{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:55:17Z","timestamp":1788843317659,"version":"build-2803163510"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,7,12]],"date-time":"2017-07-12T00:00:00Z","timestamp":1499817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The Evaluating Nilotinib Efficacy and Safety in Clinical Trials\u2013Extending Molecular Responses (<jats:styled-content style=\"fixed-case\">ENEST<\/jats:styled-content>xtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose\u2010optimization strategies on patient outcomes. The <jats:styled-content style=\"fixed-case\">ENEST<\/jats:styled-content>xtnd protocol allowed nilotinib dose escalation (from 300 to 400\u00a0mg twice daily) in the case of suboptimal response or treatment failure as well as dose re\u2010escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in <jats:styled-content style=\"fixed-case\">ENEST<\/jats:styled-content>xtnd, 70\u00b78% (95% confidence interval, 66\u00b72\u201375\u00b71%) achieved 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\u00a0<\/jats:italic>\u2264<jats:italic>\u00a0<\/jats:italic>0\u00b71% on the International Scale) by 12\u00a0months (primary endpoint). By 24\u00a0months, 81\u00b70% of patients achieved major molecular response, including 63\u00b76% (56 of 88) of those with dose escalations for lack of efficacy and 74\u00b73% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re\u2010escalation). The safety profile of nilotinib was consistent with prior studies. The most common non\u2010haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4\u00b75% of patients (grade 3\/4, 3\u00b71%). The study was registered at clinicaltrials.gov (NCT01254188).<\/jats:p>","DOI":"10.1111\/bjh.14829","type":"journal-article","created":{"date-parts":[[2017,7,12]],"date-time":"2017-07-12T10:22:57Z","timestamp":1499854977000},"page":"219-228","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Nilotinib dose\u2010optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from <scp>ENEST<\/scp>xtnd"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0910-3730","authenticated-orcid":false,"given":"Timothy P.","family":"Hughes","sequence":"first","affiliation":[{"name":"South Australian Health and Medical Research Institute (SAHMRI) University of Adelaide SA Pathology Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Munhoz","sequence":"additional","affiliation":[{"name":"Hospital Erasto Gaertner \u2013 Liga Paranaense Combate ao C\u00e2ncer Curitiba Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Aurelio Salvino","sequence":"additional","affiliation":[{"name":"Hospital S\u00e3o Rafael\u2010Monte Tabor &amp; Hospital Universitario Professor Edgard Santos\u2010Universidade Federal da Bahia Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tee Chuan","family":"Ong","sequence":"additional","affiliation":[{"name":"Hospital Ampang Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Elhaddad","sequence":"additional","affiliation":[{"name":"National Cancer Institute Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"Shortt","sequence":"additional","affiliation":[{"name":"School of Clinical Sciences at Monash Health Monash University Clayton Vic. 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