title: First-line vinorelbine-mitoxantrone combination in metastatic breast cancer patients relapsing after an adjuvant anthracycline regimen: results of a phase II study.
abstract: OBJECTIVE
  Previous studies demonstrated that doxorubicin and vinorelbine combinations in first-line chemotherapy are highly active in metastatic breast cancer. Mitoxantrone is an anthracenedione with low cardiotoxicity, and seems to be effective when combined with vinorelbine after prior exposure to anthracyclines.
  
  
  METHODS
  Seventy-two patients with metastatic breast cancer were included in a phase II study. All patients had previously received one anthracycline-containing regimen (doxorubicin or epirubicin) in an adjuvant setting. Vinorelbine was administered at 25 mg/m2 in a 20-min intravenous (i. v.) infusion, days 1 and 8. Mitoxantrone was given at 10 mg/m2 (66 patients) or 12 mg/m2 (6 patients) in a slow i.v. infusion on day 1. Courses were repeated every 3 weeks.
  
  
  RESULTS
  Sixty-five patients were evaluable for response; the objective response rate was 49% (95% CI: 37-63%), including four complete and 28 partial responses, with a median duration of response of 7 months (range 2.3-27). Median overall survival was 19 months (range 2-48). Grade 3-4 granulocytopenia was observed in 46% of patients. There were 12 admissions (3% of cycles), involving 17% of patients for febrile neutropenia. Seven patients (10%) experienced grade 3 or 4 cardiotoxicity, and 1 patient died of cardiac heart failure. Other side effects were rare and mild.
  
  
  CONCLUSIONS
  The vinorelbine and mitoxantrone combination is an active regimen with low toxic complications when cumulative doses of mitoxantrone are limited to 70 mg/m2. The results in this phase II study make it worthwhile including this regimen in a phase III study for patients who have previously received an anthracycline-containing regimen.
authors.affiliation: Department of Medicine, Institut Gustave- Roussy, Villejuif, France. ALLCPB64@teleline.es
authors.forename: A
authors.initials: A
authors.lastname: Llombart-Cussac
authors.forename: X
authors.initials: X
authors.lastname: Pivot
authors.forename: A
authors.initials: A
authors.lastname: Rhor-Alvarado
authors.forename: A
authors.initials: A
authors.lastname: Le Cesne
authors.forename: T
authors.initials: T
authors.lastname: Le Chevalier
authors.forename: T
authors.initials: T
authors.lastname: Tursz
authors.forename: M
authors.initials: M
authors.lastname: Spielmann
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D016879:Salvage Therapy; D016019:Survival Analysis; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D018943:Anthracyclines; D014747:Vinblastine; D008942:Mitoxantrone; D000077235:Vinorelbine