Patients and Methods: This single-center nonrandomized trial enrolled 40 patients. Anthracycline exposure and subsequent progression were common to all patients, and 38 of 40 were paclitaxel-refractory. Vinorelbine was given initially at 30 mg/m(2)/wk, then at 35 mg/m(2)/wk in a phase I/II design, which involved first intermittent (6 days of 7) and then continuous (daily) administration of G-CSF at 5 mu g/kg.

Results: The maximum-tolerated starting dose was 35 mg/m(2)/wk with continuous G-CSF support, The mean DDI was 27.7 mg/m(2)/wk for all patients, There were two complete responses (CRs) and eight partial responses (PRs) in 40 assessable patients for an overall response rate of 25% (95% confidence interval [CI], 13% to 41%). The median TTP was 13 weeks and median survival time 33 weeks. The dose-limiting toxicity was neutropenia, with dose delay or reduction required in 14 of 27 patients entered at 35 mg/m(2). Febrile neutropenia that required hospitalization was unusual (three of 40 patients, 8%). There were no treatment-related deaths. Grade 3/4 thrombocytopenia occurred in nine patients (23%) and 26 patients (65%) required RBC transfusions for anemia. Seven patients (18%) had reversible grade 3/4 nonhematologic complications, primarily related to neurotoxicity. Grade greater than or equal to 3 mucositis was absent.

Conclusion: Concurrent administration of weekly vinorelbine and daily G-CSF is feasible and permits an increase in DDI for vinorelbine of 43% to 76% over that reported in series without growth factor support. The response rate, TTP, and survival data are encouraging for therapy given to heavily pretreated patients with metastatic breast cancer, Vinorelbine is not cross-resistant with paclitaxel and should be considered for further trials in the dose-intensified mode made possible by G-CSF, alone or combined with other agents. (C) 1997 by American Society of Clinical Oncology.