Phase I/II trial of gemcitabine plus cyclophosphamide in patients with metastatic breast carcinoma previously treated with taxanes

The purpose of this study was to determine the maximum tolerated dose (MTD) of infusional gemcitabine given in conjunction with intravenous (I.V.) cyclophosphamide, and to determine whether the regimen produced a response rate of at least 40% in patients with metastatic breast cancer who have been previously treated with taxanes. Patients received cyclophosphamide (600 mg/m²) I.V. followed immediately by gemcitabine (100, 150, or 200 mg/m²) given as a 24-hour infusion (every 3 weeks) using an accelerated dose-escalation schema. Dose-limiting toxicity was defined as a neutrophil nadir < 500/μL, platelet nadir < 50,000/μL, or ≥ grade 2 nonhematologic toxicity (≥ grade 3 toxicity during the standard dose-escalation portion of the study). Twelve patients received a total of 32 cycles of therapy. The MTD of gemcitabine was 150 mg/m². Dose-limiting toxicities at 200 mg/m² included neutropenia and mucositis. One patient with lymphangitic lung metastases had a partial response (8%; 95% confidence intervals: 0%, 23%). This patient developed grade 4 transaminase and total bilirubin elevation that occurred affer the sixth cycle of therapy. The study was terminated due to an insufficient number of responses. The MTD of gemcitabine given as a 24-hour infusion is 150 mg/m² when used in conjunction with cyclophosphamide (600 mg/m²) every 3 weeks. This regimen is not likely to produce more than a 40% response rate in patients with metastatic breast cancer previously treated with taxanes.