A phase I study of sequential vinorelbine followed by paclitaxel

Background: In vitro experiments suggest that administration of vinorelbine preceding paclitaxel results in synergistic cytotoxic effects. A phase I d ose escalation trial of vinorelbine daily x 3 with paclitaxel on day 3 repe ated every 28 days in metastatic breast cancer patients was completed. Patients and methods: Female patients, PS 0-2, without evidence of CNS dise ase or prior neuropathies were treated with vinorelbine at dose levels 7, 1 0, 13 mg/m(2) per day and paclitaxel over three hours at dose levels of 135 , 175, and 200 mg/m(2). Results: Twenty-eight patients with six dose levels were studied. At dose l evel 1, patients developed intolerable but reversible neutropenia. Subseque nt dose levels required filgrastim. Dose limiting toxicities were myalgia a nd fatigue at vinorelbine 13 mg/m(2) /day and paclitaxel 200 mg/m(2). 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 act ivity in breast cancer patients. Phase II dosing on this schedule should be vinorelbine 13 mg/m(2)/day x 3 and paclitaxel 175 mg/m(2). With proper sel ection of patients, concern about neurologic toxicity should not impede fut ure trials of vinorelbine with paclitaxel.