{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:34:02Z","timestamp":1784892842536,"version":"3.55.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although FOLFIRINOX (<jats:sc>l<\/jats:sc>-Leucovorin\/5-FU\/Irinotecan\/Oxaliplatin) is established as one of the standard therapies for patients with metastatic pancreatic cancer, the modified FOLFIRINOX (mFOLFIRINOX) is often used in clinical practice to reduce the incidence of toxicities. Febrile neutropenia (FN) and severe neutropenia during FOLFIRINOX are especially frequently observed in Japanese patients. In this study, we evaluated the incidence of FN and severe neutropenia, and explored the risk factors for severe neutropenia in patients receiving treatment with mFOLFIRINOX. The data of patients who had received mFOLFIRINOX between December 2013 and December 2014 at the National Cancer Center Hospital East were reviewed retrospectively. We graded the neutropenia severity and defined\u2009\u2265\u2009Grade 3 neutropenia as severe neutropenia. Univariate and multivariate analysis were undertaken to evaluate the associations with risk of development of severe neutropenia. A total of 122 patients were enrolled in this study. Sixty two patients (51%) and 10 patients (8%) developed severe neutropenia and FN, respectively. Multivariate analysis identified a low baseline white blood cell count (odds ratio [OR], 14.50; 95% confidence interval (CI), 3.27\u2013111.14; <jats:italic>p<\/jats:italic>\u2009=\u20090.002) and presence of heterozygosity for <jats:italic>UGT1A1<\/jats:italic>*28 or <jats:italic>UGT1A1<\/jats:italic>*6 polymorphism (OR, 2.84; 95% CI, 1.18\u20137.17; <jats:italic>p<\/jats:italic>\u2009=\u20090.023) as independent risk factors for severe neutropenia. The incidences of severe neutropenia and FN in patients receiving mFOLFIRINOX in our clinical practice were comparable to previous reports. The risk factors for severe neutropenia in patients receiving mFOLFIRINOX were a low baseline white blood cell count and presence of heterozygosity for <jats:italic>UGT1A1<\/jats:italic>*28 or <jats:italic>UGT1A1<\/jats:italic>*6 polymorphism.<\/jats:p>","DOI":"10.1038\/s41598-022-18669-9","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T13:07:55Z","timestamp":1663333675000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Incidence of and risk factors for severe neutropenia during treatment with the modified FOLFIRINOX therapy in patients with advanced pancreatic cancer"],"prefix":"10.1038","volume":"12","author":[{"given":"Ai","family":"Irisawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misaki","family":"Takeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Mitsunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"issue":"1","key":"18669_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","volume":"72","author":"RL Siegel","year":"2022","unstructured":"Siegel, R. L., Miller, K. D. & Fuchs, H. E. Cancer statistics. CA Cancer J. Clin. 72(1), 7\u201333 (2022).","journal-title":"CA Cancer J. Clin."},{"key":"18669_CR2","unstructured":"Ministry of Health Labor and Welfare. Vital Statistics. https:\/\/www.mhlw.go.jp\/english\/database\/db-hw\/vs01.html. Accessed 31 July 2021."},{"key":"18669_CR3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1997.15.6.2403","volume":"15","author":"HA Burris","year":"1997","unstructured":"Burris, H. A. et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial. J. Clin. Oncol. 15, 2403e13 (1997).","journal-title":"J. Clin. Oncol."},{"issue":"11","key":"18669_CR4","doi-asserted-by":"publisher","first-page":"2588","DOI":"10.3390\/cancers14112588","volume":"14","author":"S Chakrabarti","year":"2022","unstructured":"Chakrabarti, S., Kamgar, M. & Mahipal, A. Systemic therapy of metastatic pancreatic adenocarcinoma: Current status, challenges, and opportunities. Cancers (Basel) 14(11), 2588 (2022).","journal-title":"Cancers (Basel)"},{"key":"18669_CR5","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1056\/NEJMoa1011923","volume":"364","author":"T Conroy","year":"2011","unstructured":"Conroy, T. et al. FOLFIRINOX versus gemcitabine for metastatic pancreas cancer. N. Engl. J. Med. 364, 1817\u20131825 (2011).","journal-title":"N. Engl. J. Med."},{"key":"18669_CR6","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1111\/cas.12501","volume":"105","author":"T Okusaka","year":"2014","unstructured":"Okusaka, T. et al. Phase II study of FOLFIRINOX for chemotherapy na\u00efve Japanese patients with metastatic pancreatic cancer. 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The other authors declare no potential conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15574"}}