2022
Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter
Lim M, Weller M, Idbaih A, Steinbach J, Finocchiaro G, Raval RR, Ansstas G, Baehring J, Taylor JW, Honnorat J, Petrecca K, De Vos F, Wick A, Sumrall A, Sahebjam S, Mellinghoff IK, Kinoshita M, Roberts M, Slepetis R, Warad D, Leung D, Lee M, Reardon DA, Omuro A. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro-Oncology 2022, 24: 1935-1949. PMID: 35511454, PMCID: PMC9629431, DOI: 10.1093/neuonc/noac116.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal Cortex HormonesAntineoplastic Agents, AlkylatingBrain NeoplasmsChemoradiotherapyDNA Modification MethylasesDNA Repair EnzymesGlioblastomaHumansNivolumabTemozolomideTumor Suppressor ProteinsConceptsProgression-free survivalOverall survivalMGMT promoterBaseline corticosteroidsTreatment-related adverse event ratesImmune checkpoint inhibitor nivolumabNew safety signalsPhase III trialsAdverse event ratesCheckpoint inhibitor nivolumabCare radiotherapyInhibitor nivolumabPrimary endpointIII trialsSame regimenExperience recurrenceNivolumabSafety signalsPlaceboPatientsRadiotherapyTemozolomideEvent ratesMonthsPhase IIIRadiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial
Omuro A, Brandes AA, Carpentier AF, Idbaih A, Reardon DA, Cloughesy T, Sumrall A, Baehring J, van den Bent M, Bähr O, Lombardi G, Mulholland P, Tabatabai G, Lassen U, Sepulveda JM, Khasraw M, Vauleon E, Muragaki Y, Di Giacomo AM, Butowski N, Roth P, Qian X, Fu AZ, Liu Y, Potter V, Chalamandaris AG, Tatsuoka K, Lim M, Weller M. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial. Neuro-Oncology 2022, 25: 123-134. PMID: 35419607, PMCID: PMC9825306, DOI: 10.1093/neuonc/noac099.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, AlkylatingBrain NeoplasmsDisease-Free SurvivalDNA Modification MethylasesDNA Repair EnzymesGlioblastomaHumansNivolumabProgression-Free SurvivalTemozolomideTumor Suppressor ProteinsConceptsOverall survivalUnmethylated MGMT promoterMedian OSPrimary endpointInternational randomized phase III trialTreatment-related adverse event ratesMedian progression-free survivalRandomized phase III trialMGMT promoterEfficacy of nivolumabLonger median OSMedian overall survivalNew safety signalsProgression-free survivalAddition of temozolomideAdverse event ratesPhase III trialsUse of temozolomideStandard of careStudy treatment armsImproved OSIII trialsTreatment armsStandard radiotherapyNivolumab
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
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 benefit
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
Editorial: what is new in the treatment of gliomas?
Omuro AM, Delattre JY. Editorial: what is new in the treatment of gliomas? Current Opinion In Neurology 2007, 20: 704-707. PMID: 17992093, DOI: 10.1097/wco.0b013e3282f1beef.Peer-Reviewed Original ResearchConceptsTreatment of gliomaTherapeutic decisionsEvidence-based therapeutic decisionsBevacizumab-based combinationsRecurrent malignant gliomaRole of chemotherapyPhase II trialStandard of carePhase III evidenceHigh response ratePhase II resultsSingle positive resultTemozolomide concomitantTemozolomide schedulesII trialSurvival benefitRandomized trialsGrade IIIMalignant gliomasResponse rateGliomasSuch trialsTraditional treatmentTrialsCodeletion statusTemozolomide 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 ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, AlkylatingAstrocytomaBrain NeoplasmsDacarbazineFemaleGlioblastomaHumansMaleMiddle AgedOligodendrogliomaRecurrenceRetrospective StudiesSalvage TherapySurvival AnalysisTemozolomideConceptsDisease 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