Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma

BACKGROUND. Currently, there is no gold standard for the treatment of patie nts with metastatic breast carcinoma who have experienced failure with anth racyclines and taxanes. A biologic rationale: suggests that the mechanism o f taxane resistance could be because of an excess of depolymerized tubulin that could enhance sensitivity to vinorelbine. The objective of the study w as to assess the tolerance and efficiency of weekly vinorelbine in metastat ic breast carcinoma after failure with taxanes. METHODS. Patients with measurable disease, a World Health Organization perf ormance status of less than 3 and a life expectancy longer than 3 months we re eligible. Persistent taxane-induced neuropathy higher than Grade I was a n exclusion criterion. The initial planned dose was 30 mg/m(2)/week on an o utpatient basis without granulocyte colony- stimulating factor (G-CSF). Neu trophil and platelet counts of 1.0 and 80 g/L, respectively, were required before each new injection; otherwise vinorelbine was delayed for 7 days wit h a dose reduction of 5 mg/m(2) at the second episode. The dose also was re duced if Grade 3 or 4 toxicity occurred. If the adverse event persisted or if the delay exceeded 14 days between 2 injections given at a dose of 20 mg /m(2), vinorelbine was definitively discontinued. RESULTS. Between November 1997 and March 1999, 40 patients with a median ag e of 49 (range, 39-69) were enrolled. All of them had previously received a nthracyclines and taxanes. Because of the delays in neutrophil recovery, th e median dose intensity did not exceed 22.5 mg/m(2)/week (range, 11.25-30), and the initial planned dose of 30 mg/m(2)/week appeared unfeasible withou t G-CSF. The starting dose therefore was 25 mg/m(2)/week after the first 6 patients. Neutropenia led to fever in only three patients. Other severe tox icities were Grade 2-3 neuropathy (n = 5), Grade 2-3 ileus (n = 7), Grade 3 anemia (n = 4), and Grade 3 sepsis (n = 1). Objective responses were obser ved in 10 of 40 patients (25%), 7 of whom had visceral metastases and 4 who were refractory to taxanes (including 2 patients with liver involvement > 50%). The median time to failure was 6 months (range, 4-12) for responding patients, Disease stabilization was achieved in 9 patients (23%) for a medi an duration of 5 months (range, 4-6). The median survival duration for the whole population was 6 months (range, 2-18+). CONCLUSIONS. Weekly vinorelbine is an active salvage therapy for metastatic breast carcinoma after failure with anthracyclines and taxanes, even in pa tients with taxane-refractory metastatic breast carcinoma. This confirms th at vinorelbine and taxanes are not cross- resistant. (C) 2001 American Canc er Society.