title: Dose-dense sequential adjuvant chemotherapy followed, as indicated, by trastuzumab for one year in patients with early breast cancer: first report at 5-year median follow-up of a Hellenic Cooperative Oncology Group randomized phase III trial.
abstract: BACKGROUND
  Dose-dense sequential chemotherapy including anthracyclines and taxanes has been established in the adjuvant setting of high-risk operable breast cancer. However, the preferable taxane and optimal schedule of administration in a dose-dense regimen have not been defined yet.
  
  
  METHODS
  From July 2005 to November 2008, 1001 patients (990 eligible) were randomized to receive, every 2 weeks, 3 cycles of epirubicin 110 mg/m2 followed by 3 cycles of paclitaxel 200 mg/m2 followed by 3 cycles of intensified CMF (Arm A; 333 patients), or 3 cycles of epirubicin followed by 3 cycles of CMF, as in Arm A, followed 3 weeks later by 9 weekly cycles of docetaxel 35 mg/m2 (Arm B; 331), or 9 weekly cycles of paclitaxel 80 mg/m2 (Arm C; 326). Trastuzumab was administered for one year to HER2-positive patients post-radiation.
  
  
  RESULTS
  At a median follow-up of 60.5 months, the 3-year disease-free survival (DFS) rate was 86%, 90% and 88%, for Arms A, B and C, respectively, while the 3-year overall survival (OS) rate was 96% in all arms. No differences were found in DFS or OS between the combined B and C Arms versus Arm A (DFS: HR = 0.81, 95% CI: 0.59-1.11, P = 0.20; OS: HR = 0.84, 95% CI: 0.55-1.30, P = 0.43). Among the 255 patients who received trastuzumab, 189 patients (74%) completed 1 year of treatment uneventfully. In all arms, the most frequently reported severe adverse events were neutropenia (30% vs. 27% vs. 26%) and leucopenia (12% vs. 13% vs. 12%), while febrile neutropenia occurred in fifty-one patients (6% vs. 4% vs. 5%). Patients in Arm A experienced more often severe pain (P = 0.002), neurological complications (P = 0.004) and allergic reactions (P = 0.004), while patients in Arm B suffered more often from severe skin reactions (P = 0.020).
  
  
  CONCLUSIONS
  No significant differences in survival between the regimens were found in the present phase III trial. Taxane scheduling influenced the type of severe toxicities. HER2-positive patients demonstrated comparable 3-year DFS and OS rates with those reported in other similar studies.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry ACTRN12610000151033.
authors.affiliation: Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki Ring Road, 564 03 Thessaloniki, Macedonia, Greece. fountzil@auth.gr.
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: Urania
authors.initials: U
authors.lastname: Dafni
authors.forename: Christos
authors.initials: C
authors.lastname: Papadimitriou
authors.forename: Eleni
authors.initials: E
authors.lastname: Timotheadou
authors.forename: Helen
authors.initials: H
authors.lastname: Gogas
authors.forename: Anastasia G
authors.initials: AG
authors.lastname: Eleftheraki
authors.forename: Ioannis
authors.initials: I
authors.lastname: Xanthakis
authors.forename: Christos
authors.initials: C
authors.lastname: Christodoulou
authors.forename: Angelos
authors.initials: A
authors.lastname: Koutras
authors.forename: Christos N
authors.initials: CN
authors.lastname: Papandreou
authors.forename: Pavlos
authors.initials: P
authors.lastname: Papakostas
authors.forename: Spyros
authors.initials: S
authors.lastname: Miliaras
authors.forename: Christos
authors.initials: C
authors.lastname: Markopoulos
authors.forename: Constantine
authors.initials: C
authors.lastname: Dimitrakakis
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Korantzopoulos
authors.forename: Charisios
authors.initials: C
authors.lastname: Karanikiotis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Bafaloukos
authors.forename: Paris
authors.initials: P
authors.lastname: Kosmidis
authors.forename: Epaminontas
authors.initials: E
authors.lastname: Samantas
authors.forename: Ioannis
authors.initials: I
authors.lastname: Varthalitis
authors.forename: Nicholas
authors.initials: N
authors.lastname: Pavlidis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.forename: Meletios-Athanassios
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D000068878:Trastuzumab; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab