Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma

Br J Cancer. 2009 Dec 15;101(12):1995-2004. doi: 10.1038/sj.bjc.6605411. Epub 2009 Nov 10.

Abstract

Background: We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs).

Methods: A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS).

Results: The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%).

Conclusions: Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzamides
  • Biomarkers, Tumor / analysis
  • Brain Neoplasms / drug therapy*
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Humans
  • Hydroxyurea / administration & dosage
  • Hydroxyurea / adverse effects
  • Hydroxyurea / pharmacokinetics
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Piperazines / pharmacokinetics
  • Proto-Oncogene Proteins c-kit / genetics
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacokinetics
  • Survival Rate

Substances

  • Adrenal Cortex Hormones
  • Benzamides
  • Biomarkers, Tumor
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit
  • Hydroxyurea