Doxorubicin and paclitaxel in the treatment of advanced breast cancer: Efficacy and cardiac considerations

Doxorubicin and paclitaxel are highly active agents in the treatment of advanced breast cancer. Although early trials of the combination reported high response rates, an unexpectedly high incidence of congestive heart failure observed on two of the early trials was cause for much concern. More recently, clinical trials that have limited the cumulative doxorubicin dose to 400 mg/m² or below when given in combination with paclitaxel have not observed an increase in cardiac toxicity. In addition, a retrospective review of over 600 women with advanced breast cancer treated with doxorubicin and paclitaxel concluded that the combination could be administered safely up to a cumulative doxorubicin dose of 340-380 mg/m². It is likely that a pharmacokinetic interaction between doxorubicin and paclitaxel is, in large part, responsible for the higher than expected incidence of congestive heart failure observed in some studies. It appears that paclitaxel decreases the clearance of doxorubicin by approximately 30% when the two drugs are administered in close succession. Because the use of combination of doxorubicin and paclitaxel may benefit women with advanced breast cancer, a review of pertinent clinical studies and the implications of the pharmacokinetic interaction is provided. Particular attention has been paid to cardiac toxicities. It can be concluded that the use of combination doxorubicin and paclitaxel is safe up to a cumulative doxorubicin dose of 340-380 mg/m². This would allow for up to six courses of therapy with doxorubicin 60 mg/m² and paclitaxel 175 mg/m² by 3-hour infusion. Therapy can be continued with single-agent paclitaxel. In order to minimize cardiac risk, patients should be selected carefully and be monitored for adverse cardiac effects.