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Journal of Neuro-Oncology

, Volume 97, Issue 2, pp 241–245 | Cite as

Intratumoral concentrations of imatinib after oral administration in patients with glioblastoma multiforme

  • Matthias Holdhoff
  • Jeffrey G. Supko
  • Gary L. Gallia
  • Christine L. Hann
  • David Bonekamp
  • Xiaobu Ye
  • Bing Cao
  • Alessandro Olivi
  • Stuart A. Grossman
Clinical Study - Patient Study

Abstract

Imatinib, an orally administered tyrosine kinase inhibitor of PDGF receptor, c-abl and c-kit, is currently in clinical trials to assess its efficacy in malignant gliomas. Although imatinib does not readily penetrate an intact blood–brain barrier (BBB), the extent to which it distributes into regions of high grade gliomas where the BBB is compromised has not been determined. Patients with recurrent high-grade gliomas for whom repeat surgical tumor debulking was clinically indicated received imatinib mesylate 600 mg orally once a day for seven days prior to surgery. Tissue samples were collected from different regions of the tumor and the approximate location of these samples was determined using frameless stereotactic neuronavigation. Plasma samples were obtained immediately before and after the resection. The concentration of imatinib in the plasma and tumor samples was determined using high performance liquid chromatography with mass spectrometric detection. Eleven tumor samples were obtained from three patients with recurrent glioblastoma multiforme. The median concentration of imatinib in these 11 tumor specimens was 1.34 μg/g (range 0.21–4.31 μg/g) and the median tumor-to-plasma ratio was 0.71 (range 0.28–3.03). These findings suggest that imatinib can reach intratumoral concentrations similar to those or higher than in plasma in regions of glioblastoma where the BBB is disrupted as indicated by contrast enhancement on magnetic resonance imaging.

Keywords

Imatinib mesylate Intratumoral concentration Glioblastoma multiforme Malignant glioma 

Notes

Acknowledgements

Thanks to Joy Fisher for her advice during protocol development and during the institutional review process. We thank Dr. Jaishri Blakeley, Dr. Jon Weingart and Dr. Alfredo Quinones-Hinojosa for referral of patients for this study. Thanks also to Kelly Szajna and Kimberly Boucher for their help in patient recruitment and data management. Novartis Pharmaceuticals kindly provided the imatinib mesylate samples that were used in this study.

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Matthias Holdhoff
    • 1
  • Jeffrey G. Supko
    • 2
  • Gary L. Gallia
    • 3
    • 1
  • Christine L. Hann
    • 1
  • David Bonekamp
    • 4
  • Xiaobu Ye
    • 1
  • Bing Cao
    • 1
  • Alessandro Olivi
    • 1
    • 3
  • Stuart A. Grossman
    • 1
  1. 1.Brain Cancer Program, Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Massachusetts General Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Department of NeurosurgeryJohns Hopkins University School of MedicineBaltimoreUSA
  4. 4.Department of RadiologyJohns Hopkins University School of MedicineBaltimoreUSA

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