title: Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy.
abstract: OBJECTIVE
  The European Cooperative Trial in Operable breast cancer (ECTO) randomly tested whether efficacy of adjuvant doxorubicin followed by i.v. cyclophosphamide, methotrexate, and fluorouracil (CMF; doxorubicin-->CMF, arm A) could be improved by adding paclitaxel (doxorubicin/paclitaxel-->CMF) as adjuvant (arm B) or primary systemic therapy (PST, arm C). We report here feasibility, tolerability, locoregional antitumor activity, and breast conservation rate.
  
  
  METHODS
  A total of 1,355 women entered the study. Feasibility and safety were compared in arm A versus arms B plus C. Surgical findings were compared in arms A plus B versus arm C.
  
  
  RESULTS
  Grade 3 or 4 National Cancer Institute toxicities were low (<5%) in all arms. Neuropathy was more frequent in the paclitaxel-containing arms (grade 2, 20.5% versus 5.0%; grade 3, 1.3% versus 0.2%). At 31 months of follow-up, asymptomatic drop of left ventricular ejection fraction was similar in all arms, whereas symptomatic cardiotoxicity was recorded in three patients (0.5%) in A and in three patients (0.3%) in B plus C. PST induced clinical complete plus partial remission in 78%, with an in-breast pathologic complete response rate of 23% and an in-breast plus axilla pathologic complete response rate of 20%. In the multivariate analysis, only estrogen receptor (ER) status was significantly associated with pathologic complete response (odds ratio for ER negative, 5.77; 95% confidence interval, 3.49-9.52; P<0.0001). PTS induced a significant axillary downstaging (P<0.001), and breast sparing surgery was feasible in 65% versus 34% (P<0.001).
  
  
  CONCLUSIONS
  Doxorubicin/paclitaxel-->CMF is feasible, safe, and well tolerated. Given as PST, it is markedly active, allowing for breast-sparing surgery in a large fraction of patients.
authors.affiliation: Istituto Nazionale Tumori, Milan, Italy, and Hospital Vall d'Hebron, Barcelona, Spain. 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: Vicente
authors.initials: V
authors.lastname: Guillem Porta
authors.forename: Vladimir
authors.initials: V
authors.lastname: Semiglazov
authors.forename: Aña
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
authors.initials: A
authors.lastname: Llombart 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
authors.initials: JJ
authors.lastname: Lopez 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
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D015999:Multivariate Analysis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011300:Preoperative Care; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil; D008727:Methotrexate