An open-label, phase I study of the polo-like kinase-1 inhibitor, BI 2536, in patients with advanced solid tumors
Purpose: This phase I, open-label, dose-escalation study investigated the maximum tolerated dose (MTD) of BI 2536, a small-molecule polo-like kinase (Plk)-1 inhibitor, in two treatment schedules in patients with advanced solid tumors. Secondary objectives included evaluation of safety, efficacy, and...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
[15 September 2010]
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| In: |
Clinical cancer research
Year: 2010, Jahrgang: 16, Heft: 18, Pages: 4666-4674 |
| ISSN: | 1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-10-0318 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-10-0318
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| Verfasserangaben: | Ralf-Dieter Hofheinz, Salah-Eddin Al-Batran, Andreas Hochhaus, Elke Jäger, Volker L. Reichardt, Holger Fritsch, Dirk Trommeshauser, and Gerd Munzert |
MARC
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| 245 | 1 | 3 | |a An open-label, phase I study of the polo-like kinase-1 inhibitor, BI 2536, in patients with advanced solid tumors |c Ralf-Dieter Hofheinz, Salah-Eddin Al-Batran, Andreas Hochhaus, Elke Jäger, Volker L. Reichardt, Holger Fritsch, Dirk Trommeshauser, and Gerd Munzert |
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| 520 | |a Purpose: This phase I, open-label, dose-escalation study investigated the maximum tolerated dose (MTD) of BI 2536, a small-molecule polo-like kinase (Plk)-1 inhibitor, in two treatment schedules in patients with advanced solid tumors. Secondary objectives included evaluation of safety, efficacy, and pharmacokinetics.Experimental Design: Patients received a single i.v. dose of BI 2536 as a 1-hour infusion on days 1 and 8 or a single 24-hour infusion on day 1 of each 21-day treatment course. MTD determination was based on dose-limiting toxicities.Results: Forty-four and 26 patients received each treatment schedule, respectively. The MTD of BI 2536 in the day 1 and 8 schedule was 100 mg per administration (200 mg per course). The MTD for the second dosing schedule was not determined; a 225-mg dose was well tolerated. The most frequently reported treatment-related nonhematologic adverse events were gastrointestinal events and fatigue. Hematotoxicity as the most relevant side effect was similar in both schedules; neutropenia grades 3 and 4 were observed in 16 patients (36.4%) of the day 1 and 8 schedule and 13 patients (50%) of the 24-hour infusion. Fourteen patients (32%) treated in the day 1 and 8 dosing schedule had a best overall response of stable disease. Plasma concentrations of BI 2536 increased dose proportionally, with no relevant accumulation of exposure in the day 1 and 8 dosing schedule. The average terminal half-life was 50 hours.Conclusions: BI 2536 administered in either treatment schedule has adequate safety in patients with advanced solid tumors, warranting further clinical investigation of polo-like kinase-1 inhibitors. Clin Cancer Res; 16(18); 4666-74. ©2010 AACR. | ||
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