title: Response to imatinib as a function of target kinase expression in recurrent glioblastoma.
abstract: BACKGROUND
  Despite some progress in the treatment of glioblastoma, most patients experience tumor recurrence. Imatinib mesylate, a tyrosine kinase inhibitor of platelet derived growth factor receptor-alpha and -beta, c-fms, c-kit, abl and arg kinase (imatinib targets), has been shown to prevent tumor progression in early studies of recurrent gliomas, but has shown weak activity in randomized controlled trials. We studied the response to oral imatinib in 24 patients with recurrent glioblastoma who showed immunohistochemical expression of these imatinib targets in the initially resected tumor tissue.
  
  
  METHODS
  We offered oral imatinib, 400 mg once daily treatment to 24 recurrent glioblastoma patients whose initial biopsy showed presence of at least one imatinib inhibitable tyrosine kinase.
  
  
  RESULTS
  Six imatinib treated patients survived over one year. Twelve patients achieved at least tumor stabilisations from 2.6 months to 13.4 months. Median progression free survival was 3 months and median overall survival was 6 months. Imatinib was well tolerated. We found evidence, though not statistically significant, that arg kinase [Abl-2] immunopositivity had shorter survival [5 months] than the arg kinase immunonegative group [9 months].
  
  
  CONCLUSIONS
  Responses to imatinib observed in this patient series where imatinib inhibitable tyrosine kinases were documented on the original biopsy are marginally better than that previously reported in imatinib treatment of unselected recurrent glioblastoma patients. We thus present a suggestion for defining a patient sub-population who might potentially benefit from imatinib.
authors: Department of Internal Medicine I, Clinical Division of Oncology, 1-3 Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria.
authors: Marco Ronald
authors: MR
authors: Hassler
authors: Department of Internal Medicine I, Clinical Division of Oncology, 1-3 Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria.
authors: Mariam
authors: M
authors: Vedadinejad
authors: Department of Internal Medicine I, Clinical Division of Oncology, 1-3 Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria.
authors: Birgit
authors: B
authors: Flechl
authors: Institute of Neurology, 1-3 Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria.
authors: Christine
authors: C
authors: Haberler
authors: Department of Internal Medicine I, Clinical Division of Oncology, 1-3 Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria.
authors: Matthias
authors: M
authors: Preusser
authors: Institute of Neurology, 1-3 Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria.
authors: Johannes Andreas
authors: JA
authors: Hainfellner
authors: Institute of Neurology, 1-3 Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria.
authors: Adelheid
authors: A
authors: Wöhrer
authors: Department of Radiotherapy and Radiobiology, 1-3 Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria.
authors: Karin Ute
authors: KU
authors: Dieckmann
authors: Department of Neurosurgery, District Hospital, Feldkirch, Austria.
authors: Karl
authors: K
authors: Rössler
authors: Department of Internal Medicine I, Clinical Division of Oncology, 1-3 Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria.
authors: Richard
authors: R
authors: Kast
authors: Department of Internal Medicine I, Clinical Division of Oncology, 1-3 Comprehensive Cancer Center-Central Nervous System Tumors Unit (CCC-CNS), Medical University of Vienna, Vienna, Austria ; Department of Internal Medicine I, Clinical Division of Oncology, Währinger Gürtel 18-20, Vienna, 1090 Austria.
authors: Christine
authors: C
authors: Marosi
keywords: Arg kinase; Cytokine; Glioblastoma; Inatinib; Markers; Platelet derived growth factor; Tyrosine kinase; c-Abl; c-Fms; c-kit