2017
Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody
Segal NH, Logan TF, Hodi FS, McDermott D, Melero I, Hamid O, Schmidt H, Robert C, Chiarion-Sileni V, Ascierto PA, Maio M, Urba WJ, Gangadhar TC, Suryawanshi S, Neely J, Jure-Kunkel M, Krishnan S, Kohrt H, Sznol M, Levy R. Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody. Clinical Cancer Research 2017, 23: 1929-1936. PMID: 27756788, DOI: 10.1158/1078-0432.ccr-16-1272.Peer-Reviewed Original ResearchConceptsTreatment-related adverse eventsAdverse eventsPharmacodynamic activityCommon treatment-related adverse eventsLiver function test abnormalitiesImmuno-oncology agentsSerious adverse eventsAdvanced solid tumorsHepatic adverse eventsClin Cancer ResSignificant transaminitisMonotherapy studiesAdvanced cancerTest abnormalitiesIFN-inducible genesStandard treatmentClinical evaluationUrelumabSafety dataAgonist antibodySolid tumorsCancer ResDoseDosesWeeks
2005
Phase I Study of the Sequential Combination of Interleukin-12 and Interferon Alfa-2b in Advanced Cancer: Evidence for Modulation of Interferon Signaling Pathways by Interleukin-12
Eisenbeis CF, Lesinski GB, Anghelina M, Parihar R, Valentino D, Liu J, Nadella P, Sundaram P, Young DC, Sznol M, Walker MJ, Carson WE. Phase I Study of the Sequential Combination of Interleukin-12 and Interferon Alfa-2b in Advanced Cancer: Evidence for Modulation of Interferon Signaling Pathways by Interleukin-12. Journal Of Clinical Oncology 2005, 23: 8835-8844. PMID: 16314644, DOI: 10.1200/jco.2005.02.1691.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsDose-Response Relationship, DrugHumansInterferon alpha-2Interferon-alphaInterferon-gammaInterleukin-12Leukocytes, MononuclearMiddle AgedNeoplasmsRecombinant ProteinsSignal TransductionSTAT1 Transcription FactorTime FactorsTreatment OutcomeConceptsPatients' peripheral blood mononuclear cellsPatient PBMCsInterferon alfa-2bIFN-gammaInterleukin-12Alfa-2bRhIL-12Advanced cancerIL-12Greater IFN-gamma productionPeripheral blood mononuclear cellsPeak levelsIL-12 administrationPlasma IFN-gammaIL-12 therapyDose-limiting toxicityIFN-gamma productionHuman interleukin-12Interferon Signaling PathwayAssessable patientsIntracellular STAT1Stable diseasePeripheral bloodMononuclear cellsLevels of STAT1
2004
A phase I trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in combination with gemcitabine for patients with advanced cancer
Yen Y, Margolin K, Doroshow J, Fishman M, Johnson B, Clairmont C, Sullivan D, Sznol M. A phase I trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in combination with gemcitabine for patients with advanced cancer. Cancer Chemotherapy And Pharmacology 2004, 54: 331-342. PMID: 15148626, DOI: 10.1007/s00280-004-0821-2.Peer-Reviewed Original ResearchConceptsPhase I trialI trialAdvanced cancerToxicity profileDiffuse coronary artery diseaseST-T wave changesGemcitabine plasma concentrationsLarge liver metastasesNon-specific ST-T wave changesPhase II trialCoronary artery diseaseAsymptomatic myocardial infarctionMild QT prolongationCytotoxicity of gemcitabineEvaluable patientsGemcitabine 1000Gemcitabine doseAcute hypotensionII trialPartial responseArtery diseaseCardiovascular reserveComplete responseLiver metastasesAcute symptomsPhase I and Pharmacokinetic Study of the Ribonucleotide Reductase Inhibitor, 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, Administered by 96-Hour Intravenous Continuous Infusion
Wadler S, Makower D, Clairmont C, Lambert P, Fehn K, Sznol M. Phase I and Pharmacokinetic Study of the Ribonucleotide Reductase Inhibitor, 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone, Administered by 96-Hour Intravenous Continuous Infusion. Journal Of Clinical Oncology 2004, 22: 1553-1563. PMID: 15117978, DOI: 10.1200/jco.2004.07.158.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityIntravenous continuous infusionContinuous infusionPreclinical tumor model systemsPhase II dosesStabilization of diseaseHepatic adverse eventsMaximum-tolerated dosePhase II dosePhase II trialPhase I trialAccelerated titration designPharmacokinetic studySerum tumor markersSubstantial inter-patient variabilityAbnormal organ functionDetailed pharmacokinetic studiesTumor model systemsInter-patient variabilityStable diseaseII trialObjective responseAdverse eventsI trialAdvanced cancer