title: A dose escalation trial of adjuvant cyclophosphamide and epirubicin in combination with 5-fluorouracil using G-CSF support for premenopausal women with breast cancer involving four or more positive nodes.
abstract: BACKGROUND
  Dose-dense and dose-intensive regimens have improved the outcome of breast cancer in high-risk women with operable disease.
  
  
  METHODS
  Sixty-three premenopausal women with Stage 2, 3 breast cancer and > or =4 positive axillary nodes were treated in three successive cohorts with 70 mg/m(2) of epirubicin, 500 mg/m(2) of 5-fluorouracil and G-CSF every 14 days for 12 cycles. Cyclophosphamide (C) was given at 700 mg/m(2), 900 mg/m(2), and 1100 mg/m(2) doses. Patients were evaluated for dose-limiting toxicities (DLTs) in the first four cycles, the primary endpoint of the trial.
  
  
  RESULTS
  No DLTs were seen at C 700 mg/m(2); at C 900 mg/m(2) two of 16 patients experienced febrile neutropenia and poor performance status; at C 1100 mg/m(2), 1 of 31 patients experienced poor performance status. Over 6 months, febrile neutropenia, grade 4 thrombocytopenia, grade 3 anemia and severe fatigue were observed. Clinical congestive heart failure occurred in three patients over 4 years.
  
  
  CONCLUSIONS
  A dose-intense and dose-dense regimen of cyclophosphamide, epirubicin and 5-fluorouracil was delivered with G-CSF without apparent increase in acute toxicity. Cyclophosphamide could be increased to more than twice the standard dose at the cost of more anemia and fatigue.
authors: Hotel Dieu Hospital, St Catharines, Ontario, Canada. brian.findlay@hdhsc.org
authors: B
authors: B
authors: Findlay
authors: K
authors: K
authors: Tonkin
authors: M
authors: M
authors: Crump
authors: B
authors: B
authors: Norris
authors: M
authors: M
authors: Trudeau
authors: M
authors: M
authors: Blackstein
authors: M
authors: M
authors: Burnell
authors: J
authors: J
authors: Skillings
authors: D
authors: D
authors: Bowman
authors: D
authors: D
authors: Walde
authors: M
authors: M
authors: Levine
authors: K I
authors: KI
authors: Pritchard
authors: M J
authors: MJ
authors: Palmer
authors: D
authors: D
authors: Tu
authors: L
authors: L
authors: Shepherd
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008207:Lymphatic Metastasis; D017697:Premenopause
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil