irinotecan + oxaliplatin + S-1

The combination of irinotecan, oxaliplatin, and S-1 is an investigational chemotherapy regimen primarily developed for treating pancreatic ductal adenocarcinoma (PDAC). This combination has been studied under various names including OX-IRIS and S-IROX in clinical trials[1][2][3]. It was designed as an alternative to FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin), offering the advantage of oral S-1 administration instead of continuous infusion of 5-fluorouracil (5-FU)[1][3]. ## Clinical Development The development of this combination therapy has progressed through several clinical trials: **Phase I Trials:** - A Phase I trial determined the maximum tolerated dose (MTD) and recommended dose (RD) for future studies[1]. - The recommended dose was established as oxaliplatin 65 mg/m², irinotecan 100 mg/m², and S-1 80 mg/m² (level -1)[1]. - Another Phase I trial (S-IROX) evaluated 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[2]. **Phase II Trials:** - The HGCSG 1803 study was initiated in December 2019 as a multicenter, non-randomized, single-arm, prospective Phase II study to evaluate the efficacy and safety of OX-IRIS[3]. - In this study, the regimen consisted of oxaliplatin at 85 mg/m², irinotecan at 150 mg/m², and S-1 at 40 mg/m²[3]. ## Efficacy and Safety The combination has shown promising efficacy in early clinical trials: - In one study, the overall response rate (ORR) was 30% at the recommended dose levels[1]. - Median progression-free survival was 4.1 months and median overall survival was 13.7 months[1]. - In the S-IROX trial, the ORR was 51.1%, with median progression-free survival of 6.9 months and median overall survival of 15.8 months[2]. Common adverse events included: - Hematological toxicities: anemia, thrombocytopenia, neutropenia - Gastrointestinal effects: nausea, anorexia, diarrhea - Other: fatigue, peripheral sensory neuropathy, elevated liver enzyme levels[1][2] ## Advantages A key advantage of this combination is that S-1 is administered orally, eliminating the need for continuous infusion of 5-FU, which is required in the FOLFIRINOX regimen. This makes the treatment more convenient for patients and potentially improves quality of life[1][3].

Other names

irinotecan + oxaliplatin + TS-1irinotecan + oxaliplatin + TS-ONEirinotecan + oxaliplatin + Teysuno