Randomized trial of doxorubicin beads for arterial embolization of hepatocellular

描述（由申请人提供）：肝细胞癌（HCC）是世界上第五大常见癌症，随着丙型肝炎发病率的增加，HCC变得更加常见。经导管化疗栓塞术（TACE）已成为不可切除HCC患者的标准治疗方法，尽管缺乏证据证明TACE优于无化疗的栓塞术。有财务和毒性的关注与化疗的使用，使重要的是，以确定最佳的方法动脉栓塞肝癌。已经开发了一种微珠，可以装载阿霉素并用于肝动脉栓塞，导致肿瘤内药物的高浓度延长。为了评估阿霉素在HCC肝动脉栓塞中的作用，我们将进行第一项随机试验，以确定使用普通珠粒与装载150 mg阿霉素的珠粒在治疗反应、进展时间和总生存期方面的差异。在目标1中，我们建议通过对比增强CT扫描中存活肿瘤的变化来表征对治疗的放射学反应。目的2旨在验证评估肿瘤坏死的自动CT容积方法，并将该方法与评估治疗反应的常规方法相关联。目的3将确定使用药物洗脱珠是否会增加进展时间或生存期，以及通过初始治疗后CT扫描中肿瘤坏死的发展估计的治疗反应是否可用作结局的替代生物标志物。这项研究很重要，因为它将提供关于阿霉素在肝动脉栓塞中的作用的客观数据，以及栓塞剂成本增加的理由。我们对毒性的了解可能会改变化疗药物经动脉给药的方式，不仅适用于HCC，也适用于任何富血管的肝脏肿瘤。针对肝肿瘤的靶向化疗有可能对临床结局产生重大影响，并可能改善没有其他公认治疗的患者的总生存期。对所有癌症患者和癌症研究人员来说，一种新的评估治疗反应的成像方法的验证可能取代目前灵敏度较低的方法。绝大多数患者在诊断时不是手术候选人，并且接受肝动脉治疗。对于动脉内治疗是否需要使用化疗药物存在争议。化疗的使用不仅增加了费用，而且增加了潜在的毒性。本研究旨在确定动脉化疗的增量价值，以及验证评估治疗反应的自动成像方法。

DESCRIPTION (provided by applicant): Hepatocellular cancer (HCC) is the 5th most common cancer in the world, and has become more common with the increased incidence of hepatitis C. Transcatheter chemoembolization (TACE) has become the standard treatment for patients with unresectable HCC, despite the lack of evidence demonstrating the superiority of TACE compared to embolization without chemotherapy. There are financial and toxicity concerns associated with the use of chemotherapy that make it important to define the best method of arterial emboliztion for HCC. A microscopic bead has been developed that can be loaded with doxorubicin and used for hepatic arterial embolization, resulting in high prolonged concentration of drug within the tumor. To assess the role of doxorubicin in hepatic arterial embolization of HCC, we will conduct the first randomized trial to determine the difference in response to treatment, time to progression and overall survival using a plain bead versus the bead loaded with 150 mg of doxorubicin. In Aim 1 we propose to characterize the radiologic response to treatment as manifest by change in viable tumor on contrast enhanced CT scans. Aim 2 is designed to validate an automated CT volumetric method of assessing tumor necrosis, and correlate this method with conventional means of assessing response to treatment. Aim 3 will establish whether use of the drug eluting bead increases the time to progression or survival, and whether response to treatment, as estimated by development of tumor necrosis on the initial post-treatment CT scans, can be used as a surrogate biomarker for outcome. This study is important because it will provide objective data regarding the role of doxorubicin in hepatic arterial embolization, and justification for the increased cost of the embolic agent. What we learn about toxicity will likely change the way that chemotherapeutic agents are administered transarterially, not just for HCC but for any hypervascular liver tumor. Targeting chemotherapy to liver tumors has the potential to have a significant impact on clinical outcome, and may improve the overall survival of patients for whom there is no other recognized treatment. The validation of a new imaging method of assessing response to treatment that might replace current less sensitive methods is important for all cancer patients and cancer investigators The incidence of hepatocellular carcinoma (HCC) in the United States is increasing. The vast majorities of patients are not operative candidates at the time of diagnosis, and are treated with hepatic arterial therapies. Controversy exists regarding the need to use chemotherapeutic agents for intra-arterial treatment. The use of chemotherapy adds not only expense, but potential toxicity. This study is designed to determine the incremental value of arterial chemotherapy, as well as to validate an automated imaging method of assessing response to treatment.