HGCSG 1403: phase I trial of oxaliplatin /irinotecan /S-1 (OX-IRIS) for unresectable pancreatic cancer

Abstract

Background: FOLFIRINOX has become one of the standard treatment for unresectable pancreatic cancer (PC) with distant metastasis. OX-IRIS is the combination therapy of oxaliplatin (L-OHP), irinotecan (IRI) and S-1. It is the useful treatment to dispense with a continuous infusion of 5FU by administering S-1 orally. For establishing OXIRIS therapy as a new standard treatment, we planned this study for evaluating dose limiting toxicity (DLT) and maximum tolerated dose (MTD)(UMIN ID: 000017002). Methods: This study was carried out as a multicenter phase I study. Chemotherapy naïve patients with unresectable PC were included. L-OHP and IRI were administered on day1 and 15, and S-1 was taken twice a day in day1-14, and then 14 days were rest for 1 cycle. The primary endpoints were the frequency of DLT and estimating of MTD. Secondary endpoints were safety, response rate, progression-free survival (PFS) and overall survival. Results: Between January 2016 and August 2017, 13 cases were enrolled. The patients' backgrounds were median age 62, man /woman; 9/4, the primary tumor sites head / body and tail; 8/5, ECOG PS 0/1; 7/6, UR-LA /UR-M; 4/9. Two of five enrolled in level 0 (L-OHP: 85 mg/m2, IRI: 100 mg/m2, S-1: 80 mg/m2) had DLT. In two of eight in level -1 (L-OHP: 65 mg/m2, IRI: 100 mg/m2, S-1: 80 mg/m2), it was impossible to evaluate DLT because the treatment of one cycle was not accomplished. And one of remaining six had DLT. At level 0, 100% of cases had anemia and fatigue, 80% anorexia, diarrhea, peripheral sensory neuropathy, 60% platelet count decrease. At level -1, 100% had anemia, 75% nausea and fatigue, 63% anorexia. Response rate was 10% and disease control rate was 70% in ten cases with evaluable lesion. Median PFS was 4.1 months (95%C.I.; 0.0-8.6 months). Conclusions: In this study, MTD was estimated to be level 0, and determined recommended dose is level -1 for the planned future study. We are going to evaluate efficacy and safety in a phase II study.