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Open Access Research

Phase I study of telatinib (BAY 57-9352): analysis of safety, pharmacokinetics, tumor efficacy, and biomarkers in patients with colorectal cancer

Klaus Mross1*, Annette Frost1, Max E Scheulen2, Jürgen Krauss2, Dirk Strumberg3, Beate Schultheiss3, Ulrike Fasol4, Martin Büchert4, Jörn Krätzschmer5, Heinz Delesen5, Prabhu Rajagopalan6 and Olaf Christensen6

Author Affiliations

1 Tumor Biology Center at the Albert-Ludwigs-University Freiburg, Germany

2 West German Cancer Center, Essen, Germany

3 Marienhospital Herne, University of Bochum, Herne, Germany

4 Magnetic Resonance Development and Application Center, University Hospital of the Albert-Ludwigs-University Freiburg, Germany

5 Bayer Schering Pharma, Berlin and Wuppertal, Germany

6 Bayer Pharmaceuticals Corporation, Montville, NJ, USA

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Vascular Cell 2011, 3:16  doi:10.1186/2045-824X-3-16

Published: 29 July 2011

Abstract

Background

Telatinib (BAY 57-9352) is an orally available, small-molecule inhibitor of vascular endothelial growth factor receptors 2 and 3 (VEGFR-2/-3) and platelet-derived growth factor receptor β tyrosine kinases.

Methods

In this multicenter phase I dose-escalation study including a phase II like expansion part, 39 patients with refractory colorectal cancer (CRC) were enrolled into 14 days on / 7 days off in repeating cycles of 28 days (n = 11) or continuous dosing groups (n = 28) to receive ≥ 600 mg telatinib twice-daily (bid).

Results

Hypertension (28%) and diarrhoea (15%) were the most frequent study drug-related adverse events of CTC grade 3. In this population, no clear relationship between telatinib dose and individual Cmax and AUC was apparent in the 600 mg bid to 1500 mg bid dose range. No partial remission according to RECIST was reached, but 41% of the patients reached some tumour shrinkage during treatment. Tumour blood flow measured by dynamic contrast-enhanced magnetic resonance imaging and sVEGFR-2 plasma levels decreased with increasing telatinib AUC(0-12).

Conclusion

Telatinib treatment was well tolerated. The observed single agent antitumor activity in heavily pretreated CRC patients was limited. Pharmacodynamic results are suggestive for the biological activity of telatinib justifying a further evaluation of telatinib bid in combination with standard chemotherapy regimens in CRC patients.