title: 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.
  
  
  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.affiliation: Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. Electronic address: roger.stupp@chuv.ch.
authors.forename: R
authors.initials: R
authors.lastname: Stupp
authors.affiliation: Department of Medical Oncology, Bellaria Maggiore Hospital, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tosoni
authors.affiliation: Department of Neuro-Oncology, Daniel den Hoed Cancer Center/Erasmus University Hospital, Rotterdam, The Netherlands.
authors.forename: J E C
authors.initials: JEC
authors.lastname: Bromberg
authors.affiliation: Department of Neurology, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Hau
authors.affiliation: Department of Medical Oncology, Institut Régional du Cancer Nantes Atlantique, CLCC René Gauducheau, Centre de Recherche en Cancérologie, St Herblain, France.
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.affiliation: Department of Neurology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Gijtenbeek
authors.affiliation: Department of Medical Oncology, Centre Antoine Lacassagne, Nice Cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Frenay
authors.affiliation: Bayer Healthcare, Montville, USA.
authors.forename: L
authors.initials: L
authors.lastname: Breimer
authors.affiliation: Bayer Schering Pharma, Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wiesinger
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Allgeier
authors.affiliation: Department of Neuro-Oncology, Daniel den Hoed Cancer Center/Erasmus University Hospital, Rotterdam, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: van den Bent
authors.affiliation: Department of Neurology, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Bogdahn
authors.affiliation: Department of Neurology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: van der Graaf
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: H J
authors.initials: HJ
authors.lastname: Yun
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Gorlia
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.affiliation: Department of Medical Oncology, Bellaria Maggiore Hospital, Bologna, Italy.
authors.forename: A A
authors.initials: AA
authors.lastname: Brandes
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001254:Astrocytoma / Q000097:blood / Q000188:drug therapy; D052160:Benzothiazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000097:blood / Q000188:drug therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D034261:Epothilones / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D034261:Epothilones; C530494:sagopilone