title: Efficacy and tolerance of vinorelbine and fluorouracil combination as first-line chemotherapy of advanced breast cancer: results of a phase II study using a sequential group method.
abstract: OBJECTIVE
  To assess the antitumor efficacy and safety profile of the combination of Fluorouracil (5FU) and vinorelbine given as first-line therapy to patients with advanced breast cancer.
  
  
  METHODS
  As defined in the seven consecutive steps of a phase II group sequential design, 63 patients received 5FU 750 mg/m2/d for 5 consecutive days as a continuous infusion and vinorelbine 30 mg/ m2 on days 1 and 5 as a short intravenous (I/V) infusion every 3 weeks.
  
  
  RESULTS
  Forty-one of 63 patients achieved an objective response, which allowed us to discontinue the study and reject a response rate less than 50% with a statistical power of 90%. The unbiased estimate of the response rate was 61.6%. Response rate did not differ significantly according to the following: (1) type of prior adjuvant therapy (none, n = 23; without anthracycline, n = 6; with anthracyline, n = 34); (2) site of metastatic disease; and (3) number of metastatic sites. The median time to progression was 8.4 months. The median response duration was 12.3 months, and the median duration of complete response (CR), from the first assessment of CR, was 7.3 months. The median overall survival time was 23 months (28.1 months for patients with a CR). The main toxicities (grades 3 and 4) were neutropenia (90% of patients), infection (12.7%), mucositis (37%), and constipation (9.5%). Nevertheless, treatment could be given on an outpatient basis to the majority of patients, and the median relative dose-intensity was 86%.
  
  
  CONCLUSIONS
  This phase II study, which used a group-sequential design, shows that the combination of 5FU and vinorelbine is an active and tolerable regimen for the treatment of first metastatic progression of breast cancer. It provides an alternative regimen for patients who have previously received anthracycline-based adjuvant chemotherapy or in whom anthracyclines cannot be used.
authors.affiliation: Department of Oncology, Hopital Saint Louis, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Dieras
authors.forename: J M
authors.initials: JM
authors.lastname: Extra
authors.forename: E
authors.initials: E
authors.lastname: Bellissant
authors.forename: M
authors.initials: M
authors.lastname: Espie
authors.forename: F
authors.initials: F
authors.lastname: Morvan
authors.forename: J Y
authors.initials: JY
authors.lastname: Pierga
authors.forename: L
authors.initials: L
authors.lastname: Mignot
authors.forename: P
authors.initials: P
authors.lastname: Tresca
authors.forename: M
authors.initials: M
authors.lastname: Marty
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D000077235:Vinorelbine; D005472:Fluorouracil