title: Carfilzomib: a second-generation proteasome inhibitor for the treatment of relapsed and refractory multiple myeloma.
abstract: OBJECTIVE
  To review and summarize data on carfilzomib, which was approved by the Food and Drug Administration (FDA) in July 2012 for the treatment of patients with relapsed and refractory multiple myeloma (MM) who received prior bortezomib and thalidomide or lenalidomide.
  
  
  METHODS
  A literature search through PubMed was conducted through October 2012 using the terms carfilzomib, PR-171, proteasome inhibitor (PI), and MM. Data were also obtained through the American Society of Clinical Oncology and American Society of Hematology abstracts and FDA briefing documents.
  
  
  METHODS
  The literature search was limited to human studies published in English. Priority was placed on trials of carfilzomib in relapsed and refractory MM.
  
  
  RESULTS
  Carfilzomib is a new PI that differs in pharmacology and pharmacokinetics from bortezomib, the first-in-class PI. The FDA approval was based on efficacy data from a Phase 2 study of carfilzomib in patients with relapsed and refractory MM (n = 266). All patients had received prior bortezomib and 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients were treated with intravenous carfilzomib 20 mg/m(2) (cycle 1) followed by 27 mg/m(2) (cycles ≥2) on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. The overall response rate was 23.7% (18.7-29.4), with a median duration of response of 7.8 (5.6-9.2) months. Safety data from an integrated analysis reported thrombocytopenia, anemia, fatigue, nausea, and diarrhea as the most common adverse events, with minimal dose-limiting neutropenia or peripheral neuropathy (PN) (n = 526). The incidence of grade 3 or higher thrombocytopenia was 24.9%, while that of neutropenia was 11.9%, and the incidence of all grades of treatment-emergent PN was 13%.
  
  
  CONCLUSIONS
  Carfilzomib is a safe and effective new treatment option for patients with relapsed MM refractory to bortezomib and thalidomide or lenalidomide. Randomized head-to-head trials with bortezomib will assist in formulary and treatment decisions in the context of PIs as a drug class.
authors.affiliation: Pharmaceutical Management Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Rockville, MD, USA. jennifer.thompson3@nih.gov
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Thompson
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D017277:Drug Approval; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061988:Proteasome Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012008:Recurrence; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D061988:Proteasome Inhibitors; C524865:carfilzomib