title: Role of carfilzomib in the treatment of multiple myeloma.
abstract: The introduction of bortezomib, a first-generation proteasome inhibitor, changed the standard-of-care for newly diagnosed and relapsed multiple myeloma patients. The next generation of proteasome inhibitors, such as carfilzomib, provides a novel pharmacokinetic and pharmacodynamic profile. In vitro data suggest a more specific and irreversible inhibition of the proteasome. Based on the clinical trials conducted to date, carfilzomib has activity in heavily pretreated as well as bortezomib-refractory/relapsed patients. The safety profile, specifically a lower incidence of peripheral neuropathy, efficacy in the high-risk setting, as defined cytogenetically, and the durability of responses indicate a great potential for carfilzomib as a promising therapy. Several trials are underway involving carfilzomib in the newly diagnosed setting and in combination with other active myeloma drugs such as immunomodulatory derivatives of thalidomide, alkylating agents and targeted therapies such as histone deacetylase inhibitors. The introduction of this agent is yet another step in improving the overall outcome of multiple myeloma patients.
authors.affiliation: University of Maryland, School of Medicine, Marlene and Stewart Greenebaum Cancer Center, 22 South Greene Street, Rm N9E12, Baltimore, MD 21201, USA.
authors.forename: Rashid Z
authors.initials: RZ
authors.lastname: Khan
authors.forename: Ashraf
authors.initials: A
authors.lastname: Badros
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000188:drug therapy*; D009842:Oligopeptides / Q000627:therapeutic use*; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use; D013792:Thalidomide / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D056572:Histone Deacetylase Inhibitors; D007166:Immunosuppressive Agents; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; C524865:carfilzomib; D010447:Peptide Hydrolases