2020
A phase II study of dose-dense temozolomide and lapatinib for recurrent low-grade and anaplastic supratentorial, infratentorial, and spinal cord ependymoma
Gilbert MR, Yuan Y, Wu J, Mendoza T, Vera E, Omuro A, Lieberman F, Robins HI, Gerstner ER, Wu J, Wen PY, Mikkelsen T, Aldape K, Armstrong TS. A phase II study of dose-dense temozolomide and lapatinib for recurrent low-grade and anaplastic supratentorial, infratentorial, and spinal cord ependymoma. Neuro-Oncology 2020, 23: 468-477. PMID: 33085768, PMCID: PMC7992893, DOI: 10.1093/neuonc/noaa240.Peer-Reviewed Original ResearchConceptsProgression-free survivalDose-dense temozolomideMedian progression-free survivalAdult patientsObjective responseSymptom burdenClinical trialsRecurrent ependymomaMD Anderson Symptom Inventory-Brain TumorProspective phase II clinical trialMedian Karnofsky performance statusPhase II clinical trialDemonstrated clinical activityModerate-severe painPatients age 18Phase II studyKarnofsky performance statusProspective clinical trialsSpinal cord tumorsStandard medical treatmentPrimary outcome measureSpinal cord ependymomasDisease-related symptomsExpression of ErbB2Daily lapatinib
2017
Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma
Thomas AA, Abrey LE, Terziev R, Raizer J, Martinez NL, Forsyth P, Paleologos N, Matasar M, Sauter CS, Moskowitz C, Nimer SD, DeAngelis LM, Kaley T, Grimm S, Louis DN, Cairncross JG, Panageas KS, Briggs S, Faivre G, Mohile NA, Mehta J, Jonsson P, Chakravarty D, Gao J, Schultz N, Brennan CW, Huse JT, Omuro A. Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma. Neuro-Oncology 2017, 19: 1380-1390. PMID: 28472509, PMCID: PMC5596171, DOI: 10.1093/neuonc/nox086.Peer-Reviewed Original ResearchConceptsAutologous stem cell transplantProgression-free survivalHigh-dose chemotherapyStem cell transplantAnaplastic oligodendrogliomaAnaplastic oligoastrocytomaHDC-ASCTMulticenter phase II studyMyeloablative high-dose chemotherapyChemotherapy-based approachesCycles of temozolomideOverall survival 93Phase II studyRadiation-related toxicityUnexpected adverse eventsNext-generation sequencingChemotherapy-sensitive tumorsWide molecular heterogeneityToxic deathsAdverse eventsII studyMyeloablative chemotherapyProspective trialIntact patientsCell transplantPhase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas
Nayak L, de Groot J, Wefel JS, Cloughesy TF, Lieberman F, Chang SM, Omuro A, Drappatz J, Batchelor TT, DeAngelis LM, Gilbert MR, Aldape KD, Yung AW, Fisher J, Ye X, Chen A, Grossman S, Prados M, Wen PY. Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas. Journal Of Neuro-Oncology 2017, 132: 181-188. PMID: 28116649, PMCID: PMC5588922, DOI: 10.1007/s11060-016-2357-9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, AlkylatingBrain NeoplasmsChemotherapy, AdjuvantCombined Modality TherapyDacarbazineDrug Therapy, CombinationFemaleGliomaHumansMaleMiddle AgedNeuropsychological TestsReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsTemozolomideTreatment OutcomeVascular Endothelial Growth Factor AConceptsHigh-grade gliomasPhase I trialI trialArm 2Arm 1Anti-vascular endothelial growth factor therapyAdult Brain Tumor ConsortiumEndothelial growth factor therapyRecombinant human fusion proteinGrowth factorFull treatment courseGrowth factor therapyPlacental growth factorSoluble decoy receptorHuman fusion proteinKPS 90Primary endpointFactor therapyDay regimenMedian ageTreatment courseArm 3Disease progressionMedian numberRadiation therapy
2016
Primary Oculocerebral Lymphoma: MTX Polychemotherapy Alone on Intraocular Disease Control
Nguyen D, Houillier C, Choquet S, Cassoux N, Soussain C, Le Cossec C, Legarf-Tavernier M, Costopoulos M, LeHoang P, Bodaghi B, Omuro A, Hoang-Xuan K, Touitou V. Primary Oculocerebral Lymphoma: MTX Polychemotherapy Alone on Intraocular Disease Control. Ophthalmology 2016, 123: 2047-2050. PMID: 27137876, DOI: 10.1016/j.ophtha.2016.03.043.Peer-Reviewed Original Research
2015
Methotrexate and temozolomide versus methotrexate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in an elderly population: an intergroup ANOCEF-GOELAMS randomised phase 2 trial
Omuro A, Chinot O, Taillandier L, Ghesquieres H, Soussain C, Delwail V, Lamy T, Gressin R, Choquet S, Soubeyran P, Huchet A, Benouaich-Amiel A, Lebouvier-Sadot S, Gyan E, Touitou V, Barrié M, del Rio M, Gonzalez-Aguilar A, Houillier C, Delgadillo D, Lacomblez L, Tanguy M, Hoang-Xuan K. Methotrexate and temozolomide versus methotrexate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in an elderly population: an intergroup ANOCEF-GOELAMS randomised phase 2 trial. The Lancet Haematology 2015, 2: e251-e259. PMID: 26688235, DOI: 10.1016/s2352-3026(15)00074-5.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntimetabolites, AntineoplasticAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCentral Nervous System NeoplasmsCytarabineDacarbazineDisease-Free SurvivalFemaleHumansLymphomaMaleMethotrexateMiddle AgedProcarbazineProspective StudiesQuality of LifeTemozolomideTreatment OutcomeVincristineConceptsPrimary CNS lymphomaProgression-free survivalKarnofsky Performance Scale scoreCytarabine groupPhase 2 trialCNS lymphomaPerformance Scale scoreTemozolomide groupElderly populationScale scoreMedian progression-free survivalPhase 2 trial designCommon grade 3Methotrexate-based regimensProphylactic G-CSFMedian overall survivalStandard chemotherapy regimenPoor prognosis patientsQuality of lifeChemotherapy regimenEfficacy endpointPrimary endpointPrognosis patientsElderly patientsImmunocompetent patientsPhase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma
Wen PY, Omuro A, Ahluwalia MS, Fathallah-Shaykh HM, Mohile N, Lager JJ, Laird AD, Tang J, Jiang J, Egile C, Cloughesy TF. Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma. Neuro-Oncology 2015, 17: 1275-1283. PMID: 26019185, PMCID: PMC4588757, DOI: 10.1093/neuonc/nov083.Peer-Reviewed Original ResearchConceptsHigh-grade gliomasAdverse eventsRadiation therapySkin biopsiesPhase I dose-escalation studyTreatment-related adverse eventsI dose-escalation studyPI3K/mTOR pathway inhibitionTreatment-related gradeDose-escalation studyDose-escalation designFavorable safety profileMTOR pathway inhibitionEvaluable patientsStable diseasePartial responsePharmacodynamic effectsPlatelet countRapamycin inhibitorsSafety profilePreliminary efficacyTumor responsePlasma pharmacokineticsVoxtalisibPatientsDiffusion and Perfusion MRI to Differentiate Treatment-Related Changes Including Pseudoprogression from Recurrent Tumors in High-Grade Gliomas with Histopathologic Evidence
Prager A, Martinez N, Beal K, Omuro A, Zhang Z, Young R. Diffusion and Perfusion MRI to Differentiate Treatment-Related Changes Including Pseudoprogression from Recurrent Tumors in High-Grade Gliomas with Histopathologic Evidence. American Journal Of Neuroradiology 2015, 36: 877-885. PMID: 25593202, PMCID: PMC4731220, DOI: 10.3174/ajnr.a4218.Peer-Reviewed Original ResearchConceptsTreatment-related changesRecurrent tumorsHigh-grade gliomasSurgical resectionRecurrent high-grade gliomaLow relative cerebral blood volumeSubanalysis of patientsUtility of DWIRelative cerebral blood volumeTreatment-related effectsCerebral blood volumeWilcoxon rank sum testConventional MR imagingRank sum testConsecutive patientsHistopathologic evidenceMass lesionDSC perfusionRadiation therapyBlood volumeGrade gliomasPatientsLow perfusionTumorsDSC maps
2014
Emerging Therapies for Glioblastoma
Thomas AA, Brennan CW, DeAngelis LM, Omuro AM. Emerging Therapies for Glioblastoma. JAMA Neurology 2014, 71: 1437-1444. PMID: 25244650, DOI: 10.1001/jamaneurol.2014.1701.Peer-Reviewed Original ResearchConceptsClinical trialsCommon primary malignant brain tumorPrimary malignant brain tumorCancer stemlike cellsInnovative clinical trialsBlood-brain barrierMalignant brain tumorsPatient-tailored treatmentNew radiotherapy techniquesHeterogeneous molecular featuresImmune system interactionsGrowth factor receptorTerms glioblastomaMedian survivalDisease courseImmune checkpointsTemozolomide chemotherapyMultimodal treatmentPatient enrollmentAggressive tumorsTreatment advancesBrain neoplasmsDrug exposureBrain microenvironmentMalignant gliomasPhase 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 volume
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 studyPatients
2010
Up-front temozolomide in elderly patients with anaplastic oligodendroglioma and oligoastrocytoma
Ducray F, Sierra del Rio M, Carpentier C, Psimaras D, Idbaih A, Dehais C, Kaloshi G, Mokhtari K, Taillibert S, Laigle-Donadey F, Omuro A, Sanson M, Delattre JY, Hoang-Xuan K. Up-front temozolomide in elderly patients with anaplastic oligodendroglioma and oligoastrocytoma. Journal Of Neuro-Oncology 2010, 101: 457-462. PMID: 20556480, DOI: 10.1007/s11060-010-0264-z.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic Agents, AlkylatingBrain NeoplasmsDacarbazineDNA MethylationDNA Modification MethylasesDNA Repair EnzymesDNA, NeoplasmFemaleFollow-Up StudiesHumansMaleOligodendrogliomaPolymerase Chain ReactionPromoter Regions, GeneticRetrospective StudiesSurvival RateTemozolomideTreatment OutcomeTumor Suppressor ProteinsConceptsProgression-free survivalAnaplastic oligodendroglial tumorsElderly patientsOverall survivalFront chemotherapyPartial responseMedian progression-free survivalLonger progression-free survivalInitial radiation therapyLonger overall survivalDuration of responseRate of respondersO6-methylguanine-DNA methyltransferase (MGMT) promoter methylationMethyltransferase promoter methylationEvaluable patientsStable diseaseConsecutive patientsConventional dosesRetrospective studyOptimal treatmentAnaplastic oligodendrogliomaRadiation therapyPatientsOligodendroglial tumorsTumor progressionNitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide
Kaloshi G, Sierra del Rio M, Ducray F, Psimaras D, Idbaih A, Laigle-Donadey F, Taillibert S, Houillier C, Dehais C, Omuro A, Sanson M, Delattre JY, Hoang-Xuan K. Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide. Journal Of Neuro-Oncology 2010, 100: 439-441. PMID: 20464625, DOI: 10.1007/s11060-010-0197-6.Peer-Reviewed Original ResearchConceptsLow-grade gliomasGrade gliomasProgressive low-grade gliomaTerms of PFSContrast enhancementEfficacy of nitrosoureasBetter PFSMedian PFSMedian OSObjective responseSalvage treatmentUpfront therapyMedian ageBetter prognosisInitial treatmentConventional radiotherapyChromosome 1p/19q codeletionNon-enhancing tumorResponse ratePatientsTemozolomidePure oligodendrogliomasPFSGliomasDisappointing results
2007
A phase II trial of vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases
Iwamoto FM, Omuro AM, Raizer JJ, Nolan CP, Hormigo A, Lassman AB, Gavrilovic IT, Abrey LE. A phase II trial of vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases. Journal Of Neuro-Oncology 2007, 87: 85-90. PMID: 17987262, DOI: 10.1007/s11060-007-9491-3.Peer-Reviewed Original ResearchConceptsKarnofsky Performance ScaleProgressive brain metastasesPhase II trialBrain metastasesII trialResponse rateMedian Karnofsky performance scaleWhole-brain radiation therapyAdequate organ functionBrain metastasis resectionObjective radiographic responseRadiographic response rateSingle-agent temozolomideGrade 3/4 toxicitiesRecurrent brain metastasesPopulation of patientsPrimary tumor siteYears of agePrior therapyStable diseaseVinorelbine 25Metastasis resectionPrimary endpointMethods PatientsOverall survivalTemozolomide and methotrexate for primary central nervous system lymphoma in the elderly
Omuro AM, Taillandier L, Chinot O, Carnin C, Barrie M, Hoang-Xuan K. Temozolomide and methotrexate for primary central nervous system lymphoma in the elderly. Journal Of Neuro-Oncology 2007, 85: 207-211. PMID: 17896079, DOI: 10.1007/s11060-007-9397-0.Peer-Reviewed Original ResearchConceptsPrimary CNS lymphomaIntra-thecal chemotherapyFavorable toxicity profileComplete responseToxicity profilePrimary central nervous system lymphomaMedian event-free survivalCentral nervous system lymphomaMedian overall survivalEvent-free survivalNervous system lymphomaNew alternative treatmentLow response rateInduction chemotherapyInnovative regimenCNS lymphomaElderly patientsIntestinal obstructionOverall survivalPCNSL patientsYounger patientsSystem lymphomaConsecutive seriesEfficacy resultsGrade 3Temozolomide for low-grade gliomas
Kaloshi G, Benouaich-Amiel A, Diakite F, Taillibert S, Lejeune J, Laigle-Donadey F, Renard M, Iraqi W, Idbaih A, Paris S, Capelle L, Duffau H, Cornu P, Simon J, Mokhtari K, Polivka M, Omuro A, Carpentier A, Sanson M, Delattre J, Hoang-Xuan K. Temozolomide for low-grade gliomas. Neurology 2007, 68: 1831-1836. PMID: 17515545, DOI: 10.1212/01.wnl.0000262034.26310.a2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, AlkylatingBrain NeoplasmsChromosome DeletionChromosomes, Human, Pair 1Chromosomes, Human, Pair 19DacarbazineDNA Mutational AnalysisDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticGenetic TestingGenotypeGliomaHumansLoss of HeterozygosityMaleMiddle AgedNeoplasm Recurrence, LocalRetrospective StudiesSurvival RateTemozolomideTreatment OutcomeConceptsProgression-free survivalLow-grade gliomasProgressive low-grade gliomaObjective responseMedian progression-free survivalLonger progression-free survivalSingle-center observational studyCenter observational studyMaximum tumor responseStable diseaseProgressive diseaseAdult patientsConsecutive patientsOverall survivalMedian timeTMZ cyclesTemozolomide chemotherapyCentral reviewTumor responseFavorable outcomeMedian numberObservational studyPatientsPredictive impactConventional scheduleDynamic history of low‐grade gliomas before and after temozolomide treatment
Ricard D, Kaloshi G, Amiel‐Benouaich A, Lejeune J, Marie Y, Mandonnet E, Kujas M, Mokhtari K, Taillibert S, Laigle‐Donadey F, Carpentier AF, Omuro A, Capelle L, Duffau H, Cornu P, Guillevin R, Sanson M, Hoang‐Xuan K, Delattre J. Dynamic history of low‐grade gliomas before and after temozolomide treatment. Annals Of Neurology 2007, 61: 484-490. PMID: 17469128, DOI: 10.1002/ana.21125.Peer-Reviewed Original ResearchConceptsMean tumor diameterLow-grade gliomasMajority of tumorsTemozolomide treatmentImpact of temozolomideSerial magnetic resonance imagesUntreated low-grade gliomaGenetic alterationsNeoadjuvant temozolomideTumor diameterContinuous administrationP53 overexpressionOptimal durationTumor progressionTumorsTemozolomidePatientsGliomasMagnetic resonance imagesNatural progressionTreatmentProgressive growthLower ratesResonance imagesP53
2006
Vinorelbine combined with a protracted course of temozolomide for recurrent brain Metastases: a phase I trial
Omuro AM, Raizer JJ, Demopoulos A, Malkin MG, Abrey LE. Vinorelbine combined with a protracted course of temozolomide for recurrent brain Metastases: a phase I trial. Journal Of Neuro-Oncology 2006, 78: 277-280. PMID: 16614943, DOI: 10.1007/s11060-005-9095-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, AlkylatingAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsBreast NeoplasmsCarcinoma, Non-Small-Cell LungDacarbazineDisease-Free SurvivalDose-Response Relationship, DrugDrug Administration ScheduleFemaleHumansLung NeoplasmsLymphopeniaMaleMaximum Tolerated DoseMiddle AgedNeutropeniaTemozolomideThrombocytopeniaTreatment OutcomeVinblastineVinorelbineConceptsCourses of temozolomideRecurrent brain metastasesBrain metastasesDose of vinorelbineProgressive brain metastasesPhase II trialPhase I trialEfficacy of temozolomideVinorelbine doseII trialStarting doseMedian survivalRadiographic responseI trialMedian ageModest efficacyNew regimenPatient 2Lung cancerPrimary tumorGrade 3PatientsVinorelbineTemozolomideDose
2005
Salvage temozolomide for prior temozolomide responders
Franceschi E, Omuro AM, Lassman AB, Demopoulos A, Nolan C, Abrey LE. Salvage temozolomide for prior temozolomide responders. Cancer 2005, 104: 2473-2476. PMID: 16270316, DOI: 10.1002/cncr.21564.Peer-Reviewed Original ResearchConceptsDisease recurrenceRecurrent/progressive gliomaInitial disease recurrencePotential hematologic complicationsSubsequent salvage therapyFirst-line therapyProgression-free survivalTime of diagnosisLow-grade oligodendrogliomasWarrants further investigationSalvage therapyStable diseaseHematologic complicationsObjective responseRadiographic responseMedian ageRetrospective reviewDisease progressionTMZ treatmentAnaplastic astrocytomaPatientsProgressive gliomasRecurrenceTemozolomideSame agents