Riina Howard A, Fraser Justin F, Fralin Sherese, Knopman Jared, Scheff Ronald J, Boockvar John A
Weill Cornell Brain Tumor Center, Department of Neurosurgery, Weill Cornell Medical College of Cornell University, New York, NY 10021, USA.
J Exp Ther Oncol. 2009;8(2):145-50.
Glioblastoma Multiforme (GBM) is a uniformly fatal disease with a median survival of approximately 15 months. Recent monoclonal antibody therapies such as Bevacizumab (Avastin) have been shown to be active in GBM and to prolong survival in patients with recurrent malignant glioma. Therefore, patients routinely receive intravenous (i.v.) Bevacizumab (10 mg/kg) every two weeks when they have recurred following standard therapy with chemoradiation. I.v Bevacizumab; however, can cause significant systemic side effects including bowel perforation and pulmonary embolism. In addition, the blood brain barrier (BBB) continues to provide an obstacle to the effective delivery of the antibody to the brain tumor bed. In order to overcome the BBB, and to limit the systemic toxicity of i.v. Bevacizumab, we have begun a Phase I clinical trial to test the safety of transient blood brain barrier disruption with intraarterial (IA) Mannitol followed by superselective intraarterial cerebral infusion (SIACI) of Bevacizumab. This case report describes the technical aspects of this procedure and its associated benefits and risks. This novel delivery method, which may herald the revival of Interventional Neuro-oncology, may significantly alter the way therapy is administered to patients with GBM.
多形性胶质母细胞瘤(GBM)是一种致死率极高的疾病,中位生存期约为15个月。最近的单克隆抗体疗法,如贝伐单抗(阿瓦斯汀),已被证明对GBM有效,并能延长复发性恶性胶质瘤患者的生存期。因此,患者在接受标准放化疗后复发时,通常每两周静脉注射(i.v.)一次贝伐单抗(10 mg/kg)。然而,静脉注射贝伐单抗会引起严重的全身副作用,包括肠穿孔和肺栓塞。此外,血脑屏障(BBB)仍然是抗体有效输送到脑肿瘤床的障碍。为了克服血脑屏障,并限制静脉注射贝伐单抗的全身毒性,我们已开始一项I期临床试验,以测试动脉内(IA)注射甘露醇短暂破坏血脑屏障,随后超选择性动脉内脑内输注(SIACI)贝伐单抗的安全性。本病例报告描述了该手术的技术细节及其相关的益处和风险。这种新的给药方法可能预示着介入神经肿瘤学的复兴,可能会显著改变GBM患者的治疗方式。