TY - JOUR
T1 - Pharmacokinetic evaluation of oblimersen sodium for the treatment of chronic lymphocytic leukemia
AU - Advani, Pooja P.
AU - Paulus, Aneel
AU - Masood, Ayesha
AU - Sher, Taimur
AU - Chanan-Khan, Asher
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
KW - Bcl-2
KW - antisense oligonucleotide
KW - antisense oligonucleotide therapy
KW - chronic lymphocytic leukemia
KW - oblimersen sodium
KW - phosphorothioate oligonucleotide
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U2 - 10.1517/17425255.2011.579105
DO - 10.1517/17425255.2011.579105
M3 - Article
C2 - 21521129
AN - SCOPUS:79956072494
SN - 1742-5255
VL - 7
SP - 765
EP - 774
JO - Expert Opinion on Drug Metabolism and Toxicology
JF - Expert Opinion on Drug Metabolism and Toxicology
IS - 6
ER -