Sandström Maria, Johansson Mikael, Bergström Per, Bergenheim A Tommy, Henriksson Roger
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
J Neurooncol. 2008 May;88(1):1-9. doi: 10.1007/s11060-008-9527-3. Epub 2008 Jan 29.
The extensive neovascularisation of malignant glioma is mainly influenced by vascular endothelial growth factor (VEGF). The effect of ZD6474, a potent inhibitor of VEGF-receptor-2, was evaluated in combination with either radiotherapy or temozolomide.
The effects on glioma growth were investigated in the intracerebral BT4C rat glioma model. ZD6474 30 mg/kg was given alone or in combination with radiotherapy 12 Gy x 1 or with temozolomide 100 mg/kg for 3 days. Two different experiments were performed comparing ZD6474 to radiotherapy or temozolomide. For each experiment 28 animals were randomized into four groups.
ZD6474 in combination with radiotherapy significantly decreased tumour area by 66% compared with controls whereas the combination with temozolomide decreased tumour area by 74%.
ZD6474 in combination with two standard modalities in the treatment of malignant glioma, radiotherapy and chemotherapy, markedly decreased the growth of an intracerebral experimental glioma. These results justify further investigations of these therapies in combination.
恶性胶质瘤广泛的新血管形成主要受血管内皮生长因子（VEGF）影响。评估了VEGF受体-2强效抑制剂ZD6474与放疗或替莫唑胺联合使用的效果。
在脑内BT4C大鼠胶质瘤模型中研究对胶质瘤生长的影响。单独给予ZD6474 30 mg/kg，或与12 Gy×1的放疗联合使用，或与100 mg/kg的替莫唑胺联合使用3天。进行了两项不同的实验，将ZD6474与放疗或替莫唑胺进行比较。每项实验将28只动物随机分为四组。
与对照组相比，ZD6474与放疗联合使用可使肿瘤面积显著减少66%，而与替莫唑胺联合使用可使肿瘤面积减少74%。
ZD6474与治疗恶性胶质瘤的两种标准模式（放疗和化疗）联合使用，显著降低了脑内实验性胶质瘤的生长。这些结果证明对这些联合疗法进行进一步研究是合理的。
