Waikato Hospital, Regional Cancer Centre, Waikato Hospital, Private Bag 3200, Hamilton 3240, New Zealand.
Expert Opin Investig Drugs. 2010 Feb;19(2):295-304. doi: 10.1517/13543780903540214.
Targeting tumor vasculature with antiangiogenic agents improves outcomes achieved with chemotherapy in some cancers, but toxicity limits their applicability. Tumor vascular-disrupting agents (tumor-VDAs) induce an acute collapse in tumor vascular supply; ASA404 (vadimezan, 5,6-dimethylxanthenone-4-acetic acid [DMXAA]) is the tumor-VDA most advanced in clinical development. Recent randomized trials of ASA404 in combination with chemotherapy suggested a survival advantage in NSCLC comparable to that achieved with bevacizumab, but with little additional toxicity. Phase III trials in advanced NSCLC have completed accrual, and a review of this exciting agent is timely.
This review focuses on the development of ASA404 to date, its mechanisms of action, the current body of clinical research and potential avenues for therapeutic use. It includes all completed clinical trials since it entered clinical testing in 1995 through to 2009.
This review will help the reader to understand why ASA404 is unique among tumor-VDAs; the clinical trial methodology required to evaluate such agents; and its remarkable potential clinical utility.
ASA404 is a tumor-VDA that offers considerable potential to improve outcomes in cancer patients in combination with existing treatments.
用抗血管生成药物靶向肿瘤血管，可提高某些癌症的化疗疗效，但毒性限制了其适用性。肿瘤血管破坏剂（tumor-VDA）可导致肿瘤血管供应的急性崩溃；ASA404（vadimezan，5,6-二甲基黄嘌呤-4-乙酸[DMXAA]）是临床开发中最先进的肿瘤-VDA。最近 ASA404 联合化疗的随机试验表明，在 NSCLC 中与贝伐单抗相比具有生存优势，但毒性增加不大。晚期 NSCLC 的 III 期试验已完成入组，及时对这一令人兴奋的药物进行审查是适时的。
本篇综述重点介绍了 ASA404 的发展历程、作用机制、目前的临床研究现状以及潜在的治疗用途。它包括自 1995 年进入临床测试以来至 2009 年所有已完成的临床试验。
这篇综述将帮助读者了解为什么 ASA404 在肿瘤 VDA 中是独一无二的；评估此类药物所需的临床试验方法；以及其显著的潜在临床应用价值。
ASA404 是一种肿瘤血管破坏剂，与现有治疗方法联合使用，有望显著改善癌症患者的治疗效果。
