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Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741

Authors :
William J. Gradishar
David D. Hurd
Eleanor H. Leung
Carolyn I. Sartor
Barbara L. Smith
Robert B. Livingston
Edith A. Perez
Silvana Martino
Jeffrey S. Abrams
James F. Holland
John T. Carpenter
Larry Norton
Nancy E. Davidson
Donald A. Berry
Eric P. Winer
Clifford A. Hudis
Marc L. Citron
Constance Cirrincione
Richard L. Schilsky
James N. Ingle
Hyman B. Muss
Source :
Journal of Clinical Oncology. 21:1431-1439
Publication Year :
2003
Publisher :
American Society of Clinical Oncology (ASCO), 2003.

Abstract

Purpose: Using a 2 × 2 factorial design, we studied the adjuvant chemotherapy of women with axillary node–positive breast cancer to compare sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) with concurrent doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) for disease-free (DFS) and overall survival (OS); to determine whether the dose density of the agents improves DFS and OS; and to compare toxicities. Patients and Methods: A total of 2,005 female patients were randomly assigned to receive one of the following regimens: (I) sequential A × 4 (doses) → T × 4 → C × 4 with doses every 3 weeks, (II) sequential A × 4 → T × 4 → C × 4 every 2 weeks with filgrastim, (III) concurrent AC × 4 → T × 4 every 3 weeks, or (IV) concurrent AC × 4 → T × 4 every 2 weeks with filgrastim. Results: A protocol-specified analysis was performed at a median follow-up of 36 months: 315 patients had experienced relapse or died, compared with 515 expected treatment failures. Dose-dense treatment improved the primary end point, DFS (risk ratio [RR] = 0.74; P = .010), and OS (RR = 0.69; P = .013). Four-year DFS was 82% for the dose-dense regimens and 75% for the others. There was no difference in either DFS or OS between the concurrent and sequential schedules. There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens. Conclusion: Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy.

Details

ISSN :
15277755 and 0732183X
Volume :
21
Database :
OpenAIRE
Journal :
Journal of Clinical Oncology
Accession number :
edsair.doi.dedup.....0c792b6f69ce415af5100ae77f406de5
Full Text :
https://doi.org/10.1200/jco.2003.09.081