Carfilzomib: A new proteasome inhibitor for relapsed or refractory multiple myeloma

J Oncol Pharm Pract. 2013 Dec;19(4):348-54. doi: 10.1177/1078155212470388. Epub 2013 Jan 4.

Abstract

Purpose: The pharmacology, pharmacokinetics, clinical trials, adverse effects, dosage recommendations, and economic considerations of carfilzomib are reviewed.

Summary: Multiple myeloma accounts for approximately 10-15% of all hematologic malignancies and 20% of blood-related cancer deaths. Despite recent advances in the treatment of multiple myeloma, most patients will eventually relapse, requiring further treatment. Carfilzomib is a new proteasome inhibitor that primarily targets the chymotrypsin-like activity of the 20S proteasome. The safety and efficacy of carfilzomib was demonstrated in the PX-171-003-A1 trial, a prospective phase II trial in patients with relapsed or refractory multiple myeloma who had received at least 2 prior therapies including a proteasome inhibitor and an immunomodulatory agent. Common adverse effects included fatigue (55.5%), anemia (46.8%), nausea (44.9%), and thrombocytopenia (36.3%). The recommended dose of carfilzomib for the first cycle is 20 mg/m(2) on 2 consecutive days each week for 3 weeks in a 4-week cycle escalating to 27 mg/m(2) for subsequent cycles. It is recommended that patients receive premedication with dexamethasone during cycle 1 and cycle 2 to minimize risk of infusion reactions.

Conclusion: Carfilzomib provides a clinical benefit to patients with relapsed or refractory multiple myeloma who have been previously treated with a proteasome inhibitor and an immunomodulatory agent.

Keywords: Carfilzomib; PX‐171‐003‐A1; kyprolis; multiple myeloma; proteasome inhibitor.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Dose-Response Relationship, Drug
  • Humans
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Oligopeptides / adverse effects
  • Oligopeptides / pharmacology
  • Oligopeptides / therapeutic use*
  • Proteasome Inhibitors / adverse effects
  • Proteasome Inhibitors / pharmacology
  • Proteasome Inhibitors / therapeutic use
  • Recurrence

Substances

  • Antineoplastic Agents
  • Oligopeptides
  • Proteasome Inhibitors
  • carfilzomib