Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue.

Abstract

Epirubicin (4'-epidoxorubicin) is an antineoplastic agent derived from doxorubicin. The compounds differ in the configuration of the hydroxyl group at the 4' position. Epirubicin, like doxorubicin, exerts its antitumor effects by interference with the synthesis and function of DNA and is most active during the S phase of the cell cycle. Epirubicin is administered by intravenous (IV) injection. It is metabolized by the liver and primarily eliminated in the bile. About 10% of the drug is eliminated in the urine. Dosage adjustments are recommended for patients with liver metastases or elevated liver function tests. The elimination half-life of epirubicin is 30 to 40 hours. Clinical studies indicate activity in breast cancer, non-Hodgkin's lymphomas, ovarian cancer, soft-tissue sarcomas, and pancreatic cancer. There is also evidence of activity against gastric cancer, small-cell lung cancer, and acute leukemia. Epirubicin has limited activity as a single agent against head and neck tumors or non-small-cell lung cancer, but may be beneficial in combination with other agents. The overall activity of epirubicin appears to be comparable with that of doxorubicin. However, more studies are needed to define its role in combination chemotherapeutic regimens. The acute dose-limiting toxicity of epirubicin is myelosuppression. Nausea, vomiting, and alopecia are also common. Epirubicin may cause transient cardiac arrhythmias and alterations of the electrocardiogram. Chronic therapy is limited, but available data indicate that epirubicin can be administered in higher cumulative doses than doxorubicin before cardiotoxicity limits further therapy.

Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation

“…This regimen was first reported in 1991, with the three drugs being selected on the basis of their single agent activity in upper GIT tumours (Beer et al, 1983;Cersosimo and Hong, 1986;Machover et al, 1986), and on the synergy demonstrated between 5-FU and cisplatin in preclinical models (Etienne et al, 1991). ECF is associated with response rates of approximately 45% in patients with metastatic gastric cancer, although higher response rates are seen when used for locally advanced disease (Findlay et al, 1994;Waters et al, 1999).…”

[18F]2-Fluoro-2-deoxy-D-glucose incorporation by AGS gastric adenocarcinoma cells in vitro during response to epirubicin, cisplatin and 5-fluorouracil

“…5-FU exposure resulted in a build up of cells in S phase (LD 10 ) and G 1 (LD 50 ). Epirubicin, an anthracycline derivative of doxorubicin, exerts its anti-tumour effects via its action as a DNA intercalating agent and as an inhibitor of topoisomerase II (Cersosimo and Hong, 1986;Bartkowiak et al, 1992;Zoli et al, 2004). The arrest of AGS cells at higher concentrations of epirubicin may be related to peak activity of topoisomerases occurring during the G 2 phase (Chow and Ross, 1987).…”

Targeting anthracyclines in early breast cancer: new candidate predictive biomarkers emerge

“…Two of the most commonly used anthracyclines are epirubicin and doxorubicin. Epirubicin is the 4 0 -epimer of doxorubicin, with a different spatial orientation of the hydroxyl group at the C-4 0 position of doxorubicin (reviewed in Cersosimo and Hong, 1986). This may contribute to the faster elimination rate and reduced toxicity of epirubicin, making it preferential, in some chemotherapy regimens, to doxorubicin.…”