Purpose: Investigation of high-dose chemotherapy (HD-CT) followed by autologous hematopoietic stem-cell support compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more positive axillary lymph nodes.
Patients and methods: Between November 1993 and September 2000, 307 patients were randomized to receive (following four cycles of epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2), intravenously every 21 days) either HD-CT of cyclophosphamide 1500 mg/m(2), thiotepa 150 mg/m(2), and mitoxantrone 10 mg/m(2), intravenously for 4 consecutive days followed by stem-cell support; or SD-CT in three cycles of cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) intravenously on days 1 and 8, every 28 days. The primary end point was event-free survival.
Results: After a median follow-up of 3.8 years, 144 events with respect to event-free survival have been observed (HD-CT: 63 events; SD-CT: 81 events). The first event of failure (HD-CT v SD-CT) was an isolated locoregional recurrence (nine v 11), a distant failure (52 v 68), and death without recurrence (two v two). The estimated relative risk of HD-CT versus SD-CT was 0.75 (95% CI, 0.54 to 1.06; P =.095). Overall survival showed no difference (HD-CT: 40 deaths; SD-CT: 49 deaths).
Conclusion: There was a trend in favor of HD-CT with respect to event-free survival, but without statistical significance. Further follow-up and a meta-analysis of all randomized studies will reveal the effect of HD-CT as compared with SD-CT as adjuvant treatment in high-risk primary breast cancer.