The addition of chloroquine and bevacizumab to standard radiochemotherapy for recurrent glioblastoma multiforme

Abstract

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.

Keywords:

• Glioblastoma multiforme
• chloroquine
• bevacizumab
• radiochemotherapy
• autophagy

Ethical approval and consent to participate

This retrospective study was approved by the ethics committee of the University of Luebeck (reference no. 19-067A) and conducted in accordance with the declaration of Helsinki. Patients had given written informed consent regarding the routine diagnostic and academic assessment of their biopsy specimen at the Department of Pathology and transfer of their clinical data.

Author contributions

Study conception and drafting of the manuscript: HW and JL. Data collection and analysis, revision of the manuscript: HW, AR, KS, NG, and JL. Initial drafting of manuscript: HW. Revision and final approval of manuscript: all authors.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data supporting the conclusions of this article are included in the article.