Abstract
Bcl-2 functions as a key survival factor for lymphocytes and is highly expressed in a majority of non-Hodgkin's lymphomas. The ability of oblimersen sodium (Genasense, previously known as G3139) to target bcl-2 messenger RNA and decrease Bcl-2 protein levels has the potential to enhance the activity of cytotoxic chemotherapy. Pretreatment with oblimersen followed by cyclophosphamide (Cytoxan, Neosar) markedly improved survival relative to single-agent cyclophosphamide in a murine xenograft model. Oblimersen has also enhanced the cytotoxicity of a variety of other agents against non-Hodgkin's lymphoma, including etoposide, rituximab (Rituxan), and alemtuzumab (Campath). An initial phase I study of oblimersen in non-Hodgkin's lymphoma demonstrated modest single-agent activity. Recent reports suggest that oblimersen may add to the activity of R-CHOP (rituximab-cyclophosphamide/doxorubicin/vincristine/prednisone) in previously untreated mantle cell lymphoma and to rituximab alone in a variety of subtypes of relapsed non-Hodgkin's lymphoma. Additional studies in both treatment-naive and relapsed patients will define the role of oblimersen in the treatment of non-Hodgkin's lymphoma.
MeSH terms
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Alemtuzumab
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Animals
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal, Humanized
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Antibodies, Monoclonal, Murine-Derived
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Antibodies, Neoplasm / pharmacology
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Clinical Trials, Phase I as Topic
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Clinical Trials, Phase II as Topic
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Cyclophosphamide / pharmacology
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Dose-Response Relationship, Drug
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Doxorubicin / pharmacology
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Etoposide / pharmacology
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Gene Expression Regulation, Leukemic / drug effects*
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Humans
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Lymphoma, Non-Hodgkin / drug therapy*
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Lymphoma, Non-Hodgkin / metabolism
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Oligonucleotides, Antisense / pharmacology*
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Oligonucleotides, Antisense / therapeutic use
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Prednisone / pharmacology
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Proto-Oncogene Proteins c-bcl-2 / drug effects*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Remission Induction
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Rituximab
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Survival Analysis
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Thionucleotides / pharmacology*
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Thionucleotides / therapeutic use
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Transplantation, Heterologous
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Vincristine / pharmacology
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antibodies, Monoclonal, Murine-Derived
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Antibodies, Neoplasm
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Antineoplastic Agents
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Oligonucleotides, Antisense
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Thionucleotides
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Alemtuzumab
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Rituximab
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Vincristine
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Etoposide
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Doxorubicin
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oblimersen
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Cyclophosphamide
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Prednisone