{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:47:48Z","timestamp":1785926868914,"version":"3.56.0"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T00:00:00Z","timestamp":1521936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002551","name":"Seoul National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002551","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002551","name":"Seoul National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002551","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Radotinib is a second\u2010generation <jats:italic><jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ABL<\/jats:styled-content>1<\/jats:italic> tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia in chronic phase (<jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content>). Here, using the data from a Phase 3 study conducted in patients with newly diagnosed <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content>, the dose\u2013efficacy as well as dose\u2013safety relationship analyses were performed to determine a safe and effective initial dosage regimen of radotinib. A significant positive association was detected between the starting dose of radotinib adjusted for body weight (Dose\/<jats:styled-content style=\"fixed-case\">BW<\/jats:styled-content>) and the probability of dose\u2010limiting toxicity (\u2265grade 3 hematologic and nonhematologic toxicity) (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.003). In contrast, a significant inverse association was discovered between Dose\/<jats:styled-content style=\"fixed-case\">BW<\/jats:styled-content> and the probability of major molecular response (<jats:italic><jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">ABL<\/jats:styled-content>1\/<jats:styled-content style=\"fixed-case\">ABL<\/jats:styled-content>1\u00a0<\/jats:italic>\u2264<jats:italic>\u00a0<\/jats:italic>0.1%) when controlled for sex (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.033). Moreover, frequent dose interruptions and reductions secondary to radotinib toxicities occurred in the Phase 3 study, resulting in nearly half (44%) of patients receiving a reduced dose at a 12\u2010month follow\u2010up. In conclusion, the results of this study demonstrate the need for initial radotinib dose attenuation to improve the long\u2010term efficacy and safety of radotinib. Hence, the authors suggest a new upfront radotinib dose of 400\u00a0mg once daily be tested in patients with newly diagnosed <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CML<\/jats:styled-content>.<\/jats:p>","DOI":"10.1002\/cam4.1436","type":"journal-article","created":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T03:18:03Z","timestamp":1522034283000},"page":"1766-1773","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Determination of a radotinib dosage regimen based on dose\u2013response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia"],"prefix":"10.1002","volume":"7","author":[{"given":"Hayeon","family":"Noh","sequence":"first","affiliation":[{"name":"Department of Pharmacy College of Pharmacy Yonsei University  Incheon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Young","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Pharmacy College of Pharmacy Seoul National University  Seoul Korea"},{"name":"Research Institute of Pharmaceutical Sciences Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Yong","family":"Kwak","sequence":"additional","affiliation":[{"name":"Chonbuk National University Medical School &amp; Hospital  Jeonju Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung\u2010Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Dong\u2010A University College of Medicine  Busan Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk Joong","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Young","family":"Zang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Hallym University Sacred Heart Hospital  Anyang Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy College of Pharmacy Seoul National University  Seoul Korea"},{"name":"Research Institute of Pharmaceutical Sciences Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Lin","family":"Park","sequence":"additional","affiliation":[{"name":"Central Research Institute IL\u2010YANG Pharmaceutical Co., Ltd.  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Yongin Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Rok","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Medicine Dongsan Medical Center Keimyung University  Daegu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Wook","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul St. Mary's Hospital Leukemia Research Institute The Catholic University of Korea  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5565-8323","authenticated-orcid":false,"given":"Jangik I.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy College of Pharmacy Seoul National University  Seoul Korea"},{"name":"Research Institute of Pharmaceutical Sciences Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055229"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022457"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055104"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-10-116475"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-036012"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-1200-7"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2008.26.15_suppl.3590"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp605"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0108-z"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.58"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-009-0315-4"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn168"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2012.02253.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21274"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-009-0263-z"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.045666"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2015.1113278"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.096776"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-0957"},{"key":"e_1_2_7_21_1","unstructured":"Common Terminology Criteria for Adverse Events v3.0 (CTCAE). 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