Epirubicin: a review of its efficacy as adjuvant therapy and in the treatment of metastatic disease in breast cancer

Drugs Aging. 1999 Nov;15(5):389-416. doi: 10.2165/00002512-199915050-00006.


Epirubicin is a semisynthetic derivative of doxorubicin which has been extensively evaluated in patients with breast cancer. It is effective in the management of metastatic disease and as adjuvant therapy in patients with early breast cancer. In the adjuvant setting, epirubicin-based therapy appears to have efficacy at least equivalent to that of the standard therapy cyclophosphamide, methotrexate and fluorouracil (CMF), with the most recent trials, predominantly in premenopausal patients, reporting significant gains in relapse-free survival and overall survival for epirubicin-based vs CMF therapy. In a single trial, the 5-year relapse-free survival of postmenopausal patients receiving long term hormonal therapy (tamoxifen) was significantly increased when epirubicin was added as single-agent chemotherapy and compared with tamoxifen alone. In patients with metastatic disease, epirubicin- and doxorubicin-containing regimens (with cyclophosphamide and fluorouracil; FEC and FAC) are therapeutically equivalent. Increasing the dose of epirubicin appears to improve response rates in patients with either metastatic or early disease but, with the exception of 1 adjuvant study, improved overall survival has not been demonstrated. Quality of life (QOL) has yet to be adequately evaluated with epirubicin. The major adverse effects of epirubicin are acute dose-limiting haematotoxicity and cumulative dose-related cardiotoxicity. Other important adverse effects include mucositis, nausea and vomiting, reversible alopecia and local cutaneous reactions. However, the tolerability of epirubicin is better than that of doxorubicin at equimolar doses.

Conclusion: Epirubicin has been extensively investigated in patients with breast cancer and has been found to be a highly effective agent, both for the treatment of patients with metastatic disease and as an adjuvant therapy. Recent trials have confirmed that, in selected patients requiring adjuvant therapy, FEC therapy is at least as effective as CMF, a standard treatment. FEC is also therapeutically equivalent to FAC in patients with metastatic breast cancer, and because the therapeutic index appears to be better the opportunity exists to increase dose intensity in an effort to improve efficacy. Such trials, and those of combinations of epirubicin with newer or alternative agents, should result in the introduction of more effective and better tolerated epirubicin-based protocols for adjuvant therapy and the management of patients with advanced breast cancer. In the meantime there is sufficient evidence to justify consideration of epirubicin for inclusion in first-line therapies for patients with early or metastatic breast cancer.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Adjuvants, Pharmaceutic / administration & dosage*
  • Adjuvants, Pharmaceutic / adverse effects
  • Adjuvants, Pharmaceutic / pharmacology
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / pharmacology
  • Antibiotics, Antineoplastic / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Clinical Trials as Topic
  • Epirubicin / adverse effects
  • Epirubicin / pharmacokinetics
  • Epirubicin / pharmacology
  • Epirubicin / therapeutic use*
  • Female
  • Humans
  • Neoplasm Metastasis
  • Quality of Life


  • Adjuvants, Pharmaceutic
  • Antibiotics, Antineoplastic
  • Epirubicin