Petek Bradley J, Loggers Elizabeth T, Pollack Seth M, Jones Robin L
University of Washington, 1959 NE Pacific St, Seattle, WA 98195, USA.
Fred Hutchinson Cancer Research Center, University of Washington, 825 Eastlake Avenue East, G-3630, Seattle, WA 98109-1023, USA.
Mar Drugs. 2015 Feb 12;13(2):974-83. doi: 10.3390/md13020974.
Soft tissue sarcomas are a group of rare tumors derived from mesenchymal tissue, accounting for about 1% of adult cancers. There are over 60 different histological subtypes, each with their own unique biological behavior and response to systemic therapy. The outcome for patients with metastatic soft tissue sarcoma is poor with few available systemic treatment options. For decades, the mainstay of management has consisted of doxorubicin with or without ifosfamide. Trabectedin is a synthetic agent derived from the Caribbean tunicate, Ecteinascidia turbinata. This drug has a number of potential mechanisms of action, including binding the DNA minor groove, interfering with DNA repair pathways and the cell cycle, as well as interacting with transcription factors. Several phase II trials have shown that trabectedin has activity in anthracycline and alkylating agent-resistant soft tissue sarcoma and suggest use in the second- and third-line setting. More recently, trabectedin has shown similar progression-free survival to doxorubicin in the first-line setting and significant activity in liposarcoma and leiomyosarcoma subtypes. Trabectedin has shown a favorable toxicity profile and has been approved in over 70 countries for the treatment of metastatic soft tissue sarcoma. This manuscript will review the development of trabectedin in soft tissue sarcomas.
软组织肉瘤是一组源自间充质组织的罕见肿瘤，约占成人癌症的1%。有60多种不同的组织学亚型，每种亚型都有其独特的生物学行为和对全身治疗的反应。转移性软组织肉瘤患者的预后很差，可用的全身治疗选择很少。几十年来，治疗的主要方法一直是使用阿霉素，可联合或不联合异环磷酰胺。曲贝替定是一种从加勒比海被囊动物海鞘中提取的合成药物。这种药物有多种潜在的作用机制，包括结合DNA小沟、干扰DNA修复途径和细胞周期，以及与转录因子相互作用。几项II期试验表明，曲贝替定在对蒽环类药物和烷化剂耐药的软组织肉瘤中具有活性，并建议在二线和三线治疗中使用。最近，曲贝替定在一线治疗中显示出与阿霉素相似的无进展生存期，并且在脂肪肉瘤和平滑肌肉瘤亚型中具有显著活性。曲贝替定已显示出良好的毒性特征，并已在70多个国家被批准用于治疗转移性软组织肉瘤。本文将综述曲贝替定在软组织肉瘤中的研发情况。
