title: Mitoxantrone, L-leucovorin and 5-fluorouracil: an effective and well tolerated first-line treatment for advanced breast cancer.
abstract: OBJECTIVE
  The combination of mitoxantrone plus leucovorin/fluorouracil in heavily pretreated patients with advanced breast cancer has shown significant activity and extremely good tolerability. The aim of this study was to evaluate the activity of this combination in patients not previously submitted to chemotherapy.
  
  
  METHODS
  From May 1993 to December 1995 we treated 80 patients with advanced breast cancer with a combination of mitoxantrone, l-leucovorin and 5-fluorouracil. All patients had histologically or cytologically proven breast cancer, WHO performance status 0-3, normal hematological parameters and normal serum bilirubin. Prior chemotherapy for metastatic disease was not allowed, whereas adjuvant CMF (cyclophosphamide, methotrexate and 5-fluorouracil) or adjuvant anthracycline (doxorubicin or epirubicin) therapy was allowed; a single prior hormone treatment was permitted. Chemotherapy consisted of mitoxantrone 12 mg/m2 i.v. day 1, l-leucovorin 150 mg/m2 i.v. days 1, 2 and 3 and 5-fluorouracil 350 mg/m2 i.v. days 1, 2 and 3. The courses were repeated every 3 weeks.
  
  
  RESULTS
  Objective response (CR + PR) was observed in 46/80 (57%) patients (95% CI, 46%-68%). Complete response (CR) was observed in 21/80 cases (26%). Response was observed in 14/24 (58%) patients with soft tissues as the dominant site of disease, in 22/34 (65%) patients with visceral involvement and in 10/22 (45%) of those with bone as the dominant site of disease. The median duration of response and survival was 9 months (range, 3-16) and 22 months (range, 2-48+), respectively. Toxicity was very manageable, with grade 4 leukopenia and thrombocytopenia in 6/80 (7.5%) and 1/80 (1.25%) patients, respectively, and negligible non-hematological toxicity.
  
  
  CONCLUSIONS
  The combination of mitoxantrone, 5-fluorouracil and high-dose l-leucovorin is a safe and effective regimen for first-line treatment of advanced breast cancer.
authors.affiliation: Medical Oncology Operative Unit, Oncology Institute of Bari, Italy. vlor@mail5.clio.it
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.forename: S
authors.initials: S
authors.lastname: Mancarella
authors.forename: A
authors.initials: A
authors.lastname: Catino
authors.forename: M
authors.initials: M
authors.lastname: Brandi
authors.forename: A
authors.initials: A
authors.lastname: Paradiso
authors.forename: A
authors.initials: A
authors.lastname: Latorre
authors.forename: A
authors.initials: A
authors.lastname: Mastria
authors.forename: A
authors.initials: A
authors.lastname: De Mitrio
authors.forename: M
authors.initials: M
authors.lastname: Guida
authors.forename: M
authors.initials: M
authors.lastname: De Lena
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D008942:Mitoxantrone; D002955:Leucovorin; D005472:Fluorouracil