX/FOLFOX)Arm B (XELOX/F

13、OLFOX + 西妥昔西妥昔)HR point estimate = 1.03895% CI 0.901.20p=0.68IFL推注 5-FU 500 mg/m2亚叶酸钙 20 mg/m2依立替康 125 mg/m2用药 4/6 周疾病进展后疾病进展后不接受贝伐单抗治疗不接受贝伐单抗治疗Hurwitz H, et al. N Engl J Med 2004;350:2335425-FU/LV推注推注5-FU 500 mg/m2 亚叶酸钙亚叶酸钙 500 mg/m2 用药用药6/8周周贝伐单抗5 mg/kg 每2周1次先前未曾治疗的转移性 CRCPDPDPD推注IFL + 安慰剂（n=412）推

14、注IFL + 贝伐单抗（n=403）5-FU/LV +贝伐单抗 （n=110）疾病进展后疾病进展后可接受贝伐单抗治疗可接受贝伐单抗治疗疾病进展后疾病进展后可接受贝伐单抗治疗可接受贝伐单抗治疗0.2010203000.81.00.40.6Progression-free survival (mo)Proportion progression-freeTreatment GroupIFL + placeboIFL + bevacizumabHurwitz et al. Proc Am Soc Clin Oncol. 2003;22. Abstract 3646 and oral presentat

15、ion.Avastin PI.HR=0.54, P20个送检淋巴结个送检淋巴结1120 送检淋巴结送检淋巴结110 送检淋巴结送检淋巴结87%80%73%79%73%59%术后月术后月如果如果 10个送检淋巴结，则诊断效力降低个送检淋巴结，则诊断效力降低Uncertain IndicationObservation 16175-FU (370 mg/m2) with low dose FA, 1622-Large randomized trial-Pragmatic trial NSABP C-07FU 500+LV 500weekly x 6every 8 weeks x 3FU 500+L

16、V 500weekly x 6every 8 weeks x 3+Oxaliplatin 85 weeks 1, 3 & 5of each 8 week cycleN = 2492Primary endpoint: 3-year DFSXELOX 5-FU/LV 1.00.00.20.40.60.80123456年年ITT人群人群4年差异年差异: 6.1%5年差异年差异: 6.3%3年差异年差异: 4.5%70.9% 68.4%3年年DFS66.5% 62.3%4年年DFS5年年DFS59.8%66.1%生存概率生存概率Haller et al. Eur J Cancer Suppl 2009;7:4(Abst 5LBA)HR=0.80(95%CI:0.69-0.93)P=0.004