Noujaim Jonathan, Alam Salma, Thway Khin, Jones Robin Lewis
Sarcoma Unit, Maisonneuve-Rosemont Hospital, Montreal, H1T 2M4, Canada.
Sarcoma Unit, The Institute of Cancer Research, Royal Marsden Hospital, London, SW3 6JJ, United Kingdom.
Indian J Med Paediatr Oncol. 2016 Jul-Sep;37(3):125-30. doi: 10.4103/0971-5851.190359.
Despite recent advances in the field, treatment options for metastatic soft tissue sarcoma patients are limited. Eribulin, an antimitotic derived from the natural marine sponge product halichondrin B, is currently approved for the treatment of metastatic breast cancer. Following the promising activity of eribulin in sarcoma in a Phase II trial, the drug was recently compared to dacarbazine in pretreated advanced leiomyosarcoma (LMS) and liposarcoma (LPS) patients in a Phase III trial. Eribulin was associated with a significant 2-month improvement in median overall survival compared to dacarbazine (13.5 vs. 11.5 months, heart rate: 0.768) despite no documented significant difference in progression-free survival. In a subgroup analysis, the survival advantage associated with eribulin was evident in the LPS subgroup but not in the LMS subgroup. Following these encouraging results, the Food and Drug Administration has approved eribulin for the treatment of advanced LPS for patients who received prior anthracycline chemotherapy. In this short review, we will evaluate the evidence for eribulin in soft tissue sarcoma, highlight its mechanisms of action, and summarize the results of the major preclinical and clinical studies with a particular focus on the results of the Phase III trial.
尽管该领域最近取得了进展,但转移性软组织肉瘤患者的治疗选择仍然有限。艾日布林是一种从天然海洋海绵产品海兔毒素B衍生而来的抗有丝分裂药物,目前已被批准用于治疗转移性乳腺癌。在一项II期试验中,艾日布林在肉瘤中显示出有前景的活性后,该药物最近在一项III期试验中与达卡巴嗪在预处理的晚期平滑肌肉瘤(LMS)和脂肪肉瘤(LPS)患者中进行了比较。尽管无进展生存期无显著差异,但与达卡巴嗪相比,艾日布林使中位总生存期显著延长了2个月(13.5个月对11.5个月,风险比:0.768)。在亚组分析中,艾日布林相关的生存优势在LPS亚组中明显,但在LMS亚组中不明显。基于这些令人鼓舞的结果,美国食品药品监督管理局已批准艾日布林用于治疗接受过蒽环类化疗的晚期LPS患者。在这篇简短的综述中,我们将评估艾日布林在软组织肉瘤中的证据,突出其作用机制,并总结主要临床前和临床研究的结果,特别关注III期试验的结果。