BACKGROUND Although initial trabectedin (1.2 mg/m2 ) is safe and effective for patients with translocation-related sarcoma (TRS) in Japan, its efficacy in other types of soft-tissue sarcomas (STSs) remains unknown. This study retrospectively investigated its efficacy and safety through postmarketing surveillance of trabectedin in patients with unresectable and relapsed STS. METHODS One hundred forty patients received intravenous trabectedin (1.2 mg/m2 on day 1 every 21 days) over the course of 24 hours. The primary endpoint was the efficacy and safety of trabectedin. RESULTS Grade 3 or higher adverse events occurred in 100 patients (71%) and included hepatotoxicity (37.8%), neutropenia (32.8%), and rhabdomyolysis (3.6%). Patients at high risk for grade 3 or higher rhabdomyolysis (36%) were classified by height (≥170.3 cm) and age (≤32 years) through a classification and regression tree model (area under the curve, 0.9). The overall median progression-free survival (PFS) was 3.7 months; with respect to the histological type, the median PFS was 17.4 months for myxoid liposarcoma, 4.9 months for leiomyosarcoma, 5.6 months for synovial sarcoma, and 3.7 months for dedifferentiated liposarcoma. Histological type (liposarcoma/leiomyosarcoma [L-sarcoma] and TRS) and grade 3 neutropenia (but not grade 4) were associated with significantly improved PFS after trabectedin treatment (P = .003, P = .04, and P = .001). The median growth modulation index (GMI) was 0.91; 37 patients (36.7%) experienced a GMI > 1.33, and among patients with solitary fibrous tumors and undifferentiated pleomorphic sarcoma, 60% and 42.9%, respectively, had a GMI > 1.33. The median overall survival (OS) was 16.4 months. A GMI > 1.33 was associated with significantly improved OS (P = .0006). CONCLUSIONS Initial trabectedin at 1.2 mg/m2 has clinically meaningful benefits for patients with L-sarcoma and certain histological subtypes of TRS.

中文翻译：

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trabectedin对日本不可切除和复发的软组织肉瘤患者的疗效和安全性：日本肌肉骨骼肿瘤小组的一项研究。

背景技术尽管在日本，最初的Trabectedin（1.2 mg / m2）对于易位相关肉瘤（TRS）患者是安全有效的，但其在其他类型的软组织肉瘤（STS）中的疗效仍然未知。这项研究通过对trabectedin的上市后监测，对无法切除和复发的STS患者进行回顾性研究，以评估其疗效和安全性。方法一百零四名患者在24小时内接受了静脉曲布汀（每21天的第1天为1.2 mg / m2）。主要终点是trabectedin的疗效和安全性。结果100例患者（71％）发生3级以上不良反应，包括肝毒性（37.8％），中性粒细胞减少（32.8％）和横纹肌溶解（3.6％）。具有3级或更高横纹肌溶解风险的高危患者（36％）按身高（≥170）进行分类。3厘米）和年龄（≤32岁），通过分类和回归树模型（曲线下的面积为0.9）。总体中位无进展生存期（PFS）为3.7个月；就组织学类型而言，粘液状脂肪肉瘤的中位PFS为17.4个月，平滑肌肉瘤为4.9个月，滑膜肉瘤为5.6个月，去分化脂肪肉瘤为3.7个月。组织学类型（脂肪肉瘤/平滑肌肉瘤[L-肉瘤]和TRS）和3级中性粒细胞减少（但不是4级）与trabectedin治疗后的PFS显着相关（P = .003，P = .04和P = .001） 。中值生长调节指数（GMI）为0.91；37例患者（36.7％）的GMI大于1.33，而患有孤立性纤维瘤和未分化多形性肉瘤的患者中GMI大于1.33的比例分别为60％和42.9％。中位总生存期（OS）为16.4个月。GMI> 1.33与OS显着改善有关（P = .0006）。结论最初的Trabectedin浓度为1.2 mg / m2对于L型肉瘤和某些TRS组织学亚型的患者具有临床意义。