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Hofheinz, Ralf-Dieter; Al-Batran, Salah-Eddin; Hochhaus, Andreas; Jäger, Elke; Reichardt, Volker L.; Fritsch, Holger; Trommeshauser, Dirk; Munzert, Gerd

An Open-Label, Phase I Study of the Polo-like Kinase-1 Inhibitor, BI 2536, in Patients with Advanced Solid Tumors

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  • Medientyp: E-Artikel
  • Titel: An Open-Label, Phase I Study of the Polo-like Kinase-1 Inhibitor, BI 2536, in Patients with Advanced Solid Tumors
  • Beteiligte: Hofheinz, Ralf-Dieter; Al-Batran, Salah-Eddin; Hochhaus, Andreas; Jäger, Elke; Reichardt, Volker L.; Fritsch, Holger; Trommeshauser, Dirk; Munzert, Gerd
  • Erschienen: American Association for Cancer Research (AACR), 2010
  • Erschienen in: Clinical Cancer Research, 16 (2010) 18, Seite 4666-4674
  • Sprache: Englisch
  • DOI: 10.1158/1078-0432.ccr-10-0318
  • ISSN: 1078-0432; 1557-3265
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: 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.
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