2018年XELOX-結(jié)直腸癌患者輔助化療的金標(biāo)準(zhǔn).ppt

早期臨床研究證實(shí)：5-Fu單藥輔助化療可顯著延長(zhǎng)結(jié)直腸癌患者的總生存期和復(fù)發(fā)時(shí)間 1,1, Sargent DJ,et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001 Oct 11;345(15):1091-7 2, NCCN Clinical Practice Guideline in Oncology. Colon Cancer. V.1.2012,p0.001,p0.001,期、期結(jié)直腸癌患者 使用氟尿嘧啶為基礎(chǔ)的輔助化療能讓患者進(jìn)一步獲益,NCCN指南2推薦,II期高危，III期結(jié)直腸癌患者術(shù)后使用聯(lián)合方案輔助治療,II期無(wú)高危因素患者推薦使用氟尿嘧啶單藥方案輔助治療,卡培他濱單藥輔助化療優(yōu)于5-Fu/Lv方案,Seidman AD, Aapro M. Introduction J. The Oncologist, 2002, 7(suppl 6): 1 - 3. Twelves C, Scheithauer W, McKendrick J, et al. Capecitabine versus 5-FU/LV in stage colon cancer: Updated 5-year efficacy data from X-ACT trial and preliminary analysis of relationship between hand-foot syndrome (HFS) and efficacy J. American Society of Clinical Oncology Gastrointestinal Cancers Symposium, 2008, 19(Suppl. 6): A274,X-ACT研究結(jié)果：希羅達(dá)組的DFS顯示出優(yōu)勢(shì)趨勢(shì),卡培他濱組顯著減少3 / 4級(jí)血液學(xué)毒性,MOSAIC (2009年發(fā)表),FOLFOX,5-FU/LV,(deGramont),NSABP C-07 (2007年發(fā)表),FLOX,5-FU/LV,(Roswell-Park),試驗(yàn),對(duì)照組,新標(biāo)準(zhǔn),X-ACT (2005年發(fā)表),卡培他濱,5-FU/LV,(Mayo),5年DFS提高5.9%,4年DFS提高5.2%,5年DFS提高4.1%,XELOX？,臨床數(shù)據(jù)證明氟尿嘧啶與奧沙利鉑聯(lián)合方案優(yōu)于單藥方案,輔助化療金標(biāo)準(zhǔn)的定義,未接受過(guò)化 放療治療的 III期結(jié)腸癌患者 n=1886 入組時(shí)間2003-2004年,快速靜推 5-FU/LV Mayo CLINIC或者Roswell PARK癌癥研究所,XELOX 希羅達(dá) 1000mg/m2每日兩次 d115 奧沙利鉑 130mg/m2 d1 每3周為一周期q3w,主要終點(diǎn): 具有無(wú)病生存期（DFS）優(yōu)勢(shì),n=944,n=942,隨 機(jī) 化,NO16968: XELOX 輔助方案的新選擇,Haller DG, Tabernero J, Maroun J, et al. Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Folinic Acid As Adjuvant Therapy for Stage Colon Cancer J. Official Journal of the American Society of Clinical Oncology, 2011, 11(29): 1465 - 71.,XELOX較5-FU/LV在輔助化療中，DFS和OS有顯著優(yōu)勢(shì),ITT 人群,估計(jì)的生存概率,(n=944) (n=942),3年時(shí)的絕對(duì)差值: 4.4% (p=0.0045),16968研究顯示：XELOX的 DFS優(yōu)勢(shì)隨觀(guān)察時(shí)間延長(zhǎng)而增加,Haller et al. JCO 2011;29:146571,16968研究顯示：XELOX方案顯著提高患者7年總生存率,4年時(shí)的絕對(duì)差值: 6.1%,7年時(shí)的絕對(duì)差值: 7% (p=0.0038),5年時(shí)的絕對(duì)差值: 6.3% (p=0.0045),1. Haller et al. JCO 2011;29:146571 2. Andr T et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009,27,310916.,DFS 與OS曲線(xiàn)顯示：XELOX方案與FOLFOX療效相當(dāng),月,月,McCleary N.A.J, Meyerhardt J, Green E, et al. Impact of older age on the efficacy of newer adjuvant therapies in 12,500 patients (pts) with stage / colon cancer: Findings from the ACCENT Database. J Clin Oncol 27:15s, 2009 (suppl; abstr 4010). Haller DG, Tabernero J, Maroun J, et al. Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Folinic Acid As Adjuvant Therapy for Stage Colon Cancer J. Official Journal of the American Society of Clinical Oncology, 2011, 11(29): 1465 - 71.,XELOX方案使老年患者一致獲益,* Values 1 favor oxaliplatin-based therapy vs. 5-FU/LV; # Data for oxaliplatin-based regimens,老年亞組分析顯示：XELOX方案使老年患者一致獲益,1. Yothers et al. JCO 2011;28:376874 2. Tournigand et al. JCO 2010;28:15s (abstr 3522),*與5-FU/LV對(duì)比 na: 未提及,老年亞組分析顯示：XELOX方案使老年患者一致獲益,2012ASCOGI回顧性研究再次佐證XELOX方案可使老年人群明顯獲益,結(jié)直腸癌患者 術(shù)后輔助治療 （n=3390）,XELOX方案顯著降低老年患者56%死亡風(fēng)險(xiǎn),5FU/LV （n=1368）,FOLFOX （n=1398）,Xeloda （n=507）,Arnold, et al. ASCO GI 2012 (abstract 470),XELOX （n=117）,回顧性分析 2004-2007年，66歲的患者 結(jié)腸癌術(shù)后輔助治療,回顧性研究：研究設(shè)計(jì),MOSAIC (2009年發(fā)表),FOLFOX,5-FU/LV,(deGramont),NSABP C-07 (2007年發(fā)表),FLOX,5-FU/LV,(Roswell-Park),試驗(yàn),對(duì)照組,新標(biāo)準(zhǔn),X-ACT (2005年發(fā)表),卡培他濱,5-FU/LV,(Mayo),5年DFS提高5.9%,4年DFS提高5.2%,5年DFS提高4.1%,XELOX！,XELOX方案超越FOLFOX，患者更多獲益,5年DFS提高6.3%,16968 (2011年發(fā)表),5-FU/LV,(deGramont),XELOX方案的血液學(xué)毒性顯著低于FOLFOX方案,Schmoll HJ, Cartwright T, Tabernero J, et al. Phase Trial of Capecitabine Plus Oxaliplatin As Adjuvant Therapy for Stage Colon Cancer: A Planned Safety Analysis in 1,864 Patients J. Journal of Clinical Oncology, 2007, 25(1): 102 - 9.,NO.16968研究與MOSAIC研究的3/4級(jí)不良反應(yīng)交叉對(duì)照分析,NCCN指南推薦: XELOX 是結(jié)直腸癌輔助化療的標(biāo)準(zhǔn)方案,National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology Colon Cancer. V.3.2011: COL-4.,2012結(jié)腸癌NCCN指南 XELOX為1類(lèi)推薦方案,2012直腸癌NCCN指南 XELOX為2A類(lèi)推薦方案,中國(guó)衛(wèi)生部頒發(fā) 結(jié)直腸癌診療規(guī)范（2010年版）,使用方便,Schmoll HJ, Cartwright T, Tabernero J, et al. Phase Trial of Capecitabine Plus Oxaliplatin As Adjuvant Therapy for Stage Colon Cancer: A Planned Safety Analysis in 1,864 Patients