TY - JOUR AU - Mross, Klaus AU - Frost, Annette AU - Scheulen, Max E AU - Krauss, Jürgen AU - Strumberg, Dirk AU - Schultheiss, Beate AU - Fasol, Ulrike AU - Büchert, Martin AU - Krätzschmer, Jörn AU - Delesen, Heinz AU - Rajagopalan, Prabhu AU - Christensen, Olaf PY - 2011 TI - Phase I study of telatinib (BAY 57-9352): analysis of safety, pharmacokinetics, tumor efficacy, and biomarkers in patients with colorectal cancer JF - Vascular Cell; Vol 3 No 1 (2011): VascularCell DO - 10.1186/2045-824X-3-16 KW - N2 - 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 C max 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. UR - https://vascularcell.com/index.php/vc/article/view/10.1186-2045-824X-3-16