Multicenter Phase II study of intravenous and intraperitoneal paclitaxel with s-1 for pancreatic ductal adenocarcinoma patients with peritoneal metastasis

Objective: To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, "an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium" in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis. Background: PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive. Methods: Paclitaxel was administered i.v. at 50mg/m² and i.p. at 20mg/m² on days 1 and 8. S-1 was administered at 80mg/m²/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446). Results: Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47-22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery. Conclusions: This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis.