4-PREGNEN-17-OL-3, 20-DIONE-3CARBOXYMETHYLOXIME:HISTAMINE from Steraloids. For over 60 years, we"ve supplied the finest research institutions, pharmaceutical companies, and law enforcement agencies with over 2,700 different androgens, estrogens, cholestins, progestins, bileacids, hormones, and metabolites synthesized to purified standards for purposes of research.
ebiomall.com
>
>
>
>
>
>
>
>
>
>
【认领须知】
1、认领翻译的战友请跟帖注明“认领本文翻译，48小时内未完成，请其他战友认领！”
2、请根据自己专业背景选择认领，如使用翻译软件翻译，被发现者扣分1-2分
3、经常认领而不能及时提供优质稿件者将被列入黑名单，取消认领资格，请大家注意！
4、翻译时请参照版规：点击查看
5、在首位认领战友未超过规定时间的其他任何认领属违规认领，将不会给予丁当或加分！
6、翻译完成后加分（或丁当）的时限为三日，请耐心等待，若超过时限未加者可进行申诉：点击进入
7、本文题目仅供译者参考，篇幅较长者可申请适当延时
8、翻译前请查一下有无重复帖
9、为保证翻译质量，每人每天最多只能认领两篇
原文链接：http://www.ascopost.com/News/40561
AdditionofIxazomibtoLenalidomide/DexamethasoneImprovesProgression-FreeSurvivalinRelapsed/RefractoryMultipleMyeloma
Moreauetalfoundthataddingtheoralproteasomeinhibitorixazomib(Ninlaro)tolenalidomide(Revlimid)anddexamethasonesignificantlyprolongedprogression-freesurvivalamongpatientswithrelapsed,refractory,orrelapsedandrefractorymultiplemyeloma.TheyreportedthefindingsfromthephaseIIITOURMALINE-MM1trialinTheNewEnglandJournalofMedicine.ThetrialsupportedtherecentU.S.FoodandDrugAdmiNISTration(FDA)approvalofixazomibinpreviouslytreatedmultiplemyeloma,makingitthefirstapprovedoralproteasomeinhibitor.
StudyDetails
Inthedouble-blindtrial,722patientsfrom147sitesin26countrieswererandomizedbetweenAugust2012andMay272014toreceiveixazomib(n=360)orplacebo(n=362)pluslenalidomideanddexamethasone.Treatmentconsistedof28-daycyclesoforalixazomibat4mgorplaceboondays1,8,and15;orallenalidomideat25mgondays1through21(10mginthosewithcreatinineclearance≤60or≤50mL/min/1.73m2accordingtolocalprescribinginformation);andoraldexamethasoneat40mgondays1,8,15,and22.Theprimaryendpointwasprogression-freesurvival.
Fortheixazomibvsplacebogroups,medianagewas66yearsinboth(53%vs51%>65years);58%vs56%weremale;86%vs83%werewhite;EasternCooperativeOncologyGroupperformancestatuswas0or1in95%vs93%;InternationalStagingSystem(ISS)stagewasIin63%vs64%,IIin25%vs24%,andIIIin12%inboth;78%vs72%hadcreatinineclearance≥60mL/min/1.73m2;55%vs60%hadstandard-and21%vs17%hadhigh-riskcytogenetics;numberofpriortherapieswas1in62%vs60%,2in27%vs31%,and3in11%vs9%;59%vs55%hadpriorstemcelltransplantation;diseasecategorywasrelapsedin77%inboth,refractoryin12%vs11%,relapsedandrefractoryin11%vs12%,andprimaryrefractoryin7%vs6%;priorproteasomeinhibitortherapywasbortezomib(Velcade)in69%inbothandcarfilzomib(Kyprolis)in<1%vs1%,with1%vs2%ofpatientshavingdiseaserefractorytopriortreatment;andpriorimmunomodulatorytherapywaslenalidomidein54%vs56%andthalidomide(Thalomid)in44%vs47%,with21%vs25%havingdiseaserefractorytopriortherapy.
ImprovedProgression-FreeSurvival
Aftermedianfollow-upof14.7months,medianprogression-freesurvivalwas20.6monthsintheixazomibgroupvs14.7monthsintheplacebogroup(hazardratio[HR]=0.74,P=.01).Benefitofixazomibwasconsistentacrossprespecifiedsubgroups,includingpoor-prognosissubgroupssuchasthosewithhigh-riskcytogenetics(24.1vs9.7months,HR=0.54),ISSstageIIIdisease(18.4vs10.1months,HR=0.72),thoseaged>75years(18.5vs13.1months,HR=0.87),andthosewhohadreceivedtwo(17.5vs14.1months,HR=0.75)orthree(notestimablevs10.2months,HR=0.37)priortherapies.
Overallresponserateswere78%vs72%,withtheratesofcompleteresponseplusverygoodpartialresponseof48%vs39%.Mediantimetoresponsewas1.1vs1.9months.Mediandurationofresponsewas20.5vs15.0months.Atmedianfollow-upofapproximately23months,medianoverallsurvivalhadnotbeenreachedineithergroup.
AdverseEvents
Adverseeventsof≥grade3occurredin74%oftheixazomibgroupvs69%oftheplacebogroup,withthemostcommonintheixazomibgroupbeingneutropenia(23%vs24%)andthrombocytopenia(19%vs9%).Rashofanygradewasmorecommonintheixazomibgroup(36%vs23%),asweregastrointestinaladverseevents(mostlylowgrade);22%ofixazomibpatientsand19%ofplacebopatientsreceivedantidiarrhealagents,and21%and13%receivedantiemeticdrugs.Peripheralneuropathyofanygradeoccurredin27%vs22%(grade3in2%ineach).
Seriousadverseeventsoccurredin47%vs49%.Adverseeventsledtodosereductionofanydrugin56%vs50%,discontinuationofanydrugin25%vs20%,anddiscontinuationofthestudyregimenin17%vs14%.Deathoccurredduringthestudyperiodin4%vs6%.
Theinvestigatorsconcluded:“Theadditionofixazomibtoaregimenoflenalidomideanddexamethasonewasassociatedwithsignificantlylongerprogression-freesurvival;theadditionaltoxiceffectswiththisall-oralregimenwerelimited.”
【认领须知】
1、认领翻译的战友请跟帖注明“认领本文翻译，48小时内未完成，请其他战友认领！”
2、请根据自己专业背景选择认领，如使用翻译软件翻译，被发现者扣分1-2分
3、经常认领而不能及时提供优质稿件者将被列入黑名单，取消认领资格，请大家注意！
4、翻译时请参照版规：点击查看互
5、在首位认领战友未超过规定时间的其他任何认领属违规认领，将不会给予丁当或加分！
6、翻译完成后加分（或丁当）的时限为三日，请耐心等待，若超过时限未加者可进行申诉：点击进入
7、本文题目仅供译者参考，篇幅较长者可申请适当延时
8、翻译前请查一下有无重复帖
9、为保证翻译质量，每人每天最多只能认领两篇
10、链接：http://www.ascopost.com/News/57763
ICML2017:PhaseIIIbMAGNIFYStudyofLenalidomideandRituximabCombinationinRelapsed/RefractoryFollicularandMarginalZoneLymphoma
AninterimanalysisofMAGNIFY,aphaseIIIb,randomized,open-label,multicenterstudyoftheR2combinationregimen(lenalidomide[Revlimid]plusrituximab[Rituxan])inpatientswithrelapsedorrefractorymarginalzonelymphoma,waspresentedattheInternationalConferenceonMalignantLymphoma(ICML)inLugano,Switzerland.ThisanalysisexpandedupondatapresentedearlierinthemonthattheASCOAnnualMeeting(Abstract7502).
TheMAGNIFYstudycontinuestoevaluatetheclinicalactivityof12cyclesofR2combinationtherapyfollowedbyrandomizationtoeither18cyclesofR2maintenanceor18cyclesofrituximabmonotherapy,inpatientswithrelapsedorrefractoryfollicularlymphoma,marginalzonelymphoma,ormantlecelllymphoma.Approximately500patientsareplannedtobeenrolledinthestudy.
Theprimaryendpointisprogression-freesurvival.Secondaryendpointsincludeoverallsurvival,overallresponserate,completeresponse,improvementofresponse,durationofresponse,durationofcompleteresponse,timetonextlymphomatreatment,timetohistologictransformation,safety,andexploratoryquality-of-lifemeasures.EnrollmentintheMAGNIFYstudyisongoing.
ASCOData
AttheASCOAnnualMeeting,interimdatawerepresentedfromananalysisofasubsetofpatientsfromtheMAGNIFYstudywithrelapsedorrefractoryfollicularlymphoma(n=160)withearly-relapse(n=52)anddouble-refractory(n=50)disease.
AttheJanuary9,2017,datacutoff,the1-yearprogression-freesurvivalforallfollicularlymphomapatientswas70%,with65%fordouble-refractorypatientsand49%forearly-relapsepatients.Additionally,evaluablefollicularlymphomapatients(n=128)hadanoverallresponserateof66%withacompleteresponse/completeresponse–unconfirmedrateof38%.Fordouble-refractorypatients(n=42),overallresponseratewas45%withacompleteresponse/completeresponse–unconfirmedrateof21%andforearly-relapsepatients(n=43),overallresponseratewas47%withacompleteresponse/completeresponse–unconfirmedrateof21%.Mediandurationofresponsewasnotmetatamedianfollow-upof10.2months.
Themostcommongrade3or4adverseeventsobservedinthestudyforallfollicularlymphoma,double-refractory,andearly-relapsepatients,respectively,wereneutropenia(29%,42%,37%),fatigue(6%,4%,8%),leukopenia(5%,8%,10%),thrombocytopenia(4%,8%,4%),andlymphopenia(3%,6%,4%).
ICMLData
DatapresentedatICMLinaseparateanalysisfocusedonpatientswithmarginalzonelymphoma(n=38),includingnodalmarginalzonelymphoma(n=18),splenicmarginalzonelymphoma(n=10),andmucosa-associatedlymphoidtissuelymphoma(n=10).
Atamedianfollow-upof13.8monthsfrominitiationoftherapywiththeR2combination,evaluablepatientswithmarginalzonelymphoma(n=32)achievedanoverallresponserateof66%withacompleteresponse/completeresponse–unconfirmedrateof44%.Evaluablenodalmarginalzonelymphomapatients(n=14)hadanoverallresponserateof57%withacompleteresponse/completeresponse–unconfirmedrateof57%.Evaluablesplenicmarginalzonelymphomapatients(n=8)hadanoverallresponserateof63%withacompleteresponserateof25%;andevaluablemucosa-associatedlymphoidtissuelymphomapatients(n=10)hadanoverallresponserateof80%withacompleteresponse/completeresponse–unconfirmedrateof40%.Mediandurationofresponsewasnotreachedforanygroup.
Themostcommongrade3or4adverseeventsobservedinpatientswithmarginalzonelymphomawereneutropenia(32%),thrombocytopenia(16%),andleukopenia(11%).
“Thechemotherapy-freecombinationoflenalidomideandrituximab,withcomplementarymechanismsofactionthatarethoughttoenhanceantibodydependentcellularcytotoxicity,continuestoshowencouragingactivityandatolerablesafetyprofileinindolentlymphomas,andparticularlyindifficult-to-treatpatientsubsets,”saidDavidJ.Andorsky,MD,co–principalinvestigatorofthestudyandmedicaloncologistattheRockyMountainCancerCentersinBoulder,Colorado.“Theseresultsinpatientswhohadfailedmultipletherapiesorrelapsedearly,aswellastheactivityinmarginalzonepatientsmeritfurtherstudyinthisareaofindolentlymphoma.”
AboutMAGNIFY
MAGNIFYisaphaseIIIb,multicenter,open-labelstudyofpatientswithgrades1–3bortransformedfollicularlymphoma,marginalzonelymphoma,ormantlecelllymphomawhoreceivedatleast1priortherapyandhadstageI–IV,measurabledisease.Approximately500patientsareplannedforenrollmentin12cyclesofR2induction,withaprojected314patientswithatleaststablediseaseafterinductionrandomized(1:1)to2maintenancearms.
Inductionincludesorallenalidomideat20mg/d,days1–21per28-daycycle(d1–21/28)plusintravenousrituximabat375mg/m2,days1,8,15,and22ofcycle1andday1ofcycles3,5,7,9,and11(28-daycycles).Patientsarethenrandomizedtomaintenancelenalidomideat10mg/d,days1to21/28,cycles13to30,plusrituximabat375mg/m2,day1ofcycles13,15,17,19,21,23,25,27,and29(R2,armA),orrituximabalone(sameschedule,armB).PatientsreceivingR2maintenanceafter18cyclesmaycontinuemaintenancelenalidomidemonotherapyat10mg/d,days1–21/28(perpatientand/orinvestigatordiscretion),untildiseaseprogressionastolerated.Patientswillbefollowedfor≥5yearsafterthelastpatientinitiatesinductiontherapy.
【认领须知】
1、认领翻译的战友请跟帖注明“认领本文翻译，48小时内未完成，请其他战友认领！”
2、请根据自己专业背景选择认领，如使用翻译软件翻译，被发现者扣分1-2分
3、经常认领而不能及时提供优质稿件者将被列入黑名单，取消认领资格，请大家注意！
4、翻译时请参照版规：点击查看
5、在首位认领战友未超过规定时间的其他任何认领属违规认领，将不会给予丁当或加分！
6、翻译完成后加分（或丁当）的时限为三日，请耐心等待，若超过时限未加者可进行申诉：点击进入
7、本文题目仅供译者参考，篇幅较长者可申请适当延时
8、翻译前请查一下有无重复帖
9、为保证翻译质量，每人每天最多只能认领两篇
10、链接:http://www.ascopost.com/News/48387
FDAApprovesLenalidomideasMaintenanceTherapyforPatientsWithMultipleMyelomaFollowingAutologousStemCellTransplant
OnFebruary22,theU.S.FoodandDrugAdmiNISTration(FDA)expandedtheexistingindicationforlenalidomide(Revlimid)10mgcapsulestoincludeuseforpatientswithmultiplemyelomaasmaintenancetherapyfollowingautologoushematopoieticstemcelltransplant.TheexpandedindicationmakeslenalidomidethefirstandonlytreatmenttoreceiveFDAapprovalformaintenanceusefollowingautologoushematopoieticstemcelltransplant.
“Autologousstemcelltransplantafterinductiontherapyispartofthecontinuumofcarefortransplant-eligIBLe[patientswith]multiplemyeloma.However,mostpatientswillstillseetheirdiseaserecurorprogressafterthistreatment,”saidPhilipMcCarthy,MD,Director,BloodandMarrowTransplantCenter,DepartmentofMedicineatRoswellParkCancerInstitute.“Lenalidomidemaintenancetherapy,whichhasbeenshowntoincreaseprogression-freesurvivalfollowingautologousstemcelltransplantinclinicaltrials,canbeconsideredastandardofcareforthesepatients.”
ClinicalTrialFindings
Theapprovalwasbasedontwolargestudies—CALGB100104andIFM2005-02—includingmorethan1,000patientscomparinglenalidomidemaintenancetherapygivenuntildiseaseprogressionorunacceptabletoxicityafterautologoushematopoieticstemcelltransplantvsnomaintenance.Inbothstudies,theprimaryefficacyendpointwasprogression-freesurvival.
Inthemostcurrentprogression-freesurvivalanalysis,Study1(CALGB100104)demonstratedamedianprogression-freesurvivalof5.7years(95%confidenceinterval[CI]=4.4–notestimable)vs1.9years(95%CI=1.6–2.5)fornomaintenance,adifferenceof3.8years(hazardratio[HR]=0.38;95%CI=0.28–0.50).
Study2(IFM2005-02)alsoshowedabenefitwithamedianprogression-freesurvivalof3.9years(95%CI=3.3–4.7)vs2years(95%CI=1.8–2.3)fornomaintenance,adifferenceof1.9years(HR=0.53;95%CI=0.44–0.64).
Individualstudieswerenotpoweredforanoverallsurvivalendpoint.
AdescriptiveanalysisshowedthemedianoverallsurvivalinStudy1was9.3years(95%CI=8.5–notestimable)forpatientswhoreceivedlenalidomidevs7years(95%CI=5.9–8.6)fornomaintenance(HR=0.59;95%CI=0.4–0.78).InStudy2,medianoverallsurvivalwas8.8years(95%CI=7.4–notestimable)forpatientswhoreceivedlenalidomidevs7.3years(95%CI=6.7–9.0)fornomaintenance(HR=0.90;95%CI=0.72–1.13).
AdverseEvents
Themostfrequentlyreportedadversereactionsin≥20%(lenalidomidearm)acrossbothmaintenancestudies(Study1,Study2respectively)wereneutropenia(79%,61%);thrombocytopenia(72%,24%);leukopenia(23%,32%);anemia(21%,9%);upperrespiratorytractinfection(27%,11%);bronchitis(5%,47%);nasopharyngitis(2%,35%);cough(10%,27%);gastroenteritis(0%,23%);diarrhea(55%,39%);rash(32%,8%);fatigue(23%,11%);asthenia(0%,30%);musclespasm(0%,33%);andpyrexia(8%,21%).ThemostfrequentlyreportedGrade3or4reactions(morethan20%inthelenalidomidearm)includedneutropenia,thrombocytopenia,andleukopenia.
Thefrequenciesofonsetofadversereactionsweregenerallyhighestinthefirst6monthsoftreatmentandthenthefrequenciesdecreasedovertimeorremainedstablethroughouttreatment.
Inpatientsreceivinglenalidomidemaintenancetherapy,hematologicsecondprimarymalignanciesoccurredin7.5%ofpatientscomparedto3.3%inpatientsreceivingplacebo.Theincidenceofhematologicplussolidtumor(excludingsquamouscellcarcinomaandbasalcellcarcinoma)secondprimarymalignancieswas14.9%,comparedto8.8%inpatientsreceivingplacebowithamedianfollow-upof91.5months.Nonmelanomaskincancersecondprimarymalignancies,includingsquamouscellcarcinomaandbasalcellcarcinoma,occurredin3.9%ofpatientsreceivinglenalidomidemaintenance,comparedto2.6%intheplaceboarm.
名称：氨氧基乙酸盐;羧甲氧基胺半盐酸盐；
分子式：C2H5NO3·0.5HCl
分子质量：109.30
熔点：156℃
