1、结直肠癌新辅助治疗结直肠癌新辅助治疗2021/1/1222021/1/1232021/1/1242021/1/1252021/1/1262021/1/1272021/1/1282021/1/1292021/1/12102021/1/12112021/1/12122021/1/12132021/1/12142021/1/12152021/1/1216liver metastasesNot resectableresectablechemotherapy85%15%+other locations of metastaseschemotherapy50%50%Patients with metas
2、tatic colorectal cancer5y Survival:5%5 y survival:5%5 y survival:20-40%2021/1/1217Response rate,9,8,7,6,5,4,3Resection rate,6,5,4,3,2,10,0Studies incl.selected pats.(liver metastases only,no extrahepat.disease)r=.96,p=.002Studies incl.all patients with metastatic CRC(solid line)r=.74,p.001Phase III
3、studies in metastatic CRC(dashed line)r=.67,p=.024,p=.024Folprecht Khne et al,Ann Oncol 20052021/1/12182021/1/1219Resectable-adjuvant-neo-adjuvantUnresectable-Conversion chemotherapy2021/1/1220Colorectal Ca R0 Resection of MetastasesControversy:Adjuvant Therapy?USA Yes (Kemeny NEJM 1999)EuropaNo(Lor
4、enz NEJM 2000)2021/1/1221Kemeny et al NEJM 1999 and 2005p=0.02Median overall survivalFong 0-2Fong 3-5HAI+systemic83.3 mo60.0 mo(10y:38.7%)systemic82.8 mo38.3 mo(10y:16.3%)p=0.132021/1/12220.000.250.500.751.00Probability153114704122LV5FUs+IRI15395654425LV5FUsNumber at risk012243648MonthsLV5FUsLV5FUs+
5、IRIadjusted Logrank p=0.43HR=0.89:95%CI 0.66-1.19Treatment1-year DFS:63%vs.77%2-year DFS:46%vs.51%Ychou et al.ASCO 20082021/1/1223 YES！Which patients?高复发风险高复发风险 which regimen?化疗？化疗？HAI？方案？方案？FU、OXA？Target？2021/1/1224RandomizeSurgeryFOLFOX4FOLFOX4Surgery6 cycles(3months)6 cycles(3 months)v364 例例2021/
6、1/1225EORTC Study 40983 CT S P3-y FPS%42.4 33.2 0.0252021/1/1226乐沙定，伊立替康和持续滴注乐沙定，伊立替康和持续滴注5-FULV(FOLFOXIRI)两周方案和两周方案和Folfiri相比一线治疗转移性结直肠癌：相比一线治疗转移性结直肠癌：III期临床结果（期临床结果（GONO）A.Falcone,et alASCO GI 2006,#2272021/1/1227伊立替康，乐沙定和持续滴注伊立替康，乐沙定和持续滴注5-FULV(FOLFOXIRI)两周两周方案和方案和Folfiri相比一线治疗转移性结直肠癌：相比一线治疗转移性结直
7、肠癌：III期临床结期临床结果（果（GONO）*Douillard Lancet 2000*Masi Ann Oncol 2004临床设计临床设计FOLFIRI*RCPT-11180 mg/m2 1-h d.1L-LV100 mg/m2 2-h d.1,25FU400 mg/m2 bolus d.1,25FU600 mg/m2 22-h d.1,2q.2 wks x 12个周期个周期FOLFOXIRI*CPT-11165 mg/m2 1-h d.1LOHP85 mg/m2 2-h d.1L-LV200 mg/m2 2-h d.15FU3200 mg/m2 48-h CI d.1q.2 wks
8、x 12 个周期个周期分层分层 中心中心 PS 0/1-2 辅助化疗辅助化疗FOLFIRI方案进展后，推荐含乐沙定的方案方案进展后，推荐含乐沙定的方案2021/1/1228A.Falcone,ASCO GI 2006,#227*p0.001有效率有效率(ITT 分析)化疗后手术切除率化疗后手术切除率(所有病人)*p0.033疗效结果疗效结果主要目标：RR次要目标：PFS,OS,post surgical resectionsn,safety QOL2021/1/1229Adam R et al,Ann surg.2004;240:644-6572021/1/1230Updated inform
9、ation based on Folprecht et al.Ann Oncol,20052021/1/1231aCochran-Mantel-Haenszel(CMH)testVan Cutsem,Khne in press2021/1/1232Randomized multicenter study of cetuximab plus FOLFOX or cetuximab plus FOLFIRI in neoadjuvant treatment of non-resectable colorectal liver metastases(CELIM study)G.Folprecht,1
10、 T.Gruenberger,2 J.T.et al2021/1/1233 Responses confirmed by 2nd CT scan according to RECIST or by resectionChi square test for comparison between FOLFOX6+Cet vs FOLFIRI+Cet would be 0.23 2021/1/1234Comparison of R0 resections between strata technically non-resectable and 5 liver mets:p=0.142021/1/12352021/1/1236More than 6 cycles of neoadjuvant systemic chemotherapy increase morbidity significantly Karoui et al.Ann surg.2006:243:1-72021/1/1237个体化！个体化！及时评估疗效，预防并发症及时评估疗效，预防并发症不忘主题不忘主题手术治疗！手术治疗！2021/1/12382021/1/1239
