title: The mechanism of action, pharmacokinetics, and clinical efficacy of carfilzomib for the treatment of multiple myeloma.
abstract: BACKGROUND
  The development of novel agents, such as immunomodulatory drugs and proteasome inhibitors, has led to a considerable increment in the response rate (RR) and outcomes for multiple myeloma (MM) patients. Unfortunately, MM patients will inevitably relapse and become resistant to new drugs. This led to the continuous development of novel agents. Carfilzomib is a second-generation proteasome inhibitor, demonstrating promising results in relapsed/refractory (RR) and newly diagnosed (ND) MM patients.
  
  
  METHODS
  Herein, the authors review Phase I and II trials on carfilzomib for the treatment of MM. They also describe the profile of the drug during Phase I escalating doses and evaluate the efficacy of carfilzomib both alone and in combination. Finally, the authors also review and discuss the carfilzomib safety profile.
  
  
  CONCLUSIONS
  Clinical trials (Phases I and II) with carfilzomib, used both as single agent or in combination with other therapies, established the maximum tolerated dose and recommended schedule of administration. Preliminary data showed that it had a high efficacy and a good safety profile both in RRMM and NDMM patients. Carfilzomib seems to be effective in patients previously treated with bortezomib. Future Phase II and III studies will better define the role of carfilzomib in the treatment of MM as well as its optimum dose.
authors.affiliation: University of Torino, Division of Hematology, Myeloma Unit, Azienda Ospedaliera Città della Salute e della Scienza di Torino , Torino , Italy +39 01 1663 5814 ; +39 01 1696 3737 ; appalumbo@yahoo.com.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pautasso
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Chiara
authors.initials: C
authors.lastname: Cerrato
authors.forename: Valeria
authors.initials: V
authors.lastname: Magarotto
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D001897:Boronic Acids; D000069286:Bortezomib; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D061988:Proteasome Inhibitors; D011719:Pyrazines
chemical_list: D001897:Boronic Acids; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; C524865:carfilzomib