Paclitaxel-containing combination chemotherapy for metastatic breast cancer

After demonstration of the marked antitumor activity against metastatic breast cancer of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), other clinical trials explored the possibility of combining this new active agent with other cytotoxic drugs with proven efficacy against breast carcinoma. Paclitaxel plus doxorubicin, thought to be the most effective single agents against breast cancer, yielded remission rates ranging from 60% to 80%, including some complete remissions. Schedule-dependent toxic interactions were observed when paclitaxel preceded the administration of doxorubicin. Paclitaxel by 3-hour infusion plus doxorubicin by bolus proved to be a highly tolerable regimen, with overall remission rates in excess of 90% and complete remission rates approaching 50%. A paclitaxel plus cisplatin combination has been studied at numerous schedules and doses with variable activity and tolerability, although one group in Vancouver, Canada, reported an 85% overall response rate with the combination administered on a 14-day schedule in previously treated patients, most of whom had received doxorubicin. Paclitaxel also has been combined with cyclophosphamide, mitoxantrone, edatrexate, 5-fluorouracil, and other agents for the treatment of breast cancer. Of interest are recent reports on paclitaxel and vinorelbine, showing this combination to be clearly active, with good tolerability and rapid recovery after myelosuppression. Trials of this combination are ongoing with granulocyte colony-stimulating factor support, on an every-14-day schedule. The doxorubicin/paclitaxel doublet remains the most promising in terms of activity, although other combinations with a high degree of activity and good tolerance are being sought.