Originally published as JCO Early Release 10.1200/JCO.2004.07.026 on April 26 2004

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High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Support Compared With Standard-Dose Chemotherapy in Breast Cancer Patients With 10 or More Positive Lymph Nodes: First Results of a Randomized Trial

From the Transplant Center, University Hospital Hamburg-Eppendorf; Albertinen-Hospital, Hamburg; Centre for Clinical Studies, University Hospital, Freiburg; University Hospital, Ulm; City Hospital, Oldenburg; Humaine Hospital, Bad Saarow; University Hospital, Münster; University Hospital, Magdeburg; Benjamin Franklin Hospital; University Hospital Charité, Berlin; Medical Hospital, Nürnberg; Hospital of the Saarland, Homburg; Evangelische Diakonissenanstalt, Bremen; University Hospital, Kiel, Germany

Address reprint requests to Axel R. Zander, MD, University Hospital Hamburg-Eppendorf, Transplant Center, Bone Marrow Transplantation, Martinistr 52, 20246 Hamburg, Germany; e-mail: zander{at}uke.uni-hamburg.de

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/m² and cyclophosphamide 600 mg/m², intravenously every 21 days) either HD-CT of cyclophosphamide 1,500 mg/m², thiotepa 150 mg/m², and mitoxantrone 10 mg/m², intravenously for 4 consecutive days followed by stem-cell support; or SD-CT in three cycles of cyclophosphamide 500 mg/m², methotrexate 40 mg/m², and fluorouracil 600 mg/m² 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.

Supported by the Dr Mildred Scheel Stiftung der Deutschen Krebshilfe, by the Hamburger Krebsgesellschaft, and by the Erich and Gertrud Roggenbuck Foundation.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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