Mani S, Swami U
Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Drugs Today (Barc). 2010 Sep;46(9):641-53. doi: 10.1358/dot.2010.46.9.1519020.
Eisai is developing eribulin mesilate (E-7389), a synthetic macrocyclic ketone analogue of the tubulin inhibitor halichondrin B, for the treatment of a variety of solid tumors that include but are not limited to breast and lung cancer. In this context, eribulin is in phase III clinical trials in breast cancer; however, it has also progressed to phase II for nonsmall cell lung cancer, soft tissue sarcomas, pancreatic, prostate, head and neck cancer, bladder and ovarian and related gynecological tumors. Eribulin has shown synergistic in vitro antiproliferative activity in combination with the breast cancer drugs gemcitabine, epirubicin, trastuzumab, docetaxel and vinorelbine. Clinical trials have established efficacy, safety and a distinct survival advantage of 2.5 months with eribulin as compared to other treatments of physician's choice in metastatic breast cancer patients with heavy pretreatment and taxane resistance. It has a manageable side effect profile, consisting mostly of neutropenia and fatigue, with distinct tolerance at full doses in renal dysfunction, a lower incidence of peripheral neuropathy, minimal chances of drug-drug interactions and hypersensitivity. It appears to be a suitable candidate for third-line monotherapy and beyond for locally advanced and metastatic breast cancer. This review will focus on published and peer-reviewed data on breast cancer.
卫材公司正在研发甲磺酸艾瑞布林（E-7389），它是微管蛋白抑制剂海兔毒素B的一种合成大环酮类似物，用于治疗多种实体瘤，包括但不限于乳腺癌和肺癌。在此背景下，艾瑞布林正在进行乳腺癌的III期临床试验；然而，它在非小细胞肺癌、软组织肉瘤、胰腺癌、前列腺癌、头颈癌、膀胱癌、卵巢癌及相关妇科肿瘤方面也已进入II期试验。艾瑞布林与乳腺癌药物吉西他滨、表柔比星、曲妥珠单抗、多西他赛和长春瑞滨联合使用时，在体外显示出协同抗增殖活性。临床试验已经证实了艾瑞布林在转移性乳腺癌患者中的疗效、安全性以及与医生选择的其他治疗方法相比有2.5个月的明显生存优势，这些患者有重度预处理且对紫杉烷耐药。它的副作用易于控制，主要包括中性粒细胞减少和疲劳，在肾功能不全患者中全剂量时耐受性良好，周围神经病变的发生率较低，药物相互作用和过敏反应的可能性极小。它似乎是局部晚期和转移性乳腺癌三线单药治疗及后续治疗的合适候选药物。本综述将聚焦于已发表的和经过同行评审的关于乳腺癌的数据。
