2023
Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma
Fanucci K, Pilat M, Shyr D, Shyr Y, Boerner S, Li J, Durecki D, Drappatz J, Puduvalli V, Lieberman F, Gonzalez J, Giglio P, Ivy S, Bindra R, Omuro A, LoRusso P. Multicenter Phase 2 Trial of the PARP Inhibitor Olaparib in Recurrent IDH1 and IDH2-Mutant Glioma. Cancer Research Communications 2023, 3: 192-201. PMID: 36968138, PMCID: PMC10035510, DOI: 10.1158/2767-9764.crc-22-0436.Peer-Reviewed Original ResearchConceptsProgression-free survivalMedian progression-free survivalProlonged stable diseaseStable diseasePhase II trialGrade 4 tumorsII trialOlaparib monotherapyGrade 2Multicenter phase 2 trialSingle-arm phase II trialWorld Health Organization classificationMedian overall survivalNeuro-Oncology criteriaPhase 2 trialOverall response rateFuture patient stratificationMutant gliomasPARP inhibitor olaparibEvaluable patientsPrimary endpointOverall survivalProgressive diseaseSelect patientsClinical benefit
2022
Phase I/randomized phase II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma: North Central Cancer Treatment Group N1174 (Alliance)
Galanis E, Anderson SK, Twohy E, Butowski NA, Hormigo A, Schiff D, Omuro A, Jaeckle KA, Kumar S, Kaufmann TJ, Geyer S, Kumthekar PU, Campian J, Giannini C, Buckner JC, Wen PY. Phase I/randomized phase II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma: North Central Cancer Treatment Group N1174 (Alliance). Neuro-Oncology Advances 2022, 4: vdac041. PMID: 35664553, PMCID: PMC9154335, DOI: 10.1093/noajnl/vdac041.Peer-Reviewed Original ResearchProgression-free survivalRandomized phase II trialPhase II trialBevacizumab monotherapyRecurrent glioblastomaII trialTreatment armsMedian progression-free survivalLimited effective treatment optionsPhase IQuestionable survival benefitEarly clinical dataEffective treatment optionPhase IIQuality of lifeCombination armPrimary endpointAdverse eventsSurvival benefitLife scoresPoor prognosisTreatment optionsMechanisms of resistanceBevacizumabClinical data
2020
CTNI-50. NEUROCOGNITIVE FUNCTION (NCF) OF THE PHOTON COHORT IN NRG-BN001
Wefel J, DeMora L, Gondi V, Tsien C, Chenevert T, Gilbert M, Omuro A, Cao Y, Srinivasan A, Rogers L, Shi W, Nedzi L, Chan M, Suh J, Battiste J, Mishra M, Shivnani A, Movsas B, Mehta M. CTNI-50. NEUROCOGNITIVE FUNCTION (NCF) OF THE PHOTON COHORT IN NRG-BN001. Neuro-Oncology 2020, 22: ii53-ii54. PMCID: PMC7651205, DOI: 10.1093/neuonc/noaa215.216.Peer-Reviewed Original ResearchNeurocognitive functionNCF testsSD-RTCycle 3Ongoing randomized phase II trialRandomized phase II trialNon-significant timeSecondary endpoint analysisPhase II trialMixed effects longitudinal modelsTreatment effect interactionEvaluable patientsNCF outcomesPhoton cohortsEligible patientsII trialOverall survivalPatient refusalRadiation therapyGroup 2Common reasonGroup 1Arm differencesPatientsEffects longitudinal models
2019
Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial
Wen PY, Touat M, Alexander BM, Mellinghoff IK, Ramkissoon S, McCluskey CS, Pelton K, Haidar S, Basu SS, Gaffey SC, Brown LE, Martinez-Ledesma JE, Wu S, Kim J, Wei W, Park MA, Huse JT, Kuhn JG, Rinne ML, Colman H, Agar NYR, Omuro AM, DeAngelis LM, Gilbert MR, de Groot JF, Cloughesy TF, S. A, Roberts TM, Zhao JJ, Lee EQ, Nayak L, Heath JR, Horky LL, Batchelor TT, Beroukhim R, Chang SM, Ligon AH, Dunn IF, Koul D, Young GS, Prados MD, Reardon DA, Yung WKA, Ligon KL. Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. Journal Of Clinical Oncology 2019, 37: jco.18.01207. PMID: 30715997, PMCID: PMC6553812, DOI: 10.1200/jco.18.01207.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesAntineoplastic AgentsBrain NeoplasmsChemotherapy, AdjuvantDisease ProgressionEnzyme ActivationFemaleGlioblastomaHumansMaleMiddle AgedMorpholinesNeoadjuvant TherapyNeoplasm Recurrence, LocalPhosphatidylinositol 3-KinasePhosphoinositide-3 Kinase InhibitorsProgression-Free SurvivalTime FactorsConceptsPhase II trialCohort 2Cohort 1PI3K pathwayTumor tissueII trialRecurrent glioblastomaBrain penetrationPan-PI3K inhibitor buparlisibPathway inhibitionPathway activationCommon grade 3K pathwayPrimary end pointGreater adverse eventsProgression-free survivalPI3K pathway inhibitionPI3K pathway activationPlasma drug levelsSingle-agent efficacySignificant brain penetrationPI3K inhibitorsMedian PFSOpen labelAdverse events
2017
NCCTG N1174: Phase I/comparative randomized phase (Ph) II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma (GBM) (Alliance).
Galanis E, Anderson S, Butowski N, Hormigo A, Schiff D, Tran D, Omuro A, Jaeckle K, Kumar S, Kaufmann T, Buckner J, Twohy E, Giannini C, Wen P. NCCTG N1174: Phase I/comparative randomized phase (Ph) II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma (GBM) (Alliance). Journal Of Clinical Oncology 2017, 35: 2023-2023. DOI: 10.1200/jco.2017.35.15_suppl.2023.Peer-Reviewed Original ResearchProgression-free survivalII trialMedian progression-free survivalRandomized phase II trialPhase II trialGlioma stem cellsOverall survivalOverall incidenceRecurrent glioblastomaMultiple time pointsVEGF inhibitionGrade 3GBM patientsPositive subsetSingle agentI cohortResponse rateHumanized antibodyFlow cytometryEndothelial cellsTime pointsTGFβ receptorsGlioblastomaBevacizumabCD105
2016
Patterns of response and relapse in primary CNS lymphomas after first-line chemotherapy: imaging analysis of the ANOCEF-GOELAMS prospective randomized trial
Tabouret E, Houillier C, Martin-Duverneuil N, Blonski M, Soussain C, Ghesquières H, Houot R, Larrieu D, Soubeyran P, Gressin R, Gyan E, Chinot O, Taillandier L, Choquet S, Alentorn A, Leclercq D, Omuro A, Tanguy ML, Hoang-Xuan K. Patterns of response and relapse in primary CNS lymphomas after first-line chemotherapy: imaging analysis of the ANOCEF-GOELAMS prospective randomized trial. Neuro-Oncology 2016, 19: 422-429. PMID: 27994065, PMCID: PMC5464299, DOI: 10.1093/neuonc/now238.Peer-Reviewed Original ResearchConceptsPrimary CNS lymphomaProgression-free survivalOverall survivalCNS lymphomaPrognostic valueMRI characteristicsRandomized phase II trialEarly MRI evaluationFirst-line chemotherapyPatterns of relapsePhase II trialBaseline tumor sizeEnd of treatmentOverall tumor burdenPotential prognostic valueComplete response achievementHypersignal lesionsInfratentorial localizationProlonged OSII trialObjective responsePoor OSProspective trialMRI abnormalitiesTumor burden
2015
Patterns of response and relapse of primary central nervous system lymphomas (PCNSL) following first line of high-dose methotrexate-based chemotherapy (hdMTX): Analysis of a prospective ANOCEF randomized phase II trial.
Tabouret E, Houillier C, Martin-Duverneuil N, Blonski M, Soussain C, Ghesquieres H, Houot R, Delwail V, Soubeyran P, Gressin R, Gyan E, Chinot O, Taillandier L, Tanguy M, Omuro A, Hoang-Xuan K. Patterns of response and relapse of primary central nervous system lymphomas (PCNSL) following first line of high-dose methotrexate-based chemotherapy (hdMTX): Analysis of a prospective ANOCEF randomized phase II trial. Journal Of Clinical Oncology 2015, 33: 2035-2035. DOI: 10.1200/jco.2015.33.15_suppl.2035.Peer-Reviewed Original Research
2014
Phase II Study of Bevacizumab, Temozolomide, and Hypofractionated Stereotactic Radiotherapy for Newly Diagnosed Glioblastoma
Omuro A, Beal K, Gutin P, Karimi S, Correa DD, Kaley TJ, DeAngelis LM, Chan TA, Gavrilovic IT, Nolan C, Hormigo A, Lassman AB, Mellinghoff I, Grommes C, Reiner AS, Panageas KS, Baser RE, Tabar V, Pentsova E, Sanchez J, Barradas-Panchal R, Zhang J, Faivre G, Brennan CW, Abrey LE, Huse JT. Phase II Study of Bevacizumab, Temozolomide, and Hypofractionated Stereotactic Radiotherapy for Newly Diagnosed Glioblastoma. Clinical Cancer Research 2014, 20: 5023-5031. PMID: 25107913, PMCID: PMC4523080, DOI: 10.1158/1078-0432.ccr-14-0822.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiopsyBrain NeoplasmsChemotherapy, AdjuvantCombined Modality TherapyDacarbazineFemaleGlioblastomaHumansMagnetic Resonance ImagingMaleMiddle AgedRadiosurgeryTemozolomideTreatment OutcomeYoung AdultConceptsObjective response rateOverall survivalRadiotherapy schedulesMedian overall survivalPhase II studyHypofractionated Stereotactic RadiotherapyPhase II trialApparent diffusion coefficient ratioRelative cerebral blood volumeDynamic susceptibility contrast perfusion MRICerebral blood volumeNeuropsychological test scoresMedian PFSPersistent hypermetabolismAdjuvant temozolomidePrimary endpointII studyII trialPoor OSStandard dosesFDG-PETPrognostic valuePoor prognosisHistorical controlsTumor volumeCurrent Role of Anti-Angiogenic Strategies for Glioblastoma
Thomas AA, Omuro A. Current Role of Anti-Angiogenic Strategies for Glioblastoma. Current Treatment Options In Oncology 2014, 15: 551-566. PMID: 25173555, DOI: 10.1007/s11864-014-0308-2.Peer-Reviewed Original ResearchConceptsProgression-free survivalPhase III trialsIII trialsOverall survivalRecurrent diseaseStandard chemoradiotherapyClinical benefitAnti-vascular endothelial growth factor monoclonal antibodyCognitive declineSimilar progression-free survivalToxicity of bevacizumabAddition of bevacizumabPhase II trialSevere neurologic symptomsFactor monoclonal antibodyNew drug combinationsAnti-angiogenic therapyReduced vascular permeabilityQuality of lifeUnquestionable clinical benefitObserved cognitive declineBevacizumab armOS trendsCorticosteroid useFree survivalPhase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma
Kaley TJ, Wen P, Schiff D, Ligon K, Haidar S, Karimi S, Lassman AB, Nolan CP, DeAngelis LM, Gavrilovic I, Norden A, Drappatz J, Lee EQ, Purow B, Plotkin SR, Batchelor T, Abrey LE, Omuro A. Phase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma. Neuro-Oncology 2014, 17: 116-121. PMID: 25100872, PMCID: PMC4483051, DOI: 10.1093/neuonc/nou148.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factor receptorPhase II trialWorld Health OrganizationGrowth factor receptorII trialPrimary endpointOverall survivalExploratory cohortIntratumoral hemorrhageGrade 3Small molecule tyrosine kinase inhibitorsSingle-arm phase II trialMalignant meningioma patientsRadiographic response rateMedian overall survivalEffective medical therapyProgression-free survivalFactor receptorEndothelial growth factor receptorPlatelet-derived growth factor receptorTyrosine kinase inhibitorsExpression of VEGFR2MR perfusion imagingHigh-grade meningiomasMedian PFSPHASE II TRIAL OF THE PHOSPHATIDYINOSITOL-3 KINASE (PI3K) INHIBITOR BUPARLISIB (BKM120) IN RECURRENT GLIOBLASTOMA CONDUCTED BY THE IVY FOUNDATION EARLY PHASE CLINICAL TRIALS CONSORTIUM
Wen P, Wen P, Yung W, Mellinghoff I, Ramkissoon S, Alexander B, Rinne M, Colman H, Omuro A, DeAngelis L, Gilbert M, DeGroot J, Cloughesy T, Lee E, Nayak L, S. A, Batchelor T, Chang S, Prados M, Reardon D, Ligon K. PHASE II TRIAL OF THE PHOSPHATIDYINOSITOL-3 KINASE (PI3K) INHIBITOR BUPARLISIB (BKM120) IN RECURRENT GLIOBLASTOMA CONDUCTED BY THE IVY FOUNDATION EARLY PHASE CLINICAL TRIALS CONSORTIUM. Neuro-Oncology 2014, 16: iii47-iii47. PMCID: PMC4144634, DOI: 10.1093/neuonc/nou209.20.Peer-Reviewed Original ResearchPI3K pathwayCohort 2Cohort 1Pan-class I PI3K inhibitorEnzyme-inducing antiepileptic drugsAdequate bone marrowGrade 4 toxicityGrowth of U87K pathwayGrade 3 toxicityPhase II studyPhase II trialRecurrent GBM patientsAdditional eligibility criteriaALT/ASTSingle-agent efficacyPotential therapeutic targetPI3K mutationsReduction of pAKTPI3K inhibitorsEvaluable patientsMedian OSMedian PFSPrior bevacizumabRadiologic progressionPhase II trial of the phosphatidyinositol-3 kinase (PI3K) inhibitor buparlisib (BKM120) in recurrent glioblastoma.
Wen P, Yung W, Mellinghoff I, Ramkissoon S, Alexander B, Rinne M, Colman H, Omuro A, DeAngelis L, Gilbert M, De Groot J, Cloughesy T, Chi A, Lee E, Nayak L, Batchelor T, Chang S, Prados M, Reardon D, Ligon K. Phase II trial of the phosphatidyinositol-3 kinase (PI3K) inhibitor buparlisib (BKM120) in recurrent glioblastoma. Journal Of Clinical Oncology 2014, 32: 2019-2019. DOI: 10.1200/jco.2014.32.15_suppl.2019.Peer-Reviewed Original Research
2013
Phase II trial of the phosphatidyinositol-3 kinase (PI3K) inhibitor BKM120 in recurrent glioblastoma (GBM).
Wen P, Yung W, Mellinghoff I, Lamborn K, Ramkissoon S, Cloughesy T, Rinne M, Omuro A, DeAngelis L, Gilbert M, Chi A, Batchelor T, Colman H, Chang S, Massacesi C, DiTomaso E, Prados M, Reardon D, Ligon K. Phase II trial of the phosphatidyinositol-3 kinase (PI3K) inhibitor BKM120 in recurrent glioblastoma (GBM). Journal Of Clinical Oncology 2013, 31: 2015-2015. DOI: 10.1200/jco.2013.31.15_suppl.2015.Peer-Reviewed Original ResearchPI3K pathwayRecurrent glioblastomaK pathwayPan-class I PI3K inhibitorMajor grade 3/4 toxicitiesEnzyme-inducing antiepileptic drugsAdequate bone marrowGrade 3/4 toxicitiesPhase II studyPhase II trialProgression-free survivalClinical Trials ConsortiumRecurrent GBM patientsAdditional eligibility criteriaPotential therapeutic targetReduction of pAKTWhole-exome sequencingPI3K inhibitorsAnalysis of tumorsRadiologic progressionUnresectable glioblastomaII trialPrimary endpointRecurrent diseaseII studyMulticenter randomized phase II trial of methotrexate (MTX) and temozolomide (TMZ) versus MTX, procarbazine, vincristine, and cytarabine for primary CNS lymphoma (PCNSL) in the elderly: An Anocef and Goelams Intergroup study.
Omuro A, Chinot O, Taillandier L, Ghesquieres H, Soussain C, Delwail V, Lamy T, Gressin R, Choquet S, Soubeyran P, Maire J, Benouaich Amiel A, Lebouvier-Sadot S, Gyan E, Barrie M, Sierra del Rio M, Gonzalez A, Houillier C, Tanguy M, Hoang-Xuan K. Multicenter randomized phase II trial of methotrexate (MTX) and temozolomide (TMZ) versus MTX, procarbazine, vincristine, and cytarabine for primary CNS lymphoma (PCNSL) in the elderly: An Anocef and Goelams Intergroup study. Journal Of Clinical Oncology 2013, 31: 2032-2032. DOI: 10.1200/jco.2013.31.15_suppl.2032.Peer-Reviewed Original ResearchPrimary CNS lymphomaAbnormal liver function testsCycles of methotrexateProphylactic G-CSFWhole brain radiotherapyLiver function testsPhase II trialProspective multicenter studyBaseline cognitive impairmentQuality of lifePre-treatment characteristicsCommon toxicitiesCytarabine consolidationCNS lymphomaEfficacy endpointII trialPrimary endpointBrain radiotherapyElderly patientsObjective responseStandard chemotherapyCR rateFunction testsIntergroup studyMulticenter studySurvival benefit from bevacizumab in newly diagnosed glioblastoma (GBM) according to transcriptional subclasses.
Huse J, Beal K, Zhang J, Kastenhuber E, Kaley T, Abrey L, Gutin P, Brennan C, Omuro A. Survival benefit from bevacizumab in newly diagnosed glioblastoma (GBM) according to transcriptional subclasses. Journal Of Clinical Oncology 2013, 31: 2057-2057. DOI: 10.1200/jco.2013.31.15_suppl.2057.Peer-Reviewed Original ResearchMedian overall survivalOverall survivalBevacizumab treatmentSurvival benefitNanoString gene expression assaysProspective phase II trialPhase II trialNew treatment optionsParaffin-embedded tissue blocksGBM molecular subtypesMGMT promoter methylationEvaluable ptsPrimary endpointII trialUnselected patientsTreatment optionsMolecular subtypesTumor volumeStereotactic radiotherapyBevacizumabSurvival advantageTherapeutic implicationsMolecular subclassesGlioblastomaTumors
2012
Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma
Omuro A, Chan TA, Abrey LE, Khasraw M, Reiner AS, Kaley TJ, Deangelis LM, Lassman AB, Nolan CP, Gavrilovic IT, Hormigo A, Salvant C, Heguy A, Kaufman A, Huse JT, Panageas KS, Hottinger AF, Mellinghoff I. Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma. Neuro-Oncology 2012, 15: 242-250. PMID: 23243055, PMCID: PMC3548585, DOI: 10.1093/neuonc/nos295.Peer-Reviewed Original ResearchConceptsKarnofsky performance scoreProgression-free survival ratesBevacizumab-naive patientsRecurrent malignant gliomaPhase II trialMalignant gliomasII trialPrimary endpointSurvival rateContinuous low-dose temozolomideMedian Karnofsky performance scoreLow Karnofsky performance scoreAdvanced malignant gliomaLow-dose temozolomideMedian overall survivalHalf of patientsFurther treatment strategiesMutations of EGFRBevacizumab exposureEligible patientsTemozolomide schedulesMG patientsOverall survivalMedian ageClinical benefitMulticenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma
Nayak L, Abrey LE, Drappatz J, Gilbert MR, Reardon DA, Wen PY, Prados M, Deangelis LM, Omuro A, Consortium F. Multicenter phase II study of rituximab and temozolomide in recurrent primary central nervous system lymphoma. Leukemia & Lymphoma 2012, 54: 58-61. PMID: 22656234, PMCID: PMC4802006, DOI: 10.3109/10428194.2012.698736.Peer-Reviewed Original ResearchConceptsPrimary central nervous system lymphomaRecurrent primary central nervous system lymphomaCentral nervous system lymphomaNervous system lymphomaSystem lymphomaDay 1Prospective multicenter phase II trialMedian progression-free survivalMulticenter phase II studyMulticenter phase II trialAggressive salvage treatmentMedian overall survivalPhase II studyPhase II trialProgression-free survivalCycles of consolidationEvaluable patientsII trialSalvage treatmentII studyImmunocompetent patientsOverall survivalComplete responseRetrospective studyPatientsRituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) followed by consolidation high-dose chemotherapy (HDC) and autologous stem-cell transplant (ASCT) for newly diagnosed primary CNS lymphoma (PCNSL).
Omuro A, Correa D, Moskowitz C, Matasar M, DeAngelis L, Kaley T, Gavrilovic I, Nolan C, Pentsova E, Grommes C, Abrey L, Sauter C. Rituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) followed by consolidation high-dose chemotherapy (HDC) and autologous stem-cell transplant (ASCT) for newly diagnosed primary CNS lymphoma (PCNSL). Journal Of Clinical Oncology 2012, 30: 2008-2008. DOI: 10.1200/jco.2012.30.15_suppl.2008.Peer-Reviewed Original ResearchAutologous stem cell transplantHigh-dose chemotherapyPrimary CNS lymphomaConsolidation high-dose chemotherapyITT populationR-MPVInduction chemotherapyInduction regimenPrimary endpointYear event-free survivalEffective induction regimenEvent-free survivalPhase II trialStem cell transplantImproved response ratesExcellent disease controlComprehensive neuropsychological evaluationHDC regimenHDC-ASCTMedian EFSYear EFSEarly complicationsMedian PFSCNS lymphomaII trial
2011
A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression
Mason WP, Belanger K, Nicholas G, Vallières I, Mathieu D, Kavan P, Desjardins A, Omuro A, Reymond D. A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression. Journal Of Neuro-Oncology 2011, 107: 343-349. PMID: 22048878, DOI: 10.1007/s11060-011-0747-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBrain NeoplasmsChromatography, LiquidDibenzazepinesErbB ReceptorsFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticGlioblastomaHumansInfusions, IntraventricularKaplan-Meier EstimateMagnetic Resonance ImagingMaleMiddle AgedPTEN PhosphohydrolaseTandem Mass SpectrometryConceptsPharmacokinetic evaluationProgressive glioblastomaFirst progressionM2/dayPhase II studyMR scansPhase II trialContinuous intravenous administrationBlood-brain barrierLack of efficacyPeripheral benzodiazepine receptorEvaluable patientsStable diseaseII trialRadiographic progressionAdverse eventsII studyRecurrent glioblastomaDisease progressionDrug levelsIntravenous administrationBiomarker assessmentPatientsAnimal modelsBenzodiazepine receptorsMethotrexate area under the curve as a prognostic factor in primary central nervous system lymphoma treated with immunochemoradiotherapy
Morris PG, Abrey LE, Reiner AS, Wu N, Panageas KS, Seko BS, Deangelis LM, Omuro A. Methotrexate area under the curve as a prognostic factor in primary central nervous system lymphoma treated with immunochemoradiotherapy. Leukemia & Lymphoma 2011, 52: 1891-1897. PMID: 21699456, DOI: 10.3109/10428194.2011.585527.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, Murine-DerivedAntineoplastic Combined Chemotherapy ProtocolsArea Under CurveCentral Nervous System NeoplasmsCombined Modality TherapyCytarabineFemaleHumansKarnofsky Performance StatusMaleMethotrexateMiddle AgedProcarbazinePrognosisRituximabSurvival AnalysisVincristineConceptsPrimary central nervous system lymphomaCentral nervous system lymphomaProgression-free survivalNervous system lymphomaMTX AUCMethotrexate areaSystem lymphomaMedian Karnofsky performance status (KPS) scoreIntra-patient dose escalationProspective phase II trialKarnofsky performance status scoreLow-dose radiotherapyFirst chemotherapy cyclePerformance status scorePhase II trialImproved tumor controlSubstantial inter-individual variabilityChemotherapy cyclesII trialMTX exposureOverall survivalDose escalationMedian agePrognostic factorsInter-individual variability