D2 切除术后辅助化疗 Nab-紫杉醇联合 S-1 治疗 III 期弥漫型Lauren 胃癌的 I 期研究（NORDICA 研究）。

Phase I study of adjuvant chemotherapy with nab-paclitaxel and S-1 for stage III Lauren's diffuse-type gastric cancer after D2 resection (NORDICA study).

机构信息

Medical Oncology Department of Zhongshan Hospital affiliated to Fudan University, Shanghai, China.

Cancer Center of Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Cancer Med. 2023 Jan;12(2):1114-1121. doi: 10.1002/cam4.4966. Epub 2022 Jun 25.

DOI:10.1002/cam4.4966

PMID:35751496

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9883443/

Abstract

PURPOSE

The prognosis of diffuse-type gastric cancer (DGC) is poorer than that of intestinal type, but S-1 is a potential treatment option in DGC. This study explored the maximal tolerated dose (MTD) and the recommended dose for phase II study (RP2D) of nab-paclitaxel combined with S-1 (AS regimen) as adjuvant chemotherapy in stage III DGC.

METHODS

Patients with stage III DGC were recruited into this phase I dose-escalation study between July 2019 and June 2020 in Zhongshan Hospital. Nab-paclitaxel and S-1 (80-120 mg/day, d1-14, q3w) were administrated for 6 cycles, and then 8 cycles of S-1 monotherapy were applied. The patients received nab-paclitaxel at 180, 220, or 260 mg/m according to the 3 + 3 design based on dose-limiting toxicity (DLT). The primary endpoint was RP2D. Secondary endpoints were the 1-year disease-free survival (DFS) rate and adverse events (AEs).

RESULTS

One case experienced DLT in 180-mg/m dose group, subsequently three additional subjects were enrolled. DLT was not observed in the 220- and 260-mg/m dose groups (both n = 3). Therefore, the MTD has not reached, and the RP2D of nab-paclitaxel would be 260 mg/m . Five participants showed progressive disease, with three and two participants in the 180- and 220-mg/m dose groups, respectively. The 6-, 12-, and 18-month DFS rates were 100%, 63.6%, and 50.9%, respectively. The most frequently observed AEs were neutropenia (83.3%) and leukopenia (66.7%).

CONCLUSION

The RP2D of nab-paclitaxel as adjuvant chemotherapy in DGC was 260 mg/m . The AS regimen had a tolerable AE profile in stage III DGC.

摘要

目的

弥漫型胃癌（DGC）的预后比肠型差，但 S-1 是 DGC 的一种潜在治疗选择。本研究旨在探讨紫杉醇白蛋白结合型联合 S-1（AS 方案）作为 III 期 DGC 辅助化疗的最大耐受剂量（MTD）和 II 期研究推荐剂量（RP2D）。

方法

本研究为 2019 年 7 月至 2020 年 6 月在中山大学附属中山医院进行的一项 I 期剂量递增研究，纳入 III 期 DGC 患者。患者接受纳武利尤单抗联合 S-1（80-120mg/天，d1-14，q3w）治疗 6 个周期，然后应用 S-1 单药治疗 8 个周期。患者按照 3+3 设计，根据剂量限制性毒性（DLT）接受nab-紫杉醇 180、220 或 260mg/m2 治疗。主要终点为 RP2D。次要终点为 1 年无病生存率（DFS）和不良事件（AEs）。

结果

180mg/m2 剂量组有 1 例发生 DLT，随后入组 3 例。220 和 260mg/m2 剂量组均未观察到 DLT（均 n=3）。因此，MTD 尚未达到，nab-紫杉醇的 RP2D 为 260mg/m2。5 例患者出现疾病进展，180 和 220mg/m2 剂量组各有 3 例和 2 例。6、12 和 18 个月的 DFS 率分别为 100%、63.6%和 50.9%。最常见的不良反应为中性粒细胞减少（83.3%）和白细胞减少（66.7%）。