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

Laurent Zelek, S. Barthier, M. Riofrio, K. Fizazi, O. Rixe, J. P. Delord, A. Lecesne, M. Spielmann

    Research output: Contribution to journalArticlepeer-review

    144 Citations (Scopus)

    Abstract

    BACKGROUND. Currently, there is no gold standard for the treatment of patients with metastatic breast carcinoma who have experienced failure with anthracyclines and taxanes. A biologic rationale suggests that the mechanism of taxane resistance could be because of an excess of depolymerized tubulin that could enhance sensitivity to vinorelbine. The objective of the study was to assess the tolerance and efficiency of weekly vinorelbine in metastatic breast carcinoma after failure with taxanes. METHODS. Patients with measurable disease, a World Health Organization performance status of less than 3 and a life expectancy longer than 3 months were eligible. Persistent taxane-induced neuropathy higher than Grade 1 was an exclusion criterion. The initial planned dose was 30 mg/m2/week on an outpatient basis without granulocyte colony-stimulating factor (G-CSF). Neutrophil and platelet counts of 1.0 and 80 g/L, respectively, were required before each new injection; otherwise vinorelbine was delayed for 7 days with a dose reduction of 5 mg/m2 at the second episode. The dose also was reduced 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/m2, vinorelbine was definitively discontinued. RESULTS. Between November 1997 and March 1999, 40 patients with a median age of 49 (range, 39-69) were enrolled. All of them had previously received anthracyclines and taxanes. Because of the delays in neutrophil recovery, the median dose intensity did not exceed 22.5 mg/m2/week (range, 11.25-30), and the initial planned dose of 30 mg/m2/week appeared unfeasible without G-CSF. The starting dose therefore was 25 mg/m2/week after the first 6 patients. Neutropenia led to fever in only three patients. Other severe toxicities 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 observed 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 median 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 patients with taxane-refractory metastatic breast carcinoma. This confirms that vinorelbine and taxanes are not cross-resistant.

    Original languageEnglish
    Pages (from-to)2267-2272
    Number of pages6
    JournalCancer
    Volume92
    Issue number9
    DOIs
    Publication statusPublished - 1 Nov 2001

    Keywords

    • Chemotherapy
    • Metastatic breast carcinoma
    • Salvage regimen
    • Vinorelbine

    Cite this