Department of Medicine, Centre Léon Bérard, 28 rue Laennec, 69008 Lyon, France.
Br J Cancer. 2013 Aug 20;109(4):909-14. doi: 10.1038/bjc.2013.442. Epub 2013 Aug 6.
Soft tissue sarcomas (STS) are rare tumours for which treatment options are limited in the advanced setting. Histone deacetylase inhibitors have shown activity in preclinical models of STS.
We conducted a single-arm, open-label, multicentre phase II study to assess the efficacy and tolerability of panobinostat given orally, 40 mg thrice weekly in patients with advanced pretreated STS. The primary endpoint was the 3-month progression-free rate.
Forty-seven STS patients were enrolled between January 2010 and December 2010. Median age was 59 (range 21-79) years, 22 (47%) patients were males. Panobinostat dose was lowered to 20 mg thrice weekly after nine patients were enrolled, based on the recommendation of an independent safety committee. The most common grade 3/4 adverse events were thrombocytopenia, fatigue, lymphopenia and anaemia. Forty-five patients were evaluable for the primary endpoint. Among them, nine patients (20%, 95% CI (10-35%)) were progression-free at 3 months. No partial response was seen, but 17 patients (36%) had stable disease (SD) as their best response. Six patients were progression-free at 6 months.
Panobinostat was poorly tolerated at 40 mg thrice a week. Efficacy in unselected advanced STS was limited, although some patients had prolonged SD.
软组织肉瘤（STS）是一种罕见的肿瘤，在晚期治疗选择有限。组蛋白去乙酰化酶抑制剂在 STS 的临床前模型中显示出活性。
我们进行了一项单臂、开放标签、多中心的 II 期研究，以评估每周三次口服 panobinostat（40mg）在晚期预处理 STS 患者中的疗效和耐受性。主要终点是 3 个月无进展率。
2010 年 1 月至 2010 年 12 月期间共纳入 47 例 STS 患者。中位年龄为 59 岁（范围 21-79 岁），22 例（47%）为男性。根据独立安全委员会的建议，在纳入 9 例患者后，将 panobinostat 的剂量降低至每周三次 20mg。最常见的 3/4 级不良事件为血小板减少、疲劳、淋巴细胞减少和贫血。45 例患者可评估主要终点。其中，9 例患者（20%，95%CI（10-35%））在 3 个月时无进展。未观察到部分缓解，但 17 例患者（36%）最佳缓解为疾病稳定（SD）。6 例患者在 6 个月时无进展。
panobinostat 在每周三次 40mg 时耐受性差。未选择的晚期 STS 疗效有限，尽管有些患者 SD 时间延长。
