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Cancer Chemother Pharmacol. 2009 Jul;64(2):425-9. doi: 10.1007/s00280-009-0968-y. Epub 2009 Mar 12.

A phase I dose escalation study of the pharmacokinetics and tolerability of ZK 304709, an oral multi-targeted growth inhibitor (MTGI), in patients with advanced solid tumours.

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Department of Oncology, University of Leicester, Leicester Royal Infirmary, Leicester, LE1 5WW, England, UK.



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.


Patients with solid tumours resistant to standard treatments were enrolled in an accelerated titration design.


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.


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.

[Indexed for MEDLINE]

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