Phase I trial of SU14813 in patients with advanced solid malignancies

assessed. Results: MTDs were 200 mg/day on schedule 4/1 and 100 mg/day with CDD. Adverse events included fatigue (64%), diarrhea (61%), nausea (44%), anorexia (43%), and vomiting (42%). SU14813 steady state was attained by day 8. Exposure increased in a generally dose-proportional manner and SU14813 was eliminated with a mean terminal half-life of 9‐34 h. Target plasma concentrations (>100 ng/ml SU14813) were achieved and sustained over 12 h at ‡100 mg/day. Progression-free survival among the 1 complete responder and 12 partial responders was 1.4‐53.2 months. Fifteen patients remained on treatment at 1 year and 3 patients at 2 years. Conclusion: SU14813 has manageable safety and tolerability and allows once-daily continuous oral dosing. SU14813 shows dose-proportional pharmacokinetics, with target plasma concentrations achieved at doses ‡100 mg/day. Clinically meaningful activity with durable responses was observed, meriting further study.