{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T14:05:49Z","timestamp":1765807549701,"version":"3.37.3"},"reference-count":28,"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\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","award":["CAMN107AKR11T"],"award-info":[{"award-number":["CAMN107AKR11T"]}],"id":[{"id":"10.13039\/100008272","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":"Abstract<\/jats:title>Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AE<\/jats:styled-content>s) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML<\/jats:styled-content>\u2010CP<\/jats:styled-content>). We investigated the 2\u2010year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNC<\/jats:styled-content>s). In this open\u2010label, multi\u2010institutional phase 4 study, 110 Philadelphia chromosome\u2010positive CML<\/jats:styled-content>\u2010CP<\/jats:styled-content> patients were treated with nilotinib at a starting dose of 300\u00a0mg twice daily. Molecular responses (MR<\/jats:styled-content>s) and AE<\/jats:styled-content>s were monitored for up to 24\u00a0months. The 24\u2010month cumulative MR<\/jats:styled-content>4.5<\/jats:sup> rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNC<\/jats:styled-content>s, and the per\u2010patient mean was used to categorize them into four mean PNC<\/jats:styled-content> (MPNC<\/jats:styled-content>) groups. Cumulative MR<\/jats:styled-content> rates and safety were compared between groups. With a median follow\u2010up of 22.2\u00a0months, the 24\u2010month cumulative MR<\/jats:styled-content>4.5<\/jats:sup> rate was 56.2% (95% confidence interval, 44.0%\u20138.3%), and the median time to MR<\/jats:styled-content>4.5<\/jats:sup> was 23.3\u00a0months. There were no significant differences in the cumulative rates of major molecular response, MR<\/jats:styled-content>4<\/jats:sup>, and MR<\/jats:styled-content>4.5<\/jats:sup> between MPNC<\/jats:styled-content> groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC<\/jats:styled-content> groups, there was no significant linear trend in the frequency of AE<\/jats:styled-content>s. Nilotinib is highly effective for the treatment of CML<\/jats:styled-content>\u2010CP<\/jats:styled-content> with manageable AE<\/jats:styled-content>s. The measurement of PNC<\/jats:styled-content> has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT<\/jats:styled-content>03332511.<\/jats:p>","DOI":"10.1002\/cam4.1450","type":"journal-article","created":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T03:18:34Z","timestamp":1522034314000},"page":"1814-1823","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome\u2010positive chronic myeloid leukemia in chronic phase: ENESTK<\/scp>orea"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6834-7217","authenticated-orcid":false,"given":"Junghoon","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Seoul National University Hospital Cancer Research Institute Seoul National University College of Medicine Seoul 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