Treatment of metastatic breast cancer with combination paclitaxel/cyclophosphamide

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated substantial single-agent activity against both minimally pretreated and resistant metastatic breast cancer. Evaluation of paclitaxel-based combinations has demonstrated appreciable activity, but also toxicity, for the paclitaxel/doxorubicin combination. The paclitaxel/cyclophosphamide combination is potentially attractive because of the significant single-agent activity of both drugs against metastatic breast cancer and the paucity of shared nonhematologic toxicities. This combination is being evaluated in women with doxorubicin-refractory metastatic breast cancer. Dose escalation to paclitaxel 200 mg/m2 over 24 hours and cyclophosphamide 2,000 mg/m2 administered every 21 days with granulocyte colony-stimulating factor support has been performed. The final dose level was complicated by dose-limiting toxicity. The maximum tolerated dose for this combination is currently being defined. There is preliminary evidence of sequence-dependent toxicity. Grade 4 neutropenia and neutropenic fevers are more frequent in cycles in which paclitaxel is administered first.