Flora Zagouri1, Georgia-Angeliki Koliou2, Foteinos Dimitrakopoulos3, Christos Papadimitriou4, Ioannis Binas5, Angelos Koutras3, Pavlos Papakostas6, Christos Markopoulos7, Vasileios Venizelos8, Grigorios Xepapadakis9, Αngeliki Andrikopoulou4, Charisios Karanikiotis10, Amanda Psyrri11, Dimitrios Bafaloukos12, Paris Kosmidis13, Gerasimos Aravantinos14, Eleni Res15, Davide Mauri16, Anna Koumarianou17, Kalliopi Petraki18, Anna Tsipoura19, Dimitrios Pectasides20, Helen Gogas21, George Fountzilas22,23,24. 1. Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. florazagouri@yahoo.co.uk. 2. Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece. 3. Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece. 4. Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 5. Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece. 6. Department of Medical Oncology, Hippokration Hospital, Athens, Greece. 7. Second Department of Prop. Surgery, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 8. Breast Unit, Metropolitan Hospital, Piraeus, Greece. 9. Breast Unit, IASO, General Maternity and Gynecology Clinic, Athens, Greece. 10. Department of Medical Oncology, 424 Army General Hospital, Thessaloniki, Greece. 11. Section of Medical Oncology, Department of Internal Medicine, Attikon University Hospital, Faculty of Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 12. First Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece. 13. Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece. 14. Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece. 15. Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece. 16. Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece. 17. Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 18. Pathology Department, Metropolitan Hospital, Piraeus, Greece. 19. Pathology Department, Agii Anargiri Cancer Hospital, Athens, Greece. 20. Oncology Section, Second Department of Internal Medicine, Hippokratio" Hospital, Athens, Greece. 21. First Department of Medicine, Laiko General Hospital, University of Athens, Medical School, Athens, Greece. 22. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece. 23. Aristotle University of Thessaloniki, Thessaloniki, Greece. 24. Department of Medical Oncology, German Oncology Center, Limassol, Cyprus.
Abstract
BACKGROUND: Dose-dense sequential chemotherapy with anthracyclines and taxanes achieved an 18% reduction of recurrence risk in early breast cancer (BC). The optimal chemotherapy schedule and interval between cycles remain under investigation. METHODS: Overall, 990 patients were randomised to receive either three cycles of epirubicin (E, 110 mg/m2) every 2 weeks followed by 3 cycles of paclitaxel (T, 200 mg/m2) every 2 weeks followed by three cycles of intensified CMF (Control Arm A, E-T-CMF) that was previously used in BC or three cycles of epirubicin followed by three cycles of CMF followed by nine consecutive weekly cycles of docetaxel (wD) 35 mg/m2 (Arm B, E-CMF-wD) or nine consecutive weekly cycles of paclitaxel (wT) 80 mg/m2 (Arm C, E-CMF-wT). Trastuzumab was administered for HER2-positive disease. RESULTS: At a median follow-up of 13.3 years, 330 disease-free survival (DFS) events (33.3%) were reported. DFS and overall survival (OS) did not differ between patients in the combined B and C arms versus arm A either in the entire cohort (HR = 0.90, P = 0.38 and HR = 0.85, P = 0.20) or among trastuzumab-treated patients (HR = 0.69, P = 0.13 and HR = 0.67, P = 0.13). Thirty-four patients (3.4%) developed secondary neoplasms. CONCLUSIONS: Overall, no significant differences in survival were found amongst the studied regimens after a long-term observational period. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000151033.
BACKGROUND: Dose-dense sequential chemotherapy with anthracyclines and taxanes achieved an 18% reduction of recurrence risk in early breast cancer (BC). The optimal chemotherapy schedule and interval between cycles remain under investigation. METHODS: Overall, 990 patients were randomised to receive either three cycles of epirubicin (E, 110 mg/m2) every 2 weeks followed by 3 cycles of paclitaxel (T, 200 mg/m2) every 2 weeks followed by three cycles of intensified CMF (Control Arm A, E-T-CMF) that was previously used in BC or three cycles of epirubicin followed by three cycles of CMF followed by nine consecutive weekly cycles of docetaxel (wD) 35 mg/m2 (Arm B, E-CMF-wD) or nine consecutive weekly cycles of paclitaxel (wT) 80 mg/m2 (Arm C, E-CMF-wT). Trastuzumab was administered for HER2-positive disease. RESULTS: At a median follow-up of 13.3 years, 330 disease-free survival (DFS) events (33.3%) were reported. DFS and overall survival (OS) did not differ between patients in the combined B and C arms versus arm A either in the entire cohort (HR = 0.90, P = 0.38 and HR = 0.85, P = 0.20) or among trastuzumab-treated patients (HR = 0.69, P = 0.13 and HR = 0.67, P = 0.13). Thirty-four patients (3.4%) developed secondary neoplasms. CONCLUSIONS: Overall, no significant differences in survival were found amongst the studied regimens after a long-term observational period. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000151033.
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