Zeyen, Thomas and Potthoff, Anna-Laura and Nemeth, Robert and Heiland, Dieter H. and Burger, Michael C. and Steinbach, Joachim P. and Hau, Peter and Tabatabai, Ghazaleh and Glas, Martin and Schlegel, Uwe and Grauer, Oliver and Krex, Dietmar and Schnell, Oliver and Goldbrunner, Roland and Sabel, Michael and Thon, Niklas and Delev, Daniel and Clusmann, Hans and Seidel, Clemens and Gueresir, Erdem and Schmid, Matthias and Schuss, Patrick and Giordano, Frank A. and Radbruch, Alexander and Becker, Albert and Weller, Johannes and Schaub, Christina and Vatter, Hartmut and Schilling, Judith and Winkler, Frank and Herrlinger, Ulrich and Schneider, Matthias (2022) Phase I/II trial of meclofenamate in progressive MGMT-methylated glioblastoma under temozolomide second-line therapy-the MecMeth/NOA-24 trial. TRIALS, 23 (1): 57. ISSN , 1745-6215
Full text not available from this repository. (Request a copy)Abstract
Background: 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. Methods: In this study, combined MFA/TMZ therapy will be administered (orally) in patients with first relapse of MGMT-methylated glioblastoma. A phase I component (6-12 patients, 2 dose levels of MFA + standard dose TMZ) evaluates safety and feasibility and determines the dose for the randomized phase II component (2 x 30 patients) with progression-free survival as the primary endpoint. Discussion: This study is set up to assess toxicity and first indications of efficacy of MFA repurposed in the setting of a very difficult-to-treat recurrent tumor. The trial is a logical next step after the identification of the role of resistance-providing TMs in glioblastoma, and results will be crucial for further trials targeting TMs. In case of favorable results, MFA may constitute the first clinically feasible TM-targeted drug and therefore might bridge the idea of a TM-targeted therapeutic approach from basic insights into clinical reality.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COMBINATION; CELLS; LIFE; Glioblastoma; Relapse; Meclofenamate; Temozolomide; Second-line therapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Feb 2024 14:21 |
| Last Modified: | 01 Feb 2024 14:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58360 |
Actions (login required)
 |
View Item |
