Latulippe Juliette, Roy Laurent-Olivier, Gobeil Fernand, Fortin David
Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Division of Neurosurgery, Department of Surgery, Centre Hospitalier de l'Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Biomolecules. 2025 Mar 16;15(3):421. doi: 10.3390/biom15030421.
Glioblastoma (GBM) is a difficult disease to treat for different reasons, with the blood-brain barrier (BBB) preventing therapeutic drugs from reaching the tumor being one major hurdle. The median overall survival is only 14.6 months after the standard first line of treatment. At relapse, there is no recognized standard second-line treatment. Our team uses intra-arterial (IA) chemotherapy as a means to bypass the BBB, hence achieving an overall median survival of 25 months. However, most patients eventually fail the treatment and progress. This is why we wish to expand our portfolio of options in terms of chemotherapy agents available for IA administration. In this study, we tested topotecan, cytarabine, and new formulations of carboplatin and paclitaxel by IA administration in the F98-Fischer glioma-bearing rat model as a screening tool for identifying potential candidate drugs. The topotecan IA group showed increased survival compared to the intravenous (IV) group (29.0 vs. 23.5), whereas the IV cytarabine group survived longer than the IA group (26.5 vs. 22.5). The new formulation of carboplatin showed a significant increase in survival compared to two previous studies with the conventional form (37.5 vs. 26.0 and 30.0). As for paclitaxel, it was too neurotoxic for IA administration. Topotecan and the new formulation of carboplatin demonstrated significant results, warranting their transition for consideration in clinical trials.
胶质母细胞瘤（GBM）因多种原因成为一种难以治疗的疾病，血脑屏障（BBB）阻碍治疗药物到达肿瘤部位是一个主要障碍。标准一线治疗后的中位总生存期仅为14.6个月。复发时，尚无公认的标准二线治疗方法。我们的团队采用动脉内（IA）化疗作为绕过血脑屏障的一种手段，从而使中位总生存期达到25个月。然而，大多数患者最终治疗失败并病情进展。这就是为什么我们希望扩大可用于IA给药的化疗药物选择范围。在本研究中，我们通过在F98 - 费希尔荷胶质瘤大鼠模型中进行IA给药来测试拓扑替康、阿糖胞苷以及卡铂和紫杉醇的新制剂，以此作为识别潜在候选药物的筛选工具。拓扑替康IA组与静脉注射（IV）组相比生存期延长（29.0天对23.5天），而IV阿糖胞苷组比IA组生存期更长（26.5天对22.5天）。卡铂新制剂与之前两项使用传统剂型的研究相比生存期显著延长（37.5天对26.0天和30.0天）。至于紫杉醇，其对IA给药的神经毒性过大。拓扑替康和卡铂新制剂显示出显著效果，值得将它们过渡到临床试验中进行考量。
