Summary

Background: In vitro experiments suggest that administration of vinorelbine preceding paclitaxel results in synergistic cyto-toxic effects. A phase I dose escalation trial of vinorelbine daily x 3 with paclitaxel on day 3 repeated every 28 days in meta-static breast cancer patients was completed. Patients and methods: Female patients, PS 0-2, without evidence of CNS disease or prior neuropathies were treated with vinorelbine at dose levels 7, 10, 13 mg/m2 per day and paclitaxel over three hours at dose levels of 135, 175, and 200 mg/m2. Results: Twenty-eight patients with six dose levels were studied. At dose level 1, patients developed intolerable but reversible neutropenia. Subsequent dose levels required filgras-tim. Dose limiting toxicities were myalgia and fatigue at vinorelbine 13 mg/m2 /day and paclitaxel 200 mg/m2. Neuro-pathy was minor. Twelve of twenty-five patients with measurable disease had a rapid response which did not correlate with dose level. Conclusions: Sequential administration of these two agents demonstrates activity in breast cancer patients. Phase II dosing on this schedule should be vinorelbine 13 mg/m2/day x 3 and paclitaxel 175 mg/m2. With proper selection of patients, con-cern about neurologic toxicity should not impede future trials of vinorelbine with paclitaxel. Key words: breast cancer, paclitaxel, phase I, vinorelbin