{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T06:42:55Z","timestamp":1777099375154,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T00:00:00Z","timestamp":1566172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This open\u2010label, phase I dose\u2010finding study evaluated the gonadotropin\u2010releasing hormone antagonist, TAK\u2010385, in Japanese patients with nonmetastatic prostate cancer. In a two\u2010part design, patients received daily oral TAK\u2010385 at doses of 320 (loading, day 1)\/80 (maintenance, day 2 and thereafter), 320\/120, 320\/160, or 360\/120\u00a0mg for 28\u00a0days in a dose\u2010escalation phase (part A, n\u00a0=\u00a013), and at 320\/80 or 320\/120\u00a0mg for up to 96\u00a0weeks in a randomized expansion phase (part B, n\u00a0=\u00a030). Primary endpoint in both parts was safety, including dose\u2010limiting toxicity in part A. Secondary endpoints included pharmacokinetics, pharmacodynamics, and prostate\u2010specific antigen concentration. Ten (77%) patients in part A and all patients in part B experienced an adverse event; hot flush (part A, n\u00a0=\u00a04; part B, n\u00a0=\u00a015), viral upper respiratory tract infection (part A, n\u00a0=\u00a01; part B, n\u00a0=\u00a010), and diarrhea (part B, n\u00a0=\u00a08) were most frequent. No dose\u2010limiting toxicities were observed (part A). In 12 evaluable patients (part A), TAK\u2010385 was rapidly absorbed after a single loading dose; on day 28 (maintenance dose), median steady\u2010state <jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub> was ~1\u20102\u00a0hours and mean <jats:italic>t<\/jats:italic><jats:sub>1\/2z<\/jats:sub> was 67\u201079\u00a0hours. All doses rapidly reduced testosterone concentrations to castration levels within 1\u00a0week. Durable reductions in prostate\u2010specific antigen of &gt;90% from baseline were observed through 96\u00a0weeks. TAK\u2010385 appeared tolerable and resulted in sustained reductions in testosterone to castration levels at all doses. The lowest loading\/maintenance dose required for a clinical effect was 320\/80\u00a0mg.<\/jats:p><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>: NCT02141659.<\/jats:p>","DOI":"10.1002\/cam4.2442","type":"journal-article","created":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T04:54:45Z","timestamp":1566276885000},"page":"5891-5902","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Phase I trial of TAK\u2010385 in hormone treatment\u2010na\u00efve Japanese patients with nonmetastatic prostate cancer"],"prefix":"10.1002","volume":"8","author":[{"given":"Hiroyoshi","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Urology Toho University Sakura Medical Center Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroji","family":"Uemura","sequence":"additional","affiliation":[{"name":"Department of Urology and Renal Transplantation Yokohama City University Medical Center Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Mizokami","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Graduate School of Medical Sciences Kanazawa University Kanazawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narihiko","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Urology Public University Corporation Yokohama City University Hospital Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhide","family":"Miyoshi","sequence":"additional","affiliation":[{"name":"Department of Urology and Renal Transplantation Yokohama City University Medical Center Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Nagamori","sequence":"additional","affiliation":[{"name":"Department of Urology Incorporated Administrative Agency National Hospital Organization Hokkaido Cancer Center Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Enomoto","sequence":"additional","affiliation":[{"name":"Department of Urology Mitsui Memorial Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideyuki","family":"Akaza","sequence":"additional","affiliation":[{"name":"Department of Strategic Investigation on Comprehensive Cancer Network Interfaculty Initiative in Information Studies\/Graduate School of Interdisciplinary Information Studies The University of Tokyo Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1307-1505","authenticated-orcid":false,"given":"Takayuki","family":"Asato","sequence":"additional","affiliation":[{"name":"Oncology Clinical Research Department Oncology Therapeutic Area Unit for Japan and Asia Takeda Pharmaceutical Company Limited Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadayuki","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Japan Development Center Takeda Pharmaceutical Company Limited Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Urology Graduate School of Medicine National University Corporation Gunma University Maebashi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,19]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"Foundation for Promotion of Cancer Research.Cancer statistics in Japan 2017.https:\/\/ganjoho.jp\/en\/professional\/statistics\/brochure\/2017_en.html. 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