2008
Enzastaurin, an Oral Serine/Threonine Kinase Inhibitor, As Second- or Third-Line Therapy of Non–Small-Cell Lung Cancer
Oh Y, Herbst RS, Burris H, Cleverly A, Musib L, Lahn M, Bepler G. Enzastaurin, an Oral Serine/Threonine Kinase Inhibitor, As Second- or Third-Line Therapy of Non–Small-Cell Lung Cancer. Journal Of Clinical Oncology 2008, 26: 1135-1141. PMID: 18309949, DOI: 10.1200/jco.2007.14.3685.Peer-Reviewed Original ResearchConceptsOral serine/threonine kinase inhibitorCell lung cancerPFS ratesMetastatic NSCLCOverall survivalLung cancerEastern Cooperative Oncology Group performance statusSix-month PFS rateProgression-free survival ratesEpidermal growth factor inhibitorsSerine/threonine kinase inhibitorProtein kinase CKinase inhibitorsPrior systemic regimensMedian overall survivalPrimary end pointThird-line therapyPhase II trialGrowth factor inhibitorsTumor cell apoptosisMedian PFSStable diseaseCommon toxicitiesPrior therapySystemic regimens
2007
Enzastaurin, a Protein Kinase Cβ–Selective Inhibitor, and Its Potential Application as an Anticancer Agent in Lung Cancer
Herbst RS, Oh Y, Wagle A, Lahn M. Enzastaurin, a Protein Kinase Cβ–Selective Inhibitor, and Its Potential Application as an Anticancer Agent in Lung Cancer. Clinical Cancer Research 2007, 13: 4641s-4646s. PMID: 17671157, DOI: 10.1158/1078-0432.ccr-07-0538.Peer-Reviewed Original ResearchConceptsSerine/threonine kinase inhibitorLung cancerOral serine/threonine kinase inhibitorProtein kinase CFavorable safety profileCurrent phase IKinase CTumor cell apoptosisAkt pathwayClinical findingsSafety profilePKC inhibitorTumor-induced angiogenesisPreclinical experienceCell apoptosisEnzastaurinKinase inhibitorsPhase ICancerA phase II study of enzastaurin as second- or third-line treatment of non-small cell lung cancer (NSCLC)
Bepler G, Oh Y, Burris H, Cleverly A, Lahn M, Herbst R. A phase II study of enzastaurin as second- or third-line treatment of non-small cell lung cancer (NSCLC). Journal Of Clinical Oncology 2007, 25: 7543-7543. DOI: 10.1200/jco.2007.25.18_suppl.7543.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalThird-line treatmentStable diseaseOverall survivalOral serine/threonine kinase inhibitorMedian progression-free survivalMulticenter phase II trialPrior platinum-based chemotherapyDays of discontinuationMedian overall survivalObjective tumor responsePhase II studyPhase II trialPlatinum-based chemotherapyCell lung cancerWeeks of enrollmentPI3K/Akt pathwayPI3K/AktTumor cell apoptosisOral enzastaurinPFS ratesCommon toxicitiesPrior therapyII study
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
Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin.
Herbst RS, Mullani NA, Davis DW, Hess KR, McConkey DJ, Charnsangavej C, O’Reilly M, Kim HW, Baker C, Roach J, Ellis LM, Rashid A, Pluda J, Bucana C, Madden TL, Tran HT, Abbruzzese JL. Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin. Journal Of Clinical Oncology 2002, 20: 3804-14. PMID: 12228200, DOI: 10.1200/jco.2002.05.102.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAngiogenesis InhibitorsApoptosisBiomarkersCD3 ComplexCollagenDose-Response Relationship, DrugEndostatinsEndotheliumFemaleFluorodeoxyglucose F18HumansIn Situ Nick-End LabelingLasersMaleMiddle AgedNeoplasmsNeovascularization, PathologicPeptide FragmentsProspective StudiesRecombinant ProteinsTomography, Emission-ComputedConceptsTumor blood flowRh-EndoTumor cell apoptosisPositron emission tomographyBlood flowEndothelial cell apoptosisCell apoptosisClinical trialsAntiangiogenic therapyEndothelial cellsWeeks of therapyStart of therapyDose-finding clinical trialsRecombinant human endostatinHuman recombinant endostatinTreatment of cancerBiologic markersAntiangiogenic treatmentBiopsy specimensAppropriate dosePET scansBiopsy analysisHuman endostatinTherapyTumor tissue