第三期臨床試驗表明TAS-102能提高全面提高結(jié)腸癌患者的存活率這些患者的結(jié)腸癌已經(jīng)轉(zhuǎn)移用普通治療方法難以治療

TAS-102是一種新型的抗癌的核苷類藥物它含有三氟胸苷（trifluridine,FTD）和地匹福林鹽酸鹽tipiracilhydrochloride,TPI其中三氟胸苷是TAS-102的活性組成部分能夠直接和癌癥的DNA互相作用使得DNA不能正常行使功能但是三氟胸苷口服會被大量降解為非活性狀態(tài)地匹福林鹽酸鹽則防止了它的降解TAS-102的作用機理與氟嘧啶奧沙利鉑和依立替康都不同在二期臨床試驗中結(jié)果表明TAS-102對于以上三種藥物都不能有效治療的結(jié)腸癌患者有著不同的療效

這項研究結(jié)果可能會給轉(zhuǎn)移性結(jié)腸癌患者帶來希望并且可能會被用于結(jié)腸癌患者的早期治療治療可能會配合奧沙利鉑或依立替康同時使用該研究表明TAS-102的前景十分光明

詳細英文報道

henewcombinationagentTAS-102isabletoimproveoverallsurvivalcomparedtoplaceboinpatientswhosemetastaticcolorectalcancerisrefractorytostandardtherapies,researcherssaidattheESMO16thWorldCongressonGastrointestinalCancerinBarcelona.

"Around50%ofpatientswithcolorectalcancerdevelopmetastasesbuteventuallymanyofthemdonotrespondtostandardtherapies,"saidTakayukiYoshinooftheNationalCancerCentreHospitalEastinChiba,Japan,leadauthorofthephaseIIIRECOURSEtrial."TheRECOURSEstudyshowsthatTAS-102improvesoverallsurvivalinthesepatientscomparedtoplacebo.IbelievethatthisagentwillbecomeoneofthestandardsofcareintherefractorysettingofmetastaticcolorectalcancerinJapanandworldwide."

TAS-102isanovelnucleosideanti-tumouragentconsistingoftrifluridineFTDandtipiracilhydrochlorideTPI.FTDistheactivecomponentofTAS-102andisdirectlyincorporatedintocancerDNA,leadingtoDNAdysfunction.However,whenFTDistakenorallyitislargelydegradedtoaninactiveform.TPIpreventsthedegradationofFTD.Thismechanismofactionisdifferenttothatoffluoropyrimidine,oxaliplatinandirinotecan.

ThephaseIItrialofTAS-102hadfoundanoverallsurvivalbenefitinJapanesepatientswithmetastaticcolorectalcancerrefractorytofluoropyrimidine5-fluorouracil5-FU,irinotecanandoxaliplatin.[1]

ThecurrentRECOURSEstudywasaglobalphaseIIItrialconductedin13countriesat114centres.Patientshadmetastaticcolorectalcancerrefractorytoallstandardtherapiesincludingfluoropyrimidines,oxaliplatin,irinotecan,bevacizumab,andcetuximaborpanitumumabforpatientswithwild-typeKRAStumours.Patientswererandomised2:1toTAS-102534patientsorplacebo266patients.Theprimaryendpointwasoverallsurvival.

TheresearchersfoundthatTAS-102prolongedoverallsurvivalcomparedtoplacebohazardratio0.68:medianoverallsurvivalwas7.1monthsforTAS-102and5.3monthsforplacebo.TAS-102alsoimprovedprogression-freesurvivalcomparedtoplacebohazardratio0.48,whichwasasecondaryendpoint.Yoshinosaid:"Wefoundastatisticallysignificantdifferenceinoverallandprogression-freesurvival,andaclinicallymeaningfulimprovement."

"TAS-102hasamildsafetyprofileandthemostcommonside-effectishematologictoxicityincludingneutropenia.Patientswithmetastaticcolorectalcancerrefractorytostandardtherapiesnowhaveastrongtreatmentoption."

Commentingonthedata,ESMOspokespersonJeanYvesDouillard,professorofmedicaloncology,InstitutdeCancérologiedel’OuestICORenéGauducheau,Saint-Herblain,France,said:"ThephaseIIItrialofTAS-102isaglobalstudyandconfirmstheresultsofthephaseIIstudyinJapanesepatients,whoseresponsetofluoropyrimidineisslightlydifferenttopatientsinEuropeandtheUS.ItisgoodtoknowthatthemagnitudeofbenefitshowninthesmallerphaseIItrialisconfirmedinthelargerphaseIIItrialandthattheresultsapplytoAsiansandCaucasi

ansalike."

TAS-102isacombinationoftwocomponents.ThetipiracilhydrochlorideTPIpreventsdegradationoftrifluridineFTDandalsohasangiogenicactivity."ThisisprobablywhyTAS-102iseffectiveinclassicalfluoropyrimidine5-fluorouracil5-FUresistantpatients.Thedrugisverypromising,toleranceisgoodanditismanageablewithsupportivecare."

Douillardconcluded:"InRECOURSE,TAS-102wastestedinpatientswhohadreceivedalltypesofchemotherapyavailableforcolorectalcancer.IwouldprobablymovethisdrugintoanearlierlineoftreatmentandIwouldalsocombineitwitheitheririnotecanoroxaliplatin."