大腸癌NCCN指南解讀-李進(jìn)-CSCO

大腸癌NCCN指南解讀復(fù)旦大學(xué)腫瘤醫(yī)院腫瘤內(nèi)科李進(jìn)結(jié)腸癌治療的焦點(diǎn)正確分期的重要性淋巴結(jié)轉(zhuǎn)移是III期的

重要標(biāo)志!III期需要輔助化療!病人診斷數(shù)（％）5年生存（％）IIIIIIIV15%20-30%30-40%20-25%85-95%60-80%30-60%5%LeVoyerTEetal.JClinOncol2003;21:2912–29191009080706050403020100生存百分比01224364860728496108120>20個(gè)送檢淋巴結(jié)11?20送檢淋巴結(jié)1?10

送檢淋巴結(jié)87%80%73%79%73%59%如果<10個(gè)送檢淋巴結(jié)，則診斷效力降低II期病人送檢淋巴結(jié)數(shù)目與生存的關(guān)系（INT-089的再分析）對(duì)于真正的無淋巴結(jié)轉(zhuǎn)移的II期患者需不需要做化療?MOSAIC

2005ASCO的4年DFS結(jié)果deGramontetal,ASCO2005,Abstract35010020406080100無疾病生存(%)

HR[95%CI]:

0.77[0.65–0.90]6.6%FOLFOX4279/1123(24.8%)LV5FU2345/1123(30.7%)月612182430364248546066p<0.001

Datacutoff:16Jan.20054年無疾病生存

(2005ASCO)

II期與III期病人deGramontetal.ASCO2005;Abstract3501Datacut-off:16January2005月HR(95%CI):0.82(0.60–1.13)StageII 0.75(0.62–0.89)StageIII1.00.90.80.70.60.50.30.40.20.10.00FOLFOX4:LV5FU2:6661218243036424854604-yr:8.6%4-yr:3.5%3-yr:7.2%672StageIII675StageIII451StageII448StageIIFOLFOX4:LV5FU2:無疾病生存II期患者較少?gòu)妮o助治療中受益，但是我們應(yīng)該識(shí)別高危的II期病人。高危的II期病人指至少含以下一項(xiàng)

HickishTetal.ESMO2004;Abstract284P最佳輔助化療方案FOLFOXXELOXLV/5-Fu卡培他濱對(duì)于輔助化療，目前沒有任何證據(jù)顯示可以聯(lián)合任何分子靶向藥物。姑息化療如何體現(xiàn)個(gè)體化?無進(jìn)展生存期分析Progression-freesurvivaltime(months)PFSestimate1.00.80.90.00.10.20.30.40.50.60.702468101214161820HR=0.851;95%CI=[0.726-0.998]Stratifiedlog-rankp-value=0.04798.9mo8.0moFOLFIRI,n=599Cetuximab+FOLFIRI,n=5991-yearPFSrate23%vs34%SubjectsatriskFOLFIRIalone599492402293178833516741Cetuximab+FOLFIRI59949939229819610358291251

2007.ASCOannualmeeting.AbstractNo.4000總生存的分層分析(wK-ras)有七個(gè)月的差距！貝伐單抗的III期研究IFL推注5-FU500mg/m2

亞葉酸鈣20mg/m2

依立替康125mg/m2

用藥4/6周疾病進(jìn)展后不接受貝伐單抗治療HurwitzH,etal.NEnglJMed2004;350:2335–425-FU/LV推注5-FU500mg/m2

亞葉酸鈣

500mg/m2

用藥6/8周貝伐單抗5mg/kg每2周1次先前未曾治療的轉(zhuǎn)移性CRCPDPDPD推注IFL+安慰劑

（n=412）推注IFL+貝伐單抗（n=403）5-FU/LV+貝伐單抗

（n=110）疾病進(jìn)展后可接受貝伐單抗治療疾病進(jìn)展后可接受貝伐單抗治療無進(jìn)展生存0.2010203000.81.00.40.6Progression-freesurvival(mo)Proportionprogression-freeTreatmentGroupIFL+placeboIFL+bevacizumabHurwitzetal.ProcAmSocClinOncol.2003;22.Abstract3646andoralpresentation.AvastinPI.HR=0.54,P<0.00001mPFS:6.210.6mo總生存HR=0.66,P=0.00004中位生存:15.6vs20.3moDurationofsurvival(mo)Proportionsurviving0.220010304000.81.00.40.6治療組IFL+安慰劑IFL+貝伐Hurwitzetal.ProcAmSocClinOncol.2003;22.Abstract3646andoralpresentation.AvastinPI.單抗應(yīng)用的要點(diǎn)參見：NCCN中文版2009COL-C6-1如何選擇一線姑息化療?如何提高患者生活質(zhì)量?DeGramontetal.,ASCO20046xFOLFOX7-12xsLV5FU2-6xFOLFOX7FOLFOX4623pts

R總劑量Oxali7801560

FOLFOX4

FOLFOX7RR(%) 58.5 58.3PFS 9.0 9.2OS 20.0 21.6G3/4神經(jīng)毒 18.7 13.3OPTIMOX-1/OPTIMOX-2OPTIMOX-1OPTIMOX-2P值ORR60%59%NS2ndORR21%25%NS奧沙利鉑再應(yīng)用52%60%NSPFS(周)36290.08OS(月)24.618.90.05生存概率治療診斷后年數(shù)StanglRetal.Lancet1994;343:1405-10入組病人:晚期或復(fù)發(fā)RFOLFIRICPT-11180mg/m2d1LV 100mg/m2d1,25-FU 400mg/m2靜注d1,25-FU 600mg/m222hd1,2FOLFOXIRICPT-11165mg/m2Oxali 85mg/m2LV 200mg/m25-FU3200mg/m248hFalconeetal.,ASCO2007結(jié)果FOLFIRI

N=122FOLFOXIRI

N=122P-valueRR*(%)3460<0.0001CR+PR+SD*(%)6881R0切除(%)

(所有病人)6150.033R0切除(%)(肝臟)12360.017PFS(月)6.99.80.0006OS(月)16.7?23.60.042*獨(dú)立評(píng)價(jià);?67%2線FOLFOXFalconeetal.,ASCO2007TheLancet

2008;

371:1007-1016

研究方案隨機(jī)分組FOLFOX4FOLFOX46周期(3月)病例數(shù)=364病人6周期(3月)結(jié)果接受化療接受手術(shù)%3-年P(guān)FS絕對(duì)差異Hazard

Ratio(ConfidenceInterval)P-value所有患者182182+7.3%

(28.1%to35.4%)0.79

(0.62-1.02)P=0.058符合條件患者171171+8.1%

(28.1%to36.2%)0.77

(0.60-1.00)P=0.041切除患者151152+9.2%

(33.2%to42.4%)0.73