Introduction
An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.
Uses
Epirubicin is an anthracycline topoisomerase II inhibitor used as an adjuvant to treating axillary node metastases in patients who have undergone surgical resection of primary breast cancer.
For use as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer.
Associated Conditions
Pharmacodynamics
Epirubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Epirubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Epirubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.
Mechanism of Action
Epirubicin has antimitotic and cytotoxic activity. It inhibits nucleic acid (DNA and RNA) and protein synthesis through a number of proposed mechanisms of action: Epirubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. It also interferes with DNA replication and transcription by inhibiting DNA helicase activity.
Absorption
100%
Volume of Distribution
- 21 ± 2 L/kg [60 mg/m2 Dose]
- 27 ± 11 L/kg [75 mg/m2 Dose]
- 23 ± 7 L/kg [120 mg/m2 Dose]
- 21 ± 7 L/kg [150 mg/m2 Dose]
Protein Binding
77%
Route of Elimination
Epirubicin and its major metabolites are eliminated through biliary excretion and, to a lesser extent, by urinary excretion.
Half Life
Half-lives for the alpha, beta, and gamma phases of about 3 minutes, 2.5 hours and 33 hours, respectively
Clearance
- 65 +/- 8 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 60 mg/m2]
- 83 +/- 14 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 75 mg/m2]
- 65 +/- 13 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 120 mg/m2]
- 69 +/- 13 L/hour [Patients1 with Solid Tumors Receiving Intravenous Epirubicin 150 mg/m2]
Toxicity
bone marrow aplasia, grade 4 mucositis, and gastrointestinal bleeding
Food Interactions
- Drink plenty of fluids. Increased fluid intake increases urine output and the excretion of uric acid.
Dosage
The recommended dose of Epirubicin is 100 to 120 mg/m². The following regimens are recommended:
CEF-120:
- Cyclophosphamide: 75 mg/m² PO D 1-14
- Epirubicin: 60 mg/m² IV D 1, 8
- 5-Fluorouracil: 500 mg/m² IV D 1, 8
- Repeated every 28 days for 6 cycles
- 5-Fluorouracil: 500 mg/m²
- Epirubicin: 100 mg/m²
- Cyclophosphamide: 500 mg/m²
