紫杉醇腹腔内给药联合 S-1 顺铂治疗胃癌腹膜转移的 I 期研究。

Phase I Study of Intraperitoneal Administration of Paclitaxel Combined with S-1 Plus Cisplatin for Gastric Cancer with Peritoneal Metastasis.

机构信息

Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan,

Department of Chemotherapy, The University of Tokyo, Tokyo, Japan.

出版信息

Oncology. 2020;98(1):48-52. doi: 10.1159/000502484. Epub 2019 Sep 5.

DOI:10.1159/000502484

PMID:31487733

Abstract

INTRODUCTION

Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer (GC) with peritoneal metastasis (PM). Recently, superiority of IP administration of paclitaxel (PTX) combined with S-1 and intravenous PTX over conventional systemic chemotherapy was suggested in a phase III study, although the difference in overall survival did not reach statistical significance in the primary analysis. Thus, attempts to combine IP PTX with other systemic therapies with higher efficacy are warranted. We designed a new regimen combining IP PTX with S-1 plus cisplatin (SP), which is regarded as the standard first-line treatment for metastatic GC in Japan, and subsequently carried out a dose-escalation study.

METHODS

The combination was a 5-weekly regimen. IP PTX was to be administered on days 1, 8, and 22 with an initial dose of 15 mg/m2 at level 1 and 20 mg/m2 at level 2. S-1 was to be administered orally at a fixed dose of 80 mg/m2 b.i.d. for 21 days followed by a -14-day rest. Cisplatin was to be administered intravenously at a dose of 60 mg/m2 on day 8. Dose-limiting toxicities (DLTs) were defined as grade 4 leukopenia, grade 3 (G3) febrile neutropenia, G3 thrombocytopenia, and G3 nonhematological toxicity.

RESULTS

A total of 9 patients with macroscopic PM were enrolled. No DLTs were observed among the 3 patients at level 1 and 6 patients at level 2. No adverse events or technical problems associated with the IP administration were observed. Consequently, the maximum-tolerated dose was not reached, and the dose for further clinical trials of IP PTX was determined as 20 mg/m2. As for efficacy, peritoneal lavage cytology turned negative after the first course in 4 of 7 patients who had positive cytology before treatment.

CONCLUSION

The present study determined the dose for further clinical trials of IP PTX to be 20 mg/m2, when combined with the 5-weekly SP regimen.

摘要

简介

腹腔内（IP）化疗是一种有前途的治疗方法，可用于治疗伴有腹膜转移（PM）的胃癌（GC）。最近，一项 III 期研究表明，紫杉醇（PTX）联合 S-1 与静脉注射 PTX 相比，在 IP 给药时优于常规全身化疗，尽管在主要分析中总生存期的差异没有达到统计学意义。因此，有必要尝试将 IP PTX 与其他疗效更高的全身治疗相结合。我们设计了一种新的联合方案，将 IP PTX 与 S-1 联合顺铂（SP）联合使用，这在日本被认为是转移性 GC 的标准一线治疗方法，随后进行了剂量递增研究。

方法

该联合方案为 5 周方案。IP PTX 于第 1、8 和 22 天给药，起始剂量为 15mg/m2（第 1 水平）和 20mg/m2（第 2 水平）。S-1 以固定剂量 80mg/m2，每日 2 次，连续 21 天，然后休息 14 天。顺铂于第 8 天静脉注射，剂量为 60mg/m2。剂量限制性毒性（DLT）定义为 4 级白细胞减少症、3 级（G3）发热性中性粒细胞减少症、G3 血小板减少症和 G3 非血液学毒性。

结果

共纳入 9 例有肉眼可见 PM 的患者。在第 1 水平的 3 例患者和第 2 水平的 6 例患者中均未观察到 DLT。未观察到与 IP 给药相关的不良事件或技术问题。因此，未达到最大耐受剂量，IP PTX 的进一步临床试验剂量确定为 20mg/m2。在 7 例治疗前细胞学阳性的患者中，有 4 例在第一疗程后腹膜灌洗液细胞学转阴。