Stanford University School of Medicine and Stanford Cancer Institute, 875 Blake Wilbur Driver, Stanford, CA, USA.
Stanford University School of Medicine and Stanford Cancer Institute, 875 Blake Wilbur Driver, Stanford, CA, USA; University of California San Francisco, 1450 3rdSt, San Francisco, CA, USA.
Lung Cancer. 2019 Nov;137:71-75. doi: 10.1016/j.lungcan.2019.09.015. Epub 2019 Sep 18.
There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor.
This was a phase 2 open-label, single arm trial of amrubicin in patients with thymoma (T) or thymic carcinoma (TC), conducted at two academic institutions. Patients were included if they had received at least one prior chemotherapy regimen. The first 18 patients received amrubicin at 40 mg/m2 IV days 1-3 repeated every 3-weeks. Due to the high incidence of febrile neutropenia, dosing was subsequently amended to 35 mg/m2 for the final 15 patients.
A total of 33 patients (14 T/19 TC) were enrolled from 2011 to 2014. Median number of prior therapies was 2. Best response included 6 partial responses, 21 stable disease, and 6 progressive disease (all TC). Objective response rate was 18% (90% exact binomial CI 8.2%-32.8%; T = 4/14 (29%), TC = 2/19 (11%)). Median progression-free survival was 7.7 months (T: 8.3 months; TC: 7.3) and median overall survival was 29.7 months (T: 54.1 months; TC: 18 months). There was a high rate of febrile neutropenia (7 patients) that occurred despite a reduction in amrubicin dose and one related death. Five patients had reduction in LVEF below 50% during the course of treatment resulting in treatment discontinuation in one patient.
Amrubicin shows promise as a single agent in heavily pre-treated patients with thymic malignancies. Notable side effects include febrile neutropenia and the use of growth factor support is essential. Further investigation of this agent is warranted.
胸腺癌患者的治疗选择有限。在此，我们提供使用第三代蒽环类药物和拓扑异构酶 II 抑制剂氨柔比星单药治疗的数据支持。
这是在两个学术机构进行的一项单臂、开放标签的氨柔比星治疗胸腺瘤（T）或胸腺癌（TC）患者的 2 期临床试验。如果患者接受过至少一种化疗方案，则纳入研究。前 18 名患者接受氨柔比星 40mg/m2 IV 第 1-3 天，每 3 周重复一次。由于中性粒细胞减少性发热的发生率较高，随后对最后 15 名患者的剂量进行了修订，为 35mg/m2。
2011 年至 2014 年共纳入 33 名患者（14 例 T/19 例 TC）。先前治疗的中位数为 2 次。最佳缓解包括 6 例部分缓解，21 例疾病稳定，6 例疾病进展（均为 TC）。客观缓解率为 18%（90%精确二项式置信区间 8.2%-32.8%；T=4/14[29%]，TC=2/19[11%]）。无进展生存期的中位数为 7.7 个月（T：8.3 个月；TC：7.3 个月），总生存期的中位数为 29.7 个月（T：54.1 个月；TC：18 个月）。尽管降低了氨柔比星的剂量，但仍有 7 例患者出现发热性中性粒细胞减少，导致 1 例相关死亡。5 例患者在治疗过程中左心室射血分数（LVEF）降至 50%以下，导致 1 例患者停止治疗。
氨柔比星作为一种单一药物，在治疗晚期胸腺癌患者方面显示出一定的潜力。显著的副作用包括发热性中性粒细胞减少，使用生长因子支持是必要的。需要进一步研究该药物。
