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Ref Type | Journal Article | ||||||||||||
PMID | (20605934) | ||||||||||||
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. | ||||||||||||
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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 |
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Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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SU14813 | FLT3 Inhibitor 65 KIT Inhibitor 57 PDGFR Inhibitor (Pan) 30 VEGFR Inhibitor (Pan) 36 | 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 |
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Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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