{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:44:35Z","timestamp":1783593875958,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,9,24]],"date-time":"2016-09-24T00:00:00Z","timestamp":1474675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/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":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:p>Sonidegib is a selective inhibitor of Smoothened receptor, which is a key regulator of the Hedgehog signaling pathway. The purpose of this study was to determine the maximum tolerated dose based on dose\u2010limiting toxicity (<jats:styled-content style=\"fixed-case\">DLT<\/jats:styled-content>) and the recommended dose (<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>) of sonidegib in Asian patients with advanced solid tumors. This was an open\u2010label, single\u2010arm, multicenter, two\u2010group, parallel, dose\u2010escalation, phase I study undertaken in Asian patients; group 1 included patients from Japan and group 2 included patients from Hong Kong and Taiwan. Dose escalation was guided by a Bayesian logistic regression model dependent on <jats:styled-content style=\"fixed-case\">DLT<\/jats:styled-content>s in cycle 1 and other safety findings. A total of 45 adult Asian patients with confirmed advanced solid tumors were enrolled. Group 1 included 21 patients (12 treated with 400 mg q.d. [once daily] and 9 treated with 600 mg q.d.) and group 2 included 24 patients (12 treated with 400 mg q.d., 8 treated with 600 mg q.d., and 4 treated with 800 mg q.d.). Elevation in creatine kinase was the <jats:styled-content style=\"fixed-case\">DLT<\/jats:styled-content> in both groups. The most common adverse events suspected to be related to sonidegib in both patient groups were increase in creatine kinase levels, myalgia, fatigue, and abnormal hepatic function. The <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content> of 400 mg q.d. was defined in both groups. Difference in tolerability was noted between the East Asian patients and Western population. The <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content> in East Asian patients (400 mg q.d.) was lower than in patients from Europe and the USA (800 mg q.d. and 250 mg twice daily). (Registered with <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/Clinicaltrials.gov\">Clinicaltrials.gov<\/jats:ext-link>: <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>01208831.)<\/jats:p>","DOI":"10.1111\/cas.13022","type":"journal-article","created":{"date-parts":[[2016,7,28]],"date-time":"2016-07-28T15:45:40Z","timestamp":1469720740000},"page":"1477-1483","source":"Crossref","is-referenced-by-count":16,"title":["Phase I, multicenter, open\u2010label, dose\u2010escalation study of sonidegib in Asian patients with advanced solid tumors"],"prefix":"10.1111","volume":"107","author":[{"given":"Hironobu","family":"Minami","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Hematology Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology 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