Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group

Annals of Oncology : Official Journal of the European Society for Medical Oncology
Roger StuppAlba A Brandes

Abstract

Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models. Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m(2) over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points. Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3-18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3-12.3), with a 1-year survival rate of 31.6% (95% CI 17.7-46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination. No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was we...Continue Reading

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Citations

Dec 20, 2012·PloS One·Katrin OrlowskiMartin Pruschy
Feb 3, 2016·Critical Reviews in Oncology/hematology·Katharina SeystahlMichael Weller
Dec 5, 2012·Journal of Veterinary Internal Medicine·V MeierCarla Rohrer Bley
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Aug 7, 2015·Toxics·Gabriella NicoliniArianna Scuteri
Jun 12, 2020·European Journal of Medicinal Chemistry·Ana R GomesFernanda M F Roleira

Related Concepts

SH-Y-03757
Antineoplastic Agents
Mixed Oligoastrocytoma
Brain Tumor, Recurrent
Glioblastoma Multiforme
Intravenous Infusion Procedures
Neoplasm Recurrence, Local
Progression-Free Survival
Epothilones
Benzothiazoles

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