Hall Walter A, Sherr Gregory T
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Neurosurg Focus. 2006 Apr 15;20(4):E10.
Historically, malignant gliomas are perhaps the most difficult intracranial neoplasms to treat. Surgery, radiation therapy, and traditional chemotherapy have not been able to significantly alter the course of this disease. By definition, these tumors are located in the protected space of the cranial vault, where the blood-brain barrier prevents most therapies from gaining access. Because of the difficulty in treating this disease, new, innovative treatments and alternative delivery techniques for those therapies are needed. Targeted toxins are fusion proteins that represent a novel medical treatment for these cancers that is under development. However, the efficacy of these agents is dependent on the method of delivery to the tumor. The administration of targeted toxins requires image-guided placement of catheters, either within the tumor or into the adjacent infiltrated brain, and positive pressure infusion. The term that has been applied to this microinfusion technique is convection-enhanced delivery (CED). This infusion method was first attempted via direct intratumoral infusion in nude mouse flank tumor models of human malignant glioma. After significant development of this delivery technique in animal models, the successful demonstration of in vivo efficacy of targeted toxins in Phase I and II clinical trials was reported. Currently, ongoing targeted toxin trials are being conducted at academic health centers to define the best clinical practice for CED. This work involves refining the details of delivery such as infusion rate, duration of treatment, and drug dosing. The early results of CED of targeted toxins supports their continued investigation, as few other treatment modalities have produced durable results in the fight against gliomas.
从历史上看，恶性胶质瘤可能是最难治疗的颅内肿瘤。手术、放射治疗和传统化疗都未能显著改变这种疾病的进程。根据定义，这些肿瘤位于颅腔内的受保护空间，血脑屏障会阻止大多数治疗方法进入。由于治疗这种疾病存在困难，因此需要新的、创新的治疗方法以及这些治疗方法的替代给药技术。靶向毒素是一种融合蛋白，是正在研发的针对这些癌症的新型医学治疗方法。然而，这些药物的疗效取决于向肿瘤给药的方法。靶向毒素的给药需要在图像引导下将导管放置在肿瘤内或邻近的浸润性脑组织中，并进行正压输注。这种微输注技术被称为对流增强递送（CED）。这种输注方法最初是在人恶性胶质瘤的裸鼠侧腹肿瘤模型中通过直接瘤内输注尝试的。在动物模型中对这种递送技术进行了大量研发之后，有报道称在I期和II期临床试验中成功证明了靶向毒素的体内疗效。目前，学术健康中心正在进行正在进行的靶向毒素试验，以确定CED的最佳临床实践。这项工作涉及完善给药细节，如输注速率、治疗持续时间和药物剂量。靶向毒素CED的早期结果支持继续对其进行研究，因为在对抗胶质瘤方面，很少有其他治疗方式能产生持久的效果。
