title: 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.affiliation: University of Washington School of Medicine/Seattle Cancer Care Alliance, 825 Eastlake Avenue East, G3-630, Seattle, WA, 98109, USA, pink@u.washington.edu.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Gralow
authors.forename: William E
authors.initials: WE
authors.lastname: Barlow
authors.forename: Danika
authors.initials: D
authors.lastname: Lew
authors.forename: Kim
authors.initials: K
authors.lastname: Dammann
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.forename: Kristine J
authors.initials: KJ
authors.lastname: Rinn
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Vogel
authors.forename: Lucas
authors.initials: L
authors.lastname: Wong
authors.forename: Robert B
authors.initials: RB
authors.lastname: Livingston
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013534:Survival; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D000077143:Docetaxel; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D043823:Taxoids; D014747:Vinblastine; D000077235:Vinorelbine; C508053:ERBB2 protein, human