title: Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG).
abstract: Sequential administration of anthracycline and taxane is the current standard of care adjuvant regimen for node-positive early breast cancer. Due to long-term toxicity concerns, anthracycline-free regimens have been developed. We compared a sequential dose-dense anthracycline and taxane regimen with the anthracycline-free regimen of docetaxel and cyclophosphamide.
  
  
  
  In this randomized, non-inferiority, phase III trial, women with HER2-negative invasive breast cancer and at least one positive axillary lymph node were randomized to receive either epirubicin (75 mg/m(2)), 5-fluorouracil (500 mg/m(2)) and cyclophosphamide (500 mg/m(2)) every 2 weeks for four cycles, followed by four cycles of docetaxel (75 mg/m(2)) every 2 weeks with prophylactic G-CSF support (FEC → D) or docetaxel (75 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 21 days for six cycles (TC). The primary end point of the study was the 3-year disease-free survival (DFS) rate.
  
  
  
  Six hundred and fifty women were randomized to either FEC → D (n = 326) or TC (n = 324). After a median follow-up of 46 and 47 months, the 3-year DFS rate was 89.5% and 91.1% for the FEC → D and TC arm, respectively (hazard ratio = 1.147, 95% confidence interval 0.716-1.839, P = 0.568). Grade 3-4 neutropenia was higher in the TC arm (32.4% versus 10.5%, P = 0.0001). The incidence of neutropenic fever was low (<1%). Nausea, vomiting, hand-foot syndrome and fatigue (grade 3-4) were more common with FEC → D. Acute cardiotoxicity was rare (1 event in each group). There were no toxic deaths.
  
  
  
  This trial did not clearly demonstrate that TC is non-inferior to dose-dense FEC → D. However, 3-year DFS rates were excellent in both arms for women with node-positive, HER2-negative early breast cancer.
  
  
  
  NCT01985724.
authors: Medical Oncology Department, University Hospital of Heraklion, Heraklion medoncsec@med.uoc.gr.
authors: D
authors: D
authors: Mavroudis
authors: Medical Oncology Department, University Hospital of Heraklion, Heraklion.
authors: A
authors: A
authors: Matikas
authors: Gynecologic Oncology Unit, 'Elena Venizelou' Hospital, Athens.
authors: N
authors: N
authors: Malamos
authors: 2nd Medical Oncology Department, 'Theageneio' Cancer Center, Thessaloniki.
authors: P
authors: P
authors: Papakotoulas
authors: Medical Oncology Department, University Hospital of Alexandroupolis, Alexandroupolis.
authors: S
authors: S
authors: Kakolyris
authors: 2nd Medical Oncology Department, 'Theageneio' Cancer Center, Thessaloniki.
authors: I
authors: I
authors: Boukovinas
authors: Medical Oncology Department, Larisa General Hospital, Larisa.
authors: A
authors: A
authors: Athanasiadis
authors: Medical Oncology Department, 251 Airforce Hospital, Athens.
authors: N
authors: N
authors: Kentepozidis
authors: 2nd Medical Oncology Department, 'Metaxas' Cancer Center, Piraeus.
authors: N
authors: N
authors: Ziras
authors: 1st Oncology Department, 'Iaso General' Hospital, Athens.
authors: P
authors: P
authors: Katsaounis
authors: Medical Oncology Department, 'Venizeleio' General Hospital, Heraklion, Greece.
authors: E
authors: E
authors: Saloustros
authors: Medical Oncology Department, University Hospital of Heraklion, Heraklion.
authors: V
authors: V
authors: Georgoulias
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D043823:Taxoids / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C508053:ERBB2 protein, human
keywords: TC; adjuvant; anthracycline; breast cancer; node-positive; taxane