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.

Abstract

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 m2·day) on days 1-7, fixed doses of oxaliplatin (85 mg/m2) biweekly, and escalating doses of irinotecan (150, 165, or 180 mg/m2) 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).

• Authors: Akihiro Ohba, Hideki Ueno, Satoshi Shiba, Naohiro Okano, Takaaki Kobayashi, Fumio Nagashima, Naoki Sasahira, Mitsuhito Sasaki, Hiroshi Imaoka, Yasunari Sakamoto, Shunsuke Kondo, Chigusa Morizane, Masato Ozaka, Masafumi Ikeda, Junji Furuse, Takuji Okusaka
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 174 Pg. 40-47 (Oct 2022) ISSN: 1879-0852 [Electronic] England
• PMID: 35970035 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Organoplatinum Compounds
• Oxaliplatin
• Irinotecan
• Fluorouracil
• Camptothecin

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Camptothecin (adverse effects)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Fluorouracil (adverse effects)
• Humans
• Irinotecan (adverse effects)
• Multicenter Studies as Topic
• Organoplatinum Compounds (adverse effects)
• Oxaliplatin (adverse effects)
• Pancreatic Neoplasms (drug therapy, etiology)
• Pancreatic Neoplasms