title: Therapy with bortezomib plus dexamethasone induces osteoblast activation in responsive patients with multiple myeloma.
abstract: Bortezomib is a novel proteasome inhibitor that has shown marked antitumor effects in patients with multiple myeloma (MM). We evaluated the feasibility and efficacy of bortezomib plus dexamethasone (BD) therapy and assessed bone metabolism in relapsed or refractory MM. Fourteen patients received 1.3 mg/m2 bortezomib on days 1, 4, 8, and 11 along with 20 mg/dose of dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 in a 21-day cycle. After 1 to 3 cycles of BD therapy, 9 patients (64%) achieved an objective response (5 very good partial responses and 4 partial responses). Notably, a rapid increase in the serum concentration of alkaline phosphatase (ALP) was observed in 6 of the treatment-responsive patients. Moreover, serum levels of bone-formation markers (bone-specific ALP and osteocalcin) significantly increased in 5 and 2 responsive patients, respectively. Radiographic examination showed improvement in bone lesions, suggesting that BD therapy induces osteoblast activation in responders. Adverse events included thrombocytopenia of grades 1 to 3, peripheral neuropathy of grades 1 to 2, and grade 3 ileus and were transient and manageable. Although severe lung injury has been reported among Japanese patients treated with bortezomib, no pulmonary complications were observed during BD therapy. Our results suggest that BD therapy is a safe and promising therapeutic approach for Japanese patients with MM.
authors: Department of Medicine and Bioregulatory Sciences, The University of Tokushima Graduate School of Health Biosciences, Kuramoto, Tokushima, Japan. ozakishu@clin.med.tokushima-u.ac.jp
authors: Shuji
authors: S
authors: Ozaki
authors: Osamu
authors: O
authors: Tanaka
authors: Shiro
authors: S
authors: Fujii
authors: Yuri
authors: Y
authors: Shigekiyo
authors: Hirokazu
authors: H
authors: Miki
authors: Masahito
authors: M
authors: Choraku
authors: Kumiko
authors: K
authors: Kagawa
authors: Jin
authors: J
authors: Asano
authors: Kyoko
authors: K
authors: Takeuchi
authors: Ken-ichi
authors: K
authors: Kitazoe
authors: Toshihiro
authors: T
authors: Hashimoto
authors: Masahiro
authors: M
authors: Abe
authors: Toshio
authors: T
authors: Matsumoto
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity; D001842:Bone and Bones / Q000378:metabolism; D001897:Boronic Acids / Q000008:administration & dosage* / Q000633:toxicity; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy*; D010006:Osteoblasts / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D011480:Protease Inhibitors / Q000627:therapeutic use / Q000633:toxicity; D011719:Pyrazines / Q000008:administration & dosage* / Q000633:toxicity; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone