2007
Phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies
Gojo I, Tidwell ML, Greer J, Takebe N, Seiter K, Pochron MF, Johnson B, Sznol M, Karp JE. Phase I and pharmacokinetic study of Triapine®, a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies. Leukemia Research 2007, 31: 1165-1173. PMID: 17324462, DOI: 10.1016/j.leukres.2007.01.004.Peer-Reviewed Original ResearchConceptsHematologic malignanciesDay 1White blood cell countPhase IAdvanced hematologic malignanciesBlood cell countPeak plasma concentrationPre-clinical modelsAnti-leukemia activityPotent ribonucleotide reductase inhibitorWarrants further investigationAdvanced leukemiaH infusionPlasma concentrationsDose levelsRibonucleotide reductase inhibitorCell countReductase inhibitorsPharmacokinetic studyMalignancyGrowth inhibitionFurther investigationPotent inhibitorAdultsDays
2004
A Phase I and Pharmacokinetic Study of VNP40101M, a Novel Sulfonylhydrazine Alkylating Agent, in Patients with Refractory Leukemia
Giles F, Thomas D, Garcia-Manero G, Faderl S, Cortes J, Verstovsek S, Ferrajoli A, Jeha S, Beran M, Koller C, Andreeff M, Cahill A, Clairmont C, Sznol M, Kantarjian H. A Phase I and Pharmacokinetic Study of VNP40101M, a Novel Sulfonylhydrazine Alkylating Agent, in Patients with Refractory Leukemia. Clinical Cancer Research 2004, 10: 2908-2917. PMID: 15131024, DOI: 10.1158/1078-0432.ccr-03-0738.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseAcute myeloid leukemiaMyelodysplastic syndromeVNP40101MExtramedullary toxicityMyeloid leukemiaDay 1Poor‐risk myelodysplastic syndromesAntileukemic activityPhase IMinimal extramedullary toxicitySignificant extramedullary toxicityFrequent adverse eventsPhase II doseInfusion-related toxicityPharmacokinetic studyCourse of treatmentSignificant antileukemic activityBroad antitumor activityNovel sulfonylhydrazineComplete remissionStarting doseAdverse eventsRefractory diseaseRefractory leukemiaPhase 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