کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2126396 | 1547291 | 2006 | 8 صفحه PDF | دانلود رایگان |
SU006668, an oral inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and fibroblast growth factor receptor (FGFR), was administered in fed conditions to 24 patients with advanced solid cancer at 100, 200 and 300 mg/m2 b.i.d. Dose escalation was discontinued because the maximum tolerated dose was defined at 400 mg/m2 b.i.d in a concomitant trial. The drug was generally well tolerated although two patients presented possibly drug-related dose-limiting toxicities (pericardial effusion and thrombocytopenia). SU006668 had a non-linear pharmacokinetic profile characterized by AUC and Cmax decreasing from day 1 to day 28 in all patients at all tested doses; a lower apparent bioavailability on day 28 compared to day 1; and a significant concomitant increase of the urinary metabolites. These findings are in agreement with the presence of saturable absorption and metabolic induction. The peculiar pharmacokinetics and >99% protein binding discouraged further clinical development of oral SU006668 in humans.
Journal: European Journal of Cancer - Volume 42, Issue 2, January 2006, Pages 171–178