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Zeiner PS, Kinzig M, Divé I, et al. Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients. J Clin Med. 2019;8(12)doi: 10.3390/jcm8122031.
Zeiner, P. S., Kinzig, M., Divé, I., Maurer, G. D., Filipski, K., Harter, P. N., Senft, C., Bähr, O., Hattingen, E., Steinbach, J. P., Sörgel, F., Voss, M., Steidl, E., & Ronellenfitsch, M. W. (2019). Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients. Journal of clinical medicine, 8(12), . https://doi.org/10.3390/jcm8122031
Zeiner, Pia S, et al. "Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients." Journal of clinical medicine vol. 8,12 (2019). doi: https://doi.org/10.3390/jcm8122031
Zeiner PS, Kinzig M, Divé I, Maurer GD, Filipski K, Harter PN, Senft C, Bähr O, Hattingen E, Steinbach JP, Sörgel F, Voss M, Steidl E, Ronellenfitsch MW. Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients. J Clin Med. 2019 Nov 21;8(12). doi: 10.3390/jcm8122031. PMID: 31766326; PMCID: PMC6947028.
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J Clin Med. 2019 Nov 21;8(12). doi: 10.3390/jcm8122031.

Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients.

Journal of clinical medicine

Pia S Zeiner, Martina Kinzig, Iris Divé, Gabriele D Maurer, Katharina Filipski, Patrick N Harter, Christian Senft, Oliver Bähr, Elke Hattingen, Joachim P Steinbach, Fritz Sörgel, Martin Voss, Eike Steidl, Michael W Ronellenfitsch

Affiliations

  1. Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, Germany.
  2. University Cancer Center (UCT) Frankfurt, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main POSTCODE, Germany.
  3. German Cancer Consortium (DKTK), 60590 Frankfurt am Main POSTCODE, Germany.
  4. Frankfurt Cancer Institute (FCI), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main POSTCODE, Germany.
  5. IBMP-Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg POSTCODE, Germany.
  6. Institute of Neurology (Edinger-Institute), University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, Germany.
  7. Department of Neurosurgery, University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, Germany.
  8. Department of Neurology, Klinikum Aschaffenburg-Alzenau, Aschaffenburg POSTCODE, Germany.
  9. Department of Neuroradiology, University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, Germany.
  10. Institute of Pharmacology, University Duisburg-Essen, Essen POSTCODE, Germany.

PMID: 31766326 PMCID: PMC6947028 DOI: 10.3390/jcm8122031

Abstract

(1) Background: The phase 2 Regorafenib in Relapsed Glioblastoma (REGOMA) trial indicated a survival benefit for patients with first recurrence of a glioblastoma when treated with the multikinase inhibitor regorafenib (REG) instead of lomustine. The aim of this retrospective study was to investigate REG penetration to cerebrospinal fluid (CSF), treatment efficacy, and effects on magnetic resonance imaging (MRI) in patients with recurrent high-grade gliomas. (2) Methods: Patients were characterized by histology, adverse events, steroid treatment, overall survival (OS), and MRI growth pattern. REG and its two active metabolites were quantified by liquid chromatography/tandem mass spectrometry in patients' serum and CSF. (3) Results: 21 patients mainly with IDH-wildtype glioblastomas who had been treated with REG were retrospectively identified. Thirteen CFS samples collected from 3 patients of the cohort were available for pharmacokinetic testing. CSF levels of REG and its metabolites were significantly lower than in serum. Follow-up MRI was available in 19 patients and showed progressive disease (PD) in all but 2 patients. Two distinct MRI patterns were identified: 7 patients showed classic PD with progression of contrast enhancing lesions, whereas 11 patients showed a T2-dominant MRI pattern characterized by a marked reduction of contrast enhancement. Median OS was significantly better in patients with a T2-dominant growth pattern (10 vs. 27 weeks respectively,

Keywords: MRI patterns of gliomas; glioblastoma; malignant glioma; regorafenib; regorafenib csf concentration

Conflict of interest statement

J.P.S. has received honoraria for lectures or advisory board participation or consulting or travel grants from Abbvie, Roche, Boehringer, Bristol-Myers Squibb, Medac, Mundipharma and UCB. All other au

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