Concomitant versus sequential administration of epirubicin and paclitaxel as first-line therapy in metastatic breast carcinoma - Results from the Gruppo Oncologico Nord Ovest randomized trial

BACKGROUND. The authors performed a randomized trial comprising patients with metastatic breast carcinoma (MBC). They used a noninferiority design to evaluate whether the results of sequential administration of epirubicin and paclitaxel were not markedly worse than the concomitant administration in terms of objective response rates (ORRs). Toxicity profile, quality of life (QOL), and pharmacoeconomic evaluations were evaluated as well. METHODS. in the current study, 202 patients with MBC were randomized to receive either the combination of epirubicin at a dose Of go mg/m(2) plus paclitaxel at a dose of 200 mg/m(2) for 8 cycles (concomitant arm, n = 108) or epirubicin at a dose of 120 mg/m(2) for 4 cycles followed by paclitaxel at a dose of 250 mg/m(2) over 3 hours for 4 cycles every 21 days (sequential arm, n = 94). RESULTS. The authors rejected the null hypothesis that the sequential treatment is less active than the standard concomitant regimen (ORRs: concomitant = 58.5%, sequential = 57.6%). The median progression-free and overall survival periods were 11.0 months (95% confidence interval [95% CI], 9.7-12.3) and 20.0 months (95% Cl, 17.2-22.6), respectively, in the concomitant arm and 10.8 months (95% Cl, 7.9-13.6) and 26 months (95% Cl, 18.1-33.8), respectively, in the sequential arm (P = not significant). Patients who received the sequential regimen experienced a higher incidence of Grade 3/4 (according to the World Health Organization grading system) neutropenia (62.2% of courses vs. 50.62%; P = 0.003) and Grade greater than or equal to 2 neuropathy (45.5% vs. 30.4% of patients; P = 0.03), whereas 6 patients who received the concomitant regimen developed Grade 11 cardiotoxicity according to New York Heart Association criteria. QOL analyses failed to provide clear differences. CONCLUSIONS. The sequential administration of epirubicin and paclitaxel at full doses was found to be as active as their association. Therefore, both the sequential and the combined administration were acceptable options. Cancer 2004;101: 704-12.