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Expert Opin Drug Metab Toxicol. 2011 Jun;7(6):765-74. doi: 10.1517/17425255.2011.579105. Epub 2011 Apr 27.

Pharmacokinetic evaluation of oblimersen sodium for the treatment of chronic lymphocytic leukemia.

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1
State University of New York at Buffalo, Department of Internal Medicine, Buffalo, NY, USA.

Abstract

INTRODUCTION:

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the western hemisphere. Developing new therapies remains a priority as present treatment options do not offer a cure. BCL-2 overexpression in CLL is associated with aggressive disease features and resists chemotherapy. Oblimersen sodium (G3139) is a phosphorothioate oligonucleotide antisense drug targeting the BCL-2 mRNA and is the first antisense to reach advanced clinical testing in oncology. Preclinical evaluation has demonstrated good antineoplastic effect in B-cell cancers; several clinical trials have confirmed its safety and efficacy both alone and in combination with other therapeutics.

AREAS COVERED:

This review focuses on the chemistry, pharmacodynamics, pharmacokinetics and clinical evaluation of oblimersen in CLL. PubMed and MEDLINE searches assisted in data collection.

EXPERT OPINION:

Bcl-2 is an important target in CLL. Antisense therapy is a novel approach to target oncoproteins; this can be beneficial in the clinical setting. Oblimersen sodium demonstrates the clinical safety of the antisense therapeutic approach and, with chemotherapy, shows survival advantage in a subset of CLL patients. However, future approval of oblimersen sodium in CLL remains uncertain. Nevertheless, BCL-2 remains a critical target in drug development and is an area of high-priority research.

PMID:
21521129
DOI:
10.1517/17425255.2011.579105
[Indexed for MEDLINE]
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