TY  - JOUR
A1  - Zeiner, Pia Susan
A1  - Kinzig, Martina
A1  - Divé, Iris
A1  - Maurer, Gabriele D.
A1  - Filipski, Katharina Johanna
A1  - Harter, Patrick Nikolaus
A1  - Senft, Christian
A1  - Bähr, Roy Oliver
A1  - Hattingen, Elke
A1  - Steinbach, Joachim Peter
A1  - Sörgel, Fritz
A1  - Voß, Martin
A1  - Steidl, Eike
A1  - Ronellenfitsch, Michael Wilfried
T1  - Regorafenib CSF penetration, efficacy, and MRI patterns in recurrent malignant glioma patients
T2  - Journal of Clinical Medicine
N2  - (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.
KW  - malignant glioma
KW  - glioblastoma
KW  - regorafenib
KW  - regorafenib csf concentration
KW  - MRI patterns of gliomas
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51827
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-518275
SN  - 2077-0383
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
VL  - 8
IS  - 12, Art. 2031
SP  - 1
EP  - 14
PB  - MDPI
CY  - Basel
ER  -