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

Anticancer Res. 2011 Jun;31(6):2297-302.

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.

Patients and 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.

Conclusion: 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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Boronic Acids / administration & dosage
  • Boronic Acids / adverse effects
  • Bortezomib
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / prevention & control*
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Retrospective Studies

Substances

  • Boronic Acids
  • Pyrazines
  • Bortezomib
  • Dexamethasone