Epirubicin/Paclitaxel as First-Line Therapy Slows Progression in Metastatic Breast Cance

HANNOVER, Germany—Epirubicin (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 epirubicin/cyclophosphamide.

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 endocrine therapy.

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 epirubicin/cyclophosphamide.

No Major Difference

In discussing this study, Clifford Hudis, MD, of Memorial Sloan-Kettering Cancer Center, said, “It doesn’t 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...There’s 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.