title: Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma.
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.
authors.affiliation: The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Box 3624, Durham, NC 27710, USA. reard003@mc.duke.edu
authors.forename: D A
authors.initials: DA
authors.lastname: Reardon
authors.forename: G
authors.initials: G
authors.lastname: Dresemann
authors.forename: S
authors.initials: S
authors.lastname: Taillibert
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.forename: M
authors.initials: M
authors.lastname: van den Bent
authors.forename: P
authors.initials: P
authors.lastname: Clement
authors.forename: E
authors.initials: E
authors.lastname: Blomquist
authors.forename: L
authors.initials: L
authors.lastname: Gordower
authors.forename: H
authors.initials: H
authors.lastname: Schultz
authors.forename: J
authors.initials: J
authors.lastname: Raizer
authors.forename: P
authors.initials: P
authors.lastname: Hau
authors.forename: J
authors.initials: J
authors.lastname: Easaw
authors.forename: M
authors.initials: M
authors.lastname: Gil
authors.forename: J
authors.initials: J
authors.lastname: Tonn
authors.forename: A
authors.initials: A
authors.lastname: Gijtenbeek
authors.forename: U
authors.initials: U
authors.lastname: Schlegel
authors.forename: P
authors.initials: P
authors.lastname: Bergstrom
authors.forename: S
authors.initials: S
authors.lastname: Green
authors.forename: A
authors.initials: A
authors.lastname: Weir
authors.forename: Z
authors.initials: Z
authors.lastname: Nikolova
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000188:drug therapy*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D015996:Survival Rate
chemical_list: D000305:Adrenal Cortex Hormones; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D006918:Hydroxyurea