Background: The MILES and ELVIS studies showed that vinorelbine is one of the best options for elderly patients with advanced non-small-cell-lung cancer (NSCLC). Oral vinorelbine at standard schedule (60-80 mg/m2/weekly) has good activity in terms of response rates and progression-free survival. In recent years, a metronomic schedule of oral vinorelbine (40-50 mg/m2 three times a week, continuously) has been studied in phase II trials, especially in unfit and elderly patients. In the MOVE trial metronomic oral vinorelbine had a clinical benefit [partial response (PR)+stable disease (SD) >12 weeks] in 58.1% of patients with mild toxicity. On this basis, in 2017 we started a phase II study with metronomic oral vinorelbine in elderly (over 70 years) or unfit [Eastern Cooperative Oncology Group performance score (ECOG-PS) of 2] patients with locally/advanced and metastatic NSCLC. Primary aims were clinical benefit (PR+SD ≥6 months) and toxicity; secondary aims were progression-free survival and overall survival. Patients and Methods: A total of 25 patients entered the study: 11 with local/advanced and 14 with metastatic NSCLC (five squamous and 20 adenocarcinoma). None of the patients had epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) translocation, or programmed death ligand 1 (PDL1) expression; those with squamous carcinoma did not have PDL1 expression. The median age was 79 (range=44-90) years. The PS was 0 in 12 patients (48%), 1 in four patients (16%) and 2 in nine patients (36%). Oral vinorelbine was administered at 40 mg three times a week continuously. Results: Clinical benefit was achieved in eight patients (32%). Objective responses were partial response in two patients (8%), stable disease in seven (28%), progressive disease in nine (36%); seven patients were not evaluable for response (28%). Median progression-free survival was 2 months; median overall survival was 4 months but four out of eight patients with clinical benefit were still alive at 18 months. Overall survival at 1 year was 32%. Toxicity was mild: only one patient experienced grade 4 neutropenia, one grade 3 peripheral neuropathy, four grade 2 asthenia, one grade 2 mucositis, and one grade 2 diarrhoea. The dose needed to be reduced to 30 mg/m2/three times a week in three patients. Conclusion: Our study confirmed the activity and safety of metronomic oral vinorelbine in patients with wild-type local/advanced and metastatic NSCLC unsuitable for treatment with standard i.v. chemotherapy, allowing patients a comfortable home-based therapy, thereby avoiding frequent hospital visits.

中文翻译：

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节律性口服长春瑞滨：老年人和 PS2 局部/晚期和转移性非癌基因成瘾 NSCLC 患者的替代方案

背景：MILES 和 ELVIS 研究表明，长春瑞滨是老年晚期非小细胞肺癌 (NSCLC) 患者的最佳选择之一。标准方案（60-80 mg/m2/周）的口服长春瑞滨在缓解率和无进展生存期方面具有良好的活性。近年来，已经在 II 期试验中研究了口服长春瑞滨（40-50 mg/m2，每周 3 次，连续）的节拍计划，特别是在不健康和老年患者中。在 MOVE 试验中，节拍式口服长春瑞滨在 58.1% 的轻度毒性患者中具有临床获益 [部分缓解 (PR) + 病情稳定 (SD) > 12 周]。以这个为基础，2017 年，我们开始了一项 II 期研究，在老年人（70 岁以上）或身体不健康 [Eastern Cooperative Oncology Group Performance score (ECOG-PS) of 2] 局部/晚期和转移性 NSCLC 患者中使用节拍器口服长春瑞滨。主要目标是临床获益（PR+SD ≥6 个月）和毒性；次要目标是无进展生存期和总生存期。患者和方法：共有 25 名患者进入研究：11 名患有局部/晚期，14 名患有转移性 NSCLC（5 名鳞癌和 20 名腺癌）。所有患者均未出现表皮生长因子受体（EGFR）突变、间变性淋巴瘤激酶（ALK）易位或程序性死亡配体 1（PDL1）表达；鳞癌患者没有 PDL1 表达。中位年龄为 79（范围 = 44-90）岁。12 名患者 (48%) 的 PS 为 0，四分之一的患者 (16%) 和九分之一的患者 (36%)。口服长春瑞滨每周 3 次，每次 40 毫克。结果：8 名患者（32%）获得了临床获益。客观反应为部分反应 2 例 (8%)，7 例疾病稳定 (28%)，9 例疾病进展 (36%)；7 名患者无法评估反应（28%）。中位无进展生存期为 2 个月；中位总生存期为 4 个月，但八分之四的临床受益患者在 18 个月时仍然存活。1 年的总生存率为 32%。毒性轻微：只有 1 名患者出现 4 级中性粒细胞减少症、1 名 3 级周围神经病变、4 名 2 级乏力、1 名 2 级粘膜炎和 1 名 2 级腹泻。三名患者的剂量需要减少到 30 毫克/平方米/每周 3 次。结论：