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PURPOSE: The toxicities, pharmacokinetics and recommended dose of oral once daily ZK 304709, a novel multi-targeted growth inhibitor (MTGI) with activity against cell-cycle progression and angiogenesis, was investigated in patients by administration for 14 consecutive days followed by 14 days recovery. METHODS: Patients with solid tumours resistant to standard treatments were enrolled in an accelerated titration design. RESULTS: Thirty-seven patients received ZK 304709 from 15 to 285 mg daily. The most common drug-related adverse events were vomiting, diarrhoea and fatigue. Systemic exposure to ZK 304709 increased with dose up to 90 mg daily but plateaued thereafter, with high inter-individual variability at all doses. Thirteen patients had stable disease as best response as per RECIST criteria. CONCLUSIONS: There was no increase in exposure to ZK 304709 with dose escalation above 90 mg, and the MTD was not determined. This study illustrates the importance of phase I pharmacokinetic data to guide dose escalation and drug development.

Original publication

DOI

10.1007/s00280-009-0968-y

Type

Journal article

Journal

Cancer Chemother Pharmacol

Publication Date

07/2009

Volume

64

Pages

425 - 429

Keywords

Administration, Oral, Adult, Aged, Angiogenesis Inhibitors, Antineoplastic Agents, Dose-Response Relationship, Drug, Drug-Related Side Effects and Adverse Reactions, Female, Growth Inhibitors, Humans, Male, Maximum Tolerated Dose, Middle Aged, Neoplasm Staging, Neoplasms, Prognosis, Safety, Survival Rate, Tissue Distribution, Treatment Outcome