title: Accelerated chemotherapy with high-dose epirubicin and cyclophosphamide plus r-met-HUG-CSF in locally advanced and metastatic breast cancer.
abstract: BACKGROUND
  This study evaluated the toxicity of high-dose epirubicin and cyclophosphamide plus r-met-HUG-CSF (G-CSF) given every 2 weeks and compared the dose-intensity achieved with this schedule with that obtained in a previous study we conducted in which the same regimen was given every 3 weeks without G-SCF (EC 21). The secondary objective was to explore the activity of this regimen.
  
  
  METHODS
  Between December 1991 and March 1994, 41 patients (pts), 19 with locally advanced breast cancer (LABC) and 22 with metastatic breast cancer (MBC), were given high-dose epirubicin (Hd-Epi) (120 mg/m2) and cyclophosphamide (CTX) (600 mg/m2) on day 1 every 14 days (EC 14) plus granulocyte colony-stimulating factor (G-CSF) (5 mcg/kg/d s.c. on days 2-12). A total of 8 cycles in LABC pts (4 pre- and post-surgery), and 6-8 cycles in MCB pts were administered. The results were compared with those obtained in the previous study.
  
  
  RESULTS
  The incidence of WHO grade 3-4 neutropenia was significantly reduced in the EC 14 + G-CSF regimen (25.2% vs. 46.8% in 214 and 250 evaluable cycles, respectively, p<0.0001), as well as the incidence of neutropenic fever (7% vs. 3%, p=0.05). Grade 3-4 anemia (36.6% vs. 8% pts, p=0.001) and grade 3-4 thrombocytopenia (17.1% vs. 0 pts, p=0.002), were significantly more frequent in EC 14 + G-CSF. No significant differences in the other side effects were found. A total of 17 of 207 of the cycles (8.2%) were delayed in the EC 14 + G-CSF vs. 58/271 (21.4%) in the EC 21 (p<0.0001). The main reasons for these treatment delays were neutropenia (1% vs. 15%), anemia (3% vs. 0) and thrombocytopenia (1% vs. 0). As a result of treatment acceleration and differences in dose delays, the patients on EC 14 + G-CSF received a higher dose-intensity (Epi 58.51 mg/m2/wk vs. 36.8 mg/m2/wk; CTX 292.52 mg/m2/wk vs. 182.9 mg/m2/wk). A complete response at surgery was obtained in 9/19 (47.4%) LABC pts. An objective CR was obtained in 11/22 MBC pts (50%) and a partial response in 8/22 (36.4%), yielding an overall response rate of 86.4%.
  
  
  CONCLUSIONS
  Hd-Epi + CTX is very active against both LABC and MBC. The administration of G-CSF allows dose intensification of both drugs (a 59.5% increase of the actual dose intensity) with acceptable clinical tolerance (a lower incidence of neutropenia but a higher incidence of anemia and thrombocytopenia). Only a specifically designed phase III trial will lead to definitive conclusions regarding the greater antitumor activity of accelerated CSF-including regimens as compared to standard chemotherapy for advanced breast cancer.
authors.affiliation: Servizio di Oncologia Medica, Istituto Regina Elena per lo Studio e la Cura dei Tumori, Rome, Italy.
authors.forename: A F
authors.initials: AF
authors.lastname: Scinto
authors.forename: V
authors.initials: V
authors.lastname: Ferraresi
authors.forename: N
authors.initials: N
authors.lastname: Campioni
authors.forename: R
authors.initials: R
authors.lastname: Tonachella
authors.forename: L
authors.initials: L
authors.lastname: Piarulli
authors.forename: I
authors.initials: I
authors.lastname: Sacchi
authors.forename: D
authors.initials: D
authors.lastname: Giannarelli
authors.forename: F
authors.initials: F
authors.lastname: Cognetti
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; 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; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction
chemical_list: D000903:Antibiotics, Antineoplastic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D000069585:Filgrastim