PURPOSE: This study investigated the metabolism and excretion of dovitinib 
(TKI258), a tyrosine kinase inhibitor that inhibits fibroblast, vascular 
endothelial, and platelet-derived growth factor receptors, in patients with 
advanced solid tumors.
METHODS: Four patients (cohort 1) received a single 500 mg oral dose of 
(14)C-dovitinib, followed by the collection of blood, urine, and feces for 
≤10 days. Radioactivity concentrations were measured by liquid scintillation 
counting and plasma concentrations of dovitinib by liquid chromatography-tandem 
mass spectrometry. Both techniques were applied for metabolite profiling and 
identification. A continuous-dosing extension phase (nonlabeled dovitinib 400 mg 
daily) was conducted with the 3 patients from cohort 1 and 9 additional patients 
from cohort 2.
RESULTS: The majority of radioactivity was recovered in feces (mean 61 %; range 
52-69 %), as compared with urine (mean 16 %; range 13-21 %). Only 6-19 % of the 
radioactivity was recovered in feces as unchanged dovitinib, suggesting high 
oral absorption. (14)C-dovitinib was eliminated predominantly via oxidative 
metabolism, with prominent primary biotransformations including hydroxylation on 
the fluorobenzyl ring and N-oxidation and carbon oxidation on the 
methylpiperazine moiety. Dovitinib was the most prominent radioactive component 
in plasma. The high apparent volume of distribution (2,160 L) may indicate that 
dovitinib distributes extensively to tissues. Adverse events were predominantly 
mild to moderate, and most common events included nausea, vomiting, 
constipation, diarrhea, and fatigue.
CONCLUSIONS: Dovitinib was well absorbed, extensively distributed, and 
eliminated mainly by oxidative metabolism, followed by excretion, predominantly 
in feces. The adverse events were as expected for this class of drug.