Annals of Oncology Advance Access published online on February 10, 2005
Annals of Oncology, doi:10.1093/annonc/mdi118
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1 Tumor Biology Center, Freiburg, Germany
* To whom correspondence should be addressed. Background: Plasma and serum biomarkers of angiogenesis and activated endothelial cells were evaluated to assess biological activity of PTK787/ZK 222584 (PTK/ZK), a novel oral angiogenesis inhibitor targeting all known vascular endothelial growth factor (VEGF) receptor tyrosine kinases. Patients and methods: Patients with colorectal cancer (CRC) (n=63) were enrolled into two phase I/II dose escalation trials of PTK/ZK in 28-day cycles until discontinuation. Patients with stable disease for Results: A dose-dependent increase in plasma VEGF-A and bFGF was observed in the first cycle of PTK/ZK treatment. The correlation of change in plasma VEGF-A with AUC and Cmax was characterized by an Emax model, suggesting that a change of Conclusions: In patients with CRC treated with PTK/ZK, changes in plasma VEGF-A and bFGF demonstrate biological activity of PTK/ZK, may help to establish optimal dose and correlate with outcome.
Received August 27, 2004
Revised November 16, 2004
Accepted November 17, 2004
Original article
Soluble markers for the assessment of biological activity with PTK787/ZK 222584 (PTK/ZK), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor in patients with advanced colorectal cancer from two phase I trials
2 ProQuinase GmbH, Freiburg, Germany
3 Translational and Clinical Development, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
4 Preclinical Research, Novartis Pharma, Basel, Switzerland
5 Leceister Royal Infirmary Hospital, Leicester, UK
6 Schering AG, Berlin, Germany
J. Drevs, E-mail: drevs{at}tumorbio.uni-freiburg.de
Abstract 
2 months were categorized as ‘non-progressors’. Plasma markers of angiogenesis, VEGF-A and basic fibroblast growth factor (bFGF), and the serum markers of activated endothelial cells, sTIE-2 and sE-Selectin, were assessed at baseline, and pre-dose on days 1, 8, 15, 22 and 28 of every cycle, with additional assessments 10 h post-dose on days 1 and 15. The percentage change from baseline was subsequently correlated with AUC and Cmax of PTK/ZK on day 1, cycle 1 and clinical outcome.150% from baseline VEGF-A correlated with non-progressive disease. Change from baseline plasma VEGF-A within the first cycle of treatment was significantly correlated with clinical outcome by logistic regression analysis (P=0.027).
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