Phase I study of vinorelbine and paclitaxel by 3-hour simultaneous infusion with and without granulocyte colony-stimulating factor support in metastatic breast carcinoma

BACKGROUND. The purpose of the study was to determine the maximum tolerated dose (MTD) of vinorelbine and paclitaxel given concomitantly in patients with advanced breast carcinoma, the toxicity of this combination, and whether the addition of granulocyte colony-stimulating factor (G-CSF) would allow administration of higher doses of the combination. METHODS. Between January 1994 and January 1995, 38 patients were entered on this study. All patients received vinorelbine and paclitaxel administered simultaneously over 3 hours and repeated every 21 days as frontline therapy for metastatic breast carcinoma. Twenty-five patients (Group 1) did not receive prophylactic G-CSF, and 13 patients (Group 2) received prophylactic G-CSF. Toxic effects were documented prospectively using the National Cancer Institute grading system. RESULTS. One hundred eighty-seven (Group 1) and 111 (Group 2) cycles were administered. For Group 1, Grade 3-4 granulocytopenia was encountered in 72% of the cycles and neutropenic fever in 30% of the cycles. For Group 2, Grade 3-4 granulocytopenia and neutropenic fever were encountered in 23% and 4% of the cycles, respectively. Grade 3-4 fatigue and myalgia, respectively, were encountered in 11% and 3% of the cycles in Group 1, whereas they were reported in 12% and 1% of the cycles in Group 2. The MTD of this combination without prophylactic G-CSF was 25 mg/m² of vinorelbine and 150 mg/m² of paclitaxel, the dose-limiting toxicity (DLT) being neutropenic fever and myalgia. The MTD of this combination with G-CSF was 36 mg/m² of vinorelbine and 150 mg/m² of paclitaxel, the DLT being myalgia and fatigue. CONCLUSIONS. The authors conclude that vinorelbine and paclitaxel can be safely administered concomitantly and are well tolerated. Phase II studies are recommended to test the efficacy of this schedule.