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

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BlankPharmacokinetic evaluation of oblimersen sodium for the treatment of

chronic lymphocytic leukemia.

PP Advani, A us, A Masood, T Sher, and A Chanan-Khan

Expert Opin Drug Metab Toxicol, April 27, 2011;

State University of New York at Buffalo, Department of Internal Medicine ,

Buffalo, NY , USA.

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 .