Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients
(1)<b> </b>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...
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MDPI AG
2019-11-01
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Online Access: | https://www.mdpi.com/2077-0383/8/12/2031 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma Patients Journal of Clinical Medicine malignant glioma glioblastoma regorafenib regorafenib csf concentration mri patterns of gliomas |
author_facet |
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 |
author_sort |
Pia S. Zeiner |
title |
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_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_sort |
regorafenib csf penetration, efficacy, and mri patterns in recurrent malignant glioma patients |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2019-11-01 |
description |
(1)<b> </b>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, <i>p</i> = 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. |
topic |
malignant glioma glioblastoma regorafenib regorafenib csf concentration mri patterns of gliomas |
url |
https://www.mdpi.com/2077-0383/8/12/2031 |
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doaj-fc8100318fb34f038081b8d87f77fb742020-11-25T01:18:30ZengMDPI AGJournal of Clinical Medicine2077-03832019-11-01812203110.3390/jcm8122031jcm8122031Regorafenib CSF Penetration, Efficacy, and MRI Patterns in Recurrent Malignant Glioma PatientsPia S. Zeiner0Martina Kinzig1Iris Divé2Gabriele D. Maurer3Katharina Filipski4Patrick N. Harter5Christian Senft6Oliver Bähr7Elke Hattingen8Joachim P. Steinbach9Fritz Sörgel10Martin Voss11Eike Steidl12Michael W. Ronellenfitsch13Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, GermanyIBMP—Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg POSTCODE, GermanyDr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, GermanyDr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, GermanyUniversity Cancer Center (UCT) Frankfurt, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main POSTCODE, GermanyUniversity Cancer Center (UCT) Frankfurt, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main POSTCODE, GermanyDepartment of Neurosurgery, University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, GermanyDr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, GermanyUniversity Cancer Center (UCT) Frankfurt, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main POSTCODE, GermanyDr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, GermanyIBMP—Institute for Biomedical and Pharmaceutical Research, Nürnberg-Heroldsberg POSTCODE, GermanyDr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, GermanyUniversity Cancer Center (UCT) Frankfurt, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main POSTCODE, GermanyDr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt am Main POSTCODE, Germany(1)<b> </b>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, <i>p</i> = 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.https://www.mdpi.com/2077-0383/8/12/2031malignant gliomaglioblastomaregorafenibregorafenib csf concentrationmri patterns of gliomas |