title: Phase I dose-escalation study of cyclophosphamide combined with bortezomib and dexamethasone in Japanese patients with relapsed and/or refractory multiple myeloma.
abstract: The present study was conducted to determine the recommended dose (RD) of cyclophosphamide (CPM) in the CBD regimen, a triplet combination of CPM, bortezomib (BTZ), and dexamethasone (Dex), for relapsed and/or refractory multiple myeloma (RRMM). Patients received intravenous CPM on days 1 and 8 at one of three dose levels: 300, 400, or 500 mg/m(2), with dose escalation in a 3 + 3 design. BTZ at 1.3 mg/m(2) was given twice weekly in 3-week cycles, with Dex at 20 mg/m(2) on the day of and day after BTZ. Of 16 patients enrolled, 15 eligible patients were allocated to the study. Dose-limiting toxicities (DLTs) were seen in two patients: one in dose level 1 with increased γ-GTP and the other in dose level 3 with increased γ-GTP and ALT. Both patients spontaneously recovered from DLT. Neither therapy-related mortality nor severe adverse events were reported during the study. Therefore, the RD of CPM was determined as 500 mg/m(2). Overall, 2 (13.3 %), 1 (6.7 %), and 8 (53.3 %) patients achieved CR, VGPR, and PR, respectively. The regimen was well tolerated and showed promising activity in patients with RRMM.
authors: Division of Hematology and Oncology, Toyohashi Municipal Hospital, 50 Hachiken-nishi, Aotake-cho, Toyohashi, 441-8570, Japan. i-sugiura@med.email.ne.jp.
authors: Isamu
authors: I
authors: Sugiura
authors: Division of Hematology and Oncology, Toyohashi Municipal Hospital, 50 Hachiken-nishi, Aotake-cho, Toyohashi, 441-8570, Japan.
authors: Satomi
authors: S
authors: Terabe
authors: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Tomohiro
authors: T
authors: Kinoshita
authors: Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan.
authors: Kazuhito
authors: K
authors: Yamamoto
authors: Department of Hematology, Anjo Kosei Hospital, Anjo, Japan.
authors: Masashi
authors: M
authors: Sawa
authors: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
authors: Yukiyasu
authors: Y
authors: Ozawa
authors: Department of Hematopoietic Stem Cell Transplantation Data Management/Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yoshiko
authors: Y
authors: Atsuta
authors: Department of Hematopoietic Stem Cell Transplantation Data Management/Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Ritsuro
authors: R
authors: Suzuki
authors: Tokai Central Hospital, Kakamigahara, Japan.
authors: Kazuyuki
authors: K
authors: Shimizu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*
chemical_list: D000069286:Bortezomib; D003907:Dexamethasone; D003520:Cyclophosphamide
keywords: CBD regimen; Cyclophosphamide; Multiple myeloma; Recommended dose