title: Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer.
abstract: OBJECTIVE
  To determine the response rate and toxicity profile of trastuzumab administered concurrently with weekly vinorelbine in women with HER2-overexpressing advanced breast cancer.
  
  
  METHODS
  Forty women with HER2-positive (+3 by immunohistochemistry, n = 30; +2 or positive, n = 10) breast cancer were enrolled onto a study of trastuzumab (4 mg/kg x 1, 2 mg/kg weekly thereafter) and vinorelbine (25 mg/m2 weekly, with dose adjusted each week for neutrophil count). Eighty-two percent of women had received prior chemotherapy as part of adjuvant (30%), metastatic (25%), or both (28%) treatment, including substantial portions of patients who had previously received either anthracyclines (20%), taxanes (15%), or both types (38%) of chemotherapy.
  
  
  RESULTS
  Responses were observed in 30 of 40 patients (overall response rate, 75%, conditional corrected 95% confidence interval, 57% to 89%). The response rate was 84% in patients treated with trastuzumab and vinorelbine as first-line therapy for metastatic disease, and 80% among HER2 +3 positive patients. High response rates were also seen in women treated with second- or third-line therapy, and among patients previously treated with anthracyclines and/or taxanes. Combination therapy was feasible; patients received concurrent trastuzumab and vinorelbine in 93% of treatment weeks. Neutropenia was the only grade 4 toxicity. No patients had symptomatic heart failure. Grade 2 cardiac toxicity was observed in three patients. Prior cumulative doxorubicin dose in excess of 240 mg/m2 and borderline pre-existing cardiac function were associated with grade 2 cardiac toxicity.
  
  
  CONCLUSIONS
  Trastuzumab in combination with vinorelbine is highly active in women with HER2-overexpressing advanced breast cancer and is well tolerated.
authors.affiliation: Division of Adult Oncology and Department of Biostatistical Science, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Burstein
authors.forename: I
authors.initials: I
authors.lastname: Kuter
authors.forename: S M
authors.initials: SM
authors.lastname: Campos
authors.forename: R S
authors.initials: RS
authors.lastname: Gelman
authors.forename: L
authors.initials: L
authors.lastname: Tribou
authors.forename: L M
authors.initials: LM
authors.lastname: Parker
authors.forename: J
authors.initials: J
authors.lastname: Manola
authors.forename: J
authors.initials: J
authors.lastname: Younger
authors.forename: U
authors.initials: U
authors.lastname: Matulonis
authors.forename: C A
authors.initials: CA
authors.lastname: Bunnell
authors.forename: A H
authors.initials: AH
authors.lastname: Partridge
authors.forename: P G
authors.initials: PG
authors.lastname: Richardson
authors.forename: K
authors.initials: K
authors.lastname: Clarke
authors.forename: L N
authors.initials: LN
authors.lastname: Shulman
authors.forename: E P
authors.initials: EP
authors.lastname: Winer
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009202:Cardiomyopathies / Q000139:chemically induced; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D014747:Vinblastine; D000077235:Vinorelbine