Phase I trial of SU14813 in patients with advanced solid malignancies
| Autor: | P. Lasch, Nicoletta Brega, Walter Fiedler, I. van der Horst, D. R. Shalinsky, G. Giaccone, Antonello Abbattista, Carsten Bokemeyer, Epie Boven, R. Courtney |
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| Přispěvatelé: | Medical oncology, CCA - Innovative therapy |
| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | Fiedler, W, Giaccone, G, Lasch, P, van der Horst, I, Brega, N, Courtney, R, Abbattista, A, Shalinsky, D R, Bokemeyer, C & Boven, E 2011, ' Phase I trial of SU14813 in patients with advanced solid malignancies ', Annals of Oncology, vol. 22, no. 1, pp. 195-201 . https://doi.org/10.1093/annonc/mdq313 Annals of Oncology, 22(1), 195-201. Oxford University Press |
| ISSN: | 0923-7534 |
| DOI: | 10.1093/annonc/mdq313 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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