The mechanism of action, pharmacokinetics, and clinical efficacy of carfilzomib for the treatment of multiple myeloma.

Abstract

INTRODUCTION:

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.

AREAS COVERED:

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.

EXPERT OPINION:

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: Chiara Pautasso, Sara Bringhen, Chiara Cerrato, Valeria Magarotto, Antonio Palumbo
• Journal: Expert opinion on drug metabolism & toxicology (Expert Opin Drug Metab Toxicol) Vol. 9 Issue 10 Pg. 1371-9 (Oct 2013) ISSN: 1744-7607 [Electronic] England
• PMID: 23834482 (Publication Type: Journal Article, Review)

Chemical References

• Boronic Acids
• Oligopeptides
• Proteasome Inhibitors
• Pyrazines
• Bortezomib
• carfilzomib

Topics

• Boronic Acids
• Bortezomib
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Humans
• Multiple Myeloma (drug therapy)
• Oligopeptides (administration & dosage, pharmacokinetics)
• Proteasome Inhibitors
• Pyrazines