Phase I study of telatinib BAY 57-9352: analysis of safety, pharmacokinetics, tumor efficacy, and biomarkers in patients with colorectal cancerReport as inadecuate




Phase I study of telatinib BAY 57-9352: analysis of safety, pharmacokinetics, tumor efficacy, and biomarkers in patients with colorectal cancer - Download this document for free, or read online. Document in PDF available to download.

Vascular Cell

, 3:16

First Online: 29 July 2011Received: 28 October 2010Accepted: 29 July 2011

Abstract

BackgroundTelatinib 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.

MethodsIn 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.

ResultsHypertension 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 AUC0-12.

ConclusionTelatinib 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.

Electronic supplementary materialThe online version of this article doi:10.1186-2045-824X-3-16 contains supplementary material, which is available to authorized users.

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Author: Klaus Mross - Annette Frost - Max E Scheulen - Jürgen Krauss - Dirk Strumberg - Beate Schultheiss - Ulrike Fasol - Martin

Source: https://link.springer.com/article/10.1186/2045-824X-3-16







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