Safety and efficacy of S-IROX (S-1, irinotecan and oxaliplatin combination therapy) in patients with advanced pancreatic cancer: A multicenter phase 1b dose-escalation and dose-expansion clinical trial.

Background: This phase 1b trial evaluated the toxicity and efficacy of S-1, irinotecan, and oxaliplatin combination therapy (S-IROX) as first-line chemotherapy in patients with advanced pancreatic cancer (APC).
Methods: Patients aged 20-75 years with APC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible to receive escalating doses of S-1 (60 or 80 mg m ² ·day) on days 1-7, fixed doses of oxaliplatin (85 mg/m ² ) biweekly, and escalating doses of irinotecan (150, 165, or 180 mg/m ² ) once every 2 weeks. In the dose-escalation cohort, a 3 + 3 design was used to determine the maximum-tolerated dose (MTD) and explore the recommended dose (RD). A dose-expansion cohort was added to further evaluate the safety and efficacy of the combination. This trial was registered at UMIN-CTR (UMIN000012054).
Results: Approximately 47 patients were enrolled, of whom 45 were eligible for the analysis. The MTD was not determined, but the RD was determined to be dose level 1 based on a review of data from each level. Among the 45 patients, the ORR was 51.1% [95% confidence interval (CI), 35.8-66.3%]. The median progression-free survival and median overall survival was 6.9 months (95% CI, 5.1-8.8 months) and 15.8 months (95% CI, 9.8-20.8 months), respectively. Common adverse events included neutropenia, elevated liver enzyme levels, diarrhoea, and nausea.
Conclusions: The S-IROX regimen showed promising efficacy with manageable toxicities in Japanese patients with APC. A randomised phase 2/3 trial comparing S-IROX, mFOLFIRINOX, and gemcitabine plus nab-paclitaxel is currently ongoing (jRCTs031190009).
Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. A.O. has received honoraria from Yakult and Taiho. N.O. has received honorarium from Taiho. F.M. has received research funding from Yakult, Taiho, and Daiichi Sankyo, honoraria from Yakult, Taiho, and Daiichi Sankyo. M.S. has received honorarium from Yakult. H.I. has received honorarium from Yakult. C.M. has received research funding from Yakult, Taiho, and Daiichi Sankyo, honoraria from Yakult and Taiho. M.O. has received honorarium from Yakult. M.I. has received research funding from Yakult, honoraria from Yakult and Taiho. J.F. has received research funding from Yakult, Taiho, and Daiichi Sankyo, honoraria from Yakult, Taiho, and Daiichi Sankyo. T.O. has received honoraria from Yakult, Taiho, and Daiichi Sankyo. All remaining authors have declared no conflicts of interest.
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