General Information

Ellence (epirubicin hydrochloride injection) is an anthracycline cytotoxic agent intended for intravenous administration.

Ellence is specifically indicated as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer.

Ellence is supplied as a solution for intravenous injection. The recommended dose is 100 to 120 mg/m2 administered as an intravenous bolus. Administer Ellence in repeated 3- to 4-week cycles. The total dose of Ellence may be given on Day 1 of each cycle or divided equally and given on Days 1 and 8 of each cycle.

Mechanism of Action

Ellence (epirubicin) is an anthracycline cytotoxic agent. Although it is known that anthracyclines can interfere with a number of biochemical and biological functions within eukaryotic cells, the precise mechanisms of epirubicin’s cytotoxic and/or antiproliferative properties have not been completely elucidated. Epirubicin forms a complex with DNA by intercalation of its planar rings between nucleotide base pairs, with consequent inhibition of nucleic acid (DNA and RNA) and protein synthesis. Such intercalation triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Epirubicin also inhibits DNA helicase activity, preventing the enzymatic separation of double-stranded DNA and interfering with replication and transcription. Epirubicin is also involved in oxidation/reduction reactions by generating cytotoxic free radicals. The antiproliferative and cytotoxic activity of epirubicin is thought to result from these or other possible mechanisms. Epirubicin is cytotoxic in vitro to a variety of established murine and human cell lines and primary cultures of human tumors. It is also active in vivo against a variety of murine tumors and human xenografts in athymic mice, including breast tumors.

Clinical Trial Results

Two randomized, open-label, multicenter studies evaluated the use of ELLENCE Injection 100 to 120 mg/m 2 in combination with cyclophosphamide and fluorouracil for the adjuvant treatment of patients with axillary-node-positive breast cancer and no evidence of distant metastatic disease (Stage II or III). The primary endpoint was relapse free survival (RFS).

Study MA-5 evaluated 120 mg/m 2 of epirubicin per course in combination with cyclophosphamide and fluorouracil (CEF-120 regimen). This study randomized premenopausal and perimenopausal women with one or more positive lymph nodes to an epirubicin-containing CEF- 120 regimen or to a CMF regimen.

Study GFEA-05 evaluated the use of 100 mg/m 2 of epirubicin per course in combination with fluorouracil and cyclophosphamide (FEC-100). This study randomized pre- and postmenopausal women to the FEC-100 regimen or to a lower-dose FEC-50 regimen. In the GFEA-05 study, eligible patients were either required to have > 4 nodes involved with tumor or, if only 1 to 3 nodes were positive, to have negative estrogen- and progesterone-receptors and a histologic tumor grade of 2 or 3. A total of 1281 women participated in these studies. Patients with T4 tumors were not eligible for either study.

In Study MA-5, Ellence-containing combination therapy (CEF-120) showed significantly longer RFS than CMF (5-year estimates were 62% versus 53%). The estimated reduction in the risk of relapse was 24% at 5 years. The OS was also greater for the Ellence-containing CEF-120 regimen than for the CMF regimen (5-year estimate 77% versus 70%). The estimated reduction in the risk of death was 29% at 5 years.

In Study GFEA-05, patients treated with the higher-dose Ellence regimen (FEC-100) had a significantly longer 5-year RFS (estimated 65% versus 52%) and OS (estimated 76% versus 65%) than patients given the lower dose regimen (FEC-50). The estimated reduction in risk of relapse was 32% at 5 years. The estimated reduction in the risk of death was 31% at 5 years.