2018
A Phase II Trial of Bortezomib and Vorinostat in Mantle Cell Lymphoma and Diffuse Large B-cell Lymphoma
Yazbeck V, Shafer D, Perkins EB, Coppola D, Sokol L, Richards KL, Shea T, Ruan J, Parekh S, Strair R, Flowers C, Morgan D, Kmieciak M, Bose P, Kimball A, Badros AZ, Baz R, Lin HY, Zhao X, Reich RR, Tombes MB, Shrader E, Sankala H, Roberts JD, Sullivan D, Grant S, Holkova B. A Phase II Trial of Bortezomib and Vorinostat in Mantle Cell Lymphoma and Diffuse Large B-cell Lymphoma. Clinical Lymphoma Myeloma & Leukemia 2018, 18: 569-575.e1. PMID: 30122201, DOI: 10.1016/j.clml.2018.05.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBortezomibDrug Resistance, NeoplasmFemaleFollow-Up StudiesHumansLymphoma, Large B-Cell, DiffuseLymphoma, Mantle-CellMaleMiddle AgedNeoplasm Recurrence, LocalPrognosisProspective StudiesSalvage TherapySurvival RateVorinostatConceptsLarge B-cell lymphomaPhase II trialStable diseaseProgressive diseaseB-cell lymphomaPartial responseII trialCohort BCohort ADay 1Median progression-free survivalNonrandomized phase II trialDiffuse large B-cell lymphomaProgression-free survivalHistone deacetylase inhibitor vorinostatOverall response rateCombination of bortezomibMantle cell lymphomaNF-κB activationProteasome inhibitor bortezomibCell lymphoma cellsPresent multicenterRefractory MCLClinical responseCohort C
2013
A Phase I Trial of Vorinostat and Alvocidib in Patients with Relapsed, Refractory, or Poor Prognosis Acute Leukemia, or Refractory Anemia with Excess Blasts-2
Holkova B, Supko JG, Ames MM, Reid JM, Shapiro GI, Perkins EB, Ramakrishnan V, Tombes MB, Honeycutt C, McGovern RM, Kmieciak M, Shrader E, Wellons MD, Sankala H, Doyle A, Wright J, Roberts JD, Grant S. A Phase I Trial of Vorinostat and Alvocidib in Patients with Relapsed, Refractory, or Poor Prognosis Acute Leukemia, or Refractory Anemia with Excess Blasts-2. Clinical Cancer Research 2013, 19: 1873-1883. PMID: 23515411, PMCID: PMC3618599, DOI: 10.1158/1078-0432.ccr-12-2926.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdultAgedAnemia, Refractory, with Excess of BlastsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCyclin-Dependent Kinase Inhibitor p21FemaleFlavonoidsHumansHydroxamic AcidsLeukemiaMaleMaximum Tolerated DoseMiddle AgedMyeloid Cell Leukemia Sequence 1 ProteinPiperidinesPrognosisProto-Oncogene Proteins c-bcl-2RecurrenceRNA Polymerase IITreatment OutcomeVorinostatYoung AdultConceptsMaximum-tolerated dosePoor-prognosis acute leukemiaExcess blasts-2Objective responseQT prolongationAcute leukemiaBlasts-2Phase I trialBone marrow responseCardiac arrhythmia atrial fibrillationArrhythmia atrial fibrillationEvaluable patientsStable diseaseVorinostat pharmacokineticsDisease stabilizationMaintenance infusionI trialMarrow responsePharmacodynamic effectsRefractory anemiaIntravenous infusionLoading infusionPatientsVorinostatSecondary objective
2010
A phase I pharmacokinetic study of pulse-dose vorinostat with flavopiridol in solid tumors
Dickson MA, Rathkopf DE, Carvajal RD, Grant S, Roberts JD, Reid JM, Ames MM, McGovern RM, Lefkowitz RA, Gonen M, Cane LM, Dials HJ, Schwartz GK. A phase I pharmacokinetic study of pulse-dose vorinostat with flavopiridol in solid tumors. Investigational New Drugs 2010, 29: 1004-1012. PMID: 20461440, PMCID: PMC3545439, DOI: 10.1007/s10637-010-9447-x.Peer-Reviewed Original ResearchConceptsSerum levelsPhase I pharmacokinetic studyIntermittent high doseResults 34 patientsD1-3I pharmacokinetic studyCyclin-dependent kinase inhibitor flavopiridolKinase inhibitor flavopiridolStable diseaseOral doseOral dosingHigh doseCombination treatmentPatientsSolid tumorsCmaxOne weekDosePharmacokinetic studyVorinostatMTDFlavopiridolNeutropeniaChemotherapyLevels
2008
Vorinostat and Sorafenib Synergistically Kill Tumor Cells via FLIP Suppression and CD95 Activation
Zhang G, Park MA, Mitchell C, Hamed H, Rahmani M, Martin AP, Curiel DT, Yacoub A, Graf M, Lee R, Roberts JD, Fisher PB, Grant S, Dent P. Vorinostat and Sorafenib Synergistically Kill Tumor Cells via FLIP Suppression and CD95 Activation. Clinical Cancer Research 2008, 14: 5385-5399. PMID: 18765530, PMCID: PMC2561272, DOI: 10.1158/1078-0432.ccr-08-0469.Peer-Reviewed Original ResearchConceptsPancreatic adenocarcinoma cellsLong-term colony formation assaysCaspase-8C-FLIPExtracellular signal-regulated kinase 1/2Full-length BidSignal-regulated kinase 1/2Activation of BaxKnockdown of CD95Multiple antiapoptotic proteinsExpression of BimColony formation assaysAdenocarcinoma cellsVorinostat treatmentCD95 activationKill Tumor CellsProapoptotic signalsProtease pathwayKinase 1/2Caspase-9Cathepsin proteasesAntiapoptotic proteinsBcl-xLFADD expressionMcl-1
2007
Extrinsic pathway- and cathepsin-dependent induction of mitochondrial dysfunction are essential for synergistic flavopiridol and vorinostat lethality in breast cancer cells
Mitchell C, Park MA, Zhang G, Yacoub A, Curiel DT, Fisher PB, Roberts JD, Grant S, Dent P. Extrinsic pathway- and cathepsin-dependent induction of mitochondrial dysfunction are essential for synergistic flavopiridol and vorinostat lethality in breast cancer cells. Molecular Cancer Therapeutics 2007, 6: 3101-3112. PMID: 18065490, DOI: 10.1158/1535-7163.mct-07-0561.Peer-Reviewed Original ResearchConceptsBcl-xLC-FLIPBreast cancer cellsMitogen-activated protein/ERK kinase 1X-chromosome-linked inhibitorCancer cellsExtracellular signal-regulated kinase 1/2Apoptosis protein levelsSignal-regulated kinase 1/2ERK kinase 1CDK inhibitor roscovitineIntrinsic apoptosis pathwayHistone deacetylase inhibitor suberoylanilide hydroxamic acidForm of AktProtease-dependent pathwayInhibition of AktTreatment of cellsBak functionBcl-xL expressionCell killingCyclin-dependent kinase inhibitor flavopiridolInhibitor suberoylanilide hydroxamic acidKinase inhibitor flavopiridolERK1/2 functionAkt activity