Doherty Mark K, Morris Patrick G
Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland.
Int J Womens Health. 2015 Jan 6;7:47-58. doi: 10.2147/IJWH.S74462. eCollection 2015.
Breast cancer remains a leading cause of cancer-related death internationally. Treatment approaches for metastatic breast cancer have evolved in recent years; however chemotherapy remains a core component for the majority of patients. Agents such as anthracyclines and taxanes have been extensively studied and form standard treatment. Eribulin mesylate is a novel synthetic microtubule-directed chemotherapy, based on a naturally-occurring compound. Through phase I studies, eribulin was found to be tolerable and activity was seen in patients with metastatic breast cancer. Phase II studies in metastatic breast cancer further demonstrated its efficacy, with responses and survival which compare favorably with other studied chemotherapy agents. The phase III EMBRACE study showed superior survival for patients treated with eribulin compared with those who received a physician's choice control. This led to its approval for use in many countries in this setting. Its toxicity profile is well established and manageable for the most part, with the commonest reported toxicities being alopecia, fatigue, neutropenia and peripheral neuropathy. A second reported phase III study comparing eribulin to capecitabine failed to show an improvement in survival in pretreated patients. This article reviews the clinical pharmacology and mechanism of action of eribulin, and summarizes the results of the major preclinical and clinical studies of eribulin in metastatic breast cancer.
在国际上，乳腺癌仍是癌症相关死亡的主要原因。近年来，转移性乳腺癌的治疗方法不断发展；然而，化疗仍然是大多数患者的核心治疗手段。蒽环类药物和紫杉烷类药物等已得到广泛研究并构成标准治疗方案。甲磺酸艾瑞布林是一种基于天然化合物的新型合成微管导向化疗药物。通过I期研究发现，艾瑞布林耐受性良好，转移性乳腺癌患者有活性表现。转移性乳腺癌的II期研究进一步证实了其疗效，其反应和生存期与其他研究过的化疗药物相比具有优势。III期EMBRACE研究表明，与接受医生选择的对照治疗的患者相比，接受艾瑞布林治疗的患者生存期更长。这使得它在这种情况下在许多国家获得批准使用。其毒性特征已得到充分确立，在很大程度上是可控的，报告的最常见毒性为脱发、疲劳、中性粒细胞减少和周围神经病变。另一项报告的将艾瑞布林与卡培他滨进行比较的III期研究未能显示出预处理患者生存期有所改善。本文综述了艾瑞布林的临床药理学和作用机制，并总结了艾瑞布林在转移性乳腺癌中的主要临床前和临床研究结果。
