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Phase I/II trial of meclofenamate in progressive MGMT-methylated glioblastoma under temozolomide second-line therapy: the MecMeth/NOA-24 trial

Glioblastoma is the most frequent and malignant primary brain tumor. Even in the subgroup with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and favorable response to first-line therapy, survival after relapse is short (12 months). Standard therapy for recurrent MGMT-methylated...

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Main Authors: Zeyen, Thomas (Author) , Potthoff, Anna-Laura (Author) , Nemeth, Robert (Author) , Heiland, Dieter H. (Author) , Burger, Michael C. (Author) , Steinbach, Joachim P. (Author) , Hau, Peter (Author) , Tabatabai, Ghazaleh (Author) , Glas, Martin (Author) , Schlegel, Uwe (Author) , Grauer, Oliver (Author) , Krex, Dietmar (Author) , Schnell, Oliver (Author) , Goldbrunner, Roland (Author) , Sabel, Michael (Author) , Thon, Niklas (Author) , Delev, Daniel (Author) , Clusmann, Hans (Author) , Seidel, Clemens (Author) , Güresir, Erdem Özer (Author) , Schmid, Matthias (Author) , Schuß, Patrick (Author) , Giordano, Frank Anton (Author) , Radbruch, Alexander (Author) , Becker, Albert (Author) , Weller, Johannes (Author) , Schaub, Christina (Author) , Vatter, Hartmut (Author) , Schilling, Judith (Author) , Winkler, Frank (Author) , Herrlinger, Ulrich (Author) , Schneider, Matthias (Author)
Format: Article (Journal)
Language:English
Published: 19 January 2022
In: Trials
Year: 2022, Volume: 23, Pages: 1-16
ISSN:1468-6694
DOI:10.1186/s13063-021-05977-0
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1186/s13063-021-05977-0
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Author Notes:Thomas Zeyen, Anna-Laura Potthoff, Robert Nemeth, Dieter H. Heiland, Michael C. Burger, Joachim P. Steinbach, Peter Hau, Ghazaleh Tabatabai, Martin Glas, Uwe Schlegel, Oliver Grauer, Dietmar Krex, Oliver Schnell, Roland Goldbrunner, Michael Sabel, Niklas Thon, Daniel Delev, Hans Clusmann, Clemens Seidel, Erdem Güresir, Matthias Schmid, Patrick Schuss, Frank A. Giordano, Alexander Radbruch, Albert Becker, Johannes Weller, Christina Schaub, Hartmut Vatter, Judith Schilling, Frank Winkler, Ulrich Herrlinger and Matthias Schneider
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Summary:Glioblastoma is the most frequent and malignant primary brain tumor. Even in the subgroup with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and favorable response to first-line therapy, survival after relapse is short (12 months). Standard therapy for recurrent MGMT-methylated glioblastoma is not standardized and may consist of re-resection, re-irradiation, and chemotherapy with temozolomide (TMZ), lomustine (CCNU), or a combination thereof. Preclinical results show that meclofenamate (MFA), originally developed as a nonsteroidal anti-inflammatory drug (NSAID) and registered in the USA, sensitizes glioblastoma cells to temozolomide-induced toxicity via inhibition of gap junction-mediated intercellular cytosolic traffic and demolishment of tumor microtube (TM)-based network morphology.
Item Description:Gesehen am 24.01.2023
Physical Description:Online Resource
ISSN:1468-6694
DOI:10.1186/s13063-021-05977-0

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