An open-label, phase I study of the polo-like kinase-1 inhibitor, BI 2536, in patients with advanced solid tumors - PubMed (original) (raw)
Clinical Trial
. 2010 Sep 15;16(18):4666-74.
doi: 10.1158/1078-0432.CCR-10-0318. Epub 2010 Aug 3.
Affiliations
- PMID: 20682708
- DOI: 10.1158/1078-0432.CCR-10-0318
Clinical Trial
An open-label, phase I study of the polo-like kinase-1 inhibitor, BI 2536, in patients with advanced solid tumors
Ralf-Dieter Hofheinz et al. Clin Cancer Res. 2010.
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.
©2010 AACR.
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