title: Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia.
abstract: OBJECTIVE
  Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy.
  
  
  METHODS
  In a multicenter study, patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy, but also had > 20% risk for FN, were randomly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). The noninferiority hypothesis was that the incidence of FN would be maximally 7.5% higher in the experimental compared with the standard arm.
  
  
  RESULTS
  After inclusion of 167 eligible patients, the independent data monitoring committee advised premature study closure. Of 84 patients randomly assigned to G-CSF throughout all chemotherapy cycles, eight (10%) experienced an episode of FN. In contrast, of 83 patients randomly assigned to G-CSF during the first two cycles only, 30 (36%) had an FN episode (95% CI, 0.13 to 0.54), with a peak incidence of 24% in the third cycle (ie, first cycle without G-CSF prophylaxis).
  
  
  CONCLUSIONS
  In patients with early breast cancer at high risk for FN, continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus cannot be abandoned.
authors: Maureen J. Aarts and Vivianne C.G. Tjan-Heijnen, Maastricht University Medical Center, Maastricht; Frank P. Peters, Orbis Medical Center, Sittard-Geleen; Caroline M. Mandigers, Canisius Wilhelmina Hospital; Hanneke W. van Laarhoven and George F. Borm, Radboud University Nijmegen Medical Center; Saskia M. van Gastel; Comprehensive Cancer Centre East; George F. Borm, Nijmegen I, Nijmegen; M. Wouter Dercksen, Maxima Medical Center, Veldhoven; Laurence J. van Warmerdam, Catharina Hospital, Eindhoven; Jacqueline M. Stouthard, Maasstad Medical Center; Carin C. van der Rijt, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam; Hans J. Nortier, Leiden University Medical Center; Erdogan Batman, Diaconessenhuis Leiden, Leiden; Agnes J. van de Wouw, VieCuri Medical Center, Venlo; Esther M. Jacobs, Elkerliek Hospital, Helmond; Vera Mattijssen, Rijnstate Hospital, Arnhem; Tineke J. Smilde, Jeroen Bosch Hospital, 's-Hertogenbosch; Annette W. van der Velden, Martini Hospital, Groningen; Mehmet Temizkan, Hospital St Jansdal, Harderwijk; and Erik W. Muller, Slingeland Hospital, Doetinchem, the Netherlands.
authors: Maureen J
authors: MJ
authors: Aarts
authors: Frank P
authors: FP
authors: Peters
authors: Caroline M
authors: CM
authors: Mandigers
authors: M Wouter
authors: MW
authors: Dercksen
authors: Jacqueline M
authors: JM
authors: Stouthard
authors: Hans J
authors: HJ
authors: Nortier
authors: Hanneke W
authors: HW
authors: van Laarhoven
authors: Laurence J
authors: LJ
authors: van Warmerdam
authors: Agnes J
authors: AJ
authors: van de Wouw
authors: Esther M
authors: EM
authors: Jacobs
authors: Vera
authors: V
authors: Mattijssen
authors: Carin C
authors: CC
authors: van der Rijt
authors: Tineke J
authors: TJ
authors: Smilde
authors: Annette W
authors: AW
authors: van der Velden
authors: Mehmet
authors: M
authors: Temizkan
authors: Erdogan
authors: E
authors: Batman
authors: Erik W
authors: EW
authors: Muller
authors: Saskia M
authors: SM
authors: van Gastel
authors: George F
authors: GF
authors: Borm
authors: Vivianne C G
authors: VC
authors: Tjan-Heijnen
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D057239:Early Termination of Clinical Trials; D064147:Febrile Neutropenia / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D015999:Multivariate Analysis; D009426:Netherlands / Q000453:epidemiology; D011092:Polyethylene Glycols; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim