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

(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...

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Autores principales: Zeiner, Pia S., Kinzig, Martina, Divé, Iris, Maurer, Gabriele D., Filipski, Katharina, Harter, Patrick N., Senft, Christian, Bähr, Oliver, Hattingen, Elke, Steinbach, Joachim P., Sörgel, Fritz, Voss, Martin, Steidl, Eike, Ronellenfitsch, Michael W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947028/
https://www.ncbi.nlm.nih.gov/pubmed/31766326
http://dx.doi.org/10.3390/jcm8122031
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author Zeiner, Pia S.
Kinzig, Martina
Divé, Iris
Maurer, Gabriele D.
Filipski, Katharina
Harter, Patrick N.
Senft, Christian
Bähr, Oliver
Hattingen, Elke
Steinbach, Joachim P.
Sörgel, Fritz
Voss, Martin
Steidl, Eike
Ronellenfitsch, Michael W.
author_facet Zeiner, Pia S.
Kinzig, Martina
Divé, Iris
Maurer, Gabriele D.
Filipski, Katharina
Harter, Patrick N.
Senft, Christian
Bähr, Oliver
Hattingen, Elke
Steinbach, Joachim P.
Sörgel, Fritz
Voss, Martin
Steidl, Eike
Ronellenfitsch, Michael W.
author_sort Zeiner, Pia S.
collection PubMed
description (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.
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spelling pubmed-69470282020-01-13 Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients Zeiner, Pia S. Kinzig, Martina Divé, Iris Maurer, Gabriele D. Filipski, Katharina Harter, Patrick N. Senft, Christian Bähr, Oliver Hattingen, Elke Steinbach, Joachim P. Sörgel, Fritz Voss, Martin Steidl, Eike Ronellenfitsch, Michael W. J Clin Med Article (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. MDPI 2019-11-21 /pmc/articles/PMC6947028/ /pubmed/31766326 http://dx.doi.org/10.3390/jcm8122031 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zeiner, Pia S.
Kinzig, Martina
Divé, Iris
Maurer, Gabriele D.
Filipski, Katharina
Harter, Patrick N.
Senft, Christian
Bähr, Oliver
Hattingen, Elke
Steinbach, Joachim P.
Sörgel, Fritz
Voss, Martin
Steidl, Eike
Ronellenfitsch, Michael W.
Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients
title Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients
title_full Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients
title_fullStr Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients
title_full_unstemmed Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients
title_short Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients
title_sort regorafenib csf penetration, efficacy, and mri patterns in recurrent malignant glioma patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947028/
https://www.ncbi.nlm.nih.gov/pubmed/31766326
http://dx.doi.org/10.3390/jcm8122031
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