A phase I/II trial of vandetanib for patients with recurrent malignant glioma

Teri N. Kreisl, Katharine A. McNeill, Joohee Sul, Fabio M. Iwamoto, Joanna Shih, Howard A. Fine

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Vandetanib is a once-daily multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and the rearranged-during-transfection oncogene. A phase I trial was conducted to describe the pharmacokinetics of vandetanib in patients with recurrent glioma on enzyme-inducing anti-epileptic drugs (EIAEDs) and to identify the maximum tolerated dose (MTD) in this population. A phase II trial evaluated the efficacy of vandetanib in patients with recurrent malignant glioma not on EIAEDs as measured by 6-month progression-free survival (PFS6). In the phase I trial, 15 patients were treated with vandetanib at doses of 300, 400, and 500 mg/day, in a standard dose-escalation design. The MTD in patients on EIAEDs was 400 mg/day, and steady-state levels were similar to those measured in patients not on EIAEDs. Dose-limiting toxicities were prolonged QTc and thromboembolism. Thirty-two patients with recurrent glioblastoma multiforme (GBM) and 32 patients with recurrent anaplastic gliomas (AGs) were treated in the phase II trial, at a dosage of 300 mg/day on 28-day cycles. Six patients (4 GBM, 2 AG) had radiographic response. PFS6 was 6.5 in the GBM arm and 7.0 in the AG arm. Median overall survival was 6.3 months in the GBM arm and 7.6 months in the AG arm. Seizures were an unexpected toxicity of therapy. Vandetanib did not have significant activity in unselected patients with recurrent malignant glioma.

Original languageEnglish (US)
Pages (from-to)1519-1526
Number of pages8
JournalNeuro-Oncology
Volume14
Issue number12
DOIs
StatePublished - Dec 2012
Externally publishedYes

Keywords

  • EGFR
  • VEGFR
  • angiogenesis
  • glioma
  • vandetanib

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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