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.