Phase I dose escalation study of telatinib (BAY 57-9352) in patients with advanced solid tumours

• DOI: 10.1038/sj.bjc.6604724
• Publication Date: 2008-11-11T23:54:12Z
• Authors: D Strumberg; B Schultheis; I A Adamietz; O Christensen; M Buechert; J Kraetzschmar; P Rajagopalan; M Ludwig; A Frost; S Steinbild; M E Scheulen; K Mross
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Pyridines; Angiogenesis Inhibitors; Antineoplastic Agents; Middle Aged; 3. Good health; Pyridazines; 03 medical and health sciences; Neoplasms; Clinical Study; Humans; Female; Aged

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 beta tyrosine kinases. In this multicentre phase I dose escalation study, 71 patients with refractory solid tumours were enroled into 14 days on/7 days off (noncontinuous dosing) or continuous dosing groups to receive telatinib two times daily (BID). Hypertension (23%) and diarrhoea (7%) were the most frequent study drug-related adverse events of CTC grade 3. The maximum-tolerated dose was not reached up to a dose of 1500 mg BID continuous dosing. Telatinib was rapidly absorbed with median t(max) of 3 hours or less. Geometric mean C(max) and AUC(0-12) increased in a less than dose-proportional manner and plateaued in the 900-1500 mg BID dose range. Two renal cell carcinoma patients reached a partial response. Tumour blood flow measured by contrast-enhanced magnetic resonance imaging and sVEGFR-2 plasma levels decreased with increasing AUC(0-12) of telatinib. Telatinib is safe and well tolerated up to a dose of 1500 mg BID continuous dosing. Based on pharmacokinetic and pharmacodynamic criteria, 900 mg telatinib BID continuously administered was selected as the recommended phase II dose.