The addition of chloroquine and bevacizumab to standard radiochemotherapy for recurrent glioblastoma multiforme
INTRODUCTION: Hypoxia-induced autophagy leads to an increase in vasculogenic-mimicry (VM) and the development of resistance of glioblastoma-cells to bevacizumab (BEV). Chloroquine (HCQ) inhibits autophagy, reduces VM and can thus produce a synergistic effect in anti-angiogenic-therapy by delaying the development of resistance to BEV.
PURPOSE: We retrospectively compared the combined addition of HCQ+BEV and adjuvant-radiochemotherapy (aRCT) to aRCT alone for recurrent-glioblastoma (rGBM) in regards of overall survival (OS).
METHODS: Between 2006 and 2016, 134 patients underwent neurosurgery for rGBM at our institution. Forty-two patients (Karnofsky-Performance-Score>60%) with primary-glioblastoma underwent repeat-surgery and aRCT for recurrence. Four patients (9.5%) received aRCT+HCQ+BEV. Five patients received aRCT+BEV.
RESULTS: In rGBM-patients who were treated with aRCT+HCQ+BEV, median OS was 36.57 months and median post-recurrence-survival (PRS) was 23.92 months while median PRS in the control-group was 9.63 months (p=0.022). In patients who received aRCT+BEV, OS and PRS were 26.83 and 12.97 months, respectively.
CONCLUSIONS: Although this study was performed on a small number of highly selected patients, it demonstrates a synergistic effect of HCQ+BEV in the treatment of rGBM which previously could be demonstrated based on experimental data. A significant increase of OS in patients who receive aRCT+HCQ+BEV cannot be ruled out and should be further investigated in randomised-controlled-trials.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
British journal of neurosurgery - 38(2024), 2 vom: 31. März, Seite 404-410 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Witte, Hanno M [VerfasserIn] |
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| Links: |
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| Themen: |
2S9ZZM9Q9V |
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| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/02688697.2021.1884648 |
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| 100 | 1 | |a Witte, Hanno M |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The addition of chloroquine and bevacizumab to standard radiochemotherapy for recurrent glioblastoma multiforme |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 22.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a INTRODUCTION: Hypoxia-induced autophagy leads to an increase in vasculogenic-mimicry (VM) and the development of resistance of glioblastoma-cells to bevacizumab (BEV). Chloroquine (HCQ) inhibits autophagy, reduces VM and can thus produce a synergistic effect in anti-angiogenic-therapy by delaying the development of resistance to BEV | ||
| 520 | |a PURPOSE: We retrospectively compared the combined addition of HCQ+BEV and adjuvant-radiochemotherapy (aRCT) to aRCT alone for recurrent-glioblastoma (rGBM) in regards of overall survival (OS) | ||
| 520 | |a METHODS: Between 2006 and 2016, 134 patients underwent neurosurgery for rGBM at our institution. Forty-two patients (Karnofsky-Performance-Score>60%) with primary-glioblastoma underwent repeat-surgery and aRCT for recurrence. Four patients (9.5%) received aRCT+HCQ+BEV. Five patients received aRCT+BEV | ||
| 520 | |a RESULTS: In rGBM-patients who were treated with aRCT+HCQ+BEV, median OS was 36.57 months and median post-recurrence-survival (PRS) was 23.92 months while median PRS in the control-group was 9.63 months (p=0.022). In patients who received aRCT+BEV, OS and PRS were 26.83 and 12.97 months, respectively | ||
| 520 | |a CONCLUSIONS: Although this study was performed on a small number of highly selected patients, it demonstrates a synergistic effect of HCQ+BEV in the treatment of rGBM which previously could be demonstrated based on experimental data. A significant increase of OS in patients who receive aRCT+HCQ+BEV cannot be ruled out and should be further investigated in randomised-controlled-trials | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Glioblastoma multiforme | |
| 650 | 4 | |a autophagy | |
| 650 | 4 | |a bevacizumab | |
| 650 | 4 | |a chloroquine | |
| 650 | 4 | |a radiochemotherapy | |
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| 650 | 7 | |a Chloroquine |2 NLM | |
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| 700 | 1 | |a Riecke, Armin |e verfasserin |4 aut | |
| 700 | 1 | |a Steinestel, Konrad |e verfasserin |4 aut | |
| 700 | 1 | |a Schulz, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Küchler, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Gebauer, Niklas |e verfasserin |4 aut | |
| 700 | 1 | |a Tronnier, Volker |e verfasserin |4 aut | |
| 700 | 1 | |a Leppert, Jan |e verfasserin |4 aut | |
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