Bortezomib in Recurrent and/or Refractory Multiple Myeloma. Initial Clinical Experience in Patients With Impared Renal Function

Cancer. 2005 Mar 15;103(6):1195-200. doi: 10.1002/cncr.20888.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Boronic Acids / adverse effects
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Clinical Trials, Phase II as Topic
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Infusions, Intravenous
  • Kidney Function Tests
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality*
  • Multiple Myeloma / pathology
  • Prognosis
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / therapeutic use*
  • Pyrazines / adverse effects
  • Pyrazines / therapeutic use*
  • Recurrence
  • Renal Insufficiency / physiopathology*
  • Retrospective Studies
  • Risk Assessment
  • Severity of Illness Index
  • Survival Rate
  • Treatment Outcome

Substances

  • Boronic Acids
  • Protease Inhibitors
  • Pyrazines
  • Bortezomib