Phase I Dose-Escalation Study of Once Weekly or Once Every Two Weeks Administration of High-Dose Sunitinib in Patients With Refractory Solid Tumors

PURPOSEDose and schedule optimization of treatment with tyrosine kinase inhibitors is of utmost importance. On the basis of preclinical data, a phase I clinical trial of once weekly or once every 2 weeks administration of high-dose sunitinib in patients with refractory solid malignancies was conducted.PATIENTS AND METHODSPatients with advanced cancer refractory to standard treatment were eligible. With use of a standard 3 + 3 phase I design, patients received escalating doses of sunitinib, in 100 mg increments, starting at 200 mg once weekly. In both the once weekly and once every 2 weeks cohorts, 10 more patients were included at the maximum tolerated dose level. Primary end points were safety and tolerability.RESULTSSixty-nine patients with advanced cancer, predominantly colorectal cancer (42%), were treated with this alternative dosing regimen. Maximum tolerated dose was established at 300 mg once weekly and 700 mg once every 2 weeks, resulting in nine- and 18-fold higher maximum plasma concentrations ...