title: Factors predicting for efficacy and safety of docetaxel in a compassionate-use cohort of 825 heavily pretreated advanced breast cancer patients.
abstract: OBJECTIVE
  To identify predictive factors for efficacy and safety in advanced breast cancer (ABC) patients treated in the French compassionate-use docetaxel program.
  
  
  METHODS
  A total of 825 ABC patients treated with docetaxel (100 mg/m(2) every 3 weeks) were source-reviewed and analyzed for prognostic factors associated with overall response rate (ORR), time to treatment failure (TTF), overall survival (OS), febrile neutropenia, mucositis, and severe fluid retention syndrome by univariate and multivariate analysis.
  
  
  RESULTS
  The ORR was 22.9% (95% confidence interval, 20.2% to 26.2%). The median TTF and OS were 4.0 and 9.8 months, respectively. By multivariate analysis, secondary anthracycline-resistant disease was significantly associated (P <. 05) with lower ORR and shorter TTF and OS, whereas anthracycline-refractory disease was associated with shorter OS. Poor performance status was associated with lower ORR, shorter TTF, and shorter OS. Liver dysfunction (transaminase levels > 1.5 times the upper limit of normal [ULN] and alkaline phosphatase [AP] level > three times ULN) and time since first relapse less than 24 months were associated with shorter TTF and OS. Other significant correlations included the following: elevated CA 15-3 serum level with lower ORR; more than two involved sites, and minor transaminase and AP level abnormalities with shorter OS; and no previous chemotherapy for ABC with shorter TTF. According to multivariate analysis, ORR, TTF, and OS were not decreased in patients with liver metastases but without liver dysfunction.
  
  
  CONCLUSIONS
  Docetaxel activity was maintained in heavily pretreated ABC patients and in those with liver metastasis; docetaxel must be used cautiously, however, in patients with liver dysfunction in whom high morbidity risk necessitates strict adherence to dose-adaptation guidelines.
authors.affiliation: Paul Brousse Hospital and Institut Gustave Roussy, Villejuif, France.
authors.forename: J
authors.initials: J
authors.lastname: Alexandre
authors.forename: P
authors.initials: P
authors.lastname: Bleuzen
authors.forename: J
authors.initials: J
authors.lastname: Bonneterre
authors.forename: W
authors.initials: W
authors.lastname: Sutherland
authors.forename: J L
authors.initials: JL
authors.lastname: Misset
authors.forename: J
authors.initials: J
authors.lastname: Guastalla
authors.forename: P
authors.initials: P
authors.lastname: Viens
authors.forename: S
authors.initials: S
authors.lastname: Faivre
authors.forename: A
authors.initials: A
authors.lastname: Chahine
authors.forename: M
authors.initials: M
authors.lastname: Spielman
authors.forename: A
authors.initials: A
authors.lastname: Bensmaïne
authors.forename: M
authors.initials: M
authors.lastname: Marty
authors.forename: M
authors.initials: M
authors.lastname: Mahjoubi
authors.forename: E
authors.initials: E
authors.lastname: Cvitkovic
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000188:drug therapy* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011379:Prognosis; D012307:Risk Factors; D013280:Stomatitis / Q000139:chemically induced; D043823:Taxoids; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel