Phase I study of the novel, fully synthetic epothilone sagopilone (ZK-EPO) in patients with solid tumors

Schmid, Peter, Kiewe, P., Possinger, K., Korfel, A., Lindemann, S., Giurescu, M., Reif, S., Wiesinger, H., Thiel, E. and Kuhnhardt, D. (2010) Phase I study of the novel, fully synthetic epothilone sagopilone (ZK-EPO) in patients with solid tumors. Annals of Oncology, 21 (3). pp. 633-639. ISSN 0923-7534

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Abstract

Background: Sagopilone (ZK-EPO) is a fully synthetic microtubule-stabilizing agent that has demonstrated high antitumor activity in preclinical models. This first-in-human phase I study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxic effects (DLTs) of 3-weekly sagopilone treatment.

Patients and methods: A total of 52 patients with advanced solid tumors received a 30-min infusion of escalating doses of sagopilone (0.6-29.4 mg/m(2)) every 3 weeks. Nine additional patients were recruited to a 3-h infusion arm (16.53-or 22.0-mg/m(2) dose) to assess the incidence of neuropathy with prolonged infusion.

Results: The MTD was established as 22.0 mg/m(2). DLTs comprised peripheral sensory neuropathy (PNP), infection, hyponatremia, diarrhea, and central ataxia. PNP was the most common grade 3 event, with a similar incidence in the 30-min and 3-h arms. Hematologic adverse events were rare and of low intensity. One confirmed partial response (PR) and one unconfirmed PR were reported in the 30-min arm, and a further unconfirmed PR was observed in the 3-h arm. Eleven patients achieved disease stabilization. Sagopilone showed high levels of tissue binding and no obvious serum accumulation in both arms.

Conclusions: These data demonstrate that sagopilone therapy is feasible and well tolerated. The recommended dose for phase II studies is 16.53 mg/m(2), once every 3 weeks.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology Including cancer and carcinogens
Depositing User: Grecia GarciaGarcia
Date Deposited: 16 Aug 2011 11:06
Last Modified: 30 Nov 2012 16:55
URI: http://sro.sussex.ac.uk/id/eprint/7225
Google Scholar:17 Citations
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