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To clarify whether a lower initial dose of bosutinib (i.e., starting at 200\u00a0mg) would reduce rates of discontinuation due to DRTs, we conducted a phase 2 study of BOsutinib Gradual Increase (BOGI trial, UMIN 000032282) as a second\/third-line treatment for chronic myeloid leukemia (CML). Between February 4, 2019 and May 24, 2022, 35 patients were enrolled. The rate of bosutinib discontinuation at 12\u00a0months was 25.7% vs. 35.9% in a historical control study (Japanese phase 1\/2 study) (<jats:italic>p<\/jats:italic>\u2009=\u20090.102). The rate of bosutinib discontinuation due to DRTs was significantly lower, at 11.4% vs. 28.2% (<jats:italic>p<\/jats:italic>\u2009=\u20090.015). The incidence of grade 3\/4 transaminase elevation was 20% vs. 29% (<jats:italic>p<\/jats:italic>\u2009=\u20090.427), while the incidence of diarrhea was 3% vs. 25% (<jats:italic>p<\/jats:italic>\u2009=\u20090.009). The median dose intensity of bosutinib was higher (391.7\u00a0mg\/day vs. 353.9\u00a0mg\/day). Pharmacokinetic analysis of bosutinib showed that patients who achieved a major molecular response tended to have high trough concentrations. Thus, a low initial dose of bosutinib followed by dose escalation reduced discontinuation due to severe DRTs while maintaining high dose intensity and efficacy.<\/jats:p>","DOI":"10.1007\/s12185-024-03830-z","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T12:02:21Z","timestamp":1723550541000},"page":"492-500","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A lower initial dose of bosutinib for patients with chronic myeloid leukemia patients resistant and\/or intolerant to prior therapy: a single-arm, multicenter, phase 2 trial (BOGI trial)"],"prefix":"10.1007","volume":"120","author":[{"given":"Hiroshi","family":"Ureshino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-3787","authenticated-orcid":false,"given":"Naoto","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ikezoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Kameoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyasu","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Ichinohe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Takamori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatomo","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"3830_CR1","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1056\/NEJMoa1609324","volume":"376","author":"A Hochhaus","year":"2017","unstructured":"Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, et al. 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T. Ikezoe received honoraria from Pfizer, Otsuka Pharmaceuticals and Novartis, and research funding from Pfizer, Novartis and Otsuka Pharmaceuticals. T. Ichinohe received honoraria from Novaritis. Shinya Kimura received honoraria from Pfizer, Otsuka Pharmaceuticals, Novartis and Bristol-Myers-Squibb, and research funding from Pfizer, Bristol-Myers-Squibb and Ohara Pharmaceuticals. All other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}