2018
First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study
Sullivan RJ, Infante JR, Janku F, Wong DJL, Sosman JA, Keedy V, Patel MR, Shapiro GI, Mier JW, Tolcher AW, Wang-Gillam A, Sznol M, Flaherty K, Buchbinder E, Carvajal RD, Varghese AM, Lacouture ME, Ribas A, Patel SP, DeCrescenzo GA, Emery CM, Groover AL, Saha S, Varterasian M, Welsch DJ, Hyman DM, Li BT. First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study. Cancer Discovery 2018, 8: 184-195. PMID: 29247021, DOI: 10.1158/2159-8290.cd-17-1119.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAminopyridinesFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesMutationNeoplasm StagingNeoplasmsProtein Kinase InhibitorsPyrrolesTomography, X-Ray ComputedTreatment OutcomeYoung AdultConceptsCommon treatment-related adverse eventsSolid tumorsHuman dose-escalation studyMulticenter phase I trialTreatment-related adverse eventsDose-escalation cohortsDose-expansion cohortsMutant solid tumorsPhase II doseAcceptable safety profileAdvanced solid tumorsDose-escalation studyPhase I trialPotent preclinical activityTreatment of patientsSolid tumor malignanciesERK1/2 kinase inhibitorEvaluable patientsDose expansionExpansion cohortAdverse eventsPartial responseDose escalationI trialSafety profile
2006
Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome
Yee KW, Cortes J, Ferrajoli A, Garcia-Manero G, Verstovsek S, Wierda W, Thomas D, Faderl S, King I, O’Brien S, Jeha S, Andreeff M, Cahill A, Sznol M, Giles FJ. Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. Leukemia Research 2006, 30: 813-822. PMID: 16478631, DOI: 10.1016/j.leukres.2005.12.013.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCytarabineDose-Response Relationship, DrugDrug Administration ScheduleDrug CombinationsFemaleHumansInjections, IntravenousLeukemia, MyeloidMaleMaximum Tolerated DoseMiddle AgedMyelodysplastic SyndromesPyridinesRecurrenceRisk FactorsThiosemicarbazonesTreatment OutcomeConceptsAra-C dose levelsDose levelsM2/dayAcute leukemiaSignificant anti-leukemia activityConsecutive daysPhase II regimenRefractory acute leukemiaHigh-risk MDSAnti-leukemia activityEvaluable patientsMyelodysplastic syndromeActive combinationPatientsPhase IIron chelatorsLeukemiaAraPotent inhibitorDaysTriapineRegimenCytarabineInfusionSyndrome
2005
Phase I Study of Cloretazine (VNP40101M), a Novel Sulfonylhydrazine Alkylating Agent, Combined with Cytarabine in Patients with Refractory Leukemia
Giles F, Verstovsek S, Thomas D, Gerson S, Cortes J, Faderl S, Ferrajoli A, Ravandi F, Kornblau S, Garcia-Manero G, Jabbour E, O'Brien S, Karsten V, Cahill A, Yee K, Albitar M, Sznol M, Kantarjian H. Phase I Study of Cloretazine (VNP40101M), a Novel Sulfonylhydrazine Alkylating Agent, Combined with Cytarabine in Patients with Refractory Leukemia. Clinical Cancer Research 2005, 11: 7817-7824. PMID: 16278404, DOI: 10.1158/1078-0432.ccr-05-1070.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlkylating AgentsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBase Pair MismatchCohort StudiesCytarabineDisease ProgressionDNADNA RepairFemaleHumansHydrazinesLeukemiaLeukocytes, MononuclearMaleMiddle AgedModels, ChemicalO(6)-Methylguanine-DNA MethyltransferaseSulfonamidesTime FactorsConceptsContinuous infusionAGT activityAra-C regimenSignificant antileukemia activityPredictors of responseAcute myeloid leukemiaCourse of treatmentGm/Significant antileukemic activityEvaluable patientsNovel sulfonylhydrazineRefractory diseaseRefractory leukemiaStarting doseComplete responseDose schedulePatient subsetsMyeloid leukemiaPatientsAlkylguanine-DNA alkyltransferaseDose levelsDay 2Antileukemia activityAntileukemic activityCloretazine
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 symptoms