A phase II study of docetaxel and vinorelbine plus filgrastim for HER-2 negative, stage IV breast cancer: SWOG S0102.

Abstract

Docetaxel and vinorelbine have demonstrated Single-agent activity in breast cancer. Preclinical studies suggest potential synergy between these antitubulin chemotherapy agents. This study evaluates these drugs in combination in metastatic breast cancer. Taxane-naive patients with HER-2 negative, stage IV breast cancer without prior chemotherapy for metastatic disease, were eligible. Docetaxel (60 mg/m(2)) was given intravenously on Day 1, vinorelbine (27.5 mg/m(2)) intravenously on Days 8 and 15, and filgrastim on Days 2-21 of a 21-day cycle. The primary study outcome was one-year overall survival (OS), with secondary outcomes of progression-free survival (PFS), response rate (RR), and toxicity. Of 95 patients registered, 92 were eligible and received treatment. One-year OS was 74 % (95 % CI 64-82 %) with a median OS of 22.3 months (95 % CI 18.8-31.4 months). One-year PFS was 34 % (95 % CI 24-43 %) with median of 7.2 months (95 % CI 6.4-10.3). OS at 2 and 3 years were 49 % (95 % CI 38-59 %) and 30 % (95 % CI 21-40 %), respectively. OS was poorer for women with estrogen-receptor negative disease (n = 32) compared to estrogen-receptor positive (n = 60) (log-rank p = 0.031), but PFS was not significantly different (p = 0.11). RR was 59 % among the 74 patients with measurable disease. Grade 3 and 4 adverse events were 48 and 16 %, respectively. Grade 4 neutropenia was 12 % and grade 3/4 febrile neutropenia was 3 %. Common grade 3/4 nonhematologic toxicities were fatigue (14 %), pneumonitis (10 %), and dyspnea (9 %). The combination of docetaxel and vinorelbine is an active first-line chemotherapy in HER-2 nonoverexpressing, metastatic breast cancer. This combination is associated with significant hematologic and nonhematologic toxicity. The safety profile and expense of the filgrastim limit recommendations for routine use.

• Authors: Julie R Gralow, William E Barlow, Danika Lew, Kim Dammann, George Somlo, Kristine J Rinn, Stanley J Vogel, Lucas Wong, Robert B Livingston, Gabriel N Hortobagyi
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 143 Issue 2 Pg. 351-8 (Jan 2014) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 24352574 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Recombinant Proteins
• Taxoids
• Granulocyte Colony-Stimulating Factor
• Docetaxel
• Vinblastine
• ERBB2 protein, human
• Receptor, ErbB-2
• Filgrastim
• Vinorelbine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Breast Neoplasms (drug therapy, mortality)
• Disease-Free Survival
• Docetaxel
• Female
• Filgrastim
• Granulocyte Colony-Stimulating Factor (adverse effects, therapeutic use)
• Humans
• Middle Aged
• Neoplasm Staging
• Receptor, ErbB-2 (metabolism)
• Recombinant Proteins (adverse effects, therapeutic use)
• Survival
• Taxoids (adverse effects, therapeutic use)
• Treatment Outcome
• Vinblastine (adverse effects, analogs & derivatives, therapeutic use)
• Vinorelbine