Annals of Oncology Advance Access originally published online on February 27, 2008
Annals of Oncology 2008 19(6):1082-1089; doi:10.1093/annonc/mdn023
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breast cancer |
Randomized trial of high-dose adjuvant chemotherapy with autologous hematopoietic stem-cell support versus standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: overall survival after 6 years of follow-up
1 Center of Oncology, Clinic for Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg
2 Centre for Clinical Studies, University Hospital Freiburg, Freiburg
3 Department of Internal Medicine C, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald
4 Department of Clinic for Gynecology, City Hospital Frankfurt, Frankfurt
5 Department of Medicine III (Hematology/Oncology), Dr. Horst Schmidt Klinik, Wiesbaden
6 Department of Internal Medicine II, Klinikum Oldenburg, Oldenburg
7 Medical Clinic, University Hospital Münster, Münster
8 Department of Oncology, University Hospital Magdeburg, Magdeburg
9 Department of Oncology and Transfusion Medicine, University Hospital Charité Berlin, Berlin
10 Bone Marrow Transplantation, Medical Hospital Nürnberg, Nürnberg
11 Department of Oncology and Hematology, Charite Humboldt-Universität Medizinische Klinik und Poliklinik II, Berlin
12 Department of Obstetrics and Gynecology, University of Ulm, Ulm
13 Department of Biometry and Data Management, University Hospital Freiburg, Freiburg
14 Department of Gynecology, University Clinic S-H, Campus Kiel, Kiel, Germany
* Correspondence to: Dr A. R. Zander, Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. Tel: +49-40-42803-4850/4851; Fax: +49-40-42803-3795; E-mail: zander{at}uke.uni-hamburg.de
Investigation of high-dose chemotherapy (HD-CT) compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 
10 axillary lymph nodes. From November 1993 to September 2000, 307 patients were randomized to receive after four cycles of epirubicin (90 mg/m2), cyclophosphamide (600 mg/m2) i.v. (every 21 days) and either HD-CT of cyclophosphamide (1500 mg/m2), thiotepa (150 mg/m2) and mitoxantrone (10 mg/m2) i.v. for four consecutive days followed by stem cell transplantation or a SD-CT of three cycles CMF (cyclophosphamide 500 mg/m2, methotrexate 40 mg/m2, 5-fluorouracil 600 mg/m2, i.v. on day 1 and 8, respectively, every 28 days). After a median follow-up of 6.1 years, 166 events with respect to event-free survival (EFS) (SD-CT: 91, HD-CT: 75) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0.80 [95% confidence interval (0.59, 1.08)], P = 0.15. The trend to a superiority of HD-CT as compared with SD-CT with respect to EFS seems to be more pronounced in premenopausal patients as compared with postmenopausal patients and in patients with tumor grade 3 as compared with patients with tumor grade 1/2. With a follow-up of 6 years, there was a trend in favor of HD-CT with respect to EFS not being significant. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients who might benefit from HD-CT.
Key words: breast cancer, high risk, randomized study
Received for publication July 11, 2007. Revision received December 18, 2007. Accepted for publication January 11, 2008.