Dose-finding study of paclitaxel and cyclophosphamide in patients with advanced breast cancer.

Escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (administered as a 3-hour infusion) and cyclophosphamide have been given to patients with advanced breast cancer every 3 weeks to determine the maximum tolerated dose of the two drugs in combination without granulocyte colony-stimulating factor (G-CSF) support. The maximum tolerated dose of the same regimen with G-CSF support will then be determined in a subsequent group of patients. Patients who had received no more than one prior chemotherapy regimen for advanced disease were eligible for this study. The need for G-CSF support was established by an absolute neutrophil count (ANC) less than 0.5 x 10(9)/L for more than 7 days, an ANC count less than 0.1 x 10(9)/L for more than 3 days, febrile neutropenia requiring intravenous antibiotics, World Health Organization grade 3 or greater mucositis for more than 7 days, or the failure of the ANC to recover by day 28. The maximum tolerated dose was defined as the dose level at which more than two of six patients treated needed G-CSF support during the second treatment cycle. To date, 20 patients have been entered at the following dose levels: paclitaxel 135 mg/m2 and cyclophosphamide 750 mg/m2 (level 1), paclitaxel 155 mg/m2 and cyclophosphamide 750 mg/m2 (level 2), paclitaxel 175 mg/m2 and cyclophosphamide 600 mg/m2 (level 3), and paclitaxel 175 mg/m2 and cyclophosphamide 750 mg/m2 (level 4). Only one patient at level 2 needed G-CSF support because of an ANC below 0.1 x 10(9)/L for more than 3 days after the first cycle. Neither febrile neutropenia nor treatment delay for more than 1 week was reported. Antitumor activity has been observed from level 3. The evaluation of the toxicity of paclitaxel 200 mg/m2 and cyclophosphamide 175 mg/m2 without G-CSF support is ongoing.