Islolated Hepatic Perfusion with Oxaliplatin

奥沙利铂离体肝灌注

• 批准号: 7056312
• 负责人: DAVID L BARTLETT
• 金额: $ 26.36万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-16 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7056312
• 关键词: antineoplastics; clinical research; lead; metastasis; neoplasm /cancer; perfusion

DESCRIPTION (provided by applicant): Cancer of the colon and rectum is expected to be the third leading cause of cancer death in the United States in 2005. Hepatic metastases as the sole or dominant site of life-limiting disease occur in approximately 20-50% of these patients. Resection of these liver metastases results in five year survival approaching 40%, suggesting that regional control of this disease can lead to improved overall survival. Unfortunately, only a small fraction of patients with isolated liver metastases are eligible for resection. We are currently exploring a novel and highly promising approach to treatment of unresectable liver metastases, isolated hepatic perfusion. It is our goal to develop a regional hepatic therapy that has a response rate approaching 100% with a long duration of response. We envision then combining this successful regional treatment with an effective anti-tumor immunotherapy to ultimately have a significant impact on overall survival. This goal led to a phase I study of isolated hepatic perfusion with oxaliplatin for colorectal metastases. In this phase I study, out of six evaluable patients we had an objective radiographic partial response rate of 50%, a complete response rate of 17%, leading to an overall objective radiographic response rate of 67%. While this is a remarkable response rate for a phase 1 trial we do not believe that oxaliplatin alone is our optimal regimen for IMP. Given the profound synergy between 5-FU and oxaliplatin, we propose to examine the combination of 5-FU and oxaliplatin delivered via an isolated hepatic perfusion circuit. The rationale for this combination is rooted on a large body of in vitro and in vivo data suggesting significant synergy and no overlapping toxicity between these agents as well as important early clinical experience with systemic oxaliplatin that suggested that this agent was most effective when combined with other cytotoxic agents.

描述（由申请人提供）：预计结肠癌和直肠的癌症将是2005年美国癌症死亡的第三大主要原因。肝转移是其中约20-50％的患者，作为生命疾病的唯一或占主导地位。这些肝转移的切除导致五年生存率接近40％，这表明该疾病的区域控制可以改善总体生存率。不幸的是，只有一小部分患有孤立肝转移的患者才有资格切除。我们目前正在探索一种新颖且高度有希望的方法来治疗不可切除的肝转移，即孤立的肝灌注。我们的目标是开发一种区域性肝疗法，该疗法的缓解率在较长的响应时间内接近100％。然后，我们设想将这种成功的区域治疗与有效的抗肿瘤免疫疗法相结合，最终对总体生存产生重大影响。该目标导致了与奥沙利铂的分离肝灌注的I期研究，用于结直肠转移。在此阶段I研究中，在六名可评估患者中，我们的客观X光摄影部分反应率为50％，完全反应率为17％，导致总体客观X光摄影响应率为67％。尽管这是1阶段试验的显着响应率，但我们不认为仅奥沙利铂是我们的最佳方案。鉴于5-FU和Oxaliptin之间的深刻协同作用，我们建议检查通过分离的肝灌注回路传递的5-FU和奥沙利铂的组合。这种组合的基本原理植根于大量的体外和体内数据，表明这些药物之间存在明显的协同作用，并且这些药物之间没有重叠的毒性，以及与全身性催产素的重要早期临床经验，这表明该药物与其他细胞毒性剂结合时最有效。