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5FU/LVXELODACPT-11L-OHP *可用于一线或二线治疗可用于一线或二线治疗 CAPIRI IFL XELIRI FOLFIRI Irinotecan CAPOX bFOL XELOX FOLFOX Oxaliplatin Xeloda 5-FU/LV 二药联合二药联合*黄：黄：LV 蓝：蓝：5-FU 红：乐沙定红：乐沙定 单位：单位：mg/m每每2周重复周重复BICC-C *5FU.CPT-11.L-OHP Grothey et al.JCO 200419.768 Grothey 2002 21.068 Tournigand 200119.460 Giacchetti 200019.560 Goldberg 200220.154 Koehne 200316.229 De Gramont 200017.416 Douilard 200014.85 Saltz 2000中位生存（中位生存（m）*用三药病人用三药病人 作作 者者OS(mos)=13.2+(%3drugs x 0.1),R2=0.85Grothey&Sargent,JCO 20050 10 20 30 40 50 60 70 80Infusional 5-FU/LV+irinotecanInfusional 5-FU/LV+oxaliplatinBolus 5-FU/LV+irinotecanIrinotecan+oxaliplatinBolus 5-FU/LV LV5FU22221201918171615141312Median OS(mo)Patients with 3 drugs(%)P=.0001First-Line TherapyMultivariate analysis:Effect on OSPFirst-line doublet0.69All 3 drugs0.005FOLFOX 7LV5FU2Oxa 130mg/m2LV 400mg/m2 BiweeklyLV 400mg/m25FU 400mg/m2 2 Bi weeklyX 6X 12AMCRCRANDOM ISED OPTIMOX 2（200）FOLFOX7/6次次 停止停止 进展进展 OPTIMOX 1（187）FOLFOX7/6次次 LV5FU2/12次次 进展进展(F.Maindrault-Goebel et al.ASCO 2006#3504)结论：维持结论：维持LV5FU延长了延长了PFS。*中位病变控制时间中位病变控制时间200 187 例数例数36 41 P=0.17 *Mddc(wks)28 36 P=0.01 mPFS(wks)53 56 CR+PR(%)51 54 PR(%)2 2 CR(%)OPTIMOX 2OPTIMOX 1 方案方案用用mFolFox7/Bv 治疗治疗mCRC 139例，例，Oxal.使用使用:IO or CO结论：结论：CONcePT试验证实与试验证实与CO相比，相比，IO能增加治疗的时能增加治疗的时 间，尤其是在一线用间，尤其是在一线用Oxal/BV的病人的病人Grothey A.etal.ASCO 2008#4010Courtesy of Jos Baselga(modified)MetastasisProliferation/MaturationCell Repair/SurvivalAngiogenesisMAPKMEKGene transcriptionCell-cycle progressionPI3-KRAS RAFSOSGRB2PTENAKTSTATpYpYK KpYMG1SG2XXXXYXEGFR小结小结:与以往用过多少化疗无关与以往用过多少化疗无关;可逆转可逆转Iri和和Ox的耐药的耐药性性;疗效与皮疹程度相关，疗效与皮疹程度相关，FDA已批准二线治疗。已批准二线治疗。P=0.014VEGFR-2VEGFR-1PPPPPPPPEndothelial cellSmall-molecule VEGFR inhibitors(TKIs)RibozymesAnti-VEGFR antibodiesSoluble VEGF receptorsAnti-VEGF antibodiesVEGFAnti-VEGFR antibodiesAnti-VEGF antibodies*Hurwitz et al.Proc ASCO 2003 Abstract 3646*FDA批准用于一线与化疗联合批准用于一线与化疗联合*BEV 10mg/kg/2w i.v.*TREE2：加：加BEV.5mg/kg,Q14d 或或7.5mg/kg,Q21d 高血压，肠穿孔，愈合损伤比高血压，肠穿孔，愈合损伤比TREE1多见。多见。(Hochster et al.ASCO 2006#3510)274620394152 ORR(%)735442597566G3+4 TOX(%)496850635363 18月S(%)5.910.36.98.38.79.9 mTTP(m)-BEV+BEV-BEV+BEV -BEV+BEVCapeOxbFOLmFOLFOX6方方 案案1.00.80.70.50.30.10.90.60.40.2051015202530Survival time(months)35400ProbabilityTREE-1TREE-2aTreatment arms combinedHochster H,et al.ASCO 2006(Abstract 3510).结论：三项研究比常用一线方案，所比较两方案疗效，生存结论：三项研究比常用一线方案，所比较两方案疗效，生存 均无明显差异，且安全性好。均无明显差异，且安全性好。Reinacher-Schick AC.etal.ASCO 2008#4030Cioleano TE.etal.ASCO 2008#4032Heinemann V.etal.ASCO 2008#40331990s 5-FU/LVIFL FOLFOXFOLFOX/FOLFIRI sequenceIFL+bevacizumab1960s Best supportive care19701980s 5-FUMedian overall survival(months)Oxaliplatin-fluoropyrimidine+bevacizumab31mVan Cutsem et al.ASCO 2008#LAB2 Teipar S.et al.ASCO 2008#4001Bokemeyer C et al.ASCO 2008#4000DI Fiore et.al.ASCO 2008#40357项以项以5FU为基础辅助化疗共为基础辅助化疗共3351例例II、III期肠癌的分析结果期肠癌的分析结果LVOXARMOSAIC:Treatment arms*Baxter LV5 infusorsLV5FU2FOLFOX4:LV5FU2+Oxaliplatin 85mg/mEvery 2 weeks,6 months of treatment(12 cycles)D15-FU bolusD25-FU bolusLVLV5-FU infusion*5-FU infusion*D15-FU bolusD25-FU bolusLVLV5-FU infusion*5-FU infusion*1.00.90.80.70.60.50.30.40.20.10.0 0FOLFOX4 451 Stage IILV5FU2 448 Stage IIFOLFOX4 672 Stage IIILV5FU2 675 Stage IIIHR 95%CI:0.82 0.60 1.13 Stage II0.75 0.62 0.89 Stage IIIMonthsDFS probability666121824303642485460Data cut-off:January 16,20058.6%3.5%7.2%6疗程6个月2407例例II/III期肠癌随机比较期肠癌随机比较FULV(F 500 i.v.b.Qw x 6 L 500 Qw x 6/每每8周，共周，共3疗程疗程)L-OHP(85mg/m2 Q2W/每每8周，共周，共3疗程疗程)，中位随访，中位随访34月。月。(Wolmark等，ASCO 2005 3500)0.004推注推注5FUNSABP C-07CALGB C89803MOSAICPETACC 3ACCORD2+-滴注滴注5FU+-Stage III colon cancer(N=2300)Stage II/III colon cancer(N=2400)mFOLFOX6 6mmFOLFOX6 6m+Bevacizumab 12mIntergroup N0147NSABP C-08mFOLFOX6 6mmFOLFOX6 6m+Cetuximab 6m Survival by Age0123020406080100Years from RandomizationPercent SurvivalAge=6566-7071+P=0.25 Survival by PS0123020406080100Years from RandomizationPercent SurvivalPS=0PS=1PS=2,3P0.0001
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