title: Phase I dose escalation study of telatinib (BAY 57-9352) in patients with advanced solid tumours.
abstract: 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.
authors.affiliation: Department of Haematology and Medical Oncology, University of Bochum (Marien Hospital, Herne), Herne, Germany. dirk.strumberg@marienhospital-herne.de
authors.forename: D
authors.initials: D
authors.lastname: Strumberg
authors.forename: B
authors.initials: B
authors.lastname: Schultheis
authors.forename: I A
authors.initials: IA
authors.lastname: Adamietz
authors.forename: O
authors.initials: O
authors.lastname: Christensen
authors.forename: M
authors.initials: M
authors.lastname: Buechert
authors.forename: J
authors.initials: J
authors.lastname: Kraetzschmar
authors.forename: P
authors.initials: P
authors.lastname: Rajagopalan
authors.forename: M
authors.initials: M
authors.lastname: Ludwig
authors.forename: A
authors.initials: A
authors.lastname: Frost
authors.forename: S
authors.initials: S
authors.lastname: Steinbild
authors.forename: M E
authors.initials: ME
authors.lastname: Scheulen
authors.forename: K
authors.initials: K
authors.lastname: Mross
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011724:Pyridazines / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011724:Pyridazines; D011725:Pyridines; C533371:telatinib