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
2012
Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours
Martin LP, Kozloff MF, Herbst RS, Samuel TA, Kim S, Rosbrook B, Tortorici M, Chen Y, Tarazi J, Olszanski AJ, Rado T, Starr A, Cohen RB. Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours. British Journal Of Cancer 2012, 107: 1268-1276. PMID: 22996612, PMCID: PMC3494424, DOI: 10.1038/bjc.2012.407.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsCommon treatment-related adverse eventsSolid tumorsTreatment-related adverse eventsAntitumour activitySelective second-generation inhibitorPhase ICo-administered agentsVascular endothelial growth factor receptorHand-foot syndromeEndothelial growth factor receptorHuman xenograft tumor modelsEfficacy of chemotherapyXenograft tumor modelMultiple tumor typesAxitinib pharmacokineticsCapecitabine pharmacokineticsGrowth factor receptorStable diseaseStarting doseAdverse eventsPartial responseComplete responseTreatment regimenDocetaxel exposurePhase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours
Kozloff MF, Martin LP, Krzakowski M, Samuel TA, Rado TA, Arriola E, De Castro Carpeño J, Herbst RS, Tarazi J, Kim S, Rosbrook B, Tortorici M, Olszanski AJ, Cohen RB. Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours. British Journal Of Cancer 2012, 107: 1277-1285. PMID: 22990652, PMCID: PMC3494447, DOI: 10.1038/bjc.2012.406.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPaclitaxel/carboplatinAdvanced non-small cell lung cancerPharmacokinetics of axitinibGemcitabine/cisplatinCell lung cancerAxitinib 5Platinum doubletsLung cancerSolid tumorsSquamous cell non-small cell lung cancerTreatment-related adverse eventsSelective second-generation inhibitorVascular endothelial growth factor receptorObjective response rateDose-limiting toxicityPhase I trialEndothelial growth factor receptorDose-finding trialDrug-drug interactionsPhase I dose-finding trialsCisplatin regimensFebrile neutropeniaGrowth factor receptorExpansion cohort
2010
Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial
Herbst RS, Sun Y, Eberhardt W, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. The Lancet Oncology 2010, 11: 619-626. PMID: 20570559, PMCID: PMC3225192, DOI: 10.1016/s1470-2045(10)70132-7.Peer-Reviewed Original ResearchConceptsProgression-free survivalMedian progression-free survivalVascular endothelial growth factor receptorCell lung cancerEpidermal growth factor receptorVandetanib groupFebrile neutropeniaGrowth factor receptorPlacebo groupAdverse eventsLung cancerCommon serious adverse eventsDefinitive phase 3 trialLonger progression-free survivalComparison of PFSDaily oral inhibitorHigher adverse eventsSecond-line treatmentFirst-line chemotherapyFirst-line therapyPhase 2 studyPhase 3 trialSerious adverse eventsFactor receptorEndothelial growth factor receptor
2008
Randomized Phase II Study of Vandetanib Alone or With Paclitaxel and Carboplatin as First-Line Treatment for Advanced Non–Small-Cell Lung Cancer
Heymach JV, Paz-Ares L, De Braud F, Sebastian M, Stewart DJ, Eberhardt WE, Ranade AA, Cohen G, Trigo JM, Sandler AB, Bonomi PD, Herbst RS, Krebs AD, Vasselli J, Johnson BE. Randomized Phase II Study of Vandetanib Alone or With Paclitaxel and Carboplatin as First-Line Treatment for Advanced Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2008, 26: 5407-5415. PMID: 18936474, DOI: 10.1200/jco.2008.17.3138.Peer-Reviewed Original ResearchConceptsProgression-free survivalPhase II studyRisk of progressionVandetanib monotherapyII studyOverall survivalLung cancerAdvanced non-small cell lung cancerNon-small cell lung cancerMedian progression-free survivalLonger progression-free survivalRandomized phase II studyShorter progression-free survivalEnd pointVascular endothelial growth factor receptorCommon adverse eventsPrimary end pointStudy end pointSquamous cell histologyEndothelial growth factor receptorCell lung cancerCNS metastasesGrowth factor receptorMonotherapy armNSCLC histology
2006
Epidermal Growth Factor Receptor Inhibitors in Development for the Treatment of Non–Small Cell Lung Cancer
Heymach JV, Nilsson M, Blumenschein G, Papadimitrakopoulou V, Herbst R. Epidermal Growth Factor Receptor Inhibitors in Development for the Treatment of Non–Small Cell Lung Cancer. Clinical Cancer Research 2006, 12: 4441s-4445s. PMID: 16857825, DOI: 10.1158/1078-0432.ccr-06-0286.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerCell lung cancerExtensive clinical testingLung cancerClinical testingRandomized phase II clinical trialEpidermal growth factor receptor inhibitor erlotinibPhase III clinical testingEpidermal growth factor receptor inhibitorsPhase II clinical trialGrowth factor receptor inhibitorsVascular endothelial growth factor receptorEndothelial growth factor receptorAdvanced clinical testingMultiple EGFR family membersGrowth factor receptorReceptor inhibitionClinical trialsEGFR family membersClinical activityReceptor inhibitorsPreclinical studiesInhibitor erlotinibClinical developmentSolid tumors
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
2002
Angiogenesis inhibitors in lung cancer
Kim ES, Herbst RS. Angiogenesis inhibitors in lung cancer. Current Oncology Reports 2002, 4: 325-333. PMID: 12044242, DOI: 10.1007/s11912-002-0008-0.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAngiostatinsCarcinoma, Non-Small-Cell LungCollagenCyclohexanesEndostatinsHumansLung NeoplasmsO-(Chloroacetylcarbamoyl)fumagillolPeptide FragmentsPlasminogenReceptor Protein-Tyrosine KinasesReceptors, Growth FactorReceptors, Vascular Endothelial Growth FactorSesquiterpenesSurvival RateThalidomideConceptsLung cancerAngiogenesis inhibitorsSurvival rateMajor public health problemVascular endothelial growth factor receptorOngoing randomized studiesCell lung cancerEndothelial growth factor receptorTraditional cytotoxic therapiesCancer-related deathImproved survival ratesPublic health problemSevere side effectsInhibitors of angiogenesisEndogenous angiogenesis inhibitorGrowth factor receptorMetastatic diseaseRandomized studyChemotherapy dosesClinical benefitCytotoxic therapyCyclooxygenase inhibitorRadiation therapySide effectsHealth problems