一项新辅助化疗联合多西他赛、顺铂和 S-1，继以 D2 淋巴结清扫术治疗高危进展期胃癌的 II 期研究：KDOG1001 试验结果。

A phase II study of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1, followed by gastrectomy with D2 lymph node dissection for high-risk advanced gastric cancer: results of the KDOG1001 trial.

机构信息

Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, 252-0374, Japan.

Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan.

出版信息

Gastric Cancer. 2019 May;22(3):598-606. doi: 10.1007/s10120-018-0884-0. Epub 2018 Oct 3.

DOI:10.1007/s10120-018-0884-0

PMID:30284080

Abstract

BACKGROUND

The prognosis of patients with gastric cancer with bulky node metastasis, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) remains poor. We conducted a phase II study to evaluate the safety and efficacy of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 (DCS) for establishing a new treatment modality that improves prognosis.

METHODS

Patients received up to four 28-day cycles of DCS therapy (docetaxel at 40 mg/m, cisplatin at 60 mg/m on day 1, and S-1 at 40 mg/m twice daily for 2 weeks) followed by gastrectomy with D2 nodal dissection. S-1 chemotherapy was administered for 1 year after surgical resection. The primary endpoint was the percentage of complete resections of the primary tumor with clear margins (R0 resection). The planned sample size was 40; this was calculated based on an expected R0 rate of 85% and a threshold R0 rate of 65%, with a one-sided alpha of 5% and a power of 90%.

RESULTS

Between 2010 and 2017, 40 patients were enrolled. The R0 resection rate was 90%. The most common grade 3 or 4 adverse events during DCS therapy were leukocytopenia (27.5%), neutropenia (55.0%), and hyponatremia (22.5%). The most common grade 3 or 4 surgical morbidity was pancreatic fistula (12.5%); mortality was 0%. The pathological response rate was 57.5% with a grade 3 histological response rate of 8%.

CONCLUSIONS

Neoadjuvant chemotherapy with DCS was feasible and showed a sufficient R0 resection rate. A future study with a sufficient follow-up period should confirm survival outcomes.

摘要

背景

胃肿瘤伴大淋巴结转移、皮革胃（类型 4）或大溃疡浸润型肿瘤（类型 3）患者的预后仍然较差。我们进行了一项 II 期研究，以评估多西他赛、顺铂和 S-1（DCS）新辅助化疗的安全性和有效性，以建立一种改善预后的新治疗模式。

方法

患者接受最多四个 28 天周期的 DCS 治疗（多西他赛 40mg/m，顺铂 60mg/m 第 1 天，S-1 40mg/m 每天两次持续 2 周），然后进行胃切除术和 D2 淋巴结清扫术。手术后用 S-1 化疗治疗 1 年。主要终点是肿瘤完全切除且切缘无肿瘤（R0 切除）的百分比。计划样本量为 40；这是根据预计 R0 率为 85%和阈值 R0 率为 65%，单侧 alpha 为 5%和功率为 90%计算得出的。

结果

2010 年至 2017 年，共纳入 40 例患者。R0 切除率为 90%。DCS 治疗期间最常见的 3 级或 4 级不良事件是白细胞减少症（27.5%）、中性粒细胞减少症（55.0%）和低钠血症（22.5%）。最常见的 3 级或 4 级手术并发症是胰瘘（12.5%）；无死亡病例。病理反应率为 57.5%，组织学 3 级反应率为 8%。