• Patrick Schöffski, Jean-Yves Blay, Jacques De Greve, Etienne Brain, Jean-Pascal Machiels, Jean-Charles Soria, Stefan Sleijfer, Pascal Wolter, Isabelle Ray-Coquard, Christel Fontaine, Gerd Munzert, Holger Fritsch, Gertraud Hanft, Claire Aerts, Jérome Rapion, Anouk Allgeier, Jan Bogaerts, and Denis Lacombe.
• Department of General Medical Oncology, University Hospitals Leuven, Laboratory of Experimental Oncology, Leuven Cancer Institute, Catholic University Leuven, Leuven, Belgium. patrick.schoffski@uzleuven.be
• Eur. J. Cancer. 2010 Aug 1; 46 (12): 2206-15.

AimsBI 2536 is a selective and potent small-molecule inhibitor of polo-like kinase 1. We performed a multi-centre, multi-tumour phase II trial to investigate the efficacy, safety and pharmacokinetics of BI 2536 in five solid tumour types.Patients And MethodsPatients with advanced head and neck, breast and ovarian cancer, soft tissue sarcoma and melanoma were selected according to protocol-defined general and tumour-specific criteria. They were 18years old, had a good performance status, adequate bone marrow, renal and liver function, measurable progressive disease and had completed other relevant systemic treatments >4weeks ago. BI 2536 200-250mg was given intravenously on day 1 every 3 weeks until intolerance, progression or refusal. The study was based on a Simon two-stage design, with 12 patients entering in stage 1 and additional 25 patients to be entered in case of at least one response in the first stage. The rate of objective responses (RECIST criteria) was chosen as primary end-point.ResultsSeventy six patients were included, 71 started treatment and received a median number of two cycles (four in ovarian cancer). Frequent grade 3-4 adverse events were neutropaenia (81.6%), thrombocytopaenia (19.7%), febrile neutropaenia (19.7%), anaemia (15.5%) and pain (9.9%). We did not observe confirmed objective responses. All cohorts were closed after the entry of 14-15 eligible non-responding patients. Pharmacokinetic analyses revealed multi-compartmental behaviour and a rapid distribution of BI 2536.ConclusionsBI 2536 showed limited antitumour activity according to the design of this trial in five different tumour types. Derivatives of BI 2536 with a more favourable pharmacological profile are currently explored further in prospective studies.Copyright 2010 Elsevier Ltd. All rights reserved.

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