Doolittle N D, Miner M E, Hall W A, Siegal T, Jerome E, Osztie E, McAllister L D, Bubalo J S, Kraemer D F, Fortin D, Nixon R, Muldoon L L, Neuwelt E A
Department of Neurology, Oregon Health Sciences University, Portland, OR 97201-3098, USA.
Cancer. 2000 Feb 1;88(3):637-47. doi: 10.1002/(sici)1097-0142(20000201)88:3<637::aid-cncr22>3.0.co;2-y.
The aim of this study was to determine the safety and efficacy of intraarterial chemotherapy with osmotic opening of the blood-brain barrier (BBB) for the treatment of malignant brain tumors when administered across multiple centers.
Patients with primary central nervous system lymphoma (PCNSL), primitive neuroectodermal tumor (PNET), germ cell tumor, cancer metastasis to the brain, or low or high grade glioma were eligible. Prior to entry, magnetic resonance imaging or computed tomography brain scan, medical history, neurologic status, and Karnofsky performance status were reviewed at the coordinating center. Standardized anesthesia and intraarterial catheterization guidelines were followed by a multidisciplinary team at each center. Between March 1994 and November 1997, 5 universities treated 221 adult patients with intraarterial chemotherapy with or without osmotic opening of the BBB (2464 procedures).
Of evaluable patients with PCNSL, 40 of 53 (75%) achieved complete response (CR). All evaluable patients with PNET (n = 17), metastatic disease (n = 12), or germ cell tumor (n = 4) achieved stable disease (SD) or better. Of 57 evaluable patients with glioblastoma multiforme, 45 (79%) achieved SD or better. Asymptomatic subintimal tear occurred in 11 of 221 patients (5%), pulmonary embolism in 6 of 221 (2.7%), and renal toxicity in 4 of 221 (1.8%). One patient with extensive glioma expired within 48 hours after treatment.
Using standard guidelines and protocols, intraarterial chemotherapy with or without osmotic opening of the BBB is feasible across multiple centers with a low incidence of catheter-related complications. In patients with chemotherapy-sensitive tumors, such as PCNSL, PNET, germ cell tumor, and cancer metastasis to the central nervous system, enhanced delivery results in a high degree of tumor response, with an efficacy profile that is reproducible across multiple centers.
本研究的目的是确定在多个中心进行动脉内化疗并通过渗透打开血脑屏障（BBB）治疗恶性脑肿瘤的安全性和有效性。
符合条件的患者包括原发性中枢神经系统淋巴瘤（PCNSL）、原始神经外胚层肿瘤（PNET）、生殖细胞瘤、脑转移癌或低级别或高级别胶质瘤患者。入选前，在协调中心对患者进行磁共振成像或计算机断层扫描脑部扫描、病史、神经状态和卡氏功能状态评估。每个中心的多学科团队遵循标准化的麻醉和动脉内插管指南。1994年3月至1997年11月，5所大学对221例成年患者进行了动脉内化疗，其中部分患者进行了或未进行BBB的渗透打开（共2464次操作）。
在可评估的PCNSL患者中，53例中有40例（75%）达到完全缓解（CR）。所有可评估的PNET患者（n = 17）、转移性疾病患者（n = 12）或生殖细胞瘤患者（n = 4）均达到疾病稳定（SD）或更好的状态。在57例可评估的多形性胶质母细胞瘤患者中，45例（79%）达到SD或更好的状态。221例患者中有11例（5%）发生无症状内膜下撕裂，221例中有6例（2.7%）发生肺栓塞，221例中有4例（1.8%）发生肾毒性。1例广泛胶质瘤患者在治疗后48小时内死亡。
使用标准指南和方案，无论是否进行BBB的渗透打开，动脉内化疗在多个中心都是可行的，与导管相关的并发症发生率较低。在化疗敏感肿瘤患者中，如PCNSL、PNET
