title: A phase 1/2 study of carfilzomib in Japanese patients with relapsed and/or refractory multiple myeloma.
abstract: We conducted a phase 1/2 study of single-agent carfilzomib in Japanese patients with relapsed/refractory multiple myeloma. Safety, pharmacokinetics and pharmacodynamics of carfilzomib were examined in phase 1. The primary endpoint in phase 2 was the overall response rate (ORR). Carfilzomib was administered in a twice-weekly, consecutive-day dosing schedule. In Phase 1, doses of 15 or 20 mg/m(2) were administered on this schedule or 20 mg/m(2) on Days 1 and 2 of Cycle 1 and then 27 mg/m(2) in the 20/27 mg/m(2) 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 (n = 4) or aggravated previously existing hypertension (n = 6) in 10 of 50 patients. Four of the eight patients who previously experienced peripheral neuropathy (PN) experienced a recurrence with carfilzomib use, but no new cases of PN occurred. The ORR of the 20/27 mg/m(2) 40 patient cohort was similar to that in the pivotal US study. The dose was efficacious and tolerable in heavily pre-treated Japanese patients; however, meticulous control of hypertension may be necessary for further carfilzomib use.
authors.affiliation: Department of Haematology, National Cancer Centre Hospital, Tokyo, Japan.|Department of Haematology, Komaki City Hospital, Komaki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Haematology, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.affiliation: Department of Haematology, National Hospital Organization Nishigunma National Hospital, Shibukawa, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Haematology, Japanese Red Cross Medical Centre, Tokyo, Japan.
authors.forename: Kenshi
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Haematology, National Hospital Organization Okayama Medical Centre, Okayama, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Sunami
authors.affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Haematology and Oncology, Tokai University School of Medicine, Isehara, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Internal Medicine, Niigata Cancer Centre Hospital, Niigata, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Chou
authors.affiliation: Department of Haematology, Tokushima Prefectural Central Hospital, Tokushima, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Ozaki
authors.affiliation: Division of Haematology 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 Haematology, National Hospital Organization Kyushu Cancer Centre, Fukuoka, Japan.
authors.forename: Naokuni
authors.initials: N
authors.lastname: Uike
authors.affiliation: Department of Haematology and Oncology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Shibayama
authors.affiliation: Department of Haematology and Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.affiliation: Department of Haematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Izutsu
authors.affiliation: Department of Haematology, Kobe City Medical Centre General Hospital, Kobe, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishikawa
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: Tomohisa
authors.initials: T
authors.lastname: Kashihara
authors.affiliation: Department of Haematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D012008:Recurrence
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; C524865:carfilzomib
keywords: cardiovascular AEs; carfilzomib; hypertension peripheral neuropathy; multiple myeloma