Medical Oncology Unit, ASST Ospedale San Gerardo, Monza, Italy.
Mesothelioma Unit, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
Clin Lung Cancer. 2021 Jul;22(4):361-370.e3. doi: 10.1016/j.cllc.2020.06.028. Epub 2020 Jul 3.
New therapeutic approaches in unresectable malignant pleural mesothelioma (MPM) are eagerly awaited. Trabectedin is an antitumor agent with an effect on cancer cell proliferation and a modulating action on tumor microenvironment. The ATREUS study explored the activity and safety of trabectedin in patients with unresectable MPM.
Epithelioid patients with MPM received trabectedin as second-line while biphasic/sarcomatoid patients with MPM as first- or second-line therapy. Treatment was given intravenously at an initially planned dose of 1.3 mg/m every 3 weeks, until progression or unacceptable toxicity. The primary endpoint was progression-free survival rate at 12 weeks (PFS).
Overall, 78 patients (54%) had epithelioid and 67 (46%) nonepithelioid MPM. PFS in 62 evaluable patients with epithelioid MPM was 43.5% (80% confidence interval 34.9%-52.5%); median progression-free and overall survival were 2.4 and 9.0 months, respectively. PFS in 52 evaluable patients with nonepithelioid MPM was 30.8% (90% confidence interval 20.3%-42.9%); median progression-free and overall survival were 1.7 and 5.4 months. Trabectedin starting dose was amended due to excess of liver toxicity. Eighty-four (64%) and 48 (36%) patients received 1.3 mg/m and 1.1. mg/m, respectively. The most common grade 3-4 toxicities were hepatotoxicity, leukopenia/neutropenia, and fatigue. Grade 3-4 hepatotoxicity was reported in 59 (70%) patients treated at 1.3 mg/m, and in 19 (40%) treated at 1.1 mg/m.
Trabectedin showed modest clinical activity, at the expense of relevant liver toxicity. Further development of this drug in MPM at full doses is not warranted.
目前迫切需要探索不可切除恶性胸膜间皮瘤（MPM）的新治疗方法。盐酸多柔比星脂质体是一种具有抗肿瘤作用的药物，可抑制肿瘤细胞增殖并调节肿瘤微环境。ATREUS 研究旨在评估盐酸多柔比星脂质体在不可切除 MPM 患者中的疗效和安全性。
上皮样 MPM 患者接受盐酸多柔比星脂质体二线治疗，双相/肉瘤样 MPM 患者接受一线或二线治疗。治疗方案为静脉滴注，初始剂量为 1.3 mg/m2，每 3 周 1 次，直至疾病进展或出现不可耐受的毒性。主要研究终点为 12 周时的无进展生存率（PFS）。
共纳入 78 例（54%）上皮样和 67 例（46%）非上皮样 MPM 患者。62 例可评估上皮样 MPM 患者的中位 PFS 为 43.5%（90%CI 34.9%-52.5%）；中位无进展生存期和总生存期分别为 2.4 个月和 9.0 个月。52 例可评估非上皮样 MPM 患者的中位 PFS 为 30.8%（90%CI 20.3%-42.9%）；中位无进展生存期和总生存期分别为 1.7 个月和 5.4 个月。由于出现肝毒性，调整了盐酸多柔比星脂质体的起始剂量。分别有 84 例（64%）和 48 例（36%）患者接受了 1.3 mg/m2和 1.1. mg/m2的治疗。最常见的 3-4 级毒性为肝毒性、白细胞减少/中性粒细胞减少和疲劳。1.3 mg/m2治疗组中有 59 例（70%）和 1.1 mg/m2治疗组中有 19 例（40%）患者发生 3-4 级肝毒性。
盐酸多柔比星脂质体显示出一定的临床疗效，但肝脏毒性明显。因此，不建议在 MPM 患者中使用全剂量的盐酸多柔比星脂质体。
