title: Phase 1 study of bortezomib in combination with melphalan and dexamethasone in Japanese patients with relapsed AL amyloidosis.
abstract: We performed a phase 1 study to evaluate the safety and feasibility of bortezomib (BOR) with melphalan and dexamethasone (BMD) in patients with light chain amyloidosis (AL) without severe cardiac failure. Patients received BOR on a twice-weekly schedule (days 1, 4, 8, and 11 of 28-day treatment cycles) at planned doses of 1.0 (dose level 1) and 1.3 (dose level 2) mg/m(2) in combination with melphalan 8 mg/m(2) on days 1-4 and dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12. Dose-limiting toxicity (DLT) was evaluated at the end of cycle one, and treatment was continued for four cycles. Six patients were enrolled at dose level 1, and one showed DLT (grade 3: herpes zoster). Further 3 patients were enrolled at dose level 2, and none experienced DLT. Thus, the maximum tolerated dose was defined as BOR doses of 1.3 mg/m(2) for the twice-weekly schedule. A total of 32 cycles of BMD therapy were given, and the most common hematologic toxicity was thrombocytopenia (47%). Peripheral neuropathy was the most common non-hematologic toxicity (16%). We demonstrated that BMD is safe and tolerable for Japanese AL patients without severe cardiac damage.
  
  
  BACKGROUND
  UMIN000006604.
authors.affiliation: Department of Hematology, Japan Community Healthcare Organization, Kyoto Kuramaguchi Medical Center, Kyoto, Japan. shimazaki-chihiro@kyoto.jcho.go.jp.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shimazaki
authors.affiliation: Department of Hematology, Japan Community Healthcare Organization, Kyoto Kuramaguchi Medical Center, Kyoto, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Fuchida
authors.affiliation: Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan.
authors.forename: Kenshi
authors.initials: K
authors.lastname: Suzuki
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 Nephrology and Rheumatology, Aichi Medical University School of Medicine, Nagakute, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Imai
authors.affiliation: Department of Hematology, National Hospital Organization Nishigunma National Hospital, Shibukawa, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Sawamura
authors.affiliation: Department of Hematology, Kanazawa University School of Medicine, Kanazawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamatsu
authors.affiliation: Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Abe
authors.affiliation: Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Department of Hematology, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hata
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Neurology, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000188:drug therapy*; D000069286:Bortezomib / Q000008:administration & dosage*; D003907:Dexamethasone / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000009:adverse effects*; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000069286:Bortezomib; D003907:Dexamethasone; D008558:Melphalan
keywords: AL amyloidosis; Bortezomib; Dexamethasone; Melpahaln