Epirubicin is an anthracycline drug used for chemotherapy.
Epirubicin is a 4’-epi-isomer of doxorubicin and a derivative of daunorubicin.
As an anthracycline antibiotic it belongs to several chemical classes such as: aminoglycosides, tetracene quinones, p-quinones, primary alpha-hydroxy ketone and tertiary alpha-hydroxy ketones.
It can be used in combination with other medications to treat breast cancer.
Trade name is Ellence.
Pregnancy category AU: D
Routes of administration Intravenous
Protein binding 77%
Metabolism-Hepatic glucuronidation and oxidation
Excretion- Biliary and renal
As with 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 favored over doxorubicin, the most popular anthracycline, in some chemotherapy regimens as it appears to cause fewer side-effects.
Epirubicin has a different spatial orientation 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.
The Standard adjuvant therapy is a combination of cyclophosphamide, methotrexate and fluorouracil (CMF).
In comparison to this the Epirubicin therapy contains fluorouracil/epirubicin/cyclophosphamide (FEC).
FEC is at least as effective as CMF in premenopausal women with node positive- or negative breast cancer and that FEC produced no additional benefit in terms of 5-year relapse-free or overall survival.
Researchers discovered a benefit for epirubicin 100 mg over epirubicin 50 mg.
Patients with FEC100 treatment of the study were relapse-free and an overall survival rate at 5 years higher as in FEC 50 treatment.
The combination of Epirubicin and tamoxifen lead to an increase survival in node-positive postmenopausal women with hormone receptor-positive breast tumours.
Epirubicin monotherapy was shown to be therapeutically equivalent to doxorubicin monotherapy in patients who had to receive previous chemotherapy for advanced breast cancer.
There are several Combination therapies: 1. FEC: fluorouracil + cyclophosphamide + epirubicin; 2. FAC: fluorouracil + cyclophosphamide + doxorubicin.
The median survival rates markedly better than those achieved with epirubicin monotherapy.
The FEC treatment seems to be less toxic.
Equimolar doses of epirubicin and doxorubicin have been shown to be therapeutically equivalent in patients with metastatic breast cancer.
The administration of more dose intensive epirubicin-containing regimens to patients with metastatic breast cancer has been associated with improved response rates, but not increased overall survival.
The mechanism of action of epirubicin is similar to that of doxorubicin and other anthracycline drugs.
The observed clinical differences between epirubicin and doxorubicin can be explained by the pharmacokinetic differences based on the different affinity to DNA and lipophilicity, as there is no indication that different mechanisms are involved in their activity.
Epirubicin first forms a complex with DNA by intercalation of its planar rings between nucleotide base pairs, and inhibits replication and transcription and triggers DNA cleavage by topoisomerase II.
Epirubicin then stabilizes the topoisomerase II-DNA complex, resulting in irreversible DNA strand breakage, leading to cell death.
Epirubicin is also generates cytotoxic free radicals, which are very reactive against DNA, cell membranes and mitochondria.
Epirubicin exhibits activity in all phases of the cell cycle, but maximal cell kill occurs during the S phase and G2 phase of the cell cycle.
The pharmacokinetic properties of epirubicin can be described by half-lives for the initial (alpha), intermediate (beta) and terminal (gamma) elimination phases of approximately 3 minutes, 1 hour and 30 hours, respectively.
The terminal elimination half-life of doxorubicin is estimated to be approximately 40-70% longer than that of epirubicin.
The pharmacokinetics of epirubicin appear to be linear for doses in the range of 40 – 150 mg/m2.
There is extensive distribution into the tissue.
The total plasma clearance of epirubicin is approximately 45 to 50 L/h/m2, which is almost 2-fold higher than that of doxorubicin.
Area under the plasma concentration versus time curve values are 1.3 to 1.7 times higher for doxorubicin than epirubicin following single-dose intravenous administration.
Epirubicin shows a 77% binding to plasma proteins, predominantly albumin, which is not affected by drug concentration.
Epirubicin is rapidly metabolized by the liver to relatively or totally inactive metabolites: epirubicinol, 2 glucuronides and 4 aglycones.
There is better tolerability of this drug compared with doxorubicin.
Epirubicin and its metabolites are primarily eliminated through biliary excretion.
About 11 to 15% of the administered dose is eliminated as an unchanged drug, which makes up 6 to 7% of the excreted compounds, and metabolites.
The most common side effects are alopecia, nausea/vomiting, cardiotoxicity, leukopenia, and stomatitis.
Cardiotoxicity is a severe side effect and the exact pathway is still unknown.
Its cardiotoxicity is caused at least in part by the avid interaction of anthracyclines with iron, resulting in the formation of metal ion complexes.
It was first observed in adult cancer patients as clinical congestive heart failure (CHF), characterized by pulmonary oedema, fluid overload, and effort intolerance.
CHF-at 2.2% overall with a cumulative doxorubicin dose-dependent incidence of CHF of 3%, 7%, and 18% at 400, 550, and 700 mg/m2, respectively.
The major common negative effects are fever, diarrhea, nausea and vomiting.
More than 50% of patients without a right prophylactic antiemetics therapy experience nausea and vomiting the first 24 h after administration.
That fact occurs if the epirubicin dose is between 50 and 75 mg/m2 single doses.
Reversible alopecia and local cutaneous reactions are adverse effects.
Radiation recall and local reactions such as cellulitis, which cause development of tissue necrosis can occur, and pain if extravasation damage occurs.
Major adverse effects are cumulative dose-related cardiotoxicity and acute dose-limiting haematotoxicity, mucositis, inflammation and ulceration in mouth or mucous membranes.
The most adverse effect is secondary leukemia produced by breast cancer treated with epirubicin, particularly with a concomitant alkylating agent therapy.
Common toxicities are neutropenia (<1 × 109 cells/L) and in lesser mesures anemia and thrombocytopenia.
Its most acute dose-limiting toxicity of epirubicin is bone marrow suppression, irreversible cardiotoxicity such as an important chronic cumulative dose-limiting toxicity illness and myelosuppression.