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.
Written by:
Angevin E, Lopez-Martin JA, Lin CC, Gschwend JE, Harzstark A, Castellano D, Soria JC, Sen P, Chang J, Shi M, Kay A, Escudier B. Are you the author?
Institut de Cancérologie Gustave Roussy, Villejuif, France.
Reference: Clin Cancer Res. 2013 Mar 1;19(5):1257-68.
doi: 10.1158/1078-0432.CCR-12-2885
PubMed Abstract
PMID: 23339124
UroToday.com Renal Cancer Section
