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
1 Department of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki Ring Road, 564 03 Thessaloniki, Macedonia, Greece
2 Laboratory of Biostatistics, University of Athens School of Nursing, Athens, Greece
3 Department of Clinical Therapeutics, “Alexandra” Hospital, University of Athens School of Medicine, Athens, Greece
4 First Department of Medicine, “Laiko” General Hospital, University of Athens, Medical School, Athens, Greece
5 Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece
6 Second Department of Medical Oncology, “Metropolitan” Hospital, Piraeus, Greece
7 Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece
8 Department of Medical Oncology, University Hospital of Larissa, University of Thessaly School of Medicine, Larissa, Greece
9 Department of Medical Oncology, “Hippokration” Hospital, Athens, Greece
10 First Department of Surgery, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece
11 Department of Obstetrics and Gynecology “Alexandra” Hospital, Athens, Greece
12 Department of Cardiology, University of Ioannina Medical School, Ioannina, Greece
13 Department of Medical Oncology, 424 Army General Hospital, Thessaloniki, Greece
14 First Department of Medical Oncology, “Metropolitan” Hospital, Piraeus, Greece
15 Second Department of Medical Oncology, “Hygeia” Hospital, Athens, Greece
16 Third Department of Medical Oncology, “Agii Anargiri” Cancer Hospital, Athens, Greece
17 Oncology Department, General Hospital of Chania, Crete, Greece
18 Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece
19 Oncology Section, Second Department of Internal Medicine, “Hippokration” Hospital, Athens, Greece
BMC Cancer 2014, 14:515 doi:10.1186/1471-2407-14-515Published: 15 July 2014
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.
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.
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).
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.
Australian New Zealand Clinical Trials Registry ACTRN12610000151033.