Epirubicin

From discovery to approval

1. 1975 · Earliest report found

   A 1975 paper by Arcamone and colleagues in the Journal of Medicinal Chemistry reported the synthesis of 4'-epi-adriamycin (epirubicin) and 4'-epi-daunorubicin by condensing a sugar with the aglycones daunomycinone or a protected adriamycinone. The label calls epirubicin the 4'-epimer of doxorubicin.^[2][3][4][1]

2. 1999-09-15 · FDA regular

   Use of Ellence as a component of adjuvant therapy in patients with evidence of axillary node tumour involvement following resection of primary breast cancer. The type regular is an inference: the letter has no accelerated-approval wording.^[5]

How it works

Forms a complex with DNA by intercalation between base pairs, inhibiting DNA, RNA and protein synthesis; the label says this intercalation triggers DNA cleavage by topoisomerase II. It also inhibits DNA helicase and generates free radicals. Its activity is thought to result from these or other possible mechanisms.^[1]

Where it came from and why

Arcamone's 1984 review says the therapeutic importance of adriamycin prompted a research programme from 1972 to develop second-generation anthracyclines, which yielded epirubicin, idarubicin and esorubicin. The 1975 abstract reports that 4'-epi-adriamycin appeared nontoxic to cultured heart cells up to 5 micrograms per millilitre.

Cancers

• Breast cancer, adjuvant

  The 1999 US label and approval letter list epirubicin as a component of adjuvant therapy in patients with axillary node tumour involvement after resection of primary breast cancer; the 2026 label keeps this indication.^[5]

• Breast cancer, dose comparison

  The French Adjuvant Study Group 05 randomised 565 patients to FEC 50 or FEC 100 (fluorouracil, cyclophosphamide, epirubicin 50 or 100 mg/m2) after surgery for node-positive early breast cancer.^[6]

Family and partners

Derived from: Doxorubicin, Daunorubicin

Worth knowing

• At 10 years in the French FASG-05 trial, disease-free survival was 45.3% with FEC 50 and 50.7% with FEC 100 (Wilcoxon p=0.036, log-rank p=0.08), and overall survival was 50.0% and 54.8% (Wilcoxon p=0.038, log-rank p=0.05).^[6]
• The 1999 US label estimates the probability of clinically evident congestive heart failure at approximately 0.9% at a cumulative dose of 550 mg/m2, 1.6% at 700 mg/m2 and 3.3% at 900 mg/m2.^[1]
• A 1985 lecture abstract states that, because of the different orientation of the 4'-hydroxyl group, epirubicin is partly detoxified in the human body by beta-glucuronidation.^[4]

References

1. U.S. Food and Drug Administration. Ellence (epirubicin hydrochloride injection): label, revised package insert 15 September 1999 (NDA 050778, original approval). Source
2. Arcamone F, Penco S, Vigevani A, Redaelli S, Franchi G, DiMarco A, et al. Synthesis and antitumor properties of new glycosides of daunomycinone and adriamycinone. J Med Chem. 1975;18(7):703-7. PubMedDOI
3. Arcamone F. [Adriamycin and its analogs]. Tumori. 1984;70(2):113-9. PubMedDOI
4. Arcamone F. Properties of antitumor anthracyclines and new developments in their application: Cain memorial award lecture. Cancer Res. 1985;45(12 Pt 1):5995-9. PubMed
5. U.S. Food and Drug Administration. Approval letter, NDA 50-778, Ellence (epirubicin hydrochloride injection), 15 September 1999. Source
6. Bonneterre J, Roché H, Kerbrat P, Brémond A, Fumoleau P, Namer M, et al. Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French Adjuvant Study Group 05 randomized trial. J Clin Oncol. 2005;23(12):2686-93. PubMedDOI
7. Pharmacia & Upjohn Company LLC. Ellence (epirubicin hydrochloride injection): prescribing information. DailyMed, set ID 0a03c798-a652-4895-b29c-3b521a89ba42, published 30 July 2026. Source