HANNOVER, GermanyEpirubicin (Ellence)/paclitaxel (Taxol) as
first-line treatment significantly slows progression of metastatic
breast cancer, compared with epirubicin/cyclophosphamide. Interim
results of a multicenter phase III trial comparing the two regimens
were reported by Hans-Joachim Luck, MD, of the Medical University,
Hannover, Germany, at the ASCO annual meeting.
Dr. Luck reported that time to progression, the primary study
endpoint, was 39 weeks with epirubicin/paclitaxel vs 32 weeks with
Overall survival was not significantly different (38 weeks with
epirubicin/paclitaxel vs 26 weeks with epirubicin/cyclophosphamide),
but the rate of primary treatment failure during the time on
treatment was 11% with epirubicin/paclitaxel vs 24% with
epirubicin/cyclophosphamide (P = .003).
Response rates were also not significantly different. Complete
responses occurred in 8% of patients on epirubicin/paclitaxel and 6%
on epirubicin/cyclophosphamide, and the overall response rates were
46% vs 40%.
Less Toxicity With Paclitaxel
The trial enrolled patients with histologically proven metastatic
breast cancer who had no prior chemotherapy and not more than one
prior hormonal therapy for metastatic disease.
About one-third of patients had prior treatment with
cyclophosphamide/methotrexate/fluorouracil (CMF), which is often used
in Germany for this indication, and about 40% had prior adjuvant
Patients were randomized to treatment either with epirubicin at 60
mg/m² and paclitaxel at 175 mg/m² or with epirubicin at 60
mg/m² and cyclophosphamide at 600 mg/m². Cycles repeated
every 21 days. Dr. Luck said that the delivered dose intensity was
59.6 mg/m² for epirubicin and 173.3 mg/m² for paclitaxel.
For this interim analysis, 489 patients were evaluable for toxicity
and 481 for response. Median follow-up was 36 weeks.
There was more hematologic toxicity with epirubicin/cyclophosphamide,
but no febrile neutropenia was observed. Cardiotoxicity occurred in
less than 1% of patients. Neutropenia was the most common toxicity,
and grade 3-4 neutropenia occurred in 34% of patients receiving
epirubicin/paclitaxel and 45% of patients receiving epirubicin/cyclophosphamide.
Dr. Luck concluded that the epirubicin/paclitaxel regimen was
associated with a lower rate of primary progression, although not
with increased overall survival. He reported that patients with
previous adjuvant chemotherapy (primarily CMF) had significantly
better progression-free survival with epirubicin/paclitaxel than with
No Major Difference
In discussing this study, Clifford Hudis, MD, of Memorial
Sloan-Kettering Cancer Center, said, It doesnt strike
most of us that there is a major difference in progression-free
survival between 32 weeks on epirubicin/cyclophosphamide and 39 weeks
with epirubicin/paclitaxel...Theres probably a lot less here
than meets the eye.
Dr. Hudis suggested that a more useful approach to test might be
doxorubicin/cyclophosphamide or epirubicin/cyclophosphamide followed
by a taxane.