Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371-8511, Japan.
Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371-8511, Japan.
Lung Cancer. 2018 Jan;115:42-48. doi: 10.1016/j.lungcan.2017.11.010. Epub 2017 Nov 13.
Amrubicin monotherapy is a treatment option for patients with relapsed small cell lung cancers (SCLCs). Topoisomerase-II (Topo-II) - a target of amrubicin - has been reported as a predictive or prognostic marker for chemosensitivity or outcomes in patients with various malignancies. Here, we investigated the prognostic role of Topo-II expression in patients with relapsed SCLCs who underwent amrubicin monotherapy.
Eighty-three patients with relapsed SCLCs who received amrubicin monotherapy between 2004 and 2015, after progression beyond first-line chemotherapy, were enrolled in the study. We retrospectively collected clinical data from their medical records, and evaluated the expression levels of Topo-II, by immunohistochemical staining of archival tumor specimens obtained through surgical resections or biopsies.
Most of the enrolled patients were elderly men (89%), with a median age of 70 years (range, 49-83); 16% of these patients showed Topo-II overexpression. Compared to patients with sensitive relapses, those with refractory relapses showed significantly higher Topo-II expression levels (P=0.03). The overall response rates in patients with high and low Topo-II expression were 38.5% and 25.7%, respectively (P=0.34). Multivariate analysis confirmed that patients with a higher Topo-II expression level had significantly longer progression-free survival (hazard ratio (HR), 0.39; P<0.01) and overall survival (HR, 0.48; P=0.04), compared to patients with a lower Topo-II expression level.
Our study identified Topo-II expression as a significant biomarker for the prediction of favorable outcomes in patients with relapsed SCLCs who underwent treatment with amrubicin, a Topo-II inhibitor. Thus, Topo-II expression may be a promising predictor of the efficacy of amrubicin.
氨柔比星单药治疗是复发性小细胞肺癌（SCLC）患者的一种治疗选择。拓扑异构酶-II（Topo-II）是氨柔比星的靶点，已被报道为多种恶性肿瘤患者化疗敏感性或疗效的预测或预后标志物。在此，我们研究了 Topo-II 表达在接受氨柔比星单药治疗的复发性 SCLC 患者中的预后作用。
本研究纳入了 83 例复发性 SCLC 患者，这些患者在一线化疗进展后，于 2004 年至 2015 年间接受了氨柔比星单药治疗。我们回顾性地从病历中收集了临床数据，并通过手术切除或活检获得的存档肿瘤标本进行免疫组织化学染色来评估 Topo-II 的表达水平。
大多数入组患者为老年男性（89%），中位年龄为 70 岁（范围，49-83）；其中 16%的患者表现出 Topo-II 过表达。与敏感复发患者相比，耐药复发患者的 Topo-II 表达水平显著更高（P=0.03）。高表达和低表达 Topo-II 的患者的总缓解率分别为 38.5%和 25.7%（P=0.34）。多变量分析证实，Topo-II 高表达的患者无进展生存期（风险比（HR），0.39；P<0.01）和总生存期（HR，0.48；P=0.04）显著长于 Topo-II 低表达的患者。
我们的研究发现 Topo-II 表达是接受拓扑异构酶-II 抑制剂氨柔比星治疗的复发性 SCLC 患者良好预后的一个显著生物标志物。因此，Topo-II 表达可能是氨柔比星疗效的一个有前途的预测指标。
