The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site. The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. My Bibliography Citation manager Save citation to file Add to Collections Add to My Bibliography Your saved search Create a file for external citation management software Purpose: Modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) and nab-paclitaxel + gemcitabine are recommended as first-line treatments for metastatic pancreatic cancer. S-1, irinotecan, and oxaliplatin (S-IROX) demonstrated activity in a phase Ib trial in this population. Therefore, these three regimens were directly compared. Methods: This randomized phase II/III trial was performed at 45 centers in Japan. Eligible patients age 20-75 years with an Eastern Cooperative Oncology Group performance status of 0 or 1 and pathologically confirmed metastatic or recurrent pancreatic cancer were randomly assigned (1:1:1) to receive mFOLFIRINOX (oxaliplatin 85 mg/m 2 over 2 hours, irinotecan 150 mg/m 2 over 90 minutes, l-leucovorin 200 mg/m 2 over 2 hours, each once daily on day 1, and fluorouracil 2,400 mg/m 2 over 46 hours on days 1-3, every 2 weeks), S-IROX (oxaliplatin 85 mg/m 2 over 2 hours, irinotecan 150 mg/m 2 over 90 minutes on day 1, and S-1 80 mg/m 2 /day administered orally twice daily on days 1-7, every 2 weeks), or nab-paclitaxel (125 mg/m 2 ) + gemcitabine (1,000 mg/m 2 ) on days 1, 8, and 15 every 4 weeks. The primary end point was overall survival (OS). Results: A total of 527 patients were enrolled, with 426 included in the planned interim analysis. The median OS was 14.0 months (hazard ratio [HR], 1.31 [95% CI, 0.97 to 1.77]) and 13.6 months (HR, 1.35 [95% CI, 1.00 to 1.82]) in the mFOLFIRINOX and S-IROX groups, respectively, as compared with 17.1 months in the nab-paclitaxel + gemcitabine group. The predictive probability of achieving superiority in the final analysis was <1% in both groups. Thus, the trial was terminated owing to its futility. Grade 3 to 4 anorexia was more frequent in the mFOLFIRINOX (23.3%) and S-IROX (27.5%) groups than in the nab-paclitaxel + gemcitabine group (5.0%). Conclusion: Neither mFOLFIRINOX nor S-IROX appeared to be superior compared with nab-paclitaxel + gemcitabine as the first-line treatment for metastatic or recurrent pancreatic cancer. PubMed Disclaimer Conflict of interest statement The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center . Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians ( Open Payments ). Honoraria: Ono Pharmaceutical, Yakult Honsha, Guardant Health, AstraZeneca, Eisai, SERVIER, Taiho Pharmaceutical, MSD Consulting or Advisory Role: Zymeworks Research Funding: Ono Pharmaceutical (Inst), Chugai Pharma (Inst), Novartis (Inst), Daiichi Sankyo/Astra Zeneca (Inst) Honoraria: Taiho Pharmaceutical, Pfizer, Novartis, Bayer, Yakult Honsha, Eisai, MSD, AstraZeneca, Ono Pharmaceutical, Takeda, SERVIER Employment: Pfizer (I) Honoraria: Chugai Pharma, Taiho Pharmaceutical Research Funding: AstraZeneca (Inst), Ono Pharmaceutical (Inst), Chugai Pharma (Inst), Takeda (Inst), Eisai (Inst) Honoraria: Taiho Pharmaceutical, Chugai Pharma, AstraZeneca, Eisai, Novartis, Johnson & Johnson/Janssen Consulting or Advisory Role: AstraZeneca, Eisai, Amgen, Nihon Medi-Physics, Jazz Pharmaceuticals, Ohara Pharmaceutical Research Funding: Eisai (Inst), Bristol Myers Squibb (Inst), AstraZeneca (Inst), Syneos Health/Immunocore (Inst), Incyte, Sysmex (Inst), Chiome Bioscience, AstraZeneca (Inst), Linical (Inst), LabCorp (Inst) Satoshi Kobayashi Honoraria: Taiho Pharmaceutical, Eisai, Yakult Honsha, Chugai Pharma, Lilly, Takeda, AstraZeneca, Zymeworks, Otsuka, MSD, SERVIER, Novartis Research Funding: Taiho Pharmaceutical (Inst), Chugai Pharma (Inst), AstraZeneca (Inst), Ono Pharmaceutical (Inst), MSD Oncology (Inst), Eisai (Inst), Daiichi Sankyo/UCB Japan (Inst) Research Funding: Abbott Laboratories, AstraZeneca, Chugai Pharma Honoraria: Taiho Pharmaceutical, Eisai, Lilly Japan, MSD, SERVIER, Chugai Pharma, Takeda, AstraZeneca, Novartis, Bristol Myers Squibb, Ono Pharmaceutical, Incyte, Teijin Pharma, Guardant Health, Nobel Pharma, EA Pharma Consulting or Advisory Role: Eisai, Novartis, Chugai Pharma, AstraZeneca, SERVIER, MSD, Guardant Health, Roche, Boehringer Ingelheim, Astellas Pharma, Bristol Myers Squibb Japan, AbbVie, GlaxoSmithKline, Ono Yakuhin, Rakuten Medical Japan, Delta-Fly Pharma, Nihon Medi-Physics Research Funding: Lilly Japan (Inst), Eisai (Inst), AstraZeneca (Inst), Chugai Pharma (Inst), Bristol Myers Squibb (Inst), Novartis (Inst), MSD (Inst), J-Pharma (Inst), Merck (Inst), Chiome Bioscience (Inst), Merus NV (Inst), Nihon Servier (Inst), Syneos Health (Inst), InVitae (Inst), Rakuten Medical Japan (Inst), AbbVie (Inst) Kazuya Sugimori Consulting or Advisory Role: J-MIT Speakers' Bureau: Olympus Medical Systems Corp, ASAHI INTECC, Viatris, Yakult Honsha Honoraria: Daiichi Sankyo/UCB Japan, Takeda, Ono Pharmaceutical, AstraZeneca, Eisai, Chugai Pharma, Taiho Pharmaceutical Research Funding: Taiho Pharmaceutical (Inst) Speakers' Bureau: Taiho Pharmaceutical, MSD, Myriad Genetics, Incyte, Nihon Servier, Chugai Pharma, AstraZeneca, Guardant Health Japan, Eisai Europe Honoraria: Taiho Pharmaceutical, Bayer Yakuhin, Lilly Japan, Chugai Pharma, Ono Pharmaceutical, Takeda, Eisai, Daiichi Sankyo, AstraZeneca, Incyte Japan, MSD Nobumasa Mizuno Honoraria: Yakult Honsha, Novartis, MIYARISAN Pharmaceutical, SERVIER, Taiho Pharmaceutical Consulting or Advisory Role: Boehringer Ingelheim, MSD Research Funding: MSD (Inst), Incyte (Inst), Ono Pharmaceutical (Inst), Seagen (Inst), Novartis (Inst), Boehringer Ingelheim (Inst), Pfizer (Inst), AstraZeneca (Inst), SERVIER (Inst) Masayuki Furukawa Research Funding: Merck (Inst), Incyte (Inst), MSD Oncology (Inst), Eisai (Inst), Ono Yakuhin (Inst), J-Pharma (Inst), Taiho Pharmaceutical (Inst) Hiroshi Katayama Honoraria: FUJIFILM Research Funding: AstraZeneca (Inst), Ono Pharmaceutical (Inst), Chugai Pharma (Inst), Natera (Inst) Honoraria: Taiho Pharmaceutical, Chugai Pharma, Astellas Pharma, Novartis, Takeda, Daiichi Sankyo, Eisai, MSD, Teijin Pharma, AstraZeneca, J-Pharma, SERVIER, Ohara Pharmaceutical Consulting or Advisory Role: Eisai, Astellas Pharma, J-Pharma, OncoTherapy Science, Delta-Fly Pharma Honoraria: Taiho Pharmaceutical, AstraZeneca, MSD, Ono Pharmaceutical, SERVIER, Chugai Pharma, Incyte, Takeda, Novartis, Daiichi Sankyo/UCB Japan, J-pharma, Boehringer Ingelheim, Eisai, Takada Pharm, Viatris, ASCA Consulting or Advisory Role: Boehringer Ingelheim Research Funding: Taiho Pharmaceutical (Inst), Eisai (Inst), AstraZeneca (Inst), Ono Pharmaceutical (Inst), MSD (Inst), Incyte (Inst), Astellas Pharma (Inst), Chugai Pharma (Inst), Delta-Fly Pharma (Inst), Chiome Bioscience (Inst), Novartis (Inst), Boehringer Ingelheim (Inst), J-Pharma (Inst), Amgen (Inst), Jazz Pharmaceuticals (Inst), Novocure (Inst), Revolution Medicines (Inst), Amgen (Inst) No other potential conflicts of interest were reported. Trial profile. mFOLFIRINOX, modified fluorouracil,… Trial profile. mFOLFIRINOX, modified fluorouracil, leucovorin, irinotecan, and oxaliplatin; NSCLC, non–small cell lung… Kaplan-Meier estimates of (A) OS… Kaplan-Meier estimates of (A) OS at the planned interim analysis, (B) updated OS,… Forest plot of overall survival… Forest plot of overall survival in selected subgroups. The overall hazard ratio is… Is FOLFIRINOX more effective than gemcitabine plus nab-paclitaxel in pancreatic adenocarcinoma? -a decade of debate! Babiker HM. Babiker HM. J Gastrointest Oncol. 2026 Apr 30;17(2):111. doi: 10.21037/jgo-2025-1-988. Epub 2026 Apr 28. J Gastrointest Oncol. 2026. PMID: 42169876 Free PMC article. No abstract available. Siegel RL, Miller KD, Fuchs HE, et al. : Cancer statistics, 2022. CA Cancer J Clin 72:7-33, 2022 - PubMed Siegel RL, Miller KD, Fuchs HE, et al. : Cancer statistics, 2022. CA Cancer J Clin 72:7-33, 2022 - PubMed Mizrahi JD, Surana R, Valle JW, et al. : Pancreatic cancer. Lancet 395:2008-2020, 2020 - PubMed Mizrahi JD, Surana R, Valle JW, et al. : Pancreatic cancer. Lancet 395:2008-2020, 2020 - PubMed Ducreux M, Cuhna AS, Caramella C, et al. : Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 26:v56-v68, 2015. (suppl 5) - PubMed Ducreux M, Cuhna AS, Caramella C, et al. : Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 26:v56-v68, 2015. (suppl 5) - PubMed Sohal DPS, Kennedy EB, Cinar P, et al. : Metastatic pancreatic cancer: ASCO guideline update. J Clin Oncol 38:3217-3230, 2020 - PMC - PubMed Sohal DPS, Kennedy EB, Cinar P, et al. : Metastatic pancreatic cancer: ASCO guideline update. J Clin Oncol 38:3217-3230, 2020 - PMC - PubMed Wainberg ZA, Melisi D, Macarulla T, et al. : NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): A randomised, open-label, phase 3 trial. Lancet 402:1272-1281, 2023 - PMC - PubMed Wainberg ZA, Melisi D, Macarulla T, et al. : NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): A randomised, open-label, phase 3 trial. 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