Weekly administration of sagopilone (ZK-EPO), a fully synthetic epothilone, in patients with refractory solid tumours: results of a phase I trial.
Br J Cancer
; 101(8): 1241-7, 2009 Oct 20.
Article
in En
| MEDLINE
| ID: mdl-19773753
ABSTRACT
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 gamma-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.
Full text:
1
Database:
MEDLINE
Main subject:
Epothilones
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Benzothiazoles
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Neoplasms
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Antineoplastic Agents
Limits:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Br J Cancer
Year:
2009
Type:
Article
Affiliation country:
Germany