2020
A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors
Varga A, Soria JC, Hollebecque A, LoRusso P, Bendell J, Huang SA, Wagle MC, Okrah K, Liu L, Murray E, Sanabria-Bohorquez SM, Tagen M, Dokainish H, Mueller L, Burris H. A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors. Clinical Cancer Research 2020, 26: 1229-1236. PMID: 31848189, DOI: 10.1158/1078-0432.ccr-19-2574.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedDose-Response Relationship, DrugFatigueFemaleHumansMaleMAP Kinase Signaling SystemMaximum Tolerated DoseMiddle AgedMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NauseaNeoplasmsPatient SafetyProtein Kinase InhibitorsPyridonesPyrimidinesTissue DistributionVomitingConceptsBRAF-mutant colorectal cancerColorectal cancerAdverse eventsFDG-PETCommon drug-related adverse eventsSolid tumorsDrug-related adverse eventsPhase IPartial metabolic responseAcceptable safety profileAdvanced solid tumorsDose-proportional increaseGrade 3 rashMetastatic solid tumorsSerial tumor biopsiesSingle-agent activityBest overall responseHuman phase IMAPK pathway inhibitionMultiple tumor typesStable diseaseEscalation studyPartial responseOral inhibitorPharmacodynamic effects
2002
Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition.
Albanell J, Rojo F, Averbuch S, Feyereislova A, Mascaro J, Herbst R, LoRusso P, Rischin D, Sauleda S, Gee J, Nicholson R, Baselga J. Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. Journal Of Clinical Oncology 2002, 20: 110-24. PMID: 11773160, DOI: 10.1200/jco.2002.20.1.110.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntineoplastic AgentsApoptosisBiomarkersCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p27Dose-Response Relationship, DrugErbB ReceptorsFemaleGefitinibHumansKeratinocytesMaleMAP Kinase Signaling SystemMiddle AgedNeoplasmsQuinazolinesSkinStatistics, NonparametricTumor Suppressor ProteinsConceptsCancer patientsEpidermal growth factor receptor tyrosine kinase inhibitor ZD1839Tyrosine kinase inhibitor ZD1839Phase I clinical trialMaximum-tolerated doseDose-limiting toxicityEGFR activationReceptor-dependent processUnacceptable toxicityDefinitive efficacyPharmacodynamic assessmentSafety trialPharmacodynamic effectsClinical trialsKeratin plugsReceptor inhibitionMaturation markersSkin biopsiesPharmacodynamic studiesProliferation indexDose levelsOral ZD1839PatientsOptimal dosesZD1839