An open-label, phase I study of the polo-like kinase-1 inhibitor, BI 2536, in patients with advanced solid tumors

• Verfasst von: Hofheinz, Ralf-Dieter [VerfasserIn]
• Verfasst von: Al-Batran, Salah-Eddin [VerfasserIn]
• Verfasst von: Hochhaus, Andreas [VerfasserIn]
• Verfasst von: Jäger, Elke [VerfasserIn]
• Verfasst von: Reichardt, Volker L. [VerfasserIn]
• Verfasst von: Fritsch, Holger [VerfasserIn]
• Verfasst von: Trommeshauser, Dirk [VerfasserIn]
• Verfasst von: Munzert, Gerd [VerfasserIn]
• Titel: An open-label, phase I study of the polo-like kinase-1 inhibitor, BI 2536, in patients with advanced solid tumors
• Verf.angabe: Ralf-Dieter Hofheinz, Salah-Eddin Al-Batran, Andreas Hochhaus, Elke Jäger, Volker L. Reichardt, Holger Fritsch, Dirk Trommeshauser, and Gerd Munzert
• E-Jahr: 2010
• Jahr: [15 September 2010]
• Umfang: 9 S.
• Fussnoten: Gesehen am 14.03.2023
• Titel Quelle: Enthalten in: Clinical cancer research
• Ort Quelle: Philadelphia, Pa. [u.a.] : AACR, 1995
• Jahr Quelle: 2010
• Band/Heft Quelle: 16(2010), 18 vom: Sept., Seite 4666-4674
• ISSN Quelle: 1557-3265
• DOI: doi:10.1158/1078-0432.CCR-10-0318
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1839090839

Abstract

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.