Incidence of and risk factors for severe neutropenia during treatment with the modified FOLFIRINOX therapy in patients with advanced pancreatic cancer

• Published in: Scientific reports 2022-09, Vol.12 (1), p.15574-9, Article 15574
• Main Authors: Irisawa, Ai, Takeno, Misaki, Watanabe, Kazuo, Takahashi, Hideaki, Mitsunaga, Shuichi, Ikeda, Masafumi
• Format: Article
• Language: English
• Subjects: 692/4020; 692/4028; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Clinical medicine; Fluorouracil - adverse effects; Heterozygosity; Humanities and Social Sciences; Humans; Incidence; Irinotecan; Irinotecan - adverse effects; Leucovorin - adverse effects; Metastases; multidisciplinary; Multivariate analysis; Neutropenia; Neutropenia - chemically induced; Neutropenia - drug therapy; Neutropenia - epidemiology; Oxaliplatin; Oxaliplatin - adverse effects; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - pathology; Patients; Polymorphism; Retrospective Studies; Risk Factors; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-18669-9

Although FOLFIRINOX ( l -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 ≥ Grade 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), 3.27–111.14; p  = 0.002) and presence of heterozygosity for UGT1A1 *28 or UGT1A1 *6 polymorphism (OR, 2.84; 95% CI, 1.18–7.17; p  = 0.023) 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 UGT1A1 *28 or UGT1A1 *6 polymorphism.