title: Addition of GM-CSF to trastuzumab stabilises disease in trastuzumab-resistant HER2+ metastatic breast cancer patients.
abstract: BACKGROUND
  One of the proposed mechanisms of trastuzumab-induced regression of human epidermal growth factor receptor 2-positive (HER2+) tumours includes facilitation of antibody-dependent cell-mediated cytotoxicity (ADCC). Granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates ADCC. We presented our pilot study of adding GM-CSF to trastuzumab in patients with trastuzumab-resistant HER2+ metastatic breast cancer.
  
  
  METHODS
  Patients with HER2+ metastatic breast cancer that progressed after trastuzumab +/- chemotherapy were continued on trastuzumab 2 mg kg(-1) intravenous weekly and GM-CSF 250 μg m(-2) subcutaneous daily. Patients were assessed for response every 8 weeks. Treatment was continued until disease progression or intolerable toxicity.
  
  
  RESULTS
  Seventeen patients were evaluable (median age 48 years, range 27-75 years). The median number of metastatic sites was 2 (range 1-3); the most common site was the liver (n=10). The median number of prior regimens for metastatic disease was 2 (range 1-5). No objective disease response was observed, but five patients (29%) had stable disease for a median duration of 15.8 (range 10-53.9) weeks. The most common adverse event was rash at the injection site. No grade 4 or irreversible adverse event was seen.
  
  
  CONCLUSIONS
  The addition of GM-CSF to trastuzumab alone had a modest clinical benefit and acceptable safety profile in heavily pretreated patients with trastuzumab-resistant HER2+ metastatic breast cancer.
authors.affiliation: Division of Neoplastic Diseases and Related Disorders, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Cheng
authors.forename: V
authors.initials: V
authors.lastname: Valero
authors.forename: M L
authors.initials: ML
authors.lastname: Davis
authors.forename: M C
authors.initials: MC
authors.lastname: Green
authors.forename: A M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.forename: R L
authors.initials: RL
authors.lastname: Theriault
authors.forename: J L
authors.initials: JL
authors.lastname: Murray
authors.forename: G N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: N T
authors.initials: NT
authors.lastname: Ueno
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; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D018734:Genes, erbB-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010865:Pilot Projects; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000068878:Trastuzumab