Goldwirt Lauriane, Beccaria Kevin, Carpentier Alexandre, Idbaih Ahmed, Schmitt Charlotte, Levasseur Camille, Labussiere Marianne, Milane Aline, Farinotti Robert, Fernandez Christine
Clinical Pharmacy Department - EA 4123, College of Pharmacy, Paris Sud University, 5 rue Jean Baptiste Clement, 92296, Châtenay Malabry, France,
J Neurooncol. 2015 Apr;122(2):273-81. doi: 10.1007/s11060-015-1717-1. Epub 2015 Jan 13.
Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Prognosis of GBM patients is poor with median overall survival around 15 months. Temozolomide is the chemotherapeutic agent used in the standard of care of newly diagnosed GBM patients relying on radiotherapy with concurrent chemotherapy followed by chemotherapy alone. Irinotecan has shown some efficacy in recurrent malignant gliomas. Bevacizumab has been combined with irinotecan in the treatment of recurrent GBM and with temozolomide in newly diagnosed GBM. As the efficacy of GBM treatments relies on their brain distribution through the blood brain barrier, the aim of the present preclinical work was to study, in in vivo models, the impact of bevacizumab on brain and tumor distribution of temozolomide and irinotecan. Our results show that bevacizumab pre-treatment was associated with a reduced temozolomide brain distribution in tumor-free mice. In tumor bearing mice, bevacizumab increased temozolomide tumor distribution, although not statistically significant. In both tumor-free and tumor-bearing mice, bevacizumab does not modify brain distribution of irinotecan and its metabolite SN-38. Bevacizumab impacts brain distribution of some anti-tumor drugs and potentially their efficacy in GBM. Further studies are warranted to investigate other therapeutic combination.
胶质母细胞瘤（GBM）是成人中最常见的原发性恶性脑肿瘤。GBM患者的预后较差，总体中位生存期约为15个月。替莫唑胺是新诊断GBM患者标准治疗中使用的化疗药物，依赖于放疗联合同步化疗，随后单独进行化疗。伊立替康在复发性恶性胶质瘤中已显示出一定疗效。贝伐单抗已与伊立替康联合用于复发性GBM的治疗，并与替莫唑胺联合用于新诊断的GBM。由于GBM治疗的疗效依赖于它们通过血脑屏障的脑内分布，本临床前研究的目的是在体内模型中研究贝伐单抗对替莫唑胺和伊立替康脑内及肿瘤内分布的影响。我们的结果表明，在无肿瘤小鼠中，贝伐单抗预处理与替莫唑胺脑内分布减少有关。在荷瘤小鼠中，贝伐单抗增加了替莫唑胺的肿瘤内分布，尽管无统计学意义。在无肿瘤和荷瘤小鼠中，贝伐单抗均不改变伊立替康及其代谢产物SN-38的脑内分布。贝伐单抗影响某些抗肿瘤药物的脑内分布，并可能影响其在GBM中的疗效。有必要进行进一步研究以探讨其他治疗组合。
