PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which 
inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate 
the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor 
fluvoxamine in patients with advanced solid tumors.
METHODS: Non-smoking patients of ≥ 18 years with advanced solid tumors, 
excluding breast cancer, were included. Patients were treated with a dose of 
300 mg in 5 days on/2 days off schedule. Steady-state pharmacokinetic 
assessments of dovitinib were performed with or without fluvoxamine.
RESULTS: Forty-five patients were enrolled; 24 were evaluable for drug-drug 
interaction assessment. Median age was 60 years (range 30-85). At steady state 
the geometric mean for dovitinib (coefficient of variation%) of the area under 
the plasma concentration-time curve (AUC0-72h) and maximum concentration (C max) 
were 2880 ng/mL h (47%) and 144 ng/mL (41%), respectively. Following 
administration of dovitinib in combination with fluvoxamine the geometric mean 
of dovitinib AUC0-72h and C max were 8290 ng/mL h (60%) and 259 ng/mL (45%), 
respectively. The estimated geometric mean ratios for dovitinib AUC0-72h and C 
max (dovitinib + fluvoxamine vs. dovitinib alone) were 2.88 [90% confidence 
interval (CI) 2.58, 3.20] and 1.80 (90% CI 1.66, 1.95). This effect is 
considered a moderate drug-drug interaction.
CONCLUSIONS: Fluvoxamine co-administration resulted in a 80% increase in C max 
and a 188% increase in AUC0-72h of dovitinib. Given the increase in exposure to 
dovitinib observed, patients are at risk of dovitinib related toxicity. 
Dovitinib should, therefore, not be co-administered with moderate and strong 
CYP1A2 inhibitors, without dose reduction.