2014
Expanded Use Trials—Are There Better Approaches to Minimize Adverse Consequences to the Clinical Trials Program?
Sznol M. Expanded Use Trials—Are There Better Approaches to Minimize Adverse Consequences to the Clinical Trials Program? The Cancer Journal 2014, 20: 25-26. PMID: 24445760, DOI: 10.1097/ppo.0000000000000022.Peer-Reviewed Original Research
2013
Advances in the systemic treatment of metastatic melanoma.
Yushak M, Kluger HM, Sznol M. Advances in the systemic treatment of metastatic melanoma. Oncology 2013, 27: 374-81. PMID: 25184258, PMCID: PMC6092183.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalDrug Therapy, CombinationHumansImidazolesImmunologic FactorsImmunotherapy, AdoptiveIndolesIpilimumabMelanomaMutationNivolumabOximesProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins B-rafPyridonesPyrimidinonesSkin NeoplasmsSulfonamidesVemurafenibConceptsMetastatic melanomaTumor-host immune interactionsRandomized phase III trialPhase III trialsCombination of dabrafenibAdoptive cell therapyStandard of carePromising new agentPhase II dataIII trialsOverall survivalSystemic treatmentPredictive biomarkersMechanisms of resistanceTreatment outcomesIndividual patientsLimited efficacyAvailable agentsImmune interactionsNew agentsMolecular alterationsEffective agentCell therapyCurrent agentsMelanoma cells
2010
Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032
Rubinstein JC, Sznol M, Pavlick AC, Ariyan S, Cheng E, Bacchiocchi A, Kluger HM, Narayan D, Halaban R. Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. Journal Of Translational Medicine 2010, 8: 67. PMID: 20630094, PMCID: PMC2917408, DOI: 10.1186/1479-5876-8-67.Peer-Reviewed Original ResearchConceptsV600K mutationsClinical trialsBRAF V600E/K mutationK mutationPotential therapeutic responseMutant BRAF inhibitorsBRAF inhibitor PLX4032BRAF V600K mutationMelanoma patientsTherapeutic responseBRAF mutationsPatientsV600E mutationInhibitor PLX4032BRAF kinasePLX4032TrialsCommon mutationsMutationsMelanomaIncidencePLX4032, a selective BRAFV600E kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAFWT melanoma cells
Halaban R, Zhang W, Bacchiocchi A, Cheng E, Parisi F, Ariyan S, Krauthammer M, McCusker JP, Kluger Y, Sznol M. PLX4032, a selective BRAFV600E kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAFWT melanoma cells. Pigment Cell & Melanoma Research 2010, 23: 190-200. PMID: 20149136, PMCID: PMC2848976, DOI: 10.1111/j.1755-148x.2010.00685.x.Peer-Reviewed Original ResearchConceptsMelanoma cellsTumor cellsMelanoma tumor cellsPrimary melanoma cellsMetastatic tumor cellsStatus of mutationsClinical responseRate of proliferationAdvanced lesionsInhibitor PLX4032Kinase inhibitorsPLX4032ERK pathwayCell migrationNRASDownstream effectorsCell adherenceERK1/2CellsProliferationCell cycle controlMobility of cellsActive ERK1/2Therapy
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 activityCloretazineA phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer
Murren J, Modiano M, Kummar S, Clairmont C, Egorin M, Chu E, Sznol M. A phase I and pharmacokinetic study of VNP40101M, a new alkylating agent, in patients with advanced or metastatic cancer. Investigational New Drugs 2005, 23: 123-135. PMID: 15744588, DOI: 10.1007/s10637-005-5857-6.Peer-Reviewed Original ResearchConceptsPhase II trialDose levelsII trialVNP40101MGrade 2 adverse eventsIntra-patient dose escalationPre-treated patient populationBroad anti-tumor activityGrade 3 thrombocytopeniaPhase I trialPeak plasma concentrationDose-related toxicityMurine tumor modelsAnti-tumor activityModerate granulocytopeniaAcute headacheStarting doseAdverse eventsI trialMajor toxicityDose escalationFacial flushingPatient populationPlasma concentrationsMetastatic cancer
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 leukemia