PURPOSE: Signaling through the fibroblast growth factor (FGF) pathway may 
account for tumor resistance to antiangiogenic therapies targeting the VEGF 
pathway. Here, dovitinib (TKI258), a potent oral inhibitor of FGF receptor, VEGF 
receptor (VEGFR), and platelet-derived growth factor receptor tyrosine kinases, 
is studied in a dose escalation trial.
EXPERIMENTAL DESIGN: Patients with advanced or metastatic renal cell carcinoma 
(RCC) with predominant clear cell histology were treated with oral dovitinib 500 
or 600 mg/day (5-days-on/2-days-off schedule).
RESULTS: Twenty heavily pretreated patients (median 3 prior regimens) were 
enrolled, with 16, 11, and 12 patients having previously received at least 1: 
VEGFR inhibitor, mTOR inhibitor, and immunotherapy, respectively. Fifteen and 5 
patients were treated in 500- and 600-mg cohorts, respectively. Three patients 
experienced dose-limiting toxicities: grade 2 bradycardia (500 mg), grade 4 
hypertensive crisis (600 mg), and grade 3 asthenia with grade 2 nausea and 
vomiting (600 mg). The most common adverse events related to dovitinib were 
nausea (75%), diarrhea (70%), vomiting (70%), and asthenia (50%), the majority 
of which were mild (grade 1 or 2), with grade 3 events 5% or less (except 
asthenia, 15%) and only one grade 4 event (hypertensive crisis). Two patients 
achieved a partial response (500 mg), and 12 patients had stable disease, 
including 2 patients with long lasting disease stabilizations (>1 year) in the 
500-mg cohort.
CONCLUSIONS: Dovitinib was tolerable and showed antitumor activity at a maximum 
tolerated dose of 500 mg on a 5-days-on/2-days-off schedule in heavily 
pretreated RCC patients.