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.

Abstract

BACKGROUND:

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 AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administration.

• Authors: R Stupp, A Tosoni, J E C Bromberg, P Hau, M Campone, J Gijtenbeek, M Frenay, L Breimer, H Wiesinger, A Allgeier, M J van den Bent, U Bogdahn, W van der Graaf, H J Yun, T Gorlia, D Lacombe, A A Brandes
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 22 Issue 9 Pg. 2144-2149 (Sep 2011) ISSN: 1569-8041 [Electronic] England
• PMID: 21321091 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzothiazoles
• Epothilones
• sagopilone

Topics

• Adult
• Aged
• Antineoplastic Agents (adverse effects, blood, pharmacokinetics, therapeutic use)
• Astrocytoma (blood, drug therapy)
• Benzothiazoles (adverse effects, blood, pharmacokinetics, therapeutic use)
• Brain Neoplasms (blood, drug therapy)
• Disease Progression
• Disease-Free Survival
• Epothilones (adverse effects, blood, pharmacokinetics, therapeutic use)
• Female
• Glioblastoma (blood, drug therapy)
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Neoplasm Recurrence, Local (blood, drug therapy)
• Young Adult