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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

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

Authors: George Fountzilas, Urania Dafni, Christos Papadimitriou, Eleni Timotheadou, Helen Gogas, Anastasia G Eleftheraki, Ioannis Xanthakis, Christos Christodoulou, Angelos Koutras, Christos N Papandreou, Pavlos Papakostas, Spyros Miliaras, Christos Markopoulos, Constantine Dimitrakakis, Panagiotis Korantzopoulos, Charisios Karanikiotis, Dimitrios Bafaloukos, Paris Kosmidis, Epaminontas Samantas, Ioannis Varthalitis, Nicholas Pavlidis, Dimitrios Pectasides, Meletios-Athanassios Dimopoulos

Published in: BMC Cancer | Issue 1/2014

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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.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12610000151​033.
Appendix
Available only for authorised users
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Metadata
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
Authors
George Fountzilas
Urania Dafni
Christos Papadimitriou
Eleni Timotheadou
Helen Gogas
Anastasia G Eleftheraki
Ioannis Xanthakis
Christos Christodoulou
Angelos Koutras
Christos N Papandreou
Pavlos Papakostas
Spyros Miliaras
Christos Markopoulos
Constantine Dimitrakakis
Panagiotis Korantzopoulos
Charisios Karanikiotis
Dimitrios Bafaloukos
Paris Kosmidis
Epaminontas Samantas
Ioannis Varthalitis
Nicholas Pavlidis
Dimitrios Pectasides
Meletios-Athanassios Dimopoulos
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-515

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