{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:07:26Z","timestamp":1792793246566,"version":"4.5.0"},"reference-count":17,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"31","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:sup>2<\/jats:sup>\n                      over 2 hours, irinotecan 150 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      over 90 minutes, l-leucovorin 200 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      over 2 hours, each once daily on day 1, and fluorouracil 2,400 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      over 46 hours on days 1-3, every 2 weeks), S-IROX (oxaliplatin 85 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      over 2 hours, irinotecan 150 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      over 90 minutes on day 1, and S-1 80 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/day administered orally twice daily on days 1-7, every 2 weeks), or nab-paclitaxel (125 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) + gemcitabine (1,000 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) on days 1, 8, and 15 every 4 weeks. The primary end point was overall survival (OS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>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 &lt;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%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.24.00936","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T18:22:38Z","timestamp":1757614958000},"page":"3345-3354","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":35,"title":["Modified Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin or S-1, Irinotecan, and Oxaliplatin Versus Nab-Paclitaxel + Gemcitabine in Metastatic or Recurrent Pancreatic Cancer (GENERATE, JCOG1611): A Randomized, Open-Label, Phase II\/III Trial"],"prefix":"10.1200","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9153-3798","authenticated-orcid":true,"given":"Akihiro","family":"Ohba","sequence":"first","affiliation":[{"name":"Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5666-1970","authenticated-orcid":true,"given":"Masato","family":"Ozaka","sequence":"additional","affiliation":[{"name":"Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8123-5298","authenticated-orcid":true,"given":"Junki","family":"Mizusawa","sequence":"additional","affiliation":[{"name":"JCOG Data Center, National Cancer Center Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1729-807X","authenticated-orcid":true,"given":"Takuji","family":"Okusaka","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Chuo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2535-6586","authenticated-orcid":true,"given":"Satoshi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3383-9131","authenticated-orcid":true,"given":"Taro","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, 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