title: Phase I dose escalation study of high dose carfilzomib monotherapy for Japanese patients with relapsed or refractory multiple myeloma.
abstract: We conducted a multicenter, open-label Phase I study of single-agent carfilzomib in Japanese patients with relapsed or refractory multiple myeloma. The primary endpoints were tolerability and safety. Carfilzomib was administrated for 30 min on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. In cycle 1, doses for days 1 and 2 were 20 mg/m2, followed by 45 or 56 mg/m2. Three and four subjects were enrolled in the 20/45 mg/m2cohort and 20/56 mg/m2cohort. No dose-limiting toxicity was observed, and the tolerability of carfilzomib was confirmed. Pyrexia, hypertension, nausea and vomiting were considered as noteworthy adverse events (AE) when carfilzomib was administered at high doses. Moreover, pyrexia, blood creatinine increased, and body weight gain were observed as acute dose effects. These findings suggest that addition of dexamethasone is important to alleviate acute dose effect. The overall response rates of the 20/45 mg/m2and 20/56 mg/m2cohort were 66.7 % (two out of three) and 50 % (two out of four), respectively. Carfilzomib administrated at up to 20/56 mg/m2was well tolerated and seemed active in Japanese patients with relapsed or refractory multiple myeloma.
  
  
  BACKGROUND
  JapicCTI-122020.
authors.affiliation: Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. iida@med.nagoya-cu.ac.jp.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
authors.affiliation: Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.affiliation: Division of Hematology and Oncology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.affiliation: Department of Oncology Clinical Development Planning, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Shumiya
authors.affiliation: Department of Oncology Clinical Development Planning, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Chou
mesh_terms: D044466:Asian People; D003907:Dexamethasone / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005334:Fever / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D020714:Maximum Tolerated Dose; D009101:Multiple Myeloma / Q000188:drug therapy*; D009325:Nausea / Q000139:chemically induced; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D014839:Vomiting / Q000139:chemically induced
chemical_list: D009842:Oligopeptides; C524865:carfilzomib; D003907:Dexamethasone
keywords: Carfilzomib; Dose escalation; Japanese patients; Phase I study; Relapsed or refractory multiple myeloma