De Sanctis Rita, Marrari Andrea, Marchetti Silvia, Mussi Chiara, Balzarini Luca, Lutman Fabio Romano, Daolio Primo, Bastoni Stefano, Bertuzzi Alexia Francesca, Quagliuolo Vittorio, Santoro Armando
Department of Medical Oncology and Haematology, Humanitas Cancer Center, IRCCS, Rozzano, Italy.
Department of Surgical Oncology, Humanitas Cancer Center, IRCCS, Rozzano, Italy.
Drug Des Devel Ther. 2015 Oct 27;9:5785-91. doi: 10.2147/DDDT.S92395. eCollection 2015.
Trabectedin is effective in leiomyosarcoma and liposarcoma, especially the myxoid variant, related to the presence of the FUS-CHOP transcript. We evaluated the efficacy of trabectedin in specific subgroups of patients with soft tissue sarcomas (STS).
Seventy-two patients with advanced anthracycline-pretreated STS, who received trabectedin at a dose of 1.5 mg/m(2) every 3 weeks by continuous 24-hour infusion, were retrospectively analyzed. Best response rate according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria and severe adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.02) were evaluated. Secondary endpoints included progression-free survival and overall survival (OS).
Median age was 48 (range, 20-75) years, with a median Eastern Cooperative Oncology Group performance status of 0. The median number of previous chemotherapy regimens was 1 (range, 0-5). Median number of trabectedin cycles was 3 (range, 1-17). About 69/72 patients (95.8%) were evaluable for response: 9 patients (13%) achieved partial response and 26 (37.7%) stable disease. According to histotype, clinical benefit (partial response + stable disease) was reported in synovial sarcoma (n=5), retroperitoneal liposarcoma (n=10), myxoid liposarcoma (n=5), leiomyosarcoma (n=8), high-grade undifferentiated pleomorphic sarcoma (n=5), Ewing/peripheral primitive neuroectodermal tumor (n=1), and malignant peripheral nerve sheath tumor (n=1). Any grade AEs were noncumulative, reversible, and manageable. G3/G4 AEs included anemia (n=1, 1.4%), neutropenia (n=7, 9.6%), liver toxicity (n=6, 8.3%), and fatigue (n=2, 2.8%). With a median follow-up time of 11 (range, 2-23) months, median progression-free survival and OS of the entire cohort were 2.97 months and 16.5 months, respectively.
Our experience confirms trabectedin as an effective therapeutic option for metastatic lipo- and leiomyosarcoma and suggests promise in synovial sarcomas and high-grade undifferentiated pleomorphic sarcoma.
曲贝替定对平滑肌肉瘤和脂肪肉瘤有效，尤其是黏液样亚型，这与FUS-CHOP转录本的存在有关。我们评估了曲贝替定在软组织肉瘤（STS）特定亚组患者中的疗效。
回顾性分析72例晚期经蒽环类药物预处理的STS患者，这些患者接受曲贝替定治疗，剂量为1.5mg/m²，每3周持续24小时静脉输注。根据实体瘤疗效评价标准（RECIST）评估最佳缓解率，根据美国国立癌症研究所不良事件通用术语标准（NCI-CTCAE v4.02）评估严重不良事件（AE）。次要终点包括无进展生存期和总生存期（OS）。
中位年龄为48岁（范围20-75岁），东部肿瘤协作组中位体能状态为0。既往化疗方案的中位次数为1次（范围0-5次）。曲贝替定治疗周期的中位次数为3次（范围1-17次）。约69/72例患者（95.8%）可评估疗效：9例患者（13%）达到部分缓解，26例（37.7%）疾病稳定。根据组织学类型，滑膜肉瘤（n=5）、腹膜后脂肪肉瘤（n=10）、黏液样脂肪肉瘤（n=5）、平滑肌肉瘤（n=8）、高级别未分化多形性肉瘤（n=5）、尤因/外周原始神经外胚层肿瘤（n=1）和恶性外周神经鞘瘤（n=1）报告有临床获益（部分缓解+疾病稳定）。任何级别的AE均无累积性、可逆且可控制。3/4级AE包括贫血（n=1，1.4%）、中性粒细胞减少（n=7，9.6%）、肝毒性（n=6，8.3%）和疲劳（n=2，2.8%）。中位随访时间为11个月（范围2-23个月），整个队列的中位无进展生存期和OS分别为2.97个月和16.5个月。
我们的经验证实曲贝替定是转移性脂肪肉瘤和平滑肌肉瘤的有效治疗选择，并提示其在滑膜肉瘤和高级别未分化多形性肉瘤中有应用前景。
