title: Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer.
abstract: OBJECTIVE
  To evaluate the addition of paclitaxel to an anthracycline-based adjuvant regimen and to compare this combination with the same regimen given as primary systemic (neoadjuvant) therapy.
  
  
  METHODS
  A total of 1,355 women with operable breast cancer were randomly assigned to one of three treatments: surgery followed by adjuvant doxorubicin (75 mg/m(2)) followed by cyclophosphamide, methotrexate, and fluorouracil (CMF; arm A); surgery followed by adjuvant paclitaxel (200 mg/m(2)) plus doxorubicin (60 mg/m(2)), followed by CMF (arm B); or paclitaxel (200 mg/m(2)) plus doxorubicin (60 mg/m(2)) followed by CMF followed by surgery (arm C). The two coprimary objectives were to assess the effects on relapse-free survival (RFS) of the addition of paclitaxel to postoperative chemotherapy (arm B v arm A) and primary chemotherapy versus adjuvant chemotherapy (arm B v arm C).
  
  
  RESULTS
  Doxorubicin plus paclitaxel followed by CMF was well-tolerated as adjuvant or as primary chemotherapy. The addition of paclitaxel to adjuvant doxorubicin followed by CMF significantly improved RFS compared with adjuvant doxorubicin alone followed by CMF (hazard ratio [HR], 0.73; P = .03). Distant RFS was similarly improved (HR, 0.70; P = .027). There was no significant difference in RFS when the paclitaxel/doxorubicin/CMF chemotherapy was given before surgery compared with the same regimen given after surgery (HR, 1.21; P = .18). However, the rate of breast-conserving surgery was significantly higher with preoperative chemotherapy (63% v 34%; P < .001).
  
  
  CONCLUSIONS
  Incorporating paclitaxel into anthracycline-based adjuvant therapy resulted in a significant improvement in RFS and distant RFS. When given as primary systemic therapy, the paclitaxel-containing regimen allowed breast-sparing surgery in a significant percentage of patients.
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. luca.gianni@istitutotumori.mi.it
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eiermann
authors.forename: Vincente Guillem
authors.initials: VG
authors.lastname: Porta
authors.forename: Vladimir
authors.initials: V
authors.lastname: Semiglazov
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Milvia
authors.initials: M
authors.lastname: Zambetti
authors.forename: Dolores
authors.initials: D
authors.lastname: Sabadell
authors.forename: Günther
authors.initials: G
authors.lastname: Raab
authors.forename: Antonio Llombart
authors.initials: AL
authors.lastname: Cussac
authors.forename: Alla
authors.initials: A
authors.lastname: Bozhok
authors.forename: Angel
authors.initials: A
authors.lastname: Martinez-Agulló
authors.forename: Marco
authors.initials: M
authors.lastname: Greco
authors.forename: Mikhail
authors.initials: M
authors.lastname: Byakhov
authors.forename: Juan Josè Lopez
authors.initials: JJ
authors.lastname: Lopez
authors.forename: Mauro
authors.initials: M
authors.lastname: Mansutti
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Valagussa
authors.forename: Gianni
authors.initials: G
authors.lastname: Bonadonna