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|Ref Type||Journal Article|
|Authors||Fiedler W, Giaccone G, Lasch P, van der Horst I, Brega N, Courtney R, Abbattista A, Shalinsky DR, Bokemeyer C, Boven E|
|Title||Phase I trial of SU14813 in patients with advanced solid malignancies.|
|Journal||Annals of oncology : official journal of the European Society for Medical Oncology|
|Abstract Text||this phase I, open-label, dose-escalation study investigated SU14813, an oral multitargeted tyrosine kinase inhibitor, in adults with solid tumors.seventy-seven patients received once-daily SU14813, either for 4 weeks followed by 1 week off treatment (schedule 4/1) or continuously [continuous daily dosing (CDD)]. The primary end point was to determine the maximum tolerated dose (MTD). Safety, pharmacokinetics, pharmacodynamics, and efficacy were assessed.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.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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|SU14813||FLT3 Inhibitor 54 KIT Inhibitor 50 PDGFR Inhibitor (Pan) 27 VEGFR Inhibitor (Pan) 32||SU14813 is a multi-kinase inhibitor with activity against VEGFR1-3, PDGFRA, PDGFRB, KIT, and FLT3, which potentially results in decreased tumor angiogenesis and growth (PMID: 16891463, PMID: 20605934).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||Advanced Solid Tumor||not applicable||SU14813||Phase I||Actionable||In a Phase I trial, SU14813 demonstrated safety and preliminary efficacy in patients with advanced solid tumors, with an objective response rate of 20% (13/65), including 1 complete response and 12 partial responses (PMID: 20605934).||20605934|