Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study
Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study
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DOI：
10.1016/s1470-2045(07)70175-4
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发表时间：
2007-07-01
期刊：
影响因子：
51.1
通讯作者：
Casali, Paola G.
中科院分区：
文献类型：
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作者：
Grosso, Federica;Jones, Robin L.;Casali, Paola G.
背景先前的研究表明，曲贝替丁(ecteinassidin-743)在软组织肉瘤中可能具有抗肿瘤活性。我们旨在研究曲贝替丁在治疗粘液性脂肪肉瘤中的有效性。该脂肪肉瘤是脂肪肉瘤的一种亚型，与导致DDIT3-FUS或DDIT3-EWSR1融合蛋白形成的特定染色体易位t(12；16)(q13；p11)或t(12；22)(q13；q12)相关。中央集权。对大多数患者进行了放射学和病理复查。曲贝替丁以1.1~1.5 mg/m~2的剂量连续滴注24 h或3 h，每21天一次。总共给予558个疗程的曲贝替丁，每个患者的中位数为10个疗程(范围1-23)。根据实体瘤反应评估标准(RECIST)，中位随访14.0个月(IQR8.7~20.0)，2例完全缓解(CR)，24例部分缓解(PR)，总有效率为51%(95%可信区间36~65)。5例患者有早期进展性疾病。根据RECIST的定义，在获得PR或CR的23名患者中，有17名患者进行了集中的放射学复查，组织密度变化，包括CT扫描的肿瘤密度下降或MRI(或两者)的对比增强减少，在肿瘤缩小之前。中位无进展生存期为14.0个月(13.1-21.0)，6个月无进展生存期为88%(79-95)。在这一系列粘液样脂肪肉瘤患者中，解释曲贝替丁与抗肿瘤活性有关。注意到的肿瘤反应模式是这样的，在一些患者中，组织密度的变化发生在肿瘤缩小之前。在一些患者中，仅见组织密度变化。在有反应的患者中注意到了长期的肿瘤控制。同情使用计划仍在进行中，这一分析导致启动了两项前瞻性研究，以评估Trabectedin在术前和转移环境下治疗粘液样脂肪肉瘤患者中的作用。此外，曲贝替丁在这种移位相关肉瘤中的选择性作用机制正在研究中。
Background Previous studies have suggested that trabectedin (ecteinascidin-743) could have antitumour activity in soft-tissue sarcoma. We aimed to study the usefulness of trabectedin in the treatment of patients with myxoid liposarcomas, a subtype of liposarcoma that is associated with specific chromosomal translocations t(12;16)(q13;p11) or t(12;22)(q13;q12) that result in the formation of DDIT3-FUS or DDIT3-EWSR1 fusion proteins.Methods 51 patients with advanced pretreated myxoid liposarcoma who started treatment with trabectedin between April 4, 2001, and Sept 18, 2006 at five institutions in a compassionate-use programme were analysed retrospectively. Centralised. radiological and pathological reviews were done for most patients. Trabectedin was given either as a 24-h continuous infusion or as a 3-h infusion, every 21 days, at 1.1-1.5 mg/m(2). 558 courses of trabectedin were given in total, with a median of ten courses for each patient (range 1-23). The primary endpoints were response rate and progression-free survival, and the secondary endpoint was overall survival.Findings According to Response Evaluation Criteria in Solid Tumors (RECIST), after a median follow-up of 14.0 months (IQR 8.7-20.0), two patients had complete responses (CR) and 24 patients had partial responses (PR); the overall response was 51% (95% CI 36-65). Five patients had early progressive disease. In 17 of the 23 patients who achieved PR or CR as defined by RECIST and who had centralised radiological review, tissue-density changes, consisting of a decrease in tumour density on CT scan or a decrease in contrast enhancement on MRI (or both), preceded tumour shrinkage. Median progression-free survival was 14.0 months (13.1-21.0), and progression-free survival at 6 months was 88% (79-95).Interpretation Trabectedin was associated with antitumour activity in this series of patients with myxoid liposarcoma. The noted patterns of tumour response were such that tissue density changes occurred before tumour shrinkage in several patients. In some patients, tissue-density changes only were seen. Long-lasting tumour control was noted in responsive patients. The compassionate-use programme is still ongoing, This analysis has resulted in the initiation of two prospective studies to assess the role of trabectedin in the treatment of patients with myxoid liposarcoma in preoperative and metastatic settings. Furthermore, the selective mechanism of action for trabectedin in this translocation-related sarcoma is being studied.