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1、OriginalArticleDurableResponsesWiththeMetronomicRituximabandThalidomidePlusPrednisone,Etoposide,Procarbazine,andCyclophosphamideRegimeninElderlyPatientsWithRecurrentMantleCellLymphoma11112JiaRuan,MD,PhD;PeterMartin,MD;MortonColeman,MD;RichardR.Furman,MD;KenCheung,PhD;11
2、341AdamFaye,BA;RebeccaElstrom,MD;MarkLachs,MD;KatherineA.Hajjar,MD;andJohnP.Leonard,MDBACKGROUND:Targetingthetumormicroenvironmentandangiogenesisisanovellymphomatherapeuticstrategy.Theauthorsreportsafety,activity,andangiogenicprofilingresultswiththerituximabandthalidomi
3、depluspredni-sone,etoposide,procarbazine,andcyclophosphamide(RT-PEPC)regimeninpatientswithrecurrentmantlecelllym-phoma(MCL).METHODS:RT-PEPCincludedinduction(Months1-3)ofrituximab4timesweekly,dailythalidomide(50mg),andPEPCfollowedbymaintenancethalidomide(100mg),oralPEPCt
4、itratedtotheneutrophilcount,andrituximabevery4months.Endpointsincludedsafety,efficacy,qualityoflife(QoL),andtranslationalstudies,includ-ingtumorangiogenicphenotyping,plasmavascularendothelialgrowthfactor(VEGF),andcirculatingendothelialcells.RESULTS:Twenty-fivepatientswe
5、reenrolled,and22wereevaluable.Themedianagewas68years(range,52-81years),24patients(96%)hadstageIIIorIVdisease,18patients(72%)hadanInternationalPrognosticIndex(IPI)scoreof3to5,and20patients(80%)hadhigh-riskMantleCellInternationalPrognosticIndex(MIPI)scores.Patientshadrece
6、ivedamedianof2previoustherapies(range,1-7previoustherapies),and15patients(60%)hadprogressedonbortezomib.Atamedianfollow-upof38months,theoverallresponseratewas73%(completeresponse[CR]/unconfirmedCRrate,32%;partialresponse[PR]rate,41%;n¼22patients),andthemedianprogres-sio
7、n-freesurvivalwas10months.FourCRswereongoing(6months,31months,48months,and50months).Toxicitiesincludedgrade1and2fatigue,rash,neuropathy,andcytopenias,includinggrade1and2thrombocytopenia(64%)andgrade3and4neutropenia(64%).Twothrombosesand5episodesofgrade3or4infections
8、occurred.QoLwasmaintainedorimproved.Correlativestudiesdemonstratedtumorautocrineangiogenicloop(expressionofVEG
