HEPATIC TUMOR MICROCIRCULATION AND MICROSPHERE THERAPY

描述：（改编自申请人的摘要） 应用是开发新的，独特的疗法，以更全面， 快速控制肝脏内的大块癌症。 的一个元件 申请人的方法是使用肝动脉给药 钇90玻璃微球（Y 90 MS）选择性辐照 肿瘤的多血管区域。 他目前的I期临床研究 发现在12，500拉德的Y 90 MS下没有剂量相关毒性。 将继续研究以确定最大耐受剂量 （根据其动物研究，预期大于或等于20，000 rads）。 根据他的研究显示肿瘤恢复正常 用短时间HA输注的示踪剂微球的肝脏沉积 肾上腺素，一项使用肾上腺素和Y 90 MS的I-II期研究 随后将使用球囊闭塞导管开发， 预防Y 90 MS肝外反流的第二要素 申请人的方法是加入HA 5-溴-2 '-脱氧尿苷（BUDR） 作为一种放射增敏剂， 他的动物和临床研究证实了这一点。 体内抗肿瘤 由BUDR诱导的Y 9 O MS放射增敏产生的效应将是 在听到VX 2肿瘤（肝内植入）的兔子中进行了研究。 毒理学研究将在相关剂量/时间表下在犬中进行 HA BUDR和Y 90 MS（如先前单独对Y 90 MS所做的）。 结果 Y 90 MS单独的临床研究和动物研究结合 Y 90 MS与BUDR将在2004 - 2005赠款年期间用于开发 I期联合研究，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.