考布他丁A-4磷酸盐前药:CA4P

A review of current status of combretastatin A-4 phosphate (CA4P)

考布他丁A-4(CA4)是从风车子科植物Combretum caffrum中提取得到的抗肿瘤化合物。CA4P为CA4的磷酸盐前药,属于血管干扰剂(VDA),可与微管蛋白结合,选择性破坏肿瘤初生血管,快速切断肿瘤血液供应,导致肿瘤中心区坏死。CA4P目前已完成多项临床试验,包括CA4P单独用药及其与化疗、放疗及血管生成抑制剂联合用药的临床试验。FDA已批准CA4P进入"快速通道",用于治疗未分化甲状腺癌(ATC)。"CA4P+卡铂+紫杉醇"治疗ATC的Ⅱ和(或)Ⅲ期临床正在进行中。

Comhretastatin A-4 phosphate （CA4P, ZybrestatTM） is the water-soluble prodrug of combretastatin A4 （CA4）, which was originally isolated from the African tree Combretum caffrum. CA4P is a vascular disrupting agent （VDA） that binds to tubulin and selectively damages established tumor vasculature. Preclinieal studies showed that CA4P causes rapid vascular shutdown, leading to central tumor necrosis, with little or no effect on quiescent endothelial cells. Clinical studies with CA4P included assessment of CA4P monothcrapy, as well as combinations with standard chemotherapy, radiation therapy, and antiangiogenic therapy. CA4P was granted ＂Fast Track Status＂ by FDA for the treatment of ATC, and an phase Ⅱ/Ⅲ trial in ATC patients to assess ＂ foshretabulin tromethamine ＋ carboplatin ＋ paclitaxel＂ on overall survival rate of ＂carboplatin ＋ paclitaxel＂ was ongoing.