title: Addition of either lonidamine or granulocyte colony-stimulating factor does not improve survival in early breast cancer patients treated with high-dose epirubicin and cyclophosphamide.
abstract: OBJECTIVE
  Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity.
  
  
  METHODS
  From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients).
  
  
  RESULTS
  Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non-G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non-G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively).
  
  
  CONCLUSIONS
  EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.
authors.affiliation: Division of Medical Oncology A, Regina Elena Cancer Institute, Via Elio Chianesi 53, 00144 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: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.forename: Eugenio
authors.initials: E
authors.lastname: Cammilluzzi
authors.forename: Mauro
authors.initials: M
authors.lastname: Antimi
authors.forename: Edmondo
authors.initials: E
authors.lastname: Terzoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lepidini
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: Cecilia
authors.initials: C
authors.lastname: Nistico
authors.forename: Paolo
authors.initials: P
authors.lastname: Carlini
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: Carlo
authors.initials: C
authors.lastname: Vitucci
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Marolla
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D000069585:Filgrastim; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011994:Recombinant Proteins; D015996:Survival Rate
chemical_list: D007191:Indazoles; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D000069585:Filgrastim; C016371:lonidamine