Division of Breast and Endocrine Surgery, Department of General Surgical Science, Graduate School of Medicine, Gunma University, Gunma, Japan.
Department of General Surgical Science, Graduate School of Medicine, Gunma University, Gunma, Japan.
BMC Cancer. 2020 Nov 6;20(1):1068. doi: 10.1186/s12885-020-07550-5.
S-1 and cyclophosphamide (CPA) can be given orally, and their combination may have great potential for treating metastatic breast cancer (MBC). A phase I study of sequential S-1 and CPA therapy was conducted in patients with MBC; the recommended doses that were determined for this regimen were 80 mg/m/day for S-1 and 100 mg/m/day for CPA. We then conducted a phase II study of this oral S-1 and CPA regimen.
This was a single-arm, open-label, single-center prospective phase II study to evaluate the efficacy of a sequential S-1 and CPA regimen for MBC. S-1 was administered orally 2×/day for 14 consecutive days, and then CPA was administered orally 2×/day for 14 consecutive days in a repeating 4-week cycle (S-1 for 2 weeks, CPA for 2 weeks). The primary endpoint was the overall response rate (ORR). Secondary endpoints included the overall survival (OS), progression-free survival (PFS), clinical benefit rate (CBR) and safety.
Thirty-six patients were enrolled in this study. The overall response was complete response in 0 (0%), partial response in 12 (33.3%), stable disease in 12 (33.3%), and progressive disease in 11 (30.1%) patients. The ORR was 33.3% (12/36). The CBR was 66.7% (24/36). The median PFS was 9.5 months (95%CI: 7.8-12.6 months). The median OS was 20.2 months (95%CI: 15.0-25.4 months) Grade 3/4 adverse events included leukopenia in seven patients (19.4%). Dose reductions because of adverse events occurred in 12 patients (33.3%). There was no treatment-related mortality.
The combination of sequential therapy with S-1 and CPA was tolerable and had efficacy with good disease control. Sequential therapy with S-1 and CPA may be a feasible new treatment option for patients with MBC; however, further study is warranted to explore the efficacy of this therapy.
JRCT, JRCTs031180296 . Registered 2 December 2019 - Retrospectively registered.
S-1 和环磷酰胺（CPA）均可口服给药，两者联合应用治疗转移性乳腺癌（MBC）具有很大的潜力。我们在 MBC 患者中进行了 S-1 和 CPA 序贯治疗的 I 期研究；该方案确定的推荐剂量为 S-1 每日 80mg/m2，CPA 每日 100mg/m2。然后，我们进行了这项口服 S-1 和 CPA 方案的 II 期研究。
这是一项单臂、开放标签、单中心前瞻性 II 期研究，旨在评估 S-1 和 CPA 序贯方案治疗 MBC 的疗效。S-1 每日 2 次口服，连用 14 天，然后 S-1 停药 2 周后再给予 CPA 每日 2 次口服，连用 14 天，重复 4 周周期（S-1 2 周，CPA 2 周）。主要终点是总缓解率（ORR）。次要终点包括总生存期（OS）、无进展生存期（PFS）、临床获益率（CBR）和安全性。
本研究共纳入 36 例患者。完全缓解 0 例（0%），部分缓解 12 例（33.3%），疾病稳定 12 例（33.3%），疾病进展 11 例（30.1%）。ORR 为 33.3%（12/36）。CBR 为 66.7%（24/36）。中位 PFS 为 9.5 个月（95%CI：7.8-12.6 个月）。中位 OS 为 20.2 个月（95%CI：15.0-25.4 个月）。3/4 级不良反应包括白细胞减少症 7 例（19.4%）。因不良反应导致剂量减少的患者有 12 例（33.3%）。无治疗相关死亡。
S-1 和 CPA 序贯治疗耐受性好，疾病控制效果好，具有疗效。S-1 和 CPA 序贯治疗可能是 MBC 患者一种可行的新治疗选择；然而，需要进一步研究来探索该治疗方法的疗效。
JRCT，JRCTs031180296。2019 年 12 月 2 日注册-回顾性注册。
