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Author Notes:

Sagar Lonial 1365 Clifton Rd, Building C, Room 4004, Atlanta, GA, 30322, USA Tel +1 404 778 3921 Fax +1 404 778 5530 Email sloni01@emory.edu

Dr Lonial is a consultant for Millennium, Celgene, Onyx, Novartis, BMS, and Sanofi. All other authors have nothing to disclose.

Subjects:

Research Funding:

Dr Lonial is supported by the Richard and Annelly Deets Foundation for Multiple Myeloma.

Keywords:

  • carfilzomib
  • epoxyketone
  • myeloma
  • proteasome inhibitor
  • second generation

Relapsed and refractory lymphoid neoplasms and multiple myeloma with a focus on carfilzomib

Tools:

Journal Title:

Biologics: Targets and Therapy

Volume:

Volume 7, Number 1

Publisher:

, Pages 13-32

Type of Work:

Article | Final Publisher PDF

Abstract:

Proteasomal inhibition revolutionized myeloma therapies in this decade of novel agents. The only US Food and Drug Administration approved proteasome inhibitor so far, bortezomib effectively targets the constitutive proteasome subunit β5 of the 26S proteasome. Bortezomib induces high and quality response rates that are durable. However, myeloma cells acquire resistance to bortezomib through various mechanisms. Further, grade 3/4 peripheral neuropathy is seen in up to a quarter of patients treated with bortezomib. While the recent change in the mode of administration via the subcutaneous route is associated with a lower incidence of grade 3/4 peripheral neuropathy, it remains a major concern. The second generation proteasome inhibitors are promising, with increased preclinical efficacy and a better administration schedule. The current review spotlights the second generation proteasome inhibitors with special focus on the safety and efficacy of carfilzomib, an epoxyketone with lesser peripheral neuropathy, which exhibits irreversible proteasome inhibition. In this article, we review the pharmacology and preclinical and clinical efficacy and safety of carfilzomib alone and in combination with other chemotherapeutic agents in the various lymphoid neoplasms and multiple myeloma as well as ongoing clinical trials.

Copyright information:

© 2013 Nooka et al, publisher and licensee Dove Medical Press Ltd.

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