Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
Eur J Cancer. 2020 Jan;124:123-130. doi: 10.1016/j.ejca.2019.10.023. Epub 2019 Nov 22.
This phase I/II study evaluated the feasibility and efficacy of S-1, leucovorin, oxaliplatin and gemcitabine (SLOG), a triplet regimen, for treating patients with metastatic pancreatic ductal adenocarcinoma (PDAC).
Patients with chemo-naive, metastatic PDAC were eligible to receive fixed-rate infusion (10 mg/m/min) of gemcitabine of 800 mg/m followed by oxaliplatin of 85 mg/m on day 1 plus oral S-1 and leucovorin (20 mg/m) twice daily from days 1 to 7 in a 2-week cycle. The dose of S-1 would be escalated from 20, 30, 35 to 40 mg/m2 in a 3 + 3 designed phase I part to determine the maximum tolerated dose (MTD) for phase II study, in which the primary end-point was objective response rate (ORR). The recommended dose of S-1 was from phase I. This trial is registered at ClinicalTrials.gov: NCT01415713.
Seventy-three patients were enrolled. In the phase I study (n = 19), the MTD of S-1 was 35 mg/m twice daily. Of 54 patients in phase II, the ORR was 40.7% (95% confidence interval [CI], 28%-55%). The median progression-free survival and overall survival were 7.6 (95% CI, 5.6-11.0) and 11.4 (95% CI, 8.1-16.3) months, respectively. The most common grade III/IV adverse event was neutropenia (40.7%). Twenty-four percent of patients had SLOG treatment for more than 1 year. The mean relative dose intensities of gemcitabine, oxaliplatin, and S-1 were 92%, 92% and 89%, respectively.
Biweekly SLOG is a feasible regimen with promising activity and safety profiles. A randomised study comparing SLOG versus modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) in advanced PDAC is ongoing (ClinicalTrials.gov: NCT03443492).
本 I/II 期研究评估了 S-1、亚叶酸、奥沙利铂和吉西他滨（SLOG）三联疗法治疗转移性胰腺导管腺癌（PDAC）患者的可行性和疗效。
初治转移性 PDAC 患者符合条件，接受吉西他滨 800mg/m 的固定率输注（10mg/m/min），随后在第 1 天输注奥沙利铂 85mg/m，加用 S-1 和亚叶酸（20mg/m），每天 2 次，第 1 天至第 7 天，每 2 周为 1 个周期。S-1 的剂量将在 3+3 设计的 I 期部分从 20、30、35 递增至 40mg/m2，以确定 II 期研究的最大耐受剂量（MTD），主要终点为客观缓解率（ORR）。S-1 的推荐剂量来自 I 期。本试验在 ClinicalTrials.gov 注册：NCT01415713。
共纳入 73 例患者。I 期研究（n=19）中，S-1 的 MTD 为每日 2 次 35mg/m。II 期 54 例患者中，ORR 为 40.7%（95%置信区间[CI]，28%-55%）。中位无进展生存期和总生存期分别为 7.6（95%CI，5.6-11.0）和 11.4（95%CI，8.1-16.3）个月。最常见的 III/IV 级不良事件为中性粒细胞减少症（40.7%）。24%的患者 SLOG 治疗超过 1 年。吉西他滨、奥沙利铂和 S-1 的平均相对剂量强度分别为 92%、92%和 89%。
SLOG 每 2 周方案是一种可行的方案，具有良好的疗效和安全性。一项比较 SLOG 与改良的亚叶酸、氟尿嘧啶、伊立替康和奥沙利铂（FOLFIRINOX）治疗晚期 PDAC 的随机研究正在进行中（ClinicalTrials.gov：NCT03443492）。
