196P - HGCSG1403: Phase I trial of oxaliplatin/irinotecan/S-1 (OX-IRIS) as first-line chemotherapy for unresectable pancreatic cancer

Abstract

Background: In recent years, FOLFIRINOX has become one of the primary 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 OX-IRIS therapy as a new standard treatment, we planned this study. Methods: Chemotherapy-naïve patients with unresectable PC were included. L-OHP and IRI were administered on day 1 and 15, and S-1 was taken twice a day in day 1-14, and 14 days were rest for 1 cycle. This study used a standard 3 plus 3 design, and we evaluated safety and tolerability in 3 to 6 cases of each levels. It was assumed until 1 cycle completion for the evaluation period of dose limiting toxicity (DLT). Maximum tolerated dose (MTD) was defined as the highest dose beyond a more of one-third within DLT evaluation period. The primary endpoint was the frequency of DLT and MTD. Secondary endpoints were the frequency of adverse events, response rate, progression-free survival (PFS) and overall survival (OS). Results: Between January 2016 and August 2017, 13 cases were enrolled. The patients’ backgrounds were median age 62 years old, 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 patients enrolled in level 0 (L-OHP: 85 mg/m2, IRI: 100 mg/m2, S-1: 80 mg/m2) had DLT. In two of eight patients enrolled in level -1 (L-OHP: 65 mg/m2, IRI: 100 mg/m2, S-1: 80 mg/m2), DLT was impossible to evaluate because the treatment of 1 cycle was not accomplished. And one of remaining six cases had DLT. At level 0, 100% of cases had anemia and fatigue, 80% had anorexia, diarrhea, peripheral sensory neuropathy, 60% had platelet count decrease. At level -1, 100% of cases had anemia, 75% had nausea and fatigue, 63% had anorexia. Response rate was 10% and disease control rate was 70% in ten cases with the evaluable lesion. Median PFS was 4.1 months. Conclusions: In this study, MTD was estimated to be level 0, and determined that recommended dose (RD) was level -1 in the planned future study. We are going to evaluate efficacy and the safety in a phase II study. Clinical trial identification: UMIN000017002 - 2015/04/01. Legal entity responsible for the study: Non-profit Organization: Hokkaido Gastrointestinal Cancer Study Group. Funding: Non-profit Organization: Hokkaido Gastrointestinal Cancer Study Group. Disclosure: S. Yuki: Honoraria: Yakult Honsha, Taiho Pharmaceutical. Y. Komatsu: Honoraria: Taiho Pharmaceutical; Donation: Taiho Pharmaceutical, Yakult Honsha; Research fund: Taiho Pharmaceutical. All other authors have declared no conflicts of interest.