Intensification of Adjuvant Chemotherapy: 5-Year Results of a Randomized Trial Comparing Conventional Doxorubicin and Cyclophosphamide With High-Dose Mitoxantrone and Cyclophosphamide With Filgrastim in Operable Breast Cancer With 10 or More Involved Axillary Nodes

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Abstract
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 = 150) were randomized to receive either four cycles of standard doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks (arm A) or four courses of intensified mitoxantrone 23 mg/m2 plus cyclophosphamide 600 mg/m2, 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 = .44), DDFS (P = .67), or OS (P = .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 dose-intensity. Analysis of patients with 15 or more positive nodes revealed a significant difference in 5-year DDFS (19% v 49% in arm B; P = .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/m2 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.