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
2004
Phase 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
2003
Phase I and pharmacokinetic study of triapine, a potent ribonucleotide reductase inhibitor, administered daily for five days in patients with advanced solid tumors.
Murren J, Modiano M, Clairmont C, Lambert P, Savaraj N, Doyle T, Sznol M. Phase I and pharmacokinetic study of triapine, a potent ribonucleotide reductase inhibitor, administered daily for five days in patients with advanced solid tumors. Clinical Cancer Research 2003, 9: 4092-100. PMID: 14519631.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityAdverse eventsSafety profilePhase IGrade 3Week scheduleDrug-related adverse eventsGrade 2 adverse eventsGrade 1Common nonhematological toxicitiesGrade 4 leukopeniaSingle-patient cohortsAcceptable safety profileAdvanced solid tumorsDose-escalation phaseHepatic adverse eventsPhase II trialCohort of patientsCumulative urinary recoveryLinear pharmacokinetic behaviorPotent ribonucleotide reductase inhibitorNonhematological toxicitiesII trialMean eliminationStarting dose