CLINICAL TRIAL: UNRESECTABLE HEPATOCELLULAR CA WITH OGF: A PHASE I STUDY

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 肝细胞癌是世界上最致命的肿瘤之一，与慢性肝损伤和肝硬化有关。随着病毒性肝炎发病率的增加，这种癌症在美国的发病率也在不断上升。手术切除提供了治愈的唯一希望;但遗憾的是，很少有患者因肝脏疾病而接受手术。肝移植是一种有效的治疗方法，但由于器官稀缺，大多数患者也不符合这种治疗条件。不适合这些手术的患者几乎没有治疗选择，因为化疗和放疗几乎没有疗效。迫切需要新的治疗方法。 阿片样物质生长因子通过受体介导的机制在体外抑制许多癌细胞系的生长。在胰腺癌中，这种现象不仅在体外而且在动物模型中得到了很好的定义。基于这些发现，已经进行了I期试验，证明OGF可以安全地用于胰腺癌患者。我们假设OGF的施用将抑制患有不可切除的肝细胞癌和肝硬化的人类受试者的癌症进展过程。作为检验这一假设的第一步，我们提出了一项I期试验，研究这种疗法在患有不能手术的肝细胞癌和肝硬化的患者中的毒性和药代动力学。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hepatocellular cancer, one of the world's most deadly tumors, is associated with chronic liver injury and cirrhosis. With the increasing occurrence of viral hepatitis, the incidence of this cancer in the United States continues to rise. Surgical resection offers the only hope for cure; but sadly, few patients are candidates for surgery due to their liver disease. Liver transplant can be an effective treatment, but due to a scarcity of organs, most patients do not qualify for this therapy either. Patients who are not candidates for these procedures have very few therapeutic options as chemotherapy and radiation have little efficacy. New therapies are desperately needed. Opioid Growth Factor inhibits the growth of a number of cancer lines in vitro by a receptor-mediated mechanism. In pancreatic cancer this phenomenon has been well defined not only in vitro but in animal models. Based upon these findings, a phase I trial has been conducted demonstrating that OGF can be administered safely to patients with pancreatic cancer. We hypothesize that administration of OGF will inhibit the course of cancer progression in human subjects with unresectable hepatocellular cancer and cirrhosis. As a first step in testing this hypothesis, we propose a phase I trial to study the toxicity and pharmacokinetics of this therapy in patients suffering from inoperable hepatocellular cancer and cirrhosis.