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外観
白色〜わずかにうすい褐色, 結晶性粉末〜粉末
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溶解性
メタノールにやや溶けにくく、エタノールに溶けにくく、水に極めて溶けにくい。
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用途
抗腫瘍薬(リンパ腫、ホジキンリンパ腫、精巣癌、肺癌(特に小細胞性)、急性白血病)
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用途
ポドフィリン系化合物です。
トポイソメラーゼⅡ阻害剤として作用しま
す。
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効能
抗悪性腫瘍薬, トポイソメラーゼII阻害薬
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商品名
ベプシド (ブリストル・マイヤーズスクイブ); ベプシド (ブリストル・マイヤーズスクイブ); ラステット (日本化薬); ラステット (日本化薬)
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説明
Etoposide is a plant alkaloid and an inhibitor of topoisomerase II (IC50 = 60.3 μM). It inhibits proliferation of a variety of adenocarcinoma cells (IC50s = 0.005-12,200 μM) and human umbilical vein endothelial (HUVEC) cells (IC50 = 0.249 μM). It reduces tumor growth in an Ma human embryonal carcinoma mouse xenograft model when administered at a dose of 25 mg/kg, an effect that is enhanced by concomitant administration of the immunosuppressant cyclosporin A . Etoposide also inhibits nuclear receptor coactivator 3 (IC50 = 2.48 μM). Formulations containing etoposide have been used in combination therapy in the treatment of cancer.
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化学的特性
White or almost white, crystalline powder, slightly hygroscopic
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使用
Etoposide is used for germinogenic tumors, ovarian, stomach, and lung cancer, Hodgkin’s
disease, and non-Hodgkin’s lymphoma for both monotherapy and in combination therapy.
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適応症
Etoposide (VePesid) is a semisynthetic derivative of
podophyllotoxin that is produced in the roots of the
American mandrake, or May apple. Unlike podophyllotoxin
and vinca alkaloids, etoposide does not bind to microtubules.
It forms a complex with the enzyme topoisomerase
II, which results in a single-strand breakage of
DNA. It is most lethal to cells in the S- and G2-phases of
the cell cycle. Drug resistance to etoposide is thought to
be caused by decreased cellular drug accumulation.
Etoposide is most useful against testicular and ovarian
germ cell cancers, lymphomas, small cell lung cancers,
and acute myelogenous and lymphoblastic
leukemia.Toxicities include mild nausea, alopecia, allergic
reaction, phlebitis at the injection site, and bone
marrow toxicity.
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臨床応用
Etoposide is utilized in the treatment of small cell lung cancer and in combination with other agents in refractory testicular cancer.
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安全性プロファイル
Poison by ingestion,
intraperitoneal, intravenous, and
subcutaneous routes. An experimental
teratogen. Human systemic effects by
ingestion and inhalation: agranulocytosis,
aplastic anemia, and other changes in bone
marrow. Experimental reproductive effects.
Human mutation data reported. When
heated to decomposition it emits acrid
smoke and fumes.
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代謝
The drug is more than 96% protein bound, undergoes biphasic elimination, and has a terminal half-life of 4 to 11 hours. Approximately 35 to 45% of a dose is eliminated via the kidneys, with less than 6% excreted in feces. The drug should be used with caution in patients with renal or liver disease.
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参考文献
Hande, K. R. "Etoposide: four decades of development of a topoisomerase II inhibitor." European Journal of Cancer34.10(1998):1514.
Noda, K, et al. "Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer." New England Journal of Medicine 346.2(2002):85-91.
