Epirubicin in combination with the taxanes

The anthracyclines, and doxorubicin in particular, have been the most widely used drugs for advanced and metastatic breast cancer. Epirubicin shares the same spectrum of antitumor activity as doxorubicin, however, a therapeutic advantage of epirubicin is the higher cumulative dose at which the anthracycline-induced cardiotoxicity becomes clinically evident. The taxanes have quickly been established as important chemotherapeutic agents in the armamentarium of drugs to treat breast cancer. Evaluation of the combination of anthracyclines with the taxanes was a logical research step with the aim to improve overall outcome and, potentially, survival of breast cancer patients. The findings of a high rate of cardiotoxicity from the initial phase II trials of combination doxorubicin/paclitaxel led investigators to alter the anthracycline and the taxane component of the combination by substitution with epirubicin and/or docetaxel, respectively. Results of phase I and II clinical trials with epirubicin plus a taxane shows a high level of antitumor activity, with the absence of significant cardiac toxicity and limited severity of other nonhematologic toxicities, thus making the epirubicin and taxane combinations highly attractive. Additional studies in metastatic breast cancer patients, for whom prolonged administration with an anthracycline is of potential clinical benefit, are underway. Evaluation of epirubicin and taxane combinations in the adjuvant setting are warranted and ongoing where prevention of cardiotoxicity is as important as efficacy.