title: Dose-dense adjuvant chemotherapy in node-positive breast cancer: docetaxel followed by epirubicin/cyclophosphamide (T/EC), or the reverse sequence (EC/T), every 2 weeks, versus docetaxel, epirubicin and cyclophosphamide (TEC) every 3 weeks. AERO B03 randomized phase II study.
abstract: BACKGROUND
  Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive patients but optimal dose and schedule remain undetermined. This study aimed to select a dose-dense regimen for further assessment in phase III studies.
  
  
  METHODS
  Ninety-nine patients with node-positive invasive breast adenocarcinoma were randomly assigned to docetaxel (Taxotere) (T) 75 mg/m2, epirubicin (E) 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 (TEC)x6, every 3 weeks; E 100 mg/m2, C 600 mg/m2 x 4, then T 100 mg/m2 x 4 (EC-->T) or the reverse sequence (T-->EC), every 2 weeks, with pegfilgrastim support. The primary end point was the incidence of grade 4 toxicity.
  
  
  RESULTS
  Dose intensity was almost doubled with dose-dense regimens, compared with TEC. Twenty-seven patients experienced grade 4 toxicity: 26%, 40% and 18% with TEC, EC-->T and T-->EC, respectively, mainly neutropenia, but febrile neutropenia occurred only in 11%, 10% and 3%. Grade 3-4 nail disorders, hand-foot syndrome and peripheral neuropathy occurred in 46%, 73% and 68% of patients with TEC, EC-->T and T-->EC, respectively.
  
  
  CONCLUSIONS
  Dose-dense regimens yield more frequent and severe nonhematological toxic effects than standard dose TEC regimen. Though grade 4 toxicity rates appear acceptable with the T-->EC regimen, the incidence of grade 3-4 events makes it difficult to recommend either dose-dense regimen for further investigation.
authors.affiliation: Hôpital Henri-Mondor, Créteil. Electronic address: pascal.piedbois@hmn.aphp.fr.
authors.forename: P
authors.initials: P
authors.lastname: Piedbois
authors.affiliation: Institut Sainte-Catherine, Avignon.
authors.forename: D
authors.initials: D
authors.lastname: Serin
authors.affiliation: Hôpital départemental, La Roche-sur-Yon.
authors.forename: F
authors.initials: F
authors.lastname: Priou
authors.affiliation: Clinique Saint-Come et Saint-Damien, Blois.
authors.forename: P
authors.initials: P
authors.lastname: Laplaige
authors.affiliation: Clinique Sainte-Clotilde, Saint-Louis de la Réunion.
authors.forename: S
authors.initials: S
authors.lastname: Greget
authors.affiliation: Hôpital Fontenoy, Chartres.
authors.forename: E
authors.initials: E
authors.lastname: Angellier
authors.affiliation: Clinique Plein Ciel, Mougins.
authors.forename: E
authors.initials: E
authors.lastname: Teissier
authors.affiliation: Clinique de l'Espérance, Hyères.
authors.forename: J-F
authors.initials: JF
authors.lastname: Berdah
authors.affiliation: CRLCC Val d'Aurelle, Montpellier.
authors.forename: M
authors.initials: M
authors.lastname: Fabbro
authors.affiliation: Centre Hospitalier, Draguignan, France, for the European Association for Research in Oncology.
authors.forename: B
authors.initials: B
authors.lastname: Valenza
authors.affiliation: Soisy-sous-Montmorency.
authors.forename: P
authors.initials: P
authors.lastname: Herait
authors.affiliation: International Drug Development Institute, Brussels, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Jehl
authors.affiliation: International Drug Development Institute, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Buyse
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000556:secondary; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide