Intensification o f A djuvant C hemotherapy: 5 -Year R esults of a R andomized T rial C omparing C onventional Doxorubicin a nd C yclophosphamide W ith H igh-Dose Mitoxantrone a nd C yclophosphamide W ith F ilgrastim in O perable B reast C ancer W ith 1 0 o r M ore I nvolved Axillary N odes

Purpose: To determine whether intensifying the dose of adjuvant chemotherapy improves the outcome of women with primary breast cancer and 10 or more involved axillary nodes. Patients and Methods: Patients (n 5 150) were randomized to receive either four cycles of standard doxorubicin 60 mg/m 2 plus cyclophosphamide 600 mg/m 2 every 3 weeks (arm A) or four courses of intensified mitoxantrone 23 mg/m 2 plus cyclophosphamide 600 mg/m 2 , with filgrastim 5 g/kg/d from days 2 to 15, every 3 weeks (arm B). Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were determined using life-table estimates. Results: There were no significant differences in DFS (P 5 .44), DDFS (P 5 .67), or OS (P 5 .99) between the two groups at 5 years; DDFS was 45% (arm A) versus 50% (arm B), and DFS was 41% versus 49%, respectively. Five-year survival was similar in both arms (61% v 60%, respectively). Failure to note an intergroup difference in outcome was unrelated to relative doseintensity. Analysis of patients with 15 or more positive nodes revealed a significant difference in 5-year DDFS (19% v 49% in arm B; P 5 .01). Toxicity was generally mild in both groups, with no toxic death. The incidence of febrile neutropenia was low (0.3% v 3%). Alopecia was less frequent in arm B (P < .001). Conclusion: This randomized trial confirms the feasibility of administering mitoxantrone 23 mg/m 2 with cyclophosphamide and filgrastim. Although there was no significant difference between conventional and intensified arms at 5 years, according to subgroup analysis, intensified treatment may decrease the risk of relapse in patients with 15 or more positive nodes compared with doxorubicin an cyclophosphamide. J Clin Oncol 19:612-620. © 2001 by American Society of Clinical Oncology.