title: Bortezomib in recurrent and/or refractory multiple myeloma. Initial clinical experience in patients with impared renal function.
abstract: BACKGROUND
  Bortezomib is a potent, reversible proteasome inhibitor that has been approved for the treatment of recurrent and/or refractory multiple myeloma, but its activity in patients with renal impairment has not been studied to date.
  
  
  METHODS
  Response rates, safety, and 20S proteasome activity were assessed in relation to baseline creatinine clearance (CrCl) among patients with recurrent and/or refractory myeloma (n = 256 patients) who were treated with bortezomib in 2 Phase II trials. Bortezomib was administered by intravenous bolus on Days 1, 4, 8, and 11 of a 21-day cycle at 2 doses, 1.0 mg/m2 (n = 28 patients) and 1.3 mg/m2 (n = 228 patients).
  
  
  RESULTS
  Of 10 patients with CrCl < or = 30 mL/minute, 7 patients completed the protocol-specified 8 cycles of treatment; 4 patients received the 1.3 mg/m2 bortezomib dose, and 3 patients received the 1.0 mg/m2 bortezomib dose. Using the European Group for Blood and Marrow Transplantation criteria, responses were assigned by an independent committee to 3 of the 10 patients (2 partial responses and 1 minimal response), a response rate similar to that of the overall treated population. Patients with CrCl > 80 mL/minute (n = 105 patients), 51-80 mL/minute (n = 99 patients), and < or = 50 mL/minute (n = 52 patients) had similar rates of discontinuation and similar adverse event profiles. Renal function did not appear to affect the 1-hour postdose proteasome inhibition or its recovery.
  
  
  CONCLUSIONS
  Clinical experience in a limited number of patients with impaired renal function suggests that bortezomib provides clinical benefit with manageable toxicities in this high-risk population.
authors.affiliation: Blood Stem Cell and Bone Marrow Transplantation, St. Vincent's Comprehensive Cancer Center, New York, New York 10011-8202, USA. sjaganna@salick.com
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: James R
authors.initials: JR
authors.lastname: Berenson
authors.forename: Seema
authors.initials: S
authors.lastname: Singhal
authors.forename: Raymond
authors.initials: R
authors.lastname: Alexanian
authors.forename: Gordan
authors.initials: G
authors.lastname: Srkalovic
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Jessica
authors.initials: J
authors.lastname: Anderson
authors.forename: Darrell
authors.initials: D
authors.lastname: Nix
authors.forename: Dixie L
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D017322:Clinical Trials, Phase II as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007677:Kidney Function Tests; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D051437:Renal Insufficiency / Q000503:physiopathology*; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib