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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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posted on 02.07.2009, 15:03 by Edwina N. Scott, Anne L. Thomas, L. Rhoda Molife, Samreen Ahmed, Sarah Blagden, Peter C. Fong, Kristin Kowal, Candice McCoy, Herbert Wiesinger, William P. Steward, Johann De Bono
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.

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Citation

Cancer Chemotherapy and Pharmacology, 2009, 64 (2), pp. 425-429.

Published in

Cancer Chemotherapy and Pharmacology

Publisher

Springer Verlag

issn

0344-5704

Available date

02/07/2009

Publisher version

http://link.springer.com/article/10.1007/s00280-009-0968-y

Notes

This is the author's final draft of the paper published as Cancer Chemotherapy and Pharmacology, 2009, 64 (2), pp. 425-429. The original publication is available at www.springerlink.com. Doi: 10.1007/s00280-009-0968-y

Language

en

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