Carfilzomib: a novel second-generation proteasome inhibitor. (May 2011)

• Record Type: Journal Article
• Authors: Khan, Meaghan L; Stewart, A Keith
• Is Part Of: Future oncology. Volume 7:Number 5(2011)
• Page Start: 607
• Page End: 612
• Publication Date: 2011-05
• Subjects: bortezomib -- carfilzomib -- chymotrypsin-like -- multiple myeloma -- PR-171 -- proteasome inhibitor; Oncology -- Periodicals; 616.99405
• DOI: 10.2217/fon.11.42
• Languages: English
• ISSNs: 1479-6694

Abstract

Carfilzomib (formerly PR-171) is a novel epoxyketone-based irreversible proteasome inhibitor. In preclinical studies, carfilzomib demonstrated irreversible binding to the proteasome and minimal off-target inhibition of other proteases. In clinical studies carfilzomib has demonstrated substantial antitumor activity in hematologic malignancies while exhibiting a well-tolerated side-effect profile. Painful neuropathy was minimally reported, suggesting a possible advantage over other proteasome inhibitors. With single-agent carfilzomib, dose-limiting toxicity was hematologic and included thrombocytopenia and neutropenia. In patients with relapsed or refractory multiple myeloma, twice-weekly consecutive-day single-agent carfilzomib 20 mg/m 2 for 3 weeks every 28 days, escalating to 27 mg/m 2 the second cycle was associated with a 54% overall response rate in bortezomib-naive patients and a 26% overall response rate in bortezomib and immunomodulatory drug refractory patients.