Weekly administration of sagopilone (ZK-EPO), a fully synthetic epothilone, in patients with refractory solid tumours: results of a phase I trial
| Autor: | H.-J. Schmoll, Wieland Voigt, S. Lindemann, H. Wiesinger, S. Reif, C. Behrmann, Philipp Kiewe, Eckhard Thiel, M. Giurescu, Dirk Arnold |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Microtubule bundle formation Antineoplastic Agents Epothilone Pharmacology Drug Administration Schedule Refractory Neoplasms Clinical Studies medicine Humans epothilone Benzothiazoles Adverse effect refractory solid tumours Aged sagopilone maximum tolerated dose dose-limiting toxicity business.industry Standard treatment Middle Aged phase I medicine.disease Surgery Peripheral neuropathy Oncology Epothilones Erythropoietin Toxicity Female business medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6605327 |
| Popis: | Background: Epothilones are a novel class of microtubule-stabilising agents, and sagopilone is a fully synthetic epothilone that has shown marked in vivo and in vitro preclinical activity. Methods: This phase I, open-label study investigated the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of weekly sagopilone. Twenty-three patients with malignancy resistant or refractory to standard treatment were enrolled into this study evaluating sagopilone doses from 0.6 to 7.0 mg m−2. Results: The incidence of drug-related haematological adverse events (AEs) was low, with two grade 3 events observed. Nonhaematological AEs were generally mild and reversible; increased γ-GT was the only grade 4 event and grade 3 events comprised peripheral neuropathy (n=2), diarrhoea (n=1) and fatigue (n=1). Two grade 3 events were DLTs (diarrhoea and peripheral neuropathy at 7.0 mg m−2). The MTD of weekly sagopilone was therefore established as 5.3 mg m−2. Stable disease was the best overall response (n=3). Microtubule bundle formation in peripheral blood mononuclear cells increased post-treatment, peaking after 1 h. Sagopilone disposition was similar across treatment courses and showed rapidly decreasing serum concentrations after infusion end and a long terminal disposition phase with no obvious accumulation in the serum, probably reflecting a fast uptake into tissues followed by a slow release. Conclusion: Weekly administration of sagopilone could represent an alternative to the 3-weekly administration currently evaluated in phase II trials. |
| Databáze: | OpenAIRE |
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