Phase I study assessing the feasibility of the triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic ductal adenocarcinoma

Abstract

Background: The objective of this study was to determine the recommended dose (RD) of a biweekly S-1, oxaliplatin, and irinotecan (SOXIRI) regimen in patients with unresectable pancreatic ductal adenocarcinoma.

Methods: This phase I study used a traditional "3+3" dose-escalation design, with four dose levels. A dose-escalation schedule consisted of two doses of S-1 (60 and 80 mg/m(2) twice daily) for 2 weeks in alternate-day administration, three doses of irinotecan (125, 150, and 180 mg/m(2)) on day 1, and a single dose of oxaliplatin (85 mg/m(2)) on day 1 of a 2-week cycle. Dose-limiting toxicities (DLTs) were assessed in the first four cycles to determine the maximum tolerated dose. This clinical study was registered at UMIN000014339.

Results: Fifteen patients received this regimen (median, eight cycles; range 4-12). At dose level 3 (S-1, 80 mg/m(2); irinotecan, 150 mg/m(2)), 2/6 patients experienced DLTs of grade 3 fatigue and grade 4 neutropenia. At dose level 4, all three patients experienced DLTs: grade 3 fatigue (n = 1) and grade 4 neutropenia (n = 2). The RD was 80, 85, and 150 mg/m(2) of S-1, oxaliplatin, and irinotecan, respectively. We found the following: response rate, 47 %; disease control rate, 80%; median progression-free survival, 6.7 months; overall survival, 13.4 months.

Conclusions: The SOXIRI regimen's RD is 80, 85, and 150 mg/m(2) of S-1, oxaliplatin, and irinotecan, respectively.

Keywords: Irinotecan; Oxaliplatin; Phase I study; S-1; Unresectable pancreatic ductal adenocarcinoma.