title: Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial.
abstract: OBJECTIVE
  This randomized, multicenter, phase III study compared doxorubicin and docetaxel (AT) with doxorubicin and cyclophosphamide (AC) as first-line chemotherapy (CT) in metastatic breast cancer (MBC).
  
  
  METHODS
  Patients (n = 429) were randomly assigned to receive doxorubicin 50 mg/m(2) plus docetaxel 75 mg/m(2) (n = 214) or doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2) (n = 215) on day 1, every 3 weeks for up to eight cycles.
  
  
  RESULTS
  Time to progression (TTP; primary end point) and time to treatment failure (TTF) were significantly longer with AT than AC (median TTP, 37.3 v 31.9 weeks; log-rank P =.014; median TTF, 25.6 v 23.7 weeks; log-rank P =.048). The overall response rate (ORR) was significantly greater for patients taking AT (59%, with 10% complete response [CR], 49% partial response [PR]) than for those taking AC (47%, with 7% CR, 39% PR) (P =.009). The ORR was also higher with AT in patients with visceral involvement (58% v 41%; liver, 62% v 42%; lung, 58% v 35%), three or more organs involved (59% v 40%), or prior adjuvant CT (53% v 41%). Overall survival (OS) was comparable in both arms. Grade 3/4 neutropenia was frequent in both groups, although febrile neutropenia and infections were more frequent for patients taking AT (respectively, 33% v 10%, P <.001; 8% v 2%, P =.01). Severe nonhematologic toxicity was infrequent in both groups, including grade 3/4 cardiac events (AT, 3%; AC, 4%).
  
  
  CONCLUSIONS
  AT significantly improves TTP and ORR compared with AC in patients with MBC, but there is no difference in OS. AT represents a valid option for the treatment of MBC.
authors.affiliation: University of California at Los Angeles, CA 90095-7077, USA. jmnabholtz@hotmail.com
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Nabholtz
authors.forename: Carla
authors.initials: C
authors.lastname: Falkson
authors.forename: Daniel
authors.initials: D
authors.lastname: Campos
authors.forename: Janos
authors.initials: J
authors.lastname: Szanto
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
authors.forename: Stephen
authors.initials: S
authors.lastname: Chan
authors.forename: Tadeuz
authors.initials: T
authors.lastname: Pienkowski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Zaluski
authors.forename: Tamas
authors.initials: T
authors.lastname: Pinter
authors.forename: Maciej
authors.initials: M
authors.lastname: Krzakowski
authors.forename: Daniel
authors.initials: D
authors.lastname: Vorobiof
authors.forename: Robert
authors.initials: R
authors.lastname: Leonard
authors.forename: Ian
authors.initials: I
authors.lastname: Kennedy
authors.forename: Nacer
authors.initials: N
authors.lastname: Azli
authors.forename: Michael
authors.initials: M
authors.lastname: Murawsky
authors.forename: Alessandro
authors.initials: A
authors.lastname: Riva
authors.forename: Pierre
authors.initials: P
authors.lastname: Pouillart
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006304:Health Status; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011788:Quality of Life; D016019:Survival Analysis; D043823:Taxoids; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel