title: Impact of five prophylactic filgrastim schedules on hematologic toxicity in early breast cancer patients treated with epirubicin and cyclophosphamide.
abstract: OBJECTIVE
  To evaluate the comparative efficacy of varying intensity schedules of recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) support in preventing febrile neutropenia in early breast cancer patients treated with relatively high-dose epirubicin plus cyclophosphamide (EC).
  
  
  METHODS
  From October 1991 to April 1994, 506 stage I and II breast cancer patients were randomly assigned to receive, in a factorial 2 x 2 design, epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 intravenously on day 1 every 21 days for 4 cycles +/- lonidamine +/- G-CSF. The following five consecutive G-CSF schedules were tested every 100 randomly assigned patients: (1) 480 microg/d subcutaneously days 8 to 14; (2) 480 microg/d days 8, 10, 12, and 14; (3) 300 microg/d days 8 to 14; (4) 300 microg/d days 8, 10, 12, and 14; and (5) 300 microg/d days 8 and 12.
  
  
  RESULTS
  All of the G-CSF schedules covered the neutrophil nadir time. Schedule 5 was equivalent to the daily schedules (schedules 1 and 3) and to the alternate day schedules (schedules 2 and 4) with respect to incidence of grade 3 and 4 neutropenia (P = .79 and P = .89, respectively), rate of fever episodes (P = .84 and P = .77, respectively), incidence of neutropenic fever (P = .74 and P = .56, respectively), need of antibiotics (P = .77 and P = .88, respectively), and percentage of delayed cycles (P = .43 and P = .42, respectively). G-CSF had no significant impact on the delivered dose-intensity compared with the non-G-CSF arms.
  
  
  CONCLUSIONS
  In the adjuvant setting, the frequency of prophylactic G-CSF administration during EC could be curtailed to only two administrations (days 8 and 12) without altering outcome. This nonrandomized trial design provides support for evaluating alternative, less intense G-CSF schedules for women with early breast cancer.
authors.affiliation: Division of Medical Oncology, Department of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy. p.papaldo@mclink.it
authors.forename: Paola
authors.initials: P
authors.lastname: Papaldo
authors.forename: Massimo
authors.initials: M
authors.lastname: Lopez
authors.forename: Paolo
authors.initials: P
authors.lastname: Marolla
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.forename: Mauro
authors.initials: M
authors.lastname: Antimi
authors.forename: Edmondo
authors.initials: E
authors.lastname: Terzoli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
authors.forename: Carlo
authors.initials: C
authors.lastname: Barone
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Ferretti
authors.forename: Serena
authors.initials: S
authors.lastname: Di Cosimo
authors.forename: Paolo
authors.initials: P
authors.lastname: Carlini
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nisticò
authors.forename: Francesca
authors.initials: F
authors.lastname: Conti
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Lauro
authors.forename: Claudio
authors.initials: C
authors.lastname: Botti
authors.forename: Franco
authors.initials: F
authors.lastname: Di Filippo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.forename: Federico
authors.initials: F
authors.lastname: Calabresi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D000069585:Filgrastim