Department of Haematology and Oncology, German Armed Forces Hospital of Ulm, Ulm, Germany.
Department of Pathology and Molecular-Pathology, German Armed Forces Hospital of Ulm, Ulm, Germany.
Br J Neurosurg. 2024 Apr;38(2):404-410. doi: 10.1080/02688697.2021.1884648. Epub 2021 Feb 16.
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.
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).
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.
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 (=0.022). In patients who received aRCT+BEV, OS and PRS were 26.83 and 12.97 months, respectively.
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.
缺氧诱导的自噬导致血管生成拟态（VM）增加，并导致胶质母细胞瘤细胞对贝伐单抗（BEV）产生耐药性。氯喹（HCQ）抑制自噬，减少 VM，从而通过延迟对 BEV 的耐药性发展，在抗血管生成治疗中产生协同作用。
我们回顾性比较了 HCQ+BEV 联合辅助放化疗（aRCT）与单独 aRCT 治疗复发性胶质母细胞瘤（rGBM）的总生存期（OS）。
2006 年至 2016 年，我们机构对 134 例 rGBM 患者进行了神经外科手术。42 例（Karnofsky 表现评分>60%）原发性胶质母细胞瘤患者行再次手术和 aRCT 治疗复发。4 例（9.5%）患者接受 aRCT+HCQ+BEV 治疗。5 例患者接受 aRCT+BEV 治疗。
在接受 aRCT+HCQ+BEV 治疗的 rGBM 患者中，中位 OS 为 36.57 个月，中位复发后生存（PRS）为 23.92 个月，而对照组的中位 PRS 为 9.63 个月（=0.022）。接受 aRCT+BEV 治疗的患者的 OS 和 PRS 分别为 26.83 个月和 12.97 个月。
尽管这项研究是在少数高度选择的患者中进行的，但它证明了 HCQ+BEV 在治疗 rGBM 中的协同作用，这一作用以前可以基于实验数据得到证明。不能排除接受 aRCT+HCQ+BEV 治疗的患者 OS 显著增加的可能性，需要进一步在随机对照试验中进行研究。
