結(jié)直腸癌患者新輔助治療,北京大學(xué)腫瘤醫(yī)院 消化腫瘤內(nèi)科,直腸癌術(shù)前放化療,新輔助治療的目的,提高手術(shù)切除率 提高保肛率 降低局部復(fù)發(fā) 延長患者無病生存期,推薦,T3和/或N+的可切除直腸癌患者，推薦術(shù)前新輔助放化療。 直腸癌術(shù)前化療推薦以氟尿嘧啶類藥物為基礎(chǔ)的化療方案,結(jié)腸癌肝轉(zhuǎn)移術(shù)前化療,推薦,結(jié)直腸癌患者合并肝轉(zhuǎn)移，可切除或者潛在可切除，推薦術(shù)前化療或化療聯(lián)合靶向藥物治療：西妥昔單抗（推薦用于K-ras基因狀態(tài)野生型患者），或聯(lián)合貝伐珠單抗 化療方案推薦FOLFOX，或者FOLFIRI，或者CapeOx，,liver metastases,Not resectable,resectable,chemotherapy,85%,15%+,other locations of metastases,chemotherapy,50%,50%,Patients with metastatic colorectal cancer,5y Survival: 5%,5 y survival: 5%,Metastatic colorectal cancer,5 y survival: 20-40%,Resection rate of metastases and tumor response,Studies incl. selected pats. (liver metastases only, no extrahepat. disease) r=.96, p=.002,Studies incl. all patients with metastatic CRC (solid line) r=.74, p.001 Phase III studies in metastatic CRC (dashed line) r=.67, p=.024, p=.024,Folprecht Khne et al, Ann Oncol 2005,新輔助化療優(yōu)勢,患者體內(nèi)化療藥物的藥敏試驗 清除微小轉(zhuǎn)移灶 觀察甄別出快速進展病例 提高R0切除率？并減少切除的正常肝組織 延長生存期？,Adjuvant, neoadjuvant, conversion therapy for CRC liver metastases,Resectable adjuvant neo-adjuvant Unresectable Conversion chemotherapy,Colorectal Ca R0 Resection of Metastases,Controversy: Adjuvant Therapy ?,USA Yes (Kemeny NEJM 1999),Europa No (Lorenz NEJM 2000),Kemeny et al NEJM 1999 and 2005,Liver metastases: adjuvant HAI + i.v. CTX,p=0.02,LV5FU vs. FOLFIRI as adjuvant therapy following resection of CLM - DFS,1-year DFS: 63% vs. 77% 2-year DFS: 46% vs. 51%,Ychou et al. ASCO 2008,Adjuvant Chemotherapy for CRC liver metastases,YES！ Which patients? 高復(fù)發(fā)風(fēng)險 which regimen? 化療？HAI？ 方案？FU、OXA？Target ？,EORTC phase III study 40983 研究設(shè)計,Randomize,Surgery,FOLFOX4,FOLFOX4,Surgery,6 cycles (3months),6 cycles (3 months),364 例潛在可切除肝轉(zhuǎn)移 (metachronous or synchronous) ，4個以上病灶，無肝外轉(zhuǎn)移,EORTC Study 40983,CT S P 3-y FPS % 42.4 33.2 0.025,樂沙定，伊立替康和持續(xù)滴注5-FULV(FOLFOXIRI)兩周方案和Folfiri相比一線治療轉(zhuǎn)移性結(jié)直腸癌： III期臨床結(jié)果（GONO）,A. Falcone, et al ASCO GI 2006, #227,不能切除的結(jié)直腸癌肝轉(zhuǎn)移新輔助化療,伊立替康，樂沙定和持續(xù)滴注5-FULV(FOLFOXIRI)兩周方案和Folfiri相比一線治療轉(zhuǎn)移性結(jié)直腸癌：III期臨床結(jié)果（GONO）,* Douillard Lancet 2000 * Masi Ann Oncol 2004,臨床設(shè)計,FOLFIRI*,R,CPT-11 180 mg/m2 1-h d.1 L-LV 100 mg/m2 2-h d.1,2 5FU 400 mg/m2 bolus d.1,2 5FU 600 mg/m2 22-h d.1,2 q. 2 wks x 12個周期,FOLFOXIRI*,CPT-11 165 mg/m2 1-h d.1 LOHP 85 mg/m2 2-h d.1 L-LV 200 mg/m2 2-h d.1 5FU 3200 mg/m2 48-h CI d.1 q. 2 wks x 12 個周期,分層 中心 PS 0/1-2 輔助化療,FOLFIRI方案進展后，推薦含樂沙定的方案,A. Falcone, ASCO GI 2006, #227,*p0.001,有效率 (ITT 分析),化療后手術(shù)切除率 (所有病人),*p0.033,療效結(jié)果,主要目標(biāo)：RR 次要目標(biāo)：PFS, OS, post surgical resectionsn, safety QOL,Rescue Surgery for Unresectable Colorectal Liver Metastases Downstaged by ChemotherapyA Model to Predict Long-term Survival,Retrospective study 1104 cases with unresectable liver metastases Chemotherapy regimens：5-FU/LV/OXA or IRI or both 138(12.5%) achieved secondary curative hepatic resection Survival rate: 5-year 33% 10-year 23%,Adam R et al,Ann surg.2004;240:644-657,Resection of liver metastases: non-selected patients treated with targeted/cytotoxic agents,First author N Regimen RR Resection rate Folprecht 21 Cetuximab/irinotecan 67% 19% /AIO (24%)* Diaz Rubio 43 Cetuximab/FOLFOX4 79% 19% Rougier 42 Cetuximab/FOLFIRI 45% 21% Fisher 27 Gefitinib/FOLFOX4 78% 22% Hurwitz 411 IFL 35% （2% 412 IFL/bevacizumab 45% resection) Hoff 21 FOLFIRI/bevacizumab 70% 19% *One patient declined offered resection,Updated information based on Folprecht et al. Ann Oncol, 2005,Liver-limited disease PFS and RR in KRAS wild-type,aCochran-Mantel-Haenszel (CMH) test,Van Cutsem, Khne in press,Randomized multicenter study of cetuximab plus FOLFOX or cetuximab plus FOLFIRI in neoadjuvant treatment of non-resectable colorectal liver metastases (CELIM study),G. Folprecht,1 T. Gruenberger,2 J.T. et al,Patients with non-resectable colorectal liver metastases No extrahepatic disease,Efficacy: Confirmed Response,Responses confirmed by 2nd CT scan according to RECIST or by resection,Chi square test for comparison between FOLFOX6+Cet vs FOLFIRI+Cet would be 0.23,Resections,Comparison of R0 resections between strata technically non-resectable and 5 liver mets: p=0.14,手術(shù)前化療時限,化療時間,最佳選擇時間？,More than 6 cycles of neoadjuvant systemic chemotherapy