HEPATIC TUMOR MICROCIRCULATION AND MICROSPHERE THERAPY

描述：(改编自申请人的摘要)这项工作的目的 应用是开发新的、独特的疗法，以更完整和 快速控制肝脏内的大块癌症。其中一个元素是 申请人的方法是使用肝动脉给药 Y-90玻璃微球(Y90-MS)选择性辐照 肿瘤的多血管区域。他目前的I期临床研究已经 在12,500拉德的Y90 MS中未发现与剂量相关的毒性 将继续进行调查，以确定最大耐受量 (从他的动物研究中预计大于或等于20,000 Rads)。基于他的研究表明肿瘤好转到正常 微量HA微球在肝脏中的沉积 肾上腺素，一项利用肾上腺素与Y90 MS进行的I-II期研究 随后将使用球囊闭塞导管来开发 预防Y90MS的肝外反流 申请人的方法是添加HA 5-溴-2‘-脱氧尿苷(BUDR) 作为一种放射增敏剂，一种在药物上合理的治疗方法 他的动物和临床研究证实了这一点。体内抗肿瘤作用 Y90 MS对BUDR诱导的放射增敏效应将是 在听到VX2肿瘤(肝内种植)的兔身上进行了探索。 毒理学研究将按照相关剂量/时间表在狗身上进行 HA Budr和Y90 MS(如之前仅针对Y90 MS所做的那样)。结果是 Y90多发性硬化症单独的临床研究和联合的动物研究 在04-05年度拨款年度内，我们会利用Y90 MS及BUDR发展一项 合并的第一阶段研究并获得NCI的批准 和FDA。

DESCRIPTION: (Adapted from applicant's abstract) The objective of this application is to develop new, unique therapies to more completely and rapidly control bulk cancer within the liver. One element of the applicant's approach is the use of hepatic arterial administration of Yttrium 90 glass microspheres (Y90 MS) to selectively irradiate hypervascular regions of tumors. His current phase I clinical study has found no dose-related toxicity at 12,500 rads of Y90 MS. This investigation will be continued to define the maximum tolerated dose (anticipated from his animal studies at greater than or equal to 20,000 rads). Based upon his studies demonstrating improvement in tumor to normal liver deposition of tracer microspheres with short HA infusion of epinephrine, a phase I-II study utilizing epinephrine with Y90 MS subsequently will be developed using a balloon occlusion catheter to prevent extrahepatic reflux of Y90 MS. The second element of the applicant's approach is the addition of HA 5-bromo-2'-deoxyuridine (BUDR) as a radiosensitizer, a treatment that is pharmacologically rational as substantiated by his animal and clinical studies. In vivo antitumor effects resulting from BUDR-induced radiosensitization with Y9O MS will be explored in rabbits hearing the VX2 tumor (intrahepatically implanted). Toxicology studies will be performed in dogs at relevant dose/schedules of HA BUDR and Y90 MS (as was previously done for Y90 MS alone). The results of the clinical studies of Y90 MS alone and of the animal studies combining Y90 MS with BUDR will be utilized during the 04-05 grant years to develop a phase I study of the combination and to gain approval of same from the NCI and FDA.