{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:16:33Z","timestamp":1792196193632,"version":"4.4.0"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Paclitaxel and nanoparticle albumin\u2010bound (nab)\u2010paclitaxel can cause early, extremely severe neutropenia, occasionally leading to fatal outcomes. As paclitaxel is a substrate of P\u2010glycoprotein, this study aimed to investigate the impact of <jats:italic>ABCB1<\/jats:italic> single\u2010nucleotide variants, which encode P\u2010glycoprotein, on early, extremely severe neutropenia in patients receiving paclitaxel\/nab\u2010paclitaxel plus ramucirumab as second\u2010line therapy for unresectable advanced\/recurrent gastric cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed patients treated at Aichi Cancer Center Hospital from January 2018 to August 2023, with DNA samples stored in the Cancer BioBank Aichi. The impact of <jats:italic>ABCB1<\/jats:italic> variants T1236C (rs1128503), G2677T\/A (rs2032582) and C3435T (rs1045642) on early, extremely severe neutropenia was examined. Neutropenia was defined as a decline in neutrophil count to &lt;100\/\u03bcL within 28\u2009days of therapy initiation. Firth's logistic regression evaluated the association between the <jats:italic>ABCB1<\/jats:italic> C3435T (rs1045642) TT genotype and early, extremely severe neutropenia, adjusted for age, sex, baseline neutrophil count, and serum albumin and aspartate aminotransferase levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 203 eligible patients, 5 (2%) experienced neutropenia with neutrophil counts of &lt;100\/\u03bcL. The odds ratio for neutrophil counts of &lt;100\/\u03bcL was 28.1 (95% confidence interval 2.8\u2013283.3) in patients with the <jats:italic>ABCB1<\/jats:italic> C3435T (rs1045642) TT genotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:italic>ABCB1<\/jats:italic> C3435T (rs1045642) TT genotype was significantly associated with early, extremely severe neutropenia in patients receiving paclitaxel\/nab\u2010paclitaxel. Evaluating this genotype status may help predict those at increased risk for early, extremely severe neutropenia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16359","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T01:08:07Z","timestamp":1733188087000},"page":"1216-1222","source":"Crossref","is-referenced-by-count":4,"title":["Impact of <i>ABCB1<\/i> single\u2010nucleotide variants on early, extremely severe neutropenia induced by paclitaxel\/nanoparticle albumin\u2010bound paclitaxel in patients with gastric cancer"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0709-3911","authenticated-orcid":false,"given":"Akimitsu","family":"Maeda","sequence":"first","affiliation":[{"name":"Department of Pharmacy Aichi Cancer Center Hospital  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keitaro","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Prevention Aichi Cancer Center  Nagoya Aichi Japan"},{"name":"Division of Cancer Epidemiology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Function Analysis Kanazawa University Graduate School of Medical Sciences  Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010ichi","family":"Morishige","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Function Analysis Kanazawa University Graduate School of Medical Sciences  Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Muro","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology Aichi Cancer Center Hospital  Nagoya Aichi 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