Optimal dosing of paclitaxel and doxorubicin in metastatic breast cancer

The taxanes and the anthracyclines are clearly the most effective agents available to treat breast cancer. Developing combinations based on these two drug types is a logical direction in clinical investigation. The doxorubicin/paclitaxel doublet has been evaluated by several groups using a variety of doses and schedules of administration. Preliminary data from single-arm phase I/II trials suggest that when administered as consecutive short infusions, these two drugs produce a high overall response rate with tolerable toxicity. Whether the complete remission rates, response durations, and survival rates achieved with this combination are equally promising awaits additional confirmatory trials, including ongoing randomized trials that compare this doublet with doxorubicin/cyclophosphamide. The apparent increase in the incidence of clinical congestive heart failure (approximately 20%) observed in the Milan and Copenhagen trials is a potential limitation of the long-term administration of this combination. Limiting the cumulative dose of doxorubicin, adding cardioprotectors, and substituting less cardiotoxic anthracylines (ie, epirubicin) represent investigational efforts to minimize cardiac toxicity.