2007
A Phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders
Karp JE, Giles FJ, Gojo I, Morris L, Greer J, Johnson B, Thein M, Sznol M, Low J. A Phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders. Leukemia Research 2007, 32: 71-77. PMID: 17640728, PMCID: PMC2726775, DOI: 10.1016/j.leukres.2007.05.003.Peer-Reviewed Original ResearchConceptsAggressive myeloproliferative disorderDaily x 5Refractory acute leukemiaMyeloproliferative disordersAcute leukemiaRibonucleotide reductase inhibitorReductase inhibitorsDays of fludarabineRefractory myeloid malignanciesPhase I trialDrug-related toxicityNovel ribonucleotide reductase inhibitorNucleoside analog fludarabinePotent ribonucleotide reductase inhibitorPartial responseI trialMetabolic acidosisSchedule AFludarabineMyeloid malignanciesPatientsPhase ILeukemiaDisordersInhibitorsPhase 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
2003
Phase I and pharmacodynamic study of Triapine®, a novel ribonucleotide reductase inhibitor, in patients with advanced leukemia
Giles FJ, Fracasso PM, Kantarjian HM, Cortes JE, Brown RA, Verstovsek S, Alvarado Y, Thomas DA, Faderl S, Garcia-Manero G, Wright LP, Samson T, Cahill A, Lambert P, Plunkett W, Sznol M, DiPersio JF, Gandhi V. Phase I and pharmacodynamic study of Triapine®, a novel ribonucleotide reductase inhibitor, in patients with advanced leukemia. Leukemia Research 2003, 27: 1077-1083. PMID: 12921943, DOI: 10.1016/s0145-2126(03)00118-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overDeoxyadenine NucleotidesDeoxyguanine NucleotidesDNADNA, NeoplasmEnzyme InhibitorsFemaleHumansInfusions, IntravenousLeukemia, LymphoidLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukocyte CountMaleMiddle AgedPyridinesRibonucleotide ReductasesSafetyThiosemicarbazonesConceptsDose-limiting toxicityNovel ribonucleotide reductase inhibitorDay 1Ribonucleotide reductase inhibitorReductase inhibitorsWhite blood cell countPhase IContinuous intravenous infusionBlood cell countWarrants further studyObjective responseRefractory leukemiaStarting doseAdvanced leukemiaIntravenous infusionH infusionSecond infusionHematologic malignanciesPlasma concentrationsPharmacodynamic studiesPharmacodynamic dataPatientsSecond courseDay 8H beginning