Epirubicin

Epirubicin
Clinical data
Trade names	Ellence
AHFS/Drugs.com	Monograph
MedlinePlus	a603003
Pregnancy; category	AU: D; ;
Routes of; administration	Intravenous
ATC code	L01DB03 (WHO) ;
Legal status
Legal status	UK: POM (Prescription only) ; US: ℞-only ;
Pharmacokinetic data
Bioavailability	NA
Protein binding	77%
Metabolism	Hepatic glucuronidation and oxidation
Excretion	Biliary and renal
Identifiers
	IUPAC name (8S,10S)-10-{[(2R,4S,5R,6S)-4-Amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione;
CAS Number	56420-45-2 ;
PubChem CID	41867;
DrugBank	DB00445 ;
ChemSpider	38201 ;
UNII	3Z8479ZZ5X;
KEGG	D07901 ;
ChEBI	CHEBI:47898 ;
ChEMBL	ChEMBL417 ;
CompTox Dashboard (EPA)	DTXSID0022987 ;
Chemical and physical data
Formula	C27H29NO11
Molar mass	543.525 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C2c1c(O)c5c(c(O)c1C(=O)c3cccc(OC)c23)C[C@@](O)(C(=O)CO)C[C@@H]5O[C@@H]4O[C@H]([C@H](O)[C@@H](N)C4)C;
	InChI InChI=1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,17-,22-,27-/m0/s1 ; Key:AOJJSUZBOXZQNB-VTZDEGQISA-N ;

Epirubicin is an anthracycline drug used for chemotherapy. It can be used in combination with other medications to treat breast cancer in patients who have had surgery to remove the tumor. It is marketed by Pfizer under the trade name Ellence in the US and Pharmorubicin or Epirubicin Ebewe elsewhere.

Similarly to other anthracyclines, epirubicin acts by intercalating DNA strands. Intercalation results in complex formation which inhibits DNA and RNA synthesis. It also triggers DNA cleavage by topoisomerase II, resulting in mechanisms that lead to cell death. Binding to cell membranes and plasma proteins may be involved in the compound's cytotoxic effects. Epirubicin also generates free radicals that cause cell and DNA damage.

Epirubicin is favoured over doxorubicin, the most popular anthracycline, in some chemotherapy regimens as it appears to cause fewer side-effects. Epirubicin has a different spatial orientation of the hydroxyl group at the 4' carbon of the sugar - it has the opposite chirality - which may account for its faster elimination and reduced toxicity. Epirubicin is primarily used against breast and ovarian cancer, gastric cancer, lung cancer and lymphomas.

Development history[]

The first trial of epirubicin in humans was published in 1980.^[1] Upjohn applied for approval by the U.S. Food and Drug Administration (FDA) in node-positive breast cancer in 1984, but was turned down because of lack of data.^[2] In 1999 Pharmacia (who had by then merged with Upjohn) received FDA approval for the use of epirubicin as a component of adjuvant therapy in node-positive patients.

Patent protection for epirubicin expired in August 2007.

Side effects[]

Anthracyclines (including Epirubicin) have been shown to have cardiotoxic properties.^[3]

References[]

^ Bonfante V, Bonadonna G, Villani F, Martini A (1980). "Preliminary clinical experience with 4-epidoxorubicin in advanced human neoplasia". Recent Results in Cancer Research. Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer. Recent Results in Cancer Research. 74: 192–9. doi:10.1007/978-3-642-81488-4_24. ISBN 978-3-642-81490-7. PMID 6934564.
^ "Oncology Approval: epirubicin hydrochloride (Ellence)". On Target. Target Health Inc. September 15, 1999. Archived from the original on 2008-05-10. Retrieved 2007-08-04.
^ Mecinaj A, Gulati G, Heck SL, Holte E, Fagerland MW, Larsen AI, Blix ES, Geisler J, Wethal T, Omland T. Rationale and design of the PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA II) trial: a randomized, placebo-controlled, multicenter trial. Cardiooncology. 2021 Sep 27;7(1):33. doi: 10.1186/s40959-021-00115-w. PMID 34579775; PMCID: PMC8474901.

[1] Bonfante V, Bonadonna G, Villani F, Martini A (1980). "Preliminary clinical experience with 4-epidoxorubicin in advanced human neoplasia". Recent Results in Cancer Research. Fortschritte der Krebsforschung. Progres dans les Recherches Sur le Cancer. Recent Results in Cancer Research. 74: 192–9. doi:10.1007/978-3-642-81488-4_24. ISBN 978-3-642-81490-7. PMID 6934564.

[2] "Oncology Approval: epirubicin hydrochloride (Ellence)". On Target. Target Health Inc. September 15, 1999. Archived from the original on 2008-05-10. Retrieved 2007-08-04.

[3] Mecinaj A, Gulati G, Heck SL, Holte E, Fagerland MW, Larsen AI, Blix ES, Geisler J, Wethal T, Omland T. Rationale and design of the PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA II) trial: a randomized, placebo-controlled, multicenter trial. Cardiooncology. 2021 Sep 27;7(1):33. doi: 10.1186/s40959-021-00115-w. PMID 34579775; PMCID: PMC8474901.

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