Title: Multicentric parallel phase II trial of the polo-like kinase 1 inhibitor BI 2536 in patients with advanced head and neck cancer, breast cancer, ovarian cancer, soft tissue sarcoma and melanoma. The first protocol of the European Organization for Research and Treatment of Cancer (EORTC) Network Of Core Institutes (NOCI)
Authors: Sch√∂ffski, Patrick ×
Blay, Jean-Yves
De Greve, Jacques
Brain, Etienne
Machiels, Jean-Pascal
Soria, Jean-Charles
Sleijfer, Stefan
Wolter, Pascal
Ray-Coquard, Isabelle
Fontaine, Christel
Munzert, Gerd
Fritsch, Holger
Hanft, Gertraud
Aerts, Claire
Rapion, Jérome
Allgeier, Anouk
Bogaerts, Jan
Lacombe, Denis #
Issue Date: Aug-2010
Publisher: Pergamon
Series Title: European Journal of Cancer vol:46 issue:12 pages:2206-2215
Abstract: AIMS: BI 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 METHODS: Patients 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. RESULTS: Seventy 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. CONCLUSIONS: BI 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.
ISSN: 0959-8049
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science