Phase I Trial of the Oral Antiangiogenesis Agent AG-013736 in Patients With Advanced Solid Tumors: Pharmacokinetic and Clinical Results
Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD, Freddo JL, Wilding G. Phase I Trial of the Oral Antiangiogenesis Agent AG-013736 in Patients With Advanced Solid Tumors: Pharmacokinetic and Clinical Results. Journal Of Clinical Oncology 2005, 23: 5474-5483. PMID: 16027439, DOI: 10.1200/jco.2005.04.192.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsAG-013736Clinical activityOral receptor tyrosine kinase inhibitorSolid tumorsReceptor tyrosine kinase inhibitorsGrowth factorSingle test dosesMaximum-tolerated dosePhase II doseDose-limiting toxicitySignificant drug interactionsPeak plasma concentrationEndothelial cell growth factorPhase II testingVascular endothelial cell growth factorTyrosine kinase inhibitorsHighest dose levelPlatelet-derived growth factorIndividual PK parametersEffect of foodCell growth factorObserved hypertensionDrug holidayPartial responseDynamic Contrast-Enhanced Magnetic Resonance Imaging As a Pharmacodynamic Measure of Response After Acute Dosing of AG-013736, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors: Results From a Phase I Study
Liu G, Rugo HS, Wilding G, McShane TM, Evelhoch JL, Ng C, Jackson E, Kelcz F, Yeh BM, Lee FT, Charnsangavej C, Park JW, Ashton EA, Steinfeldt HM, Pithavala YK, Reich SD, Herbst RS. Dynamic Contrast-Enhanced Magnetic Resonance Imaging As a Pharmacodynamic Measure of Response After Acute Dosing of AG-013736, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors: Results From a Phase I Study. Journal Of Clinical Oncology 2005, 23: 5464-5473. PMID: 16027440, DOI: 10.1200/jco.2005.04.143.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsAG-013736Vascular responsesMagnetic resonance imagingAcute dosingDay 2Solid tumorsAngiogenesis inhibitorsResonance imagingContrast-enhanced magnetic resonance imagingOral angiogenesis inhibitorSchedule of therapyTumor vascular functionDynamic contrast-enhanced magnetic resonance imagingObjective disease responsePhase II testingDCE-MRI scansEffect of treatmentTumor vascular parametersVolume transfer constantMorning doseSuitable markerPharmacodynamic measuresVascular functionPharmacodynamic response