Etoposide

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

Etoposide

Systematic (IUPAC) name
4'-demethyl-epipodophyllotoxin 9-[4,6-O-(R)-ethylidene-beta-D-glucopyranoside], 4' -(dihydrogen phosphate)
Clinical data
Trade names	Vepesid
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 Y
ATC code	L01CB01
PubChem	CID 36462
DrugBank	APRD00239
ChemSpider	33510 Y
UNII	6PLQ3CP4P3 Y
KEGG	D00125 Y
ChEBI	CHEBI:4911 Y
ChEMBL	CHEMBL44657 Y
Chemical data
Formula	C29H32O13
Mol. mass	588.557 g/mol
SMILES	eMolecules & PubChem
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 Y Key:VJJPUSNTGOMMGY-MRVIYFEKSA-N Y
N (what is this?)  (verify)

Etoposide phosphate (brand names: Eposin, Etopophos, Vepesid, VP-16) is an anti-cancer agent. It is known in the laboratory as a topoisomerase inhibitor. It exploits the normal mechanism of action of the enzyme topoisomerase II, which aids in DNA unwinding, and by doing so causes DNA strands to break. Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. It is used as a form of chemotherapy for cancers such as Ewing's sarcoma, lung cancer, testicular cancer, lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme. It is often given in combination with other drugs. It is also sometimes used in a conditioning regimen prior to a bone marrow or blood stem cell transplant.

Its chemical make-up derives from podophyllotoxin, a toxin found in the American Mayapple.

The name 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. Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologist Hartmann F. Stähelin.

Mechanism of Action

Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme, preventing re-ligation of the DNA strands. This causes errors in DNA synthesis and promotes apoptosis of the cancer cell.

Administration

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.

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 litres of water on the day of treatment and for several days after.

Side-effects

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

External links

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