Sequential dose-dense adjuvant therapy with doxorubicin, paclitaxel, and cyclophosphamide

The recognition of paclitaxel's (Taxol) activity and non-cross-resistance with doxorubicin (Adriamycin) in the treatment of metastatic breast cancer has motivated study of the agent in the adjuvant setting. However, the ideal means of incorporating this new agent is not yet known. In stage IV disease, exciting results have been seen with combinations of doxorubicin plus paclitaxel, and this approach is being tested as adjuvant treatment. An alternative approach that has produced superior results with other non-cross-resistant regimens is sequential administration of the combination agents. Based on prior clinical trials, we tested sequential dose-dense therapy with high-dose doxorubicin, followed first by paclitaxel and then by cyclophosphamide (Cytoxan) for high-risk operable breast cancer. This regimen was associated with marked toxicity but was nonetheless tolerable and resulted in promising relapse-free survival. This regimen is now being compared to high-dose chemotherapy with autologous stem cell support for women with operable breast cancer, metastatic to four to nine axillary lymph nodes.