Experimental Theraputics Program, Samuel Oschin Comprehensive Cancer Center, Cedars Sinai Medical Center, LA, CA, USA.
Expert Opin Investig Drugs. 2013 Mar;22(3):317-28. doi: 10.1517/13543784.2013.759557. Epub 2013 Jan 15.
Vascular-disrupting agents (VDAs) are a new class of oncology drugs, which specifically target established tumor neovasculature and have a relatively low toxicity profile. VDAs generally have non-overlapping side effects when concomitantly used with conventional cytotoxics. Several members of the VDA class have recently progressed through mid-to-late stages of clinical trials.
We examined recent publications on preclinical findings and Phase I/II/III clinical trial data on mechanisms of actions, toxicities, and optimal use of VDA class drugs. It is becoming apparent that VDAs should be used in combination with other classes of cytotoxic agents for the optimization of their effect in treating various cancers. In this article we describe doses, timing of delivery, and sequence of combined therapy. We also address the combined mechanisms of actions of VDAs and conventional cytotoxic medications.
Vascular-disrupting agents represent a new class of promising anticancer agents, which exhibit synergistic and/or additive effects in combination with many conventional cytotoxics. Pharmacological evaluation of the optimal combinations of VDAs with agents of other classes and drug interactions need to be continued. Further clinical and preclinical studies are required for distinguishing cancer patients' subpopulations that would most benefit from VDAs, identifying tumor biomarkers predictive of response as well as reliable and reproducible imaging and/or biological assays indicative of pharmacodynamic effects, and establishing clinical algorithms for treatment.
血管破坏剂（VDAs）是一类新型的肿瘤药物，专门针对已建立的肿瘤新生血管，且具有相对较低的毒性特征。VDAs 通常与传统细胞毒药物同时使用时具有非重叠的副作用。最近，该 VDA 类别的几个成员已通过临床试验的中晚期阶段。
我们研究了关于作用机制、毒性和 VDA 类药物最佳使用的临床前发现和 I/II/III 期临床试验的最新出版物。显然，VDAs 应该与其他类别的细胞毒药物联合使用，以优化其治疗各种癌症的效果。在本文中，我们描述了剂量、给药时间和联合治疗的顺序。我们还讨论了 VDA 和传统细胞毒性药物的联合作用机制。
血管破坏剂代表了一类有前途的新型抗癌药物，与许多传统细胞毒药物联合使用时具有协同作用和/或相加作用。需要继续对 VDA 与其他类药物的最佳组合进行药理学评价以及药物相互作用。需要进一步的临床前和临床研究来区分最受益于 VDA 的癌症患者亚群，确定预测反应的肿瘤生物标志物以及可靠和可重复的影像学和/或生物学检测以指示药效学作用，并建立治疗的临床算法。
