title: Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma.
abstract: BACKGROUND
  Bortezomib, a first-in-class proteasome inhibitor, is active with manageable toxicities in relapsed and/or refractory myeloma.
  
  
  METHODS
  Bortezomib 1.0 or 1.3 mg/m2 was administered Days 1, 4, 8, and 11 every 21 days for up to 8 cycles to patients with relapsed and/or refractory myeloma participating in two Phase II trials. Dexamethasone could be added because of progressive disease after 2 cycles or stable disease after 4 cycles. Continuation of or retreatment with bortezomib was offered to patients who, in the investigator's opinion, would benefit from extended treatment.
  
  
  RESULTS
  Sixty-three patients with relapsed/refractory myeloma treated in this extension trial received a median of 7 additional cycles of therapy, for a total of 14 cycles (range, 7-32) over a median duration of therapy of 45.1 weeks in the parent and extension studies. Seventy-eight percent of patients completed this study at the same or higher bortezomib dose than they started on during this study, and the treatment schedule of twice-weekly administration remained unchanged in 89%. Overall, 75% of patients received dexamethasone in combination with bortezomib for a median of 5 cycles starting either in the parent or extension study. The safety profile was similar between the extension and parent trials, with no evidence of new cumulative toxicity. The most commonly reported Grade 3/4 toxicities were thrombocytopenia (29%), with a consistent pattern of recovery during the rest period of each cycle, diarrhea (11%), anemia (11%), and neutropenia (10%). Neuropathy was reported less frequently.
  
  
  CONCLUSIONS
  Retreatment with or continuation of bortezomib +/- dexamethasone beyond 6 months was safe, and toxicities were manageable, in patients with relapsed and/or refractory myeloma.
authors.affiliation: Institute for Myeloma Bone Cancer Research, West Hollywood, California 90069, USA. jberenson@myelomasource.org
authors.forename: James R
authors.initials: JR
authors.lastname: Berenson
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: David T
authors.initials: DT
authors.lastname: Siegel
authors.forename: Raymond
authors.initials: R
authors.lastname: Alexanian
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: David
authors.initials: D
authors.lastname: Irwin
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Gordon
authors.initials: G
authors.lastname: Srkalovic
authors.forename: Seema
authors.initials: S
authors.lastname: Singhal
authors.forename: Steven
authors.initials: S
authors.lastname: Limentani
authors.forename: Ruben
authors.initials: R
authors.lastname: Niesvizky
authors.forename: Dixie L
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Trehu
authors.forename: David P
authors.initials: DP
authors.lastname: Schenkein
authors.forename: Kenneth
authors.initials: K
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D003907:Dexamethasone / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011719:Pyrazines / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone