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Open AccessArticle

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

1
Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, 60528 Frankfurt am Main, Germany
2
University Cancer Center (UCT) Frankfurt, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
3
German Cancer Consortium (DKTK), 60590 Frankfurt am Main, Germany
4
Frankfurt Cancer Institute (FCI), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany
5
IBMP—Institute for Biomedical and Pharmaceutical Research, 90562 Nürnberg-Heroldsberg, Germany
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Institute of Neurology (Edinger-Institute), University Hospital Frankfurt, Goethe University, 60528 Frankfurt am Main, Germany
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Department of Neurosurgery, University Hospital Frankfurt, Goethe University, 60528 Frankfurt am Main, Germany
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Department of Neurology, Klinikum Aschaffenburg-Alzenau, 63739 Aschaffenburg, Germany
9
Department of Neuroradiology, University Hospital Frankfurt, Goethe University, 60528 Frankfurt am Main, Germany
10
Institute of Pharmacology, University Duisburg-Essen, 45141 Essen, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to the manuscript.
J. Clin. Med. 2019, 8(12), 2031; https://doi.org/10.3390/jcm8122031
Received: 25 September 2019 / Revised: 28 October 2019 / Accepted: 18 November 2019 / Published: 21 November 2019
(This article belongs to the Section Oncology)
(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, p = 0.003). Diffusion restrictions were observed in 13 patients. (4) Conclusion: REG and its metabolites were detectable in CSF. A distinct MRI pattern that might be associated with an improved OS was observed in half of the patient cohort. Treatment response in the total cohort was poor. View Full-Text
Keywords: malignant glioma; glioblastoma; regorafenib; regorafenib csf concentration; MRI patterns of gliomas malignant glioma; glioblastoma; regorafenib; regorafenib csf concentration; MRI patterns of gliomas
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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. Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients. J. Clin. Med. 2019, 8, 2031.

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