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"VP-16" redirects here. For the viral protein, see Herpes simplex virus protein vmw65

Etoposide, etoposide phosphate or VP-16 (current brand name: Etopophos, according to FDA Orange Book) is a cytotoxic agent (anticancer drug), which belongs to the drug type topoisomerase inhibitor.

Background[edit]

Etoposide was first synthesised in 1966, and U.S. Food and Drug Administration approval was granted in 1983.^[1] Its chemical make-up derives from podophyllotoxin, a toxin found in the American Mayapple.

The nickname VP-16 likely comes from a compounding of the last name of the chemists who performed early work on the drug (von Wartburg and von Kuhn) and podophyllotoxin.^[2] Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologist Hartmann F. Stähelin.

Mechanism of action[edit]

Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme (which aids in DNA unwinding), prevents re-ligation of the DNA strands, and by doing so causes DNA strands to break.^[3] Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. Therefore, this causes errors in DNA synthesis and promotes apoptosis of the cancer cell.^[1]^[4]

Use[edit]

Etoposide is used as a form of chemotherapy for cancers such as Kaposi’s sarcoma, Ewing's sarcoma, lung cancer, testicular cancer, lymphoma, nonlymphocytic leukemia, and glioblastoma multiforme. It is often given in combination with other drugs (such as bleomycin in treating testicular cancer). It is also sometimes used in a conditioning regimen prior to a bone marrow or blood stem cell transplant.^[1]

Administration[edit]

It is given intravenously or orally in capsule form. If the drug is given by IV, it must be done slowly over a 30- to 60-minute period because it can lower blood pressure as it is being administered. Blood pressure is checked often during infusing, with the speed of administration adjusted accordingly.

In general, patients are advised to call their doctor in case of fever, symptoms of infection, or painful injection sites, as these may progress severely without adequate medical attention.^[5]

Patients are advised to drink large amounts of fluids after treatment to prevent damage to the bladder and kidneys, typically 1.5 to 3.5 liters of water on the day of treatment and for several days after.

Side-effects[edit]

Common are:

low blood pressure
hair loss
pain and or burning at the IV site
constipation or diarrhea
metallic food taste
Bone marrow suppression, leading to:
- decreased white blood cell counts (leading to increased susceptibility to infections)
- low red blood cell counts (anemia)
- low platelet counts (leading to easy bruising and bleeding)

Less common are:

nausea and vomiting
allergic-type reactions
rash
fever, often occurring shortly after IV administration and not due to infection
mouth sores
Acute myeloid leukemia (which ironically can be treated with etoposide itself)

Besides, when given with warfarin, it may cause bleeding.^[5]

References[edit]

^ ^a ^b ^c Hande, K. R. (1998). "Etoposide: Four decades of development of a topoisomerase II inhibitor". European Journal of Cancer 34 (10): 1514–1521. doi:10.1016/S0959-8049(98)00228-7. PMID 9893622.
^ Kuhn M, Von Wartbung A (1967). "Podophyllum- Lignane: Struktur und Absolutkonfiguration von Podorhizol-β-D-glucosid ( = Lignan F). 19. Mitt. über mitosehemmende Naturstoffe [1]". Helvetica Chimica Acta 50 (6): 1546–65. doi:10.1002/hlca.19670500614.
^ Pommier, Y, Leo, E., Zhang, H., Marchand (2012) DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol. 17 (5): 421-433.
^ Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA (2004). "Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives". Toxicon 44 (4): 441–59. doi:10.1016/j.toxicon.2004.05.008. PMID 15302526.
^ ^a ^b Longe, Jacqueline L. (2002). Gale Encyclopedia Of Cancer: A Guide To Cancer And Its Treatments. Detroit: Thomson Gale. pp. 397–399. ISBN 978-1-4144-0362-5.

External links[edit]

Etoposide information at the U.S. National Institutes of Health

UpToDate Contents

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English Journal

Suppression of basal autophagy reduces lung cancer cell proliferation and enhances caspase-dependent and -independent apoptosis by stimulating ROS formation.

Kaminskyy V, Piskunova T, Zborovskaya I, Tchevkina E, Zhivotovsky B.SourceInstitute of Environmental Medicine; Division of Toxicology; Karolinska Institutet; Stockholm, Sweden.
Autophagy.Autophagy.2012 Jul 1;8(7). [Epub ahead of print]
Autophagy is a catabolic process involved in the turnover of organelles and macromolecules which, depending on conditions, may lead to cell death or preserve cell survival. We found that some lung cancer cell lines and tumor samples are characterized by increased levels of lipidated LC3. Inhibition
PMID 22562073

The anticancer thiosemicarbazones Dp44mT and triapine lack inhibitory effects as catalytic inhibitors or poisons of DNA topoisomerase IIα.

Yalowich JC, Wu X, Zhang R, Kanagasabai R, Hornbaker M, Hasinoff BB.SourceDivision of Pharmacology, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Biochemical pharmacology.Biochem Pharmacol.2012 Jul 1;84(1):52-8. Epub 2012 Apr 4.
The thiosemicarbazones Dp44mT (di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone) and triapine have potent antiproliferative activity and have been evaluated as anticancer agents. While these compounds strongly bind iron and copper, their mechanism(s) of action are incompletely understood. A recen
PMID 22503743

Japanese Journal

化学療法とTURで膀胱温存できた膀胱原発小細胞癌の1例

金宮健翁,新井浩樹,室崎伸和,本多正人,吉田恭太郎
泌尿器科紀要 58(3), 165-168, 2012-03
… Considering the patient's age and the location of the tumor, we administered chemotherapy using carboplatin and etoposide after resection of the tumor. …
NAID 120003988384

Decreases in CD31 and CD47 Levels on the Cell Surface during Etoposide-Induced Jurkat Cell Apoptosis

AZUMA Yutaro,NAKAGAWA Hideaki,DOTE Kanae [他]
Biological & pharmaceutical bulletin 34(12), 1828-1834, 2011-12
NAID 40019073402

Related Pictures

★リンクテーブル★

リンク元	「絨毛癌」「トポイソメラーゼII阻害剤」「エトポシド」「抗悪性腫瘍薬」「VP-16」

「絨毛癌」

Etoposide
Systematic (IUPAC) name
	4'-demethyl-epipodophyllotoxin 9-[4,6-O-(R)-ethylidene-beta-D-glucopyranoside], 4' -(dihydrogen phosphate)
Clinical data
Trade names	Etopophos
AHFS/Drugs.com	monograph
MedlinePlus	a684055
Pregnancy cat.	D (AU) D (US)
Legal status	POM (UK) ℞-only (US)
Routes	Oral, intravenous
Pharmacokinetic data
Bioavailability	Highly variable, 25 to 75%
Protein binding	97%
Metabolism	Hepatic (CYP3A4 involved)
Half-life	Oral: 6 h., IV: 6-12 h., IV in children: 3 h.
Excretion	Renal and fecal
Identifiers
CAS number	33419-42-0
ATC code	L01CB01
PubChem	CID 36462
DrugBank	DB00773
ChemSpider	33510
UNII	6PLQ3CP4P3
KEGG	D00125
ChEBI	CHEBI:4911
ChEMBL	CHEMBL44657
Chemical data
Formula	C29H32O13
Mol. mass	588.557 g/mol
	SMILES C[C@@H]1OC[C@@H]2[C@@H](O1)[C@@H]([C@H]([C@@H](O2)O[C@@H]3c4cc5c(cc4[C@H]([C@@H]6[C@@H]3COC6=O)c7cc(c(c(c7)OC)O)OC)OCO5)O)O;
	InChI InChI=1S/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15+,20-,21-,22+,24-,25-,26-,27-,29+/m1/s1 ; Key:VJJPUSNTGOMMGY-MRVIYFEKSA-N ;
(what is this?) (verify)

　　[★]

chorio
英: choriocarcinoma
同: 絨毛上皮腫 chorioepithelioma
関: 悪性合胞体腫、絨毛疾患

疫学

日本、東南アジア、中東、ラテンアメリカに多い
人口10万人にたいして年間0.05人
正常妊娠からは5-10万例に1例、全胞状奇胎の1-2%に発症、部分胞状奇胎では稀とされる(G9M.184)

病理

NGY.242

組織構造：絨毛構造無し。破壊的増殖。出血、壊死。
細胞形態：細胞性、合胞体、中間型栄養膜細胞に類似した細胞。破壊的な増殖像。細胞異型あり

failpicload@./t_image/097D023.jpg

転移

血行性転移

治療

化学療法：(参考1)

EMA/CO regimen

エトポシド(etoposide)、メトトレキサート(methotrexate)、ダクチノマイシン(dactinomycin)、ロイコボリン(leucovorin)、シクロホスファミド(cyclophosphamide)、ビンクリスチン(vincristine Oncovin)

EMA regimen
MAC regimen

手術療法：子宮、肺の病変に関しては適応となることがある。
放射線療法：脳、肝臓に対して行われる。

参考

1. [charged]Malignant gestational trophoblastic disease: Staging and treatment - uptodate

[1]

国試

097D041

「トポイソメラーゼII阻害剤」

　　[★]

関: トポイソメラーゼII、抗悪性腫瘍薬

[show details]

トポイソメラーゼ阻害薬 : 約 85,100 件
トポイソメラーゼ阻害剤 : 約 123,000 件
トポイソメラーゼII阻害薬 : 74 件
トポイソメラーゼII阻害剤 : 約 36,500 件
II型トポイソメラーゼ阻害薬 : 11 件
II型トポイソメラーゼ阻害剤 : 7 件

エトポシド etoposide

副作用：二次白血病。治療開始から2-3年後にAMLを経ずにAMLを発症。11q23の以上を含む事が多い。

「エトポシド」

　　[★]

英: etoposide
同: VP-16, VePesid
商: ベプシド、ラステット
関: 抗悪性腫瘍薬、トポイソメラーゼII阻害剤

S期とG2期に特異的に作用
トポイソメラーゼIIによるDNA鎖切断を阻害し、DNA合成を阻害

添付文書

ベプシド注100mg

http://www.info.pmda.go.jp/go/pack/4240403A2050_1_03/4240403A2050_1_03?view=body

参考

1. KEGG DRUG: D00125

http://www.genome.jp/dbget-bin/www_bget?dr_ja:D00125

「抗悪性腫瘍薬」

　　[★]

英: antineoplastic drug, antitumor agent, antitumor drug
同: 抗腫瘍薬 antineoplastics、抗癌薬 anticancer drug AZT
関: 制癌薬

細胞周期依存性

first aid step1 2006 p.307,308

細胞周期依存的

antimetabolites (MTX,5-FU, 6-MP), etoposide,bleomycin, vinca alkaloids,paclitaxel

細胞周期非依存的

alkylating agents,antibiotics (dactinomycin,doxorubicin(adriamycin), bleomycin)

「VP-16」

　　[★] エトポシド etoposide

[wow-1] Hande, K. R. (1998). "Etoposide: Four decades of development of a topoisomerase II inhibitor". European Journal of Cancer 34 (10): 1514–1521. doi:10.1016/S0959-8049(98)00228-7. PMID 9893622.

[2] Kuhn M, Von Wartbung A (1967). "Podophyllum- Lignane: Struktur und Absolutkonfiguration von Podorhizol-β-D-glucosid ( = Lignan F). 19. Mitt. über mitosehemmende Naturstoffe [1]". Helvetica Chimica Acta 50 (6): 1546–65. doi:10.1002/hlca.19670500614.

[3] Pommier, Y, Leo, E., Zhang, H., Marchand (2012) DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol. 17 (5): 421-433.

[4] Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA (2004). "Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives". Toxicon 44 (4): 441–59. doi:10.1016/j.toxicon.2004.05.008. PMID 15302526.

[gale-5] Longe, Jacqueline L. (2002). Gale Encyclopedia Of Cancer: A Guide To Cancer And Its Treatments. Detroit: Thomson Gale. pp. 397–399. ISBN 978-1-4144-0362-5.

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検索

案内

案内

etoposide