Randomized phase III trial of intravenous and intraperitoneal paclitaxel with S-1 versus gemcitabine plus nab-paclitaxel for pancreatic ductal adenocarcinoma with peritoneal metastasis (SP study)

Joji Kitayama,Tsutomu Fujii,Michiaki Unno,Kenichiro Uemura,Mitsugu Sekimoto,Hiroki Yamaue,So Yamaki,Daisuke Hashimoto,Fumihiko Miura,Satoshi Hirano,Hideki Ueno,Sohei Satoi,Tomohisa Yamamoto,Goro Honda,Yasuhiro Kodera,Toshio Shimokawa,Hideyuki Yoshitomi,Fuyuhiko Motoi

doi:10.1186/s13063-022-06049-7

Abstract

The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong the overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 1:1 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles. Japan Registry of Clinical Trials jRCTs051180199 (https://jrct.niph.go.jp/).

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of death in Japan, with a 5-year survival rate of less than 10% [1]
Patients with peritoneal metastasis are generally treated with systemic chemotherapy with the same regimens as patients with other distant metastases
PTX combined with S-1 in PDAC patients with peritoneal metastasis without other distant organ metastases

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of death in Japan, with a 5-year survival rate of less than 10% [1]. Ishigami et al conducted a phase II study of weekly intravenous (i.v.) and i.p. PTX with S-1 in gastric cancer with peritoneal metastases, with remarkable results, such as an ORR of 56%, disappearance or marked decrease in malignant ascites in 62% of patients, and a 1-year overall survival (OS) rate of 78% [9]. PTX with S-1 in gastric cancer with peritoneal metastases, with remarkable results, such as an ORR of 56%, disappearance or marked decrease in malignant ascites in 62% of patients, and a 1-year overall survival (OS) rate of 78% [9] Based on these results, we conducted a phase II multicenter trial to evaluate the clinical efficacy and tolerability of i.v. and i.p. PTX combined with S-1 in PDAC patients with peritoneal metastasis without other distant organ metastases. Conversion surgery for patients whose peritoneal metastasis disappeared was performed for 24.2% of the enrolled patients, and the MST in patients who received conversion surgery reached 27.8 months

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