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Safety, pharmacokinetics and pharmacodynamics of carfilzomib were examined in phase 1. The primary endpoint in phase 2 was the overall response rate (<jats:styled-content style=\"fixed-case\">ORR<\/jats:styled-content>). Carfilzomib was administered in a twice\u2010weekly, consecutive\u2010day dosing schedule. In Phase 1, doses of 15 or 20\u00a0mg\/m<jats:sup>2<\/jats:sup> were administered on this schedule or 20\u00a0mg\/m<jats:sup>2<\/jats:sup> on Days 1 and 2 of Cycle 1 and then 27\u00a0mg\/m<jats:sup>2<\/jats:sup> in the 20\/27\u00a0mg\/m<jats:sup>2<\/jats:sup> cohort. Patients had a median of five prior therapies, including bortezomib and an immunomodulatory agent. The dose level did not reach the maximum tolerated dose. The most common adverse events were haematological. Notably, carfilzomib either induced new hypertension (<jats:italic>n<\/jats:italic>\u00a0=\u00a04) or aggravated previously existing hypertension (<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>6) in 10 of 50 patients. Four of the eight patients who previously experienced peripheral neuropathy (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>) experienced a recurrence with carfilzomib use, but no new cases of <jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content> occurred. The <jats:styled-content style=\"fixed-case\">ORR<\/jats:styled-content> of the 20\/27\u00a0mg\/m<jats:sup>2<\/jats:sup> 40 patient cohort was similar to that in the pivotal <jats:styled-content style=\"fixed-case\">US<\/jats:styled-content> study. The dose was efficacious and tolerable in heavily pre\u2010treated Japanese patients; however, meticulous control of hypertension may be necessary for further carfilzomib use.<\/jats:p>","DOI":"10.1111\/bjh.13900","type":"journal-article","created":{"date-parts":[[2016,1,6]],"date-time":"2016-01-06T03:07:47Z","timestamp":1452049667000},"page":"745-756","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A phase 1\/2 study of carfilzomib in Japanese patients with relapsed and\/or refractory multiple myeloma"],"prefix":"10.1111","volume":"172","author":[{"given":"Takashi","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Haematology National Cancer Centre Hospital Tokyo Japan"},{"name":"Department of Haematology Komaki City Hospital Komaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kensei","family":"Tobinai","sequence":"additional","affiliation":[{"name":"Department of Haematology National Cancer Centre Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morio","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Haematology National Hospital Organization Nishigunma National Hospital Shibukawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Haematology Japanese Red Cross Medical Centre Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazutaka","family":"Sunami","sequence":"additional","affiliation":[{"name":"Department of Haematology National Hospital Organization Okayama Medical Centre Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadao","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Rheumatology and Clinical Immunology Sapporo Medical University School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoshi","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology Tokai University School of Medicine Isehara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaaki","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Niigata Cancer Centre Hospital Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Haematology Tokushima Prefectural Central Hospital Tokushima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Taniwaki","sequence":"additional","affiliation":[{"name":"Division of Haematology and Oncology Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naokuni","family":"Uike","sequence":"additional","affiliation":[{"name":"Department of Haematology National Hospital Organization Kyushu Cancer Centre Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirohiko","family":"Shibayama","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology Osaka University Graduate School of Medicine Suita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyohiko","family":"Hatake","sequence":"additional","affiliation":[{"name":"Department of Haematology and Oncology The Cancer Institute Hospital of Japanese Foundation for Cancer Research Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Izutsu","sequence":"additional","affiliation":[{"name":"Department of Haematology Toranomon Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Haematology Kobe City Medical Centre General Hospital Kobe 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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