The evidence supporting this protocol is provided by a phase III multicentre international randomised trial ADEBAR involving 1364 patients comparing FEC120 with EC-D in patients with node positive breast cancer.r FEC120 has previously been shown to be superior to three-weekly AC-paclitaxel and equivalent to EC-paclitaxel in the MA21 trial.r
Between September 2001 and May 2005, a total of 748 patients were randomised to four 21-day cycles of EC-D (epirubicin 90mg/m2 and cyclophosphamide 600mg/m2 on day 1) followed by four 21-day cycles of docextaxel 100 mg/m2 on day 1, and 745 patients were randomised to six 28-day cycles of FEC120 (epirubicin 60mg/m2 and 5-fluorouracil 500mg/m2 IV on day 1 and 8, plus cyclophosphamide 75mg/m2 PO on day 1-14). Hormone-receptor positive breast cancer patients received appropriate endocrine therapy at the end of chemotherapy for 5 years.
The primary end point was 5-year disease-free survival (DFS) and secondary end points were overall survival (OS) and toxicity.
Efficacy
After a median follow up of 5 years, the DFS was 74% in the EC-D group and 76.9% in the FEC120 group with no difference in treatment confirmed on multivariate cox regressions adjusting for other prognostic variables (HR 1.087, 95% CI, 0.878 to 1.346, p=0.444).
5-year overall survival rates were 80.6% in both the EC-D and FEC120 groups (p=0.841).r
Kaplan-Meier curve for disease-free survivalr
© Br J Cancer 2016
Toxicity
The rate of serious adverse events was significantly higher in the FEC120 treatment arm than those patients treated with EC-D (29.7% versus 22.5%, p=0.003) and significantly more patients ceased treatment prematurely in the FEC120 arm than with EC-D (8.3% versus 4.2%, p=0.002).r
Similarly more patients in the FEC120 arm required dose reductions (6.2% versus 2.7%, p<0.001), delays to chemotherapy delivery (8.5% versus 5.9%, p<0.001) and supportive treatments such as G-CSF, EPO stimulation or antibiotic therapy (p<0.001).
Adverse eventsr
Toxicity (≥ grade 3) |
EC-D
n = 684
|
FEC120
n = 674
|
Neutropenia (%) |
59.4 |
62.3 |
Anaemia (%) |
2.8 |
15.6
|
Thrombocytopenia (%) |
1.9 |
23.7 |
Infection (%) |
9.6 |
15.4 |
Nausea (%) |
1.2 |
1.6 |
Vomiting (%) |
3.5 |
1.8 |
Diarrhoea (%) |
1.0 |
1.8 |
Mucositis (%) |
7.6 |
8.8 |
Arthralgia/myalgia (%) |
8.3 |
1.2 |
Cardiac toxicity (%) |
0.1 |
0.6 |
Neurological symptoms (%) |
0.7 |
0.1 |