2013
Phase I–IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours
Soria JC, Baselga J, Hanna N, Laurie SA, Bahleda R, Felip E, Calvo E, Armand JP, Shepherd FA, Harbison CT, Berman D, Park JS, Zhang S, Vakkalagadda B, Kurland JF, Pathak AK, Herbst RS. Phase I–IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours. European Journal Of Cancer 2013, 49: 1815-1824. PMID: 23490650, DOI: 10.1016/j.ejca.2013.02.012.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedArea Under CurveCarcinoma, Non-Small-Cell LungDiarrheaDose-Response Relationship, DrugDrug Resistance, NeoplasmErbB ReceptorsErlotinib HydrochlorideExanthemaFemaleHumansLung NeoplasmsMaleMetabolic Clearance RateMiddle AgedNeoplasm MetastasisNeoplasmsPiperidinesProtein Kinase InhibitorsPyrrolesQuinazolinesReceptor, ErbB-2Treatment OutcomeTriazinesVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-3ConceptsIIa studyBMS-690514Growth factor receptorPhase IAdverse eventsEGFR mutationsHER-2Phase IIaFrequent treatment-related adverse eventsSolid tumorsTreatment-related adverse eventsOral tyrosine kinase inhibitorDisease controlVascular endothelial growth factor receptorManageable safety profileObjective response rateAdvanced solid tumorsFactor receptorMetastatic solid tumorsEndothelial growth factor receptorCell lung cancerTyrosine kinase inhibitorsInhibition of VEGFREpidermal growth factor receptorWild-type EGFR
2006
Toxicities of Antiangiogenic Therapy in Non–Small-Cell Lung Cancer
Herbst RS. Toxicities of Antiangiogenic Therapy in Non–Small-Cell Lung Cancer. Clinical Lung Cancer 2006, 8: s23-s30. PMID: 17239287, DOI: 10.3816/clc.2006.s.010.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBenzenesulfonatesBevacizumabCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellHumansIndolesLung NeoplasmsNiacinamidePhenylurea CompoundsPiperidinesPyridinesPyrrolesQuinazolinesSorafenibSunitinibVascular Endothelial Growth FactorsConceptsAnti-VEGF antibodyCell lung cancerVascular endothelial growth factorAntiangiogenic agentsOverall survivalLung cancerPhase III pivotal trialsClass-effect toxicitiesFirst-line chemotherapyAdverse event profileSquamous cell histologyChemotherapy-associated toxicityVEGFR tyrosine kinaseTyrosine kinase inhibitorsEndothelial growth factorMetastatic NSCLCThromboembolic eventsCell histologyPivotal trialsEvent profileRisk factorsVEGF receptor activityAntiangiogenic therapySmall molecule inhibitorsTumor types
2005
Pharmacodynamic Analysis of Target Inhibition and Endothelial Cell Death in Tumors Treated with the Vascular Endothelial Growth Factor Receptor Antagonists SU5416 or SU6668
Davis DW, Takamori R, Raut CP, Xiong HQ, Herbst RS, Stadler WM, Heymach JV, Demetri GD, Rashid A, Shen Y, Wen S, Abbruzzese JL, McConkey DJ. Pharmacodynamic Analysis of Target Inhibition and Endothelial Cell Death in Tumors Treated with the Vascular Endothelial Growth Factor Receptor Antagonists SU5416 or SU6668. Clinical Cancer Research 2005, 11: 678-689. PMID: 15701856, DOI: 10.1158/1078-0432.678.11.2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsApoptosisDose-Response Relationship, DrugEndothelium, VascularFemaleHumansIndolesMaleMiceMice, NudeMiddle AgedNeovascularization, PathologicOxindolesPancreatic NeoplasmsPhosphorylationPropionatesPyrrolesReceptor, Platelet-Derived Growth Factor betaTransplantation, HeterologousVascular Endothelial Growth Factor Receptor-2ConceptsPlatelet-derived growth factor receptorTumor microvessel densityGrowth factor receptorMicrovessel densityCell apoptosisVascular endothelial growth factor receptorAdvanced solid malignanciesFactor receptorEndothelial growth factor receptorPrimary patient tumorsG core biopsyDose-dependent effectPhosphorylated VEGFR-2Primary human tumorsEndothelial cell deathCell deathEndothelial cell apoptosisTumor cell apoptosisTumor cell deathPost therapyCore biopsyPharmacodynamic analysisSolid malignanciesVessel sizeClinical trials
2004
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Does Not Improve Paclitaxel Effect in an Orthotopic Mouse Model of Lung Cancer
Onn A, Isobe T, Wu W, Itasaka S, Shintani T, Shibuya K, Kenji Y, O’Reilly M, Fidler IJ, Herbst RS. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Does Not Improve Paclitaxel Effect in an Orthotopic Mouse Model of Lung Cancer. Clinical Cancer Research 2004, 10: 8613-8619. PMID: 15623645, DOI: 10.1158/1078-0432.ccr-04-1241.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, Bronchiolo-AlveolarAnimalsAntineoplastic Agents, PhytogenicCarcinoma, Non-Small-Cell LungDrug Therapy, CombinationEnzyme ActivationEnzyme InhibitorsErbB ReceptorsFibroblast Growth Factor 2HumansLung NeoplasmsMaleMiceMice, NudeMitogen-Activated Protein KinasesModels, AnimalPaclitaxelPhosphorylationPyrimidinesPyrrolesSurvival RateConceptsEGFR tyrosine kinase inhibitorsTumor implantationLung cancerKinase inhibitorsEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsBasic fibroblast growth factor expressionCombination of paclitaxelFibroblast growth factor expressionGroups of miceLungs of miceOrthotopic mouse modelHuman lung cancerTyrosine kinase inhibitorsGrowth factor expressionMaximal therapeutic effectHuman lung adenocarcinoma cellsLung adenocarcinoma cellsPaclitaxel 100Phosphorylation of EGFRConcurrent administrationEGFR-TKITherapeutic effectEpidermal growth factor receptor (EGFR) activationA phase I surrogate endpoint study of SU6668 in patients with solid tumors
Xiong HQ, Herbst R, Faria SC, Scholz C, Davis D, Jackson EF, Madden T, McConkey D, Hicks M, Hess K, Charnsangavej C, Abbruzzese JL. A phase I surrogate endpoint study of SU6668 in patients with solid tumors. Investigational New Drugs 2004, 22: 459-466. PMID: 15292716, DOI: 10.1023/b:drug.0000036688.96453.8d.Peer-Reviewed Original ResearchConceptsCore needle biopsyBiologic effectsNeedle biopsyDay 1Solid tumorsMean apparent oral clearanceContrast-enhanced magnetic resonance imagingApparent oral clearanceDynamic contrast-enhanced magnetic resonance imagingCorrelative studiesHigh-performance liquid chromatography assayMagnetic resonance imagingDCE-MRI resultsEligible patientsOral clearanceLiquid chromatography assayEndpoint studiesAntiangiogenic agentsFunctional CTBlood flowTumor specimensPatientsTissue biopsiesDay 22PK studies