直肠癌辅助治疗新进展

直肠癌辅助治疗新进展李玉升直肠癌的存活与分期直肠癌VS结肠癌:存活相似YearNo5YOS(%)RectalCancer5YOS(%)ColonCancerP-Value199023643.8(34.9,54.9)53.7(46.0,62.7)0.0969StageII8355.2(39.7,76.6)63.6(51.8,78.2)0.3954StageIII15338.8(28.7,52.4)47.7(38.2,59.5)0.20881995-9656359.3(53.1,66.3)61.7(56.7,67.2)0.5607StageII23368(58.3,79.2)72.3(65.3,80)0.4675StageIII33054.4(46.6,63.4)53.5(46.8,61.2)0.86542001-02105263.7(58.5,69.4)66.2(62.4,70.1)0.4543StageII43070.6(63.1,78.9)77.1(71.9,82.7)0.158StageIII62258.4(51.4,66.4)59.1(54.2,64.4)0.8818UFT辅助化疗改善III期直肠癌存活

日本NSCS-CC7试验ASCO2007Abstr4049Outcomeofpreoperativechemotherapy(POC)inlocallyadvancedrectalcancer(LARC):Meta-

analysisofrandomizedclinicaltrials(RCT).

Surrogateendpointsinneoadjuvantrectalcancertrials:StatisticalevaluationusingdatafromtheFFCD9203trial

Lymphnodeharvestand

survivalinrectalcancer.mOS(Years)

SurgOnlyPreopXRT,SurgeSurgery,PostopTx------------------------------------------------------------------------------------NodesIIIIIIIIIIIIIIIIII-------------------------------------------------------------------------------05.91.45.13.94.43.31-117.63.61.87.75.43.46.06.14.9>129.34.82.16.37.23.16.18.44.9P<.001<.001.08.02.005.49.04<.001.78-----------------------------------------------------------------------------8580例I-III期直肠癌，28%患者检测≥12个淋巴结，

14%患者未检测淋巴结。淋巴结检测数目与存活显著相关。PhaseIIstudyofpreoperativeoxaliplatin,capecitabineandexternalbeamradiotherapyinpatientswithrectalcancer:theRadiOxCapestudy；3.

奥沙利铂联合卡培他滨

同期化放疗pCR高。

RTOG0247研究（1）146例T3T4直肠癌，中位年龄57岁，88%T3病变。1组：放疗50.4GY同步卡培他滨1200mg/m2/d周1-周5，CPT-1150mg/m2weeklyX4;2组：放疗50.4GY同步卡培他滨1650mg/m2/d周1-周5，奥沙利铂

50mg/m2weeklyX53.

奥沙利铂联合卡培他滨同期化放疗pCR高。

RTOG0247研究（2）A组B组------------------------------------------------------------------------------------肿瘤降期56%58%淋巴结降期36%33%pCR10%24%¾度血液学毒性

8%4%¾度非血液学毒性

24%29%----------------------------------------------------伊立替康联合LV5-FU2：直肠癌辅助化疗

FrenchIntergroupR98trial4.结肠癌辅助化疗的提示（1）：

延迟辅助化疗导致生存益处下降4.结肠癌辅助化疗的提示（2）：

提前中断辅助化疗导致生存率下降ResultsofpostoperativechemotherapyfollowingneoadjuvantchemoradiotherapyinptaientswithypN0tumors.

肠系膜癌结节与III期结直肠癌的预后西妥昔单抗用于直肠癌辅助治疗：Predictionofpathologicalresponse

topreoperativechemoradiotherapy

withcetuximabinrectalcancerKhambata-Ford,S.etal.JClinOncol;25:3230-32372007CetuximabandK-rasmodulatesignalingthroughtheepidermalgrowthfactorreceptor(EGFR)pathwayK-ras有助于调节细胞存活，增殖和分化，胰腺癌患者K-ras突变率高达95%，NSCLC和CRC>30%。同VEGFR家族一样，K-ras参与MAPK增殖的信号通路。PA.3significantimprovementinoverallsurvivalinpatientswithmetastaticdisease*1.000.750.500.250

0 6 12 18 24 30 36Time(months)TarcevaSummaryofProductCharacteristicsSurvivalprobabilityHR=0.80,p=0.029(95%CI:0.66–0.98)*100mgcohortLedtoEUapprovalforthetreatmentofmetastaticpancreaticcancer1-year

survivalGemcitabine+Tarceva21%Gemcitabine+placebo15%ComparisonofPA.3andAVITA

(10thWCGC2008;Barcelona,Spain.)PA.3*PA.3*AVITAAVITAGEMGEM+

Tarceva

GEM+

Tarceva+

AvastinMedianoverallsurvival(months)5.065.936.07.1Diseasecontrolrate(%)43.856.053.862.71-yearsurvival(%)15212026*Metastaticpopulation,100mgcohortMooreM,etal.AnnOncol2007;18(Suppl.7):vii14(Abs.O-0010);Roche,dataonfile;

VervenneW,VanCutsemE,etal.JClinOncol2008;26(Suppl.15PtI):214s(Abs.4507)K-ras突变可通过上调VEGF来调节血管生成，VEGF表达与K-ras密切相关