Waikato Hospital, Oncology Dept, Private Bag 3200, Pembroke St, Hamilton 3240, New Zealand.
Expert Opin Drug Metab Toxicol. 2011 Oct;7(10):1315-26. doi: 10.1517/17425255.2011.614389. Epub 2011 Aug 26.
Understanding the pharmacokinetics (PK) and pharmacodynamics of a drug is important to optimizing its use. Vadimezan is a tumor vascular-disrupting agent that acutely disrupts blood flow within tumors and induces innate tumor immunity. It has enhanced the activity of anticancer treatments in preclinical models and early phase trials, although one Phase III trial result was negative and another is yet to be reported.
Areas covered in this review are the preclinical and human PK and the inter-relationship among PK, toxicity and efficacy of vadimezan as a single agent and in combination with other therapies. These data are derived from a literature search on Medline and also from conference proceedings, abstracts and trial reports available up to June 2011.
The disappointing results of one Phase III trial, despite the promising randomized Phase II trial data, highlight the challenges in translational research, especially in selecting the optimal development strategy. This paper discusses how different scheduling of vadimezan could significantly enhance the anticancer efficacy of this drug in combination with other therapies, especially those that do not require concurrent corticosteroid administration.
了解药物的药代动力学（PK）和药效动力学对于优化其使用非常重要。Vadimezan 是一种肿瘤血管破坏剂，可在肿瘤内迅速破坏血流，并诱导先天肿瘤免疫。在临床前模型和早期试验中，它增强了抗癌治疗的活性，尽管一项三期临床试验结果为阴性，另一项试验结果尚未报告。
本综述涵盖了 vadimezan 的临床前和人体 PK 以及 PK、毒性和疗效之间的相互关系，作为单一药物以及与其他疗法联合应用的情况。这些数据源自对 Medline 的文献检索，也源自会议记录、摘要和截至 2011 年 6 月的试验报告。
尽管有令人鼓舞的随机二期临床试验数据，但一项三期临床试验的令人失望结果突出了转化研究的挑战，特别是在选择最佳开发策略方面。本文讨论了vadimezan 的不同给药方案如何显著增强该药与其他疗法联合应用的抗癌疗效，特别是那些不需要同时使用皮质类固醇的疗法。
