title: A multicentre phase II study of the efficacy and safety of docetaxel as first-line treatment of advanced breast cancer: report of the Clinical Screening Group of the EORTC.
abstract: BACKGROUND
  Two previous phase II trials of docetaxels as first line chemotherapy of advanced breast cancer have been conducted by the Clinical Screening Group of the EORTC. In these 2 studies, docetaxel 100 mg/m2 and 75 mg/m2 were administered without routine premedication and produced overall response rates of 68% and 52% respectively. Fluid retention was the most problematic adverse event in these 2 studies in which premedication was not routinely administered. This study investigated the efficacy and safety profile of docetaxel with a 1-day prophylactic premedication.
  
  
  METHODS
  Docetaxel 100 mg/m2 was administered intravenously over 1 hour, every 3 weeks, to 37 women (aged 29-65 years) with advanced breast cancer. A 1-day regimen of intravenous antihistamine and oral corticosteroids was given with each dose. Full doses of docetaxel were administered in 179 of 200 cycles (89.5%), giving a median relative dose intensity of 0.98.
  
  
  RESULTS
  Tumour regression was achieved in 25 patients (7.66%) after a median of 7 weeks, and 2 patients (5.4%) had a complete response. Response rates were 67.9% in patients with visceral metastases, 76.9% in liver metastases and 83.3% in patients with > 2 organs involved. The median time to progression was 31 weeks (range 1-36+). After a median follow-up time of 6.9 months (range 4.6-9.4), 31 patients (83.7%) were still alive. The most common adverse events (AE) were neutropenia (97%), alopecia (97%, grade 1-2), fluid retention (89%, mainly mild to moderate) and neurosensory disorders (81%, mainly mild to moderate). Only 5 patients experienced febrile neutropenia requiring hospitalisation and/or antibiotic therapy. Sixteen patients discontinued treatment because of fluid retention; nevertheless, 13 of these achieved an objective antitumour response and none had any significant deterioration in performance status. AEs were generally reversible and easily managed, and there were no deaths attributable to docetaxel-related AEs.
  
  
  CONCLUSIONS
  Docetaxel produces very effective tumour response with acceptable tolerability when used as first-line chemotherapy in patients with advanced breast cancer. The 1-day premedication regimen used in this study was less effective in reducing the incidence and severity or delaying the onset of fluid retention than the currently recommended 5-day corticosteroid premedication. The optimum premedication regimen remains to be defined.
authors.affiliation: Centre Régionale de Lutte Contre le Cancer, Nantes Atlantique-ICERC, Saint Herblain, France.
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
authors.forename: B
authors.initials: B
authors.lastname: Chevallier
authors.forename: P
authors.initials: P
authors.lastname: Kerbrat
authors.forename: Y
authors.initials: Y
authors.lastname: Krakowski
authors.forename: J L
authors.initials: JL
authors.lastname: Misset
authors.forename: C
authors.initials: C
authors.lastname: Maugard-Louboutin
authors.forename: V
authors.initials: V
authors.lastname: Dieras
authors.forename: N
authors.initials: N
authors.lastname: Azli
authors.forename: N
authors.initials: N
authors.lastname: Bougon
authors.forename: A
authors.initials: A
authors.lastname: Riva
authors.forename: H
authors.initials: H
authors.lastname: Roche
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016001:Confidence Intervals; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015996:Survival Rate; D043823:Taxoids; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel