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Up-Front Tandem High-Dose Chemotherapy Compared With Standard Chemotherapy With Doxorubicin and Paclitaxel in Metastatic Breast Cancer: Results of a Randomized Trial

From the Berlin Breast Cancer Research Group, Medizinische Klinik mit Schwerpunkt Onkologie und Hämatologie, Charité Campus Mitte, Humboldt Universität zu Berlin, Berlin; Department of Oncology and Hematology, Franziskus Hospital, Bielefeld; Department of Oncology and Hematology, Westpfalz-Klinikum, Kaiserslautern; Department of Gynecology and Obstetrics, Universitätsfrauenklinik, Ulm; Humaine Klinikum, Bad Saarow; Department for Intelligent Systems, University of Bremen, Bremen; Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz; Department of Oncology and Hematology, Landesklinik, Salzburg, Austria

Address reprint requests to Peter Schmid, MD, Department of Oncology and Hematology, Charité Campus Mitte, Humboldt University Berlin, Schumannstr 20/21, 10117 Berlin, Germany; e-mail: peter.schmid{at}charite.de

PURPOSE: The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer.

PATIENTS AND METHODS: Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates.

RESULTS: A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity.

CONCLUSION: This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.

Supported by Bristol-Myers Squibb (Munich, Germany), Amgen Pharma (Munich, Germany), and Wyeth Lederle, Germany.

Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 18-21, 2002, at the 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003, and at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

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

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