Paclitaxel and anthracycline combination chemotherapy for metastatic breast cancer

Numerous clinical trials have demonstrated that the combination of paclitaxel and doxorubicin is extremely active in metastatic breast cancer. Overall response rates of 42% to 94% and complete response rates of 4% to 41% have been reported. However, several trials with the highest response rates were associated with the development of congestive heart failure (CHF) in approximately 20% of patients. These early findings resulted in reducing the maximum permitted cumulative dosages of doxorubicin in subsequent trials, with a corresponding decrease in cardiac toxicity being noted. Several subsequent series suggest that with cumulative dosing of 360 mg/m2 doxorubicin, the rate of CHF can be reduced to approximately 5%. A recently completed Eastern Cooperative Oncology Group phase III randomized trial comparing paclitaxel versus doxorubicin versus combination therapy with paclitaxel and doxorubicin noted an overall response rate of 33% and 34% in each single-agent arm, respectively, and a response rate of 46% with the combination therapy. There was an acceptable incidence of CHF. However, no difference in overall survival was noted with the combination therapy compared with the single-agent treatment. Losoxantrone, an anthrapyrazole in clinical development, has shown promising single-agent activity in metastatic breast cancer. An initial phase III randomized clinical trial comparing treatment with either paclitaxel alone versus losoxantrone and paclitaxel was recently completed. With no maximal cumulative dosage of losoxantrone incorporated into this trial design, an overall incidence of CHF of 4.9% was noted with combination therapy. Other hematologic and nonhematologic toxicities were overall acceptable with this new regimen as well. Additionally, preliminary analyses of clinical efficacy suggest that this new combination is promising therapy for the treatment of patients with metastatic breast cancer.