title: An EORTC pilot study of filgrastim (recombinant human granulocyte colony stimulating factor) as support to a high dose-intensive epiadriamycin-cyclophosphamide regimen in chemotherapy-naive patients with locally advanced or metastatic breast cancer.
abstract: BACKGROUND
  In an attempt to increase chemotherapy dose intensity by step-wise reduction of the time interval between treatment cycles, filgrastim was administered to breast cancer patients receiving a three-month combination chemotherapy with epirubicin (E) and cyclophosphamide (C).
  
  
  METHODS
  Chemotherapy-naïve patients with locally advanced or metastatic breast cancer received fixed doses of E (120 mg/m2) and C 9830 mg/m2) by 15-min i.v. infusion on day 1 of each cycle and filgrastim at a dose of 4 micrograms/kg once daily by SC injection starting 24 hours after chemotherapy. Cohorts of patients were treated in successive schedules, each schedule corresponding to a specified time interval between chemotherapy cycles. The toxicity observed in each schedule was evaluated before patients were accrued to the next schedule, which corresponded to a shorter time interval between chemotherapy cycles.
  
  
  RESULTS
  The maximum tolerated schedule was E (120 mg/m2) plus C 9830 mg/m2) given every 14 days with filgrastim support from day 2 until day 13. On this schedule, 5 of 12 patients experienced dose-intensity-limiting toxicities (DLT) during the 3-month study period. Non-hematological DLT occurred in 2/12 patients (mucositis, skin toxicity) while /312 experienced febrile neutropenia requiring i.v. antibiotics. All patients achieved recovery of ANC to >1.5 x 10(9)/l by the time of scheduled retreatment. The combination of filgrastim with this regimen did not seem to add major toxicities. The efficacy was high, with 87% of patients achieving an objective response and a median response duration of 18 months (range: 4-52 months).
  
  
  CONCLUSIONS
  Filgrastim permits at 33% increase in 'EC' dose intensification over that of the conventional every-3-week administration. Randomized studies should now be initiated to evaluate the merit, if any, of 'accelerated' chemotherapy in advanced breast cancer.
authors.affiliation: Jules Bordet Institute, Brussels, Belgium.
authors.forename: M J
authors.initials: MJ
authors.lastname: Piccart
authors.forename: P
authors.initials: P
authors.lastname: Bruning
authors.forename: J
authors.initials: J
authors.lastname: Wildiers
authors.forename: A
authors.initials: A
authors.lastname: Awada
authors.forename: J H
authors.initials: JH
authors.lastname: Schornagel
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.forename: E
authors.initials: E
authors.lastname: Tomiak
authors.forename: S
authors.initials: S
authors.lastname: Bartholomeus
authors.forename: P O
authors.initials: PO
authors.lastname: Witteveen
authors.forename: R
authors.initials: R
authors.lastname: Paridaens
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005060:Europe; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D000069585:Filgrastim