title: Carfilzomib: a novel agent for multiple myeloma.
abstract: OBJECTIVE
  Carfilzomib is a new agent for the treatment of relapsed and refractory multiple myeloma (MM). This article presents a comprehensive overview of the pharmacokinetics, pharmacodynamics, dosing schedule, safety, efficacy, preparation and administration of carfilzomib, and its role in treating MM patients.
  
  
  RESULTS
  Carfilzomib is a selective proteasome inhibitor that differs structurally and mechanistically from bortezomib. In patients' whole-blood and peripheral-blood mononuclear cells, carfilzomib inhibited proteasomal and immunoproteasomal activity by 70-80%. Approved carfilzomib dosing is based on body surface area, and is given on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle (20 mg/m(2) in cycle 1; 27 mg/m(2) in cycle 2+). Premedication with dexamethasone and adequate hydration are recommended to reduce the risk of adverse events. The median t1/2 of carfilzomib is short (0.29-0.48 h), with no accumulation detected between doses. In clinical studies in relapsed and refractory MM. and in combinations in newly diagnosed MM, single-agent carfilzomib demonstrated significant durable activity, good tolerability and a favourable safety profile, supporting its extended use.
  
  
  CONCLUSIONS
  Carfilzomib represents an important addition to the treatment armamentarium for patients with relapsed and/or refractory MM, and studies are underway evaluating the role of single-agent carfilzomib in additional clinical settings as well as in different combinations.
authors.affiliation: University of Michigan College of Pharmacy, Ann Arbor, MI, USA; University of Michigan Health System, Ann Arbor, MI 48109, USA. kredic@umich.edu
authors.forename: Kimberly
authors.initials: K
authors.lastname: Redic
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D015394:Molecular Structure; D009101:Multiple Myeloma / Q000188:drug therapy*; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061988:Proteasome Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D061988:Proteasome Inhibitors; C524865:carfilzomib
keywords: carfilzomib; multiple myeloma; proteasome inhibitor