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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.

Author information

1
Department of Oncology, University of Leicester, Leicester Royal Infirmary, Leicester, LE1 5WW, England, UK.

Abstract

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.

PMID:
19280191
DOI:
10.1007/s00280-009-0968-y
[Indexed for MEDLINE]

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