title: Phase I study of telatinib (BAY 57-9352): analysis of safety, pharmacokinetics, tumor efficacy, and biomarkers in patients with colorectal cancer.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Tumor Biology Center at the Albert-Ludwigs-University Freiburg, Germany. mross@tumorbio.uni-freiburg.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Mross
authors.forename: Annette
authors.initials: A
authors.lastname: Frost
authors.forename: Max E
authors.initials: ME
authors.lastname: Scheulen
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauss
authors.forename: Dirk
authors.initials: D
authors.lastname: Strumberg
authors.forename: Beate
authors.initials: B
authors.lastname: Schultheiss
authors.forename: Ulrike
authors.initials: U
authors.lastname: Fasol
authors.forename: Martin
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authors.lastname: Büchert
authors.forename: Jörn
authors.initials: J
authors.lastname: Krätzschmer
authors.forename: Heinz
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authors.lastname: Delesen
authors.forename: Prabhu
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authors.lastname: Rajagopalan
authors.forename: Olaf
authors.initials: O
authors.lastname: Christensen