Epirubicin, alone or in combination chemotherapy, for metastatic breast cancer. Provincial Breast Cancer Disease Site Group and the Provincial Systemic Treatment Disease Site Group.

Guideline question: How effective is epirubicin compared with doxorubicin in the treatment of metastatic breast cancer?

Objective: To make recommendations about the use of epirubicin, particularly compared with doxorubicin, in women with metastatic breast cancer.

Outcomes: Outcomes of interest are response rate, survival and toxicity.

Perspective (values): Evidence was reviewed and summarized by a member of the Provincial Systemic Treatment Disease Site Group (DSG) of the Cancer Care Ontario Practice Guidelines Initiative. Drafts of the practice guideline were reviewed and discussed by the Breast Cancer DSG of the Cancer Care Ontario Practice Guidelines Initiative. The 2 DSGs comprise medical oncologists, radiation oncologists, surgeons, epidemiologists, pathologists, nurses, pharmacists, a medical sociologist and a community representative.

Quality of evidence: Thirteen randomized controlled trials (11 published reports and 2 reports in abstract form) were reviewed that compared epirubicin and doxorubicin at equal doses, epirubicin at a higher dose than that of doxorubicin, and epirubicin at escalating doses.

Benefits: No significant differences were observed in response rate or median survival in the 7 trials comparing equal doses of epirubicin and doxorubicin or in the 3 trials comparing epirubicin at a higher dose than that of doxorubicin. An increased response rate was observed with higher doses of epirubicin in the 3 trials that compared escalating doses; no difference in survival was observed.

Harms: Compared with doxorubicin, epirubicin was associated with less nausea and vomiting (risk ratio [RR] 0.76; 95% confidence interval [CI] 0.63 to 0.92; p = 0.0048), less neutropenia (RR 0.52; 95% CI 0.35 to 0.78; p = 0.0017) and less cardiotoxicity (RR 0.43; 95% CI 0.24 to 0.77; p = 0.0044), including a trend toward fewer episodes of congestive heart failure (RR 0.38; 95% CI 0.14 to 1.04; p = 0.059).

Practice guideline: For the treatment of metastatic breast cancer in which the goal of treatment is palliation, epirubicin (at doses equivalent to doxorubicin) has been shown to be equally efficacious and less toxic than doxorubicin. Doxorubicin, however, is an acceptable alternative. CLINICAL PRACTICE GUIDELINE DATE: Oct. 2, 1997.