Etoposide

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Etoposide
Etoposide.svg
Etoposide ball-and-stick.png
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.
Legal status
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 YesY
ATC code L01CB01
PubChem CID 36462
DrugBank DB00773
ChemSpider 33510 YesY
UNII 6PLQ3CP4P3 YesY
KEGG D00125 YesY
ChEBI CHEBI:4911 YesY
ChEMBL CHEMBL44657 YesY
Synonyms VP-16; VP-16-213
Chemical data
Formula C29H32O13 
Mol. mass 588.557 g/mol
Physical data
Melt. point 243.5 °C (470 °F)
 YesY (what is this?)  (verify)

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

Background[edit]

Etoposide was first synthesized 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:

Less common are:

When given with warfarin, it may cause bleeding.[5]

References[edit]

  1. ^ a b c Hande KR (1998). "Etoposide: four decades of development of a topoisomerase II inhibitor". Eur. J. Cancer 34 (10): 1514–21. 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 C (2010). "DNA topoisomerases and their poisoning by anticancer and antibacterial drugs". Chem. Biol. 17 (5): 421–33. doi:10.1016/j.chembiol.2010.04.012. PMID 20534341. 
  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. 
  5. ^ a b Longe JL (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]