title: Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events.
abstract: BACKGROUND
  To establish the clinical use of bortezomib with fewer adverse events, we retrospectively analyzed the efficacy and safety of bortezomib plus dexamethasone (BD) therapy for relapsed or refractory multiple myeloma.
  
  
  METHODS
  Patients received bortezomib (1.3 mg/m2) as an intravenous bolus on days 1, 4, 8 and 11 in a 3-week cycle (twice-weekly administration), or on days 1, 8, 15 and 22 in a 5-week cycle (once-weekly administration). Dexamethasone (20 mg) was given on the day of and day after bortezomib treatment.
  
  
  RESULTS
  From January 2007 to July 2010, 22 patients began to receive BD therapy. Initially, bortezomib was administered twice-weekly, but some severe adverse events developed; therefore, from January 2008, bortezomib was administered twice-weekly for the first two courses, followed by once-weekly for the subsequent courses. Patients who were expected to have severe adverse events beforehand were treated initially with once-weekly administration. Of the 22 patients, 14 were treated with twice-weekly followed by once-weekly administration, five with only twice-weekly administration and three with only once-weekly administration. Seventeen patients (77.3%) achieved at least partial response, including three with complete response and seven with very good partial response. The median progression-free survival and the median overall survival of 22 patients were 512 days and not reached, respectively. The median progression-free survival and the median overall survival of 17 patients who received at least one course of once-weekly administration were 615 days and not reached, respectively. The most frequent ≥grade 3 adverse events with twice-weekly administration were gastrointestinal, especially paralytic ileus and constipation. Among seven patients who developed ≥grade 3 gastrointestinal adverse events with twice-weekly administration, all four patients changed the schedule to once-weekly were able to continue BD therapy.
  
  
  CONCLUSIONS
  Once-weekly administration of bortezomib in BD therapy may reduce the incidence of gastrointestinal adverse events without reducing the clinical efficacy of this therapy for refractory or relapsed multiple myeloma.
authors: Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan. tfukus@kanazawa-med.ac.jp
authors: Toshihiro
authors: T
authors: Fukushima
authors: Takuji
authors: T
authors: Nakamura
authors: Haruka
authors: H
authors: Iwao
authors: Akio
authors: A
authors: Nakajima
authors: Miyuki
authors: M
authors: Miki
authors: Tomomi
authors: T
authors: Sato
authors: Tomoyuki
authors: T
authors: Sakai
authors: Toshioki
authors: T
authors: Sawaki
authors: Yoshimasa
authors: Y
authors: Fujita
authors: Masao
authors: M
authors: Tanaka
authors: Yasufumi
authors: Y
authors: Masaki
authors: Hideo
authors: H
authors: Nakajima
authors: Yoshiharu
authors: Y
authors: Motoo
authors: Hisanori
authors: H
authors: Umehara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone