{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T14:31:34Z","timestamp":1768401094837,"version":"3.49.0"},"reference-count":15,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T00:00:00Z","timestamp":1538611200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:p>Prexasertib is a novel inhibitor of checkpoint kinase 1. The primary objective of this study was to evaluate prexasertib tolerability in Japanese patients with advanced solid tumors. This nonrandomized single\u2010arm open\u2010label phase 1 study of prexasertib consisted of 2 dose levels, 80\u00a0mg\/m<jats:sup>2<\/jats:sup> and the global\u2010recommended dose based on a US study of 105\u00a0mg\/m<jats:sup>2<\/jats:sup>, administered intravenously once every 14\u00a0days (n<jats:italic>\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>6 for each dose). Transition to the higher dose proceeded if the frequency of dose\u2010limiting toxicity observed in cycle 1 was &lt;33% at the lower dose. Safety measures, pharmacokinetics and antitumor activity were assessed. A total of 12 patients were treated. Two patients, one in each dose group, experienced dose\u2010limiting toxicities of febrile neutropenia, one grade 4 and the other grade 3; both patients recovered and continued the study treatment. The grade 4 treatment\u2010emergent adverse events related to study treatment were neutropenia (6 patients [50.0%]), leukopenia (4 patients [33.3%]), and 1 instance each (8.3%) of anemia, febrile neutropenia and thrombocytopenia. Neutropenia was generally transient and reversible; 11 patients (91.7%) required granulocyte colony\u2010stimulating factor treatment during the study. There were no discontinuations due to adverse events or deaths. The prexasertib pharmacokinetics displayed dose\u2010independent and time\u2010independent behavior across both dose levels, similar to the profile observed in the US\u2010based phase 1 study. Eight patients had a best overall response of stable disease. These data are consistent with the known safety profile for prexasertib and confirm its tolerability in Japanese patients with advanced solid tumors.<\/jats:p>","DOI":"10.1111\/cas.13750","type":"journal-article","created":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T22:55:44Z","timestamp":1532472944000},"page":"3216-3223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Dose\u2010finding study of the checkpoint kinase 1 inhibitor, prexasertib, in Japanese patients with advanced solid tumors"],"prefix":"10.1111","volume":"109","author":[{"given":"Satoru","family":"Iwasa","sequence":"first","affiliation":[{"name":"National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noboru","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohei","family":"Shitara","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital East Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3514-9927","authenticated-orcid":false,"given":"Kenji","family":"Tamura","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuaki","family":"Matsubara","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital East Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaomi","family":"Tajimi","sequence":"additional","affiliation":[{"name":"Eli Lilly Japan K.K. Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aimee B.","family":"Lin","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroya","family":"Asou","sequence":"additional","affiliation":[{"name":"Eli Lilly Japan K.K. Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihong","family":"Cai","sequence":"additional","affiliation":[{"name":"Eli Lilly Japan K.K. Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Eli Lilly Japan K.K. Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Shibasaki","sequence":"additional","affiliation":[{"name":"Eli Lilly Japan K.K. Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanako","family":"Saito","sequence":"additional","affiliation":[{"name":"Eli Lilly Japan K.K. Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Takai","sequence":"additional","affiliation":[{"name":"Eli Lilly Japan K.K. Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2042-6829","authenticated-orcid":false,"given":"Toshihiko","family":"Doi","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital East Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-14-1037"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.10.005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0083"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-014-2380-5"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.57.5027"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-016-0368-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1782"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.5788"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2876"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.22195"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0352"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30009-3"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-013-2234-6"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2011.29.15_suppl.3033"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-014-0114-5"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.13750","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.13750","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T20:56:16Z","timestamp":1694811376000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.13750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10]]},"references-count":15,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1111\/cas.13750"],"URL":"https:\/\/doi.org\/10.1111\/cas.13750","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10]]},"assertion":[{"value":"2018-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}