title: Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study.
abstract: OBJECTIVE
  To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas.
  
  
  METHODS
  This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging. Three different histologic groups were studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD), and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of 600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design was one-stage Fleming; both an objective response and 6 months of progression-free survival (PFS) were considered a successful outcome to treatment.
  
  
  RESULTS
  A total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients with OD) were enrolled. Imatinib was in general well tolerated. The median number of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial response, including three patients with GBM; all had 6 months of PFS. The 6-month PFS rate was 16% (95% CI, 8.0% to 34.0%) in GBM, 4.0% (95% CI, 0.3% to 15.0%) in OD, and 9% (95% CI, 2.0% to 25.0%) in A. The exposure to imatinib was significantly lower in patients using enzyme-inducing antiepileptic drugs. The presence of ABCG2 point mutations were not correlated with pharmacokinetic findings. No somatic activating mutations of KIT or platelet-derived growth factor receptor-A or -B were found.
  
  
  CONCLUSIONS
  In the dose range of 600 to 1,000 mg/d, single-agent imatinib is well tolerated but has limited antitumor activity in patients with recurrent gliomas.
authors.affiliation: Service Inter Hospitalier de Cancérologie, Beaujon University Hospital, Clichy.
authors.forename: Eric
authors.initials: E
authors.lastname: Raymond
authors.forename: Alba A
authors.initials: AA
authors.lastname: Brandes
authors.forename: Christian
authors.initials: C
authors.lastname: Dittrich
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.forename: Bruno
authors.initials: B
authors.lastname: Coudert
authors.forename: Paul M J
authors.initials: PM
authors.lastname: Clement
authors.forename: Marc
authors.initials: M
authors.lastname: Frenay
authors.forename: Roy
authors.initials: R
authors.lastname: Rampling
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
authors.forename: Johan M
authors.initials: JM
authors.lastname: Kros
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heinrich
authors.forename: Thierry
authors.initials: T
authors.lastname: Gorlia
authors.forename: Denis
authors.initials: D
authors.lastname: Lacombe
authors.forename: Martin J
authors.initials: MJ
authors.lastname: van den Bent
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D000068877:Imatinib Mesylate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate