INTRA-ARTERIAL BUDR RADIOSENSITIZATION-MALIGNANT

这项I/II期研究的目的是开发一种改进的治疗方法， 单侧恶性脑胶质瘤患者的计划， 动脉内（IA）输注放射增敏药物， 放射治疗。 最近的一项研究结果表明， BUdR的输注应递送11- 16倍高浓度的 与静脉内（IV）给药相比，BUdR对脑肿瘤的作用。 它 得出的结论是，安全的颈动脉输送系统是必要的， BUDR的疗效。 我们已经开发了这样一种颈动脉药物输送 并建议将其用于猴研究和临床 人的审判 在人类研究之前，我们将检查IA BUdR和 对正常灵长类动物的大脑进行放射治疗。 这些研究 国家癌症研究所和食品药品监督管理局要求 人类临床试验开始前给药。 我们将 还通过测量IA BUdR和5-FU的 给药后猴的颈内动脉血BUdR和5-FU水平 颈动脉内和IV给药。 将研究5-FU，因为 其增加BUdR掺入DNA和增强BUdR 放射增敏。 IA BUdR和放射治疗的I/II期临床试验将在以下时间开始： 完成灵长类动物毒性研究。 患者将接受 开颅手术进行诊断和最大限度地切除肿瘤，然后 一周后，通过放置完全可植入的泵， 通过推注或连续输注将药物直接输送到 颈内动脉 他们将接受持续的 放射增敏剂BUdR，500 mg/m2/天。 输注将开始14天 在放射治疗之前和期间继续。 放射治疗将 由递送到肿瘤床和3cm边缘的6000拉德组成。 肿瘤放射增敏和放射治疗失败的患者将接受 通过泵间歇推注高剂量BCNU（150 mg/m2） 每隔6周进行一次侧孔。 我们期望这项研究将进一步了解IA 放射增敏剂和化疗剂的施用。 我们进一步 我希望这项治疗计划能提高患有 恶性胶质瘤，并最终导致第三阶段的发展 合作研究。

The purpose of this phase I/II study is to develop an improved treatment program for patients with unilateral malignant cerebral gliomas using intra-arterial (IA) infusions of a radiosensitizing drug in conjunction with radiotherapy. The results of a recent study indicate that carotid infusion of BUdR should deliver an 11- to 16-fold higher concentration of BUdR to cerebral tumors compared to intravenous (IV) administration. It was concluded that a safe carotid delivery system is necessary to maximize the efficacy of BUdR. We have developed such a carotid drug delivery system and propose to utilize it for investigations in monkeys and clinical trials in man. Prior to human studies, we will examine the effects of IA BUdR and radiotherapy on the normal primate brain. These studies have been requested by the National Cancer Institute and the Food and Drug Administration prior to the initiation of human clinical trials. We will also determine the regional advantage of IA BUdR and 5-FU by measuring the internal carotid artery blood levels of BUdR and 5-FU in the monkey after both intracarotid and IV administration. 5-FU will be studied because of its potential to increase BUdR incorporation into DNA and enhance BUdR radiosensitization. A phase I/II clinical trial of IA BUdR and radiotherapy will begin after the completion of primate toxicity studies. Patients will undergo a craniotomy for diagnosis and maximum resection of their tumors, followed one week later by placement of a totally implantable pump capable of delivering drugs by either bolus or continuous infusion directly into the internal carotid artery. They will receive continuous infusion of the radiosensitizer BUdR at 500 mg/m2/day. The infusion will begin 14 days prior to and continue during radiation therapy. Radiation therapy will consist of 6000 rads delivered to the tumor bed and a 3 cm margin. Patients whose tumors fail radiosensitization and radiotherapy will receive intermittent bolus infusions of high dose BCNU (150 mg/m2) via the pump sideport at 6-week intervals. We anticipate that this study will further knowledge about the IA administration of radiosensitizers and chemotherapeutic agents. We further hope this treatment program will increase survival for patients with malignant gliomas and eventually lead to the development of Phase III cooperative studies.