title: Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer: mature results of an AGO phase III study.
abstract: OBJECTIVE
  Patients with primary breast cancer who have extensive axillary lymph node involvement have a poor prognosis after conventional adjuvant therapy. We compared intense dose-dense (IDD) adjuvant chemotherapy with conventionally scheduled adjuvant chemotherapy in patients with high-risk primary breast cancer.
  
  
  METHODS
  In this randomized, phase III trial, a total of 1,284 eligible patients with four or more involved axillary lymph nodes were randomly assigned to receive IDD sequential epirubicin, paclitaxel, and cyclophosphamide (IDD-ETC) every 2 weeks or conventionally scheduled epirubicin/cyclophosphamide followed by paclitaxel every three weeks. The primary end point was event-free survival (EFS).
  
  
  RESULTS
  At a median follow-up of 62 months, 5-year event-free survival rates were 62% in the conventional arm and 70% in the IDD-ETC arm, representing a 28% reduction of the relative risk of relapse (P < .001). This benefit was independent of menopausal, hormone receptor, or human epidermal growth factor receptor 2 status. The 5-year overall survival rates were 77% versus 82%, representing a 24% reduction of the relative risk of death (P = .0285). IDD therapy was associated with significantly more nonhematologic and hematologic toxicities, but no treatment-related death occurred. Four occurrences of acute myeloid leukemia or myelodysplastic syndrome (MDS) were observed in the IDD-ETC arm. No severe congestive heart failure was reported.
  
  
  CONCLUSIONS
  IDD-ETC was less well tolerated compared with conventional chemotherapy but significantly improved event-free and overall survivals in patients with high-risk primary breast cancer who had four or more positive axillary lymph nodes.
authors.affiliation: Department of Gynecology and Obstetrics, Klinikum Frankfurt Hoechst, Academic Hospital of Goethe University Frankfurt, Gotenstrasse 6-8, D-65929, Frankfurt, Germany. studien-frauenklinik@KlinikumFrankfurt.de
authors.forename: Volker
authors.initials: V
authors.lastname: Moebus
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lueck
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
authors.forename: Christoph
authors.initials: C
authors.lastname: Thomssen
authors.forename: Christian
authors.initials: C
authors.lastname: Kurbacher
authors.forename: Walther
authors.initials: W
authors.lastname: Kuhn
authors.forename: Ulrike
authors.initials: U
authors.lastname: Nitz
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Ingo B
authors.initials: IB
authors.lastname: Runnebaum
authors.forename: Axel
authors.initials: A
authors.lastname: Hinke
authors.forename: Rolf
authors.initials: R
authors.lastname: Kreienberg
authors.forename: Gottfried E
authors.initials: GE
authors.lastname: Konecny
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel