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.
RCT Entities:
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.
Authors: A VanderWalde; W Ye; P Frankel; D Asuncion; L Leong; T Luu; R Morgan; P Twardowski; M Koczywas; R Pezner; I B Paz; K Margolin; J Wong; J H Doroshow; S Forman; S Shibata; G Somlo Journal: Biol Blood Marrow Transplant Date: 2012-02-02 Impact factor: 5.742
Authors: Donald A Berry; Naoto T Ueno; Marcella M Johnson; Xiudong Lei; Jean Caputo; Dori A Smith; Linda J Yancey; Michael Crump; Edward A Stadtmauer; Pierre Biron; John P Crown; Peter Schmid; Jean-Pierre Lotz; Giovanni Rosti; Marco Bregni; Taner Demirer Journal: J Clin Oncol Date: 2011-07-18 Impact factor: 44.544
Authors: Antonia M S Müller; Holbrook E K Kohrt; Steven Cha; Ginna Laport; Jared Klein; Alice E Guardino; Laura J Johnston; Keith E Stockerl-Goldstein; Elie Hanania; Christopher Juttner; Karl G Blume; Robert S Negrin; Irving L Weissman; Judith A Shizuru Journal: Biol Blood Marrow Transplant Date: 2011-07-20 Impact factor: 5.742
Authors: Davina Ghersi; Melina L Willson; Matthew Ming Ki Chan; John Simes; Emma Donoghue; Nicholas Wilcken Journal: Cochrane Database Syst Rev Date: 2015-06-10