2019
Red blood cell alloimmunization is associated with lower expression of FcγR1 on monocyte subsets in patients with sickle cell disease
Balbuena‐Merle R, Curtis SA, Devine L, Gibb DR, Karafin MS, Luckey CJ, Tormey CA, Siddon AJ, Roberts JD, Hendrickson JE. Red blood cell alloimmunization is associated with lower expression of FcγR1 on monocyte subsets in patients with sickle cell disease. Transfusion 2019, 59: 3219-3227. PMID: 31355970, PMCID: PMC7075520, DOI: 10.1111/trf.15463.Peer-Reviewed Original ResearchConceptsSickle cell diseaseMonocyte subsetsTotal monocytesCell diseaseComplications of SCDRed blood cell alloimmunizationRed blood cell alloantibodiesElectronic medical recordsTransfusion exposureSerum cytokinesIntermediate monocytesRBC alloantibodiesInflammatory milieuCD64 expressionClassical monocytesPeripheral bloodInflammatory functionsMedical recordsAntibody formationClinical significancePatientsMonocytesFlow cytometryLow expressionResponders
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
2017
Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial
Himelstein AL, Foster JC, Khatcheressian JL, Roberts JD, Seisler DK, Novotny PJ, Qin R, Go RS, Grubbs SS, O’Connor T, Velasco MR, Weckstein D, O’Mara A, Loprinzi CL, Shapiro CL. Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial. JAMA 2017, 317: 48-58. PMID: 28030702, PMCID: PMC5321662, DOI: 10.1001/jama.2016.19425.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBone and BonesBone Density Conservation AgentsBone NeoplasmsBreast NeoplasmsDiphosphonatesDrug Administration ScheduleFemaleHumansImidazolesMaleMiddle AgedMultiple MyelomaPain MeasurementProstatic NeoplasmsSample SizeSpinal Cord CompressionSpinal FracturesZoledronic AcidConceptsSkeletal morbidity rateProportion of patientsDosing groupZoledronic acidBone metastasesMultiple myelomaProstate cancerBreast cancerSkeletal eventsKidney dysfunctionBone turnoverMorbidity rateClinical trialsEastern Cooperative Oncology Group performance statusOpen-label clinical trialEnd pointIncidence of osteonecrosisYear of randomizationPerformance status scorePrimary end pointSecondary end pointsBrief Pain InventoryMetastatic breast cancerMetastatic prostate cancerAcceptable treatment option
2016
Phase I study of pemetrexed with sorafenib in advanced solid tumors
Poklepovic A, Gordon S, Shafer DA, Roberts JD, Bose P, Geyer CE, McGuire WP, Tombes MB, Shrader E, Strickler K, Quigley M, Wan W, Kmieciak M, Massey HD, Booth L, Moran RG, Dent P. Phase I study of pemetrexed with sorafenib in advanced solid tumors. Oncotarget 2016, 7: 42625-42638. PMID: 27213589, PMCID: PMC5173162, DOI: 10.18632/oncotarget.9434.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCohort StudiesFemaleHumansInflammationMaleMaximum Tolerated DoseMiddle AgedNeoplasmsNiacinamidePemetrexedPhenylurea CompoundsPTEN PhosphohydrolaseSorafenibTreatment OutcomeTriple Negative Breast NeoplasmsConceptsAdvanced solid tumorsDay 1Solid tumorsOral sorafenibDose scheduleBreast cancerTriple-negative breast cancerDose-escalation schemaPhase II dosePhase I trialSorafenib dosingSorafenib therapyStable diseaseCohort BComplete responseI trialPartial responseTolerable combinationRadiographic assessmentCumulative toxicityCombination treatmentPatientsSorafenibPhase IAntitumor activityA phase I study of indoximod in patients with advanced malignancies
Soliman HH, Minton SE, Han HS, Ismail-Khan R, Neuger A, Khambati F, Noyes D, Lush R, Chiappori AA, Roberts JD, Link C, Vahanian NN, Mautino M, Streicher H, Sullivan DM, Antonia SJ. A phase I study of indoximod in patients with advanced malignancies. Oncotarget 2016, 7: 22928-22938. PMID: 27008709, PMCID: PMC5008412, DOI: 10.18632/oncotarget.8216.Peer-Reviewed Original ResearchConceptsStable diseaseDose levelsC-reactive protein levelsReactive protein levelsAdvanced solid tumorsTumor-mediated immunosuppressionPhase I trialUntreated brain metastasesMetastatic solid malignanciesMultiple dose levelsAntigen autoantibodiesBrain metastasesCheckpoint inhibitorsImmune correlatesPrimary endpointSecondary endpointsAdvanced malignanciesCRP levelsI trialOral inhibitorAutoimmune diseasesMarrow functionSolid malignanciesInclusion criteriaExclusion criteriaA Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma
Holkova B, Zingone A, Kmieciak M, Bose P, Badros AZ, Voorhees PM, Baz R, Korde N, Lin HY, Chen JQ, Herrmann M, Xi L, Raffeld M, Zhao X, Wan W, Tombes MB, Shrader E, Weir-Wiggins C, Sankala H, Hogan KT, Doyle A, Annunziata CM, Wellons M, Roberts JD, Sullivan D, Landgren O, Grant S. A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma. Clinical Cancer Research 2016, 22: 1067-1075. PMID: 26446942, PMCID: PMC4775365, DOI: 10.1158/1078-0432.ccr-15-1076.Peer-Reviewed Original ResearchConceptsRefractory multiple myelomaPartial responseMultiple myelomaRelapsed/Refractory Multiple MyelomaMedian progression-free survival timeResponse rateProgression-free survival timeTwo-stage Simon designCommon grade 3Good partial responsePhase II studyPhase II trialMEK1/2 inhibitorSignificant preclinical activityMultiple myeloma cellsPrior therapyStable diseaseII trialClinical responseII studyProgressive diseaseMedian ageMean durationPreclinical activityDisease progression
2015
Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors
Wong SJ, Karrison T, Hayes DN, Kies MS, Cullen KJ, Tanvetyanon T, Argiris A, Takebe N, Lim D, Saba NF, Worden FP, Gilbert J, Lenz HJ, Razak AR, Roberts JD, Vokes EE, Cohen EE. Phase II trial of dasatinib for recurrent or metastatic c-KIT expressing adenoid cystic carcinoma and for nonadenoid cystic malignant salivary tumors. Annals Of Oncology 2015, 27: 318-323. PMID: 26598548, PMCID: PMC4722891, DOI: 10.1093/annonc/mdv537.Peer-Reviewed Original ResearchConceptsMalignant salivary gland tumorsAdverse eventsStable diseaseObjective responseACC patientsCystic carcinomaECOG performance status 0Grade 3 adverse eventsMedian age 56 yearsGrade 4 adverse eventsMedian progression-free survivalFrequent adverse eventsMedian overall survivalNon-ACC patientsPerformance status 0Noncardiac chest painPhase II studyPhase II trialProgression-free survivalAge 56 yearsMalignant salivary tumorsAdenoid cystic carcinomaSalivary gland tumorsCycle 2Prior chemotherapy
2014
Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Nonhybrid” (Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms
Holkova B, Kmieciak M, Perkins EB, Bose P, Baz RC, Roodman GD, Stuart RK, Ramakrishnan V, Wan W, Peer CJ, Dawson J, Kang L, Honeycutt C, Tombes MB, Shrader E, Weir-Wiggins C, Wellons M, Sankala H, Hogan KT, Colevas AD, Doyle LA, Figg WD, Coppola D, Roberts JD, Sullivan D, Grant S. Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Nonhybrid” (Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms. Clinical Cancer Research 2014, 20: 5652-5662. PMID: 25248382, PMCID: PMC4233160, DOI: 10.1158/1078-0432.ccr-14-0805.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityCombination of bortezomibCommon hematologic toxicityCommon nonhematologic toxicitiesIndolent B-cell neoplasmsRefractory multiple myelomaDose-escalation designNon-Hodgkin lymphomaTotal response rateB-cell malignanciesB-cell neoplasmsPharmacodynamic study resultsNonhematologic toxicitySchedule regimenStable diseaseComplete remissionHematologic toxicityPartial remissionClinical responseInvestigator's discretionDosing regimenI trialPharmacokinetic findingsSensory neuropathyInfusion schedule
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 objectivePhase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma
Poklepovic A, Youseffian L, Winning M, Birdsell CA, Crosby NA, Ramakrishnan V, Ernstoff MS, Roberts JD. Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma. Investigational New Drugs 2013, 31: 937-942. PMID: 23315028, PMCID: PMC3844155, DOI: 10.1007/s10637-012-9913-8.Peer-Reviewed Original ResearchConceptsSoft tissue sarcomasPhase I trialTissue sarcomasPartial responseI trialPhase II dosesDurable complete responseAmine precursor uptakeTwenty-eight patientsProteasome inhibitor bortezomibHuman melanoma cell linesMurine xenograft tumor modelXenograft tumor modelCKIT mutationsDecarboxylation (APUD) tumorsProphylactic antiemeticsRECIST v1.0Eight patientsComplete responseMelanoma cell linesWeekly dosesDose escalationAgent dacarbazinePreclinical studiesDose levels
2012
Phase I trial of the combination of flavopiridol and imatinib mesylate in patients with Bcr-Abl+ hematological malignancies
Bose P, Perkins EB, Honeycut C, Wellons MD, Stefan T, Jacobberger JW, Kontopodis E, Beumer JH, Egorin MJ, Imamura CK, Douglas Figg W, Karp JE, Koc ON, Cooper BW, Luger SM, Colevas AD, Roberts JD, Grant S. Phase I trial of the combination of flavopiridol and imatinib mesylate in patients with Bcr-Abl+ hematological malignancies. Cancer Chemotherapy And Pharmacology 2012, 69: 1657-1667. PMID: 22349810, PMCID: PMC3365614, DOI: 10.1007/s00280-012-1839-5.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsCombination of flavopiridolStable diseasePhase I dose-escalation studyPhiladelphia chromosome-positive acute leukemiaSecond-generation BCR-ABL tyrosine kinase inhibitorBone marrow blast countI dose-escalation studyBCR-ABL tyrosine kinase inhibitorsKinase inhibitorsImatinib-resistant diseaseIntravenous infusion weeklyPhase II dosesDose-escalation studyMarrow blast countPhase I trialNovel combination regimenMajor pharmacokinetic interactionsBCR-ABL tyrosine kinaseChronic myelogenous leukemiaInfusion weeklyCyclin-dependent kinase inhibitorBlast countCombination regimenComplete response
2011
Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory B-Cell Neoplasms
Holkova B, Perkins EB, Ramakrishnan V, Tombes MB, Shrader E, Talreja N, Wellons MD, Hogan KT, Roodman GD, Coppola D, Kang L, Dawson J, Stuart RK, Peer C, Figg WD, Kolla S, Doyle A, Wright J, Sullivan DM, Roberts JD, Grant S. Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory B-Cell Neoplasms. Clinical Cancer Research 2011, 17: 3388-3397. PMID: 21447728, PMCID: PMC3096752, DOI: 10.1158/1078-0432.ccr-10-2876.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityCombination of bortezomibFebrile neutropeniaPharmacodynamic studiesDay 1Refractory B-cell neoplasmsElevated aspartate aminotransferase levelsCommon hematologic toxicityCommon nonhematologic toxicitiesPhase II studyRefractory multiple myelomaPhase I studiesAspartate aminotransferase levelsB-cell malignanciesB-cell neoplasmsHematologic toxicityIntravenous pushNonhematologic toxicityStable diseaseAminotransferase levelsI trialII studyPartial responseComplete responseDose escalation
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
2009
Phase I study of bryostatin 1, a protein kinase C modulator, preceding cisplatin in patients with refractory non-hematologic tumors
Pavlick AC, Wu J, Roberts J, Rosenthal MA, Hamilton A, Wadler S, Farrell K, Carr M, Fry D, Murgo AJ, Oratz R, Hochster H, Liebes L, Muggia F. Phase I study of bryostatin 1, a protein kinase C modulator, preceding cisplatin in patients with refractory non-hematologic tumors. Cancer Chemotherapy And Pharmacology 2009, 64: 803. PMID: 19221754, PMCID: PMC3901370, DOI: 10.1007/s00280-009-0931-y.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsPhase INon-hematologic tumorsPhase II dosesPhase II doseDose-limiting toxicityResultsFifty-three patientsBlood mononuclear cellsNon-hematologic malignanciesBryostatin 1Cytotoxicity of cisplatinCisplatin 50PurposePreclinical dataObjective responseContinuous infusionMononuclear cellsTolerable dosesProtein kinase C modulatorsCisplatin effectComputerized tomographyPatientsConsistent inhibitionCisplatin cytotoxicityCisplatinMinimal toxicity
2006
Phase I Study of Bryostatin 1 and Fludarabine in Patients with Chronic Lymphocytic Leukemia and Indolent (Non-Hodgkin's) Lymphoma
Roberts JD, Smith MR, Feldman EJ, Cragg L, Millenson MM, Roboz GJ, Honeycutt C, Thune R, Padavic-Shaller K, Carter WH, Ramakrishnan V, Murgo AJ, Grant S. Phase I Study of Bryostatin 1 and Fludarabine in Patients with Chronic Lymphocytic Leukemia and Indolent (Non-Hodgkin's) Lymphoma. Clinical Cancer Research 2006, 12: 5809-5816. PMID: 17020988, DOI: 10.1158/1078-0432.ccr-05-2730.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBryostatinsDose-Response Relationship, DrugDrug Administration ScheduleFemaleHumansLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Non-HodgkinMacrolidesMaleMaximum Tolerated DoseMiddle AgedPrognosisSurvival RateVidarabineConceptsChronic lymphocytic leukemiaIndolent lymphomaLymphocytic leukemiaBryostatin 1Dose-limiting toxic eventsTreatment of CLLMonoclonal antibodiesPhase II dosePhase II dosesPhase II studyCD20 monoclonal antibodyII studyPersistent diseaseSuccessive patientsSingle doseContinuous infusionI studiesHematologic malignanciesPreclinical studiesTherapeutic effectFludarabinePatientsPrior treatmentLymphomaPhase IPhase 2 Study of the g209-2M Melanoma Peptide Vaccine and Low-Dose Interleukin-2 in Advanced Melanoma
Roberts JD, Niedzwiecki D, Carson WE, Chapman PB, Gajewski TF, Ernstoff MS, Hodi FS, Shea C, Leong SP, Johnson J, Zhang D, Houghton A, Haluska FG. Phase 2 Study of the g209-2M Melanoma Peptide Vaccine and Low-Dose Interleukin-2 in Advanced Melanoma. Journal Of Immunotherapy 2006, 29: 95-101. PMID: 16365605, DOI: 10.1097/01.cji.0000195295.74104.ad.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCancer VaccinesDose-Response Relationship, DrugFemaleGp100 Melanoma AntigenHumansInterleukin-2Leukocytes, MononuclearMaleMelanomaMembrane GlycoproteinsMiddle AgedNeoplasm Recurrence, LocalPeptide FragmentsPeptidesSkin NeoplasmsConceptsLow-dose IL-2G209-2MG209-2M peptideHigh-dose IL-2Phase 2 studyAdvanced melanomaInterleukin-2T cellsHigh-dose interleukin-2Low-dose interleukin-2Melanoma tumor-infiltrating lymphocytesGrade 4 toxicityMelanoma peptide vaccineSubcutaneous IL-2Grade 2 toxicityGrade 3 toxicityTumor-infiltrating lymphocytesEnzyme-linked immunospotHuman leukocyte antigenDifferent toxicity profilesM peptideSignificant biologic effectsTetramer analysisToxic deathsMost patients
2002
Phase I trial and correlative laboratory studies of bryostatin 1 (NSC 339555) and high-dose 1-B-D-arabinofuranosylcytosine in patients with refractory acute leukemia.
Cragg LH, Andreeff M, Feldman E, Roberts J, Murgo A, Winning M, Tombes MB, Roboz G, Kramer L, Grant S. Phase I trial and correlative laboratory studies of bryostatin 1 (NSC 339555) and high-dose 1-B-D-arabinofuranosylcytosine in patients with refractory acute leukemia. Clinical Cancer Research 2002, 8: 2123-33. PMID: 12114412.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPhase I trialComplete remissionCorrelative laboratory studiesI trialAcute leukemiaSplit courseContinuous infusionVivo administrationBryostatin 1Ara-C dose levelsAutologous bone marrow transplantationMajor dose-limiting toxicityEx vivoRefractory acute leukemiaUnfavorable prognostic characteristicsHigh-risk featuresLeukemia-free survivalBone marrow transplantationCourse of therapyPKC activityTransfusion requirementsRefractory leukemiaRefractory/Latter patientsHigher doses of mitoxantrone among men with hormone‐refractory prostate carcinoma
Levine EG, Halabi S, Roberts JD, Kaplan EB, Rago R, Atkins JN, Vogelzang NJ. Higher doses of mitoxantrone among men with hormone‐refractory prostate carcinoma. Cancer 2002, 94: 665-672. PMID: 11857298, DOI: 10.1002/cncr.10217.Peer-Reviewed Original ResearchConceptsHormone-refractory prostate carcinomaHigh dosesPelvic irradiationProstate carcinomaArm IFrequency of thrombocytopeniaLow-dose glucocorticoidsArm IIPhase II trialPhase III trialsPhase III testingMedian survival timeGranulocyte-macrophage colony-stimulating factorColony-stimulating factorAssessable patientsEstramustine combinationsII trialIII trialsMedian survivalPartial responsePSA valuesFavorable outcomeSurvival timePatientsSame schedule
2000
Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034.
McLeod HL, Cassidy J, Powrie RH, Priest DG, Zorbas MA, Synold TW, Shibata S, Spicer D, Bissett D, Pithavala YK, Collier MA, Paradiso LJ, Roberts JD. Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide formyltransferase inhibitor AG2034. Clinical Cancer Research 2000, 6: 2677-84. PMID: 10914709.Peer-Reviewed Original ResearchConceptsGlycinamide ribonucleotide formyltransferaseCourse 1Systemic clearanceGrade III/IV toxicityGrade II toxicityMin/m2Rapid systemic clearanceVolume of distributionEvaluable patientsSystemic exposurePharmacodynamic evaluationClinical centersBolus injectionPharmacokinetic approachBlood samplesPatient toxicityPatientsElimination patternReproducible ELISAAG2034Course 3Phase IAnticancer agentsPurine synthesis pathwayDe novo purine synthesis pathwayPhase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks
Roberts J, Shibata S, Spicer D, McLeod H, Tombes M, Kyle B, Carroll M, Sheedy B, Collier M, Pithavala Y, Paradiso L, Clendeninn N. Phase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks. Cancer Chemotherapy And Pharmacology 2000, 45: 423-427. PMID: 10803927, DOI: 10.1007/s002800051012.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityPhase II doseCumulative toxicityAdvanced malignanciesIntravenous bolusAUC0-24Pharmacodynamic factorsFolate supplementationPlasma concentrationsIntermediate dosePharmacokinetic analysisDose levelsELISA assaysDosePhase IAG2034Progressive increaseGARFT inhibitorToxicityWeeksInhibitorsMucositisThrombocytopeniaDiarrheaHyperbilirubinemia