{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T06:46:51Z","timestamp":1744181211241,"version":"3.37.3"},"reference-count":11,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T00:00:00Z","timestamp":1536105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013170","name":"Ono Pharmaceutical","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013170","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:p>This open\u2010label multicenter phase 1 study evaluated the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of weekly carfilzomib and dexamethasone (Cd) in Japanese patients with relapsed or refractory multiple myeloma (<jats:styled-content style=\"fixed-case\">RRMM<\/jats:styled-content>). Carfilzomib was administered by 30\u2010minute intravenous infusion on Days 1, 8 and 15 in a 28\u2010day cycle starting at 20\u00a0mg\/m<jats:sup>2<\/jats:sup> on Day 1\/Cycle 1 and 70\u00a0mg\/m<jats:sup>2<\/jats:sup> thereafter until progressive disease or unacceptable toxicity. Dexamethasone 40\u00a0mg was administered on Days 1, 8, 15 and 22 in Cycles 1\u20109 and on Days 1, 8 and 15 thereafter. Six patients were enrolled between March 2015 and June 2015. Patients had received a median of 4.5 (range, 4\u20108) prior regimens; all patients had previous therapies with bortezomib and immunomodulatory drugs. Of the 6\u00a0patients, 1 had a dose\u2010limiting toxicity (<jats:styled-content style=\"fixed-case\">DLT<\/jats:styled-content>), and tolerability was confirmed. The <jats:styled-content style=\"fixed-case\">DLT<\/jats:styled-content> was grade 3 thrombotic microangiopathy, which was considered serious and occurred on Day 11\/Cycle 1. All 6 patients (100%) experienced at least 1 grade \u22653 adverse event (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>). Two patients (33.3%) experienced <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content> (also considered adverse drug reactions) leading to study discontinuation: thrombotic microangiopathy (Day 11\/Cycle 1) and thrombotic thrombocytopenic purpura (Day 6\/Cycle 2). The overall response rate was 83.3% (95% confidence interval, 43.6\u201097.0). The weekly Cd regimen at a carfilzomib dose of 20\/70\u00a0mg\/m<jats:sup>2<\/jats:sup> was well\u2010tolerated among Japanese patients with <jats:styled-content style=\"fixed-case\">RRMM<\/jats:styled-content>. Our results could be the basis for the further development of carfilzomib treatment considering safety profiles including microangiopathy\u2010related events and efficacy.<\/jats:p>","DOI":"10.1111\/cas.13753","type":"journal-article","created":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T07:29:57Z","timestamp":1532935797000},"page":"3245-3252","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Weekly carfilzomib and dexamethasone in Japanese patients with relapsed or refractory multiple myeloma: A phase 1 and <scp>PK<\/scp>\/<scp>PD<\/scp> trial"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0654-6920","authenticated-orcid":false,"given":"Dai","family":"Maruyama","sequence":"first","affiliation":[{"name":"Department of Hematology National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kensei","family":"Tobinai","sequence":"additional","affiliation":[{"name":"Department of Hematology National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaaki","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Niigata Cancer Center Hospital Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Taniwaki","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihisa","family":"Shumiya","sequence":"additional","affiliation":[{"name":"Department of Oncology Clinical Development Planning Ono Pharmaceutical Co., Ltd. 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