| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2005 Oxford University Press
ARTICLE |
Dose-Dense Adjuvant Chemotherapy in Early Breast Cancer Patients: Results From a Randomized Trial
Affiliations of authors: Institutions of Oncologia Medica (MV, LDM, MRS, RR), Senologia Chirurgica (G. Canavese), Sperimentazioni Cliniche Controllate Istituto Nazionale per la Ricerca sul Cancro, Genova (PB); Ospedale C. Poma, Mantova (EA, G. Cavazzini); Ospedale S. Chiara Pisa (EB); Ospedale Galliera Genova (CC); UO Oncologia Medica, ASL 1, Sassari (AC); UO Oncologia Medica, ASL 19, Asti (FT); UO Oncologia Medica, Savona (FB); UO Oncologia Medica, La Spezia (PP); Università degli Studi, Genova (MRS), Italy
Correspondence to: Marco Venturini, MD, National Cancer Research Institute, L.go R. Benzi 10, 16132 Genoa, Italy (e-mail: marco.venturini{at}istge.it).
Background: To determine whether a dose-dense regimen improves outcome in early breast cancer patients, we compared outcomes with the same fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapeutic regimen administered every 3 weeks (FEC21) or administered every 2 weeks (FEC14 including support with filgrastim, a granulocyte colony-stimulating factor) in a multicenter phase III randomized trial. Methods: A total of 1214 patients with early-stage breast cancer were randomly assigned to receive six cycles of FEC14 (604 patients) or of FEC21 (610 patients). Study endpoints were overall survival and event-free survival. Associations were assessed by multivariable analysis with adjustment for age; tumor size; grade; proliferative rate; and menopausal, lymph node, estrogen receptor, and progesterone receptor status. All statistical tests were two-sided. Results: Patients in the FEC14 arm had fewer dose reductions or treatment delays or discontinuation (26%) than those in the FEC21 arm (33%) (difference = 7%, 95% confidence interval [CI] = 2% to 12%; P = .008). FEC14 therapy, compared with FEC21 therapy, was associated with more asthenia (36% versus 29%, difference = 7%, 95% CI = 2% to 12%; P = .01), bone pain (33% versus 4%, difference = 29%, 95% CI = 25% to 33%; P<.001), anemia (38% versus 19%, difference = 19%, 95% CI = 14% to 24%; P<.001), and thrombocytopenia (8% versus 2%, difference = 6%, 95% CI = 4% to 9%; P<.001), but with less leukopenia (12% versus 45%, difference = 33%, 95% CI = 28% to 37%; P<.001). No acute myelogenous leukemia or myelodysplastic syndrome was observed. At a median follow-up of 10.4 years, no statistically significant difference in the hazard of death (hazard ratio [HR] = 0.87, 95% CI = 0.67 to 1.13) or recurrence (HR = 0.88, 95% CI = 0.71 to 1.08) was found between FEC14 and FEC21 groups after adjustment by multivariable analysis. Although the study was underpowered for subset analysis, we found no evidence that the effect of the treatment type was associated with any of the potential prognostic factors. Conclusion: Our results support the long-term safety of FEC14 chemotherapy as an adjuvant treatment of breast cancer. However, this therapy was not associated with improved outcome, but because of the limited statistical power of our study, we cannot rule out a modest improvement in outcome associated with FEC14 therapy.
CiteULike 
Connotea 
Del.icio.us What's this?
Editorial about this Article
- Dose Density in Breast Cancer: A Simple Message?
- Nancy U. Lin, Rebecca Gelman, and Eric P. Winer
J Natl Cancer Inst 2005 97: 1712-1714.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
|
|
 |
|
  M. Untch, V. Mobus, W. Kuhn, B. R. Muck, C. Thomssen, I. Bauerfeind, N. Harbeck, C. Werner, A. Lebeau, A. Schneeweiss, et al. Intensive Dose-Dense Compared With Conventionally Scheduled Preoperative Chemotherapy for High-Risk Primary Breast Cancer J. Clin. Oncol., June 20, 2009; 27(18): 2938 - 2945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Morris, H. L. McArthur, C. T. Dang, and C. A. Hudis Selection of Appropriate Patients for Anthracycline Therapy ASCO Educational Book, January 1, 2009; 2009(1): 11 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fountzilas, U. Dafni, H. Gogas, H. Linardou, H. P. Kalofonos, E. Briasoulis, D. Pectasides, E. Samantas, D. Bafaloukos, G. P. Stathopoulos, et al. Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00 Ann. Onc., May 1, 2008; 19(5): 853 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Gluz, U. A. Nitz, N. Harbeck, E. Ting, R. Kates, A. Herr, W. Lindemann, C. Jackisch, W. E. Berdel, H. Kirchner, et al. Triple-negative high-risk breast cancer derives particular benefit from dose intensification of adjuvant chemotherapy: results of WSG AM-01 trial Ann. Onc., May 1, 2008; 19(5): 861 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-P. P. Tran and J. L. Grabinski Chemotherapy for Early-Stage Breast Cancer: A Paradigm in Flux Journal of Pharmacy Practice, February 1, 2008; 21(1): 46 - 56. [Abstract] [PDF]
|
|
|
|
|
|
L. Del Mastro, B. Dozin, E. Aitini, T. Catzeddu, E. Baldini, A. Contu, A. Durando, S. Danese, G. Cavazzini, G. Canavese, et al. Timing of adjuvant chemotherapy and tamoxifen in women with breast cancer: findings from two consecutive trials of Gruppo Oncologico Nord-Ovest-Mammella Intergruppo (GONO-MIG) Group Ann. Onc., February 1, 2008; 19(2): 299 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Smith and J. L. Khatcheressian Re: Neutropenic events in community practices reduced by first and subsequent cycle pegfilgrastim use. Oncologist, December 1, 2007; 12(12): 1464 - 1464. [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hershman, A. I. Neugut, and V. Grann Response: Re: Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte Colony-Stimulating Factors During Breast Cancer Adjuvant Chemotherapy J Natl Cancer Inst, July 4, 2007; 99(13): 1051 - 1052. [Full Text] [PDF]
|
|
|
|
|
|
M. Clavarezza, L. Del Mastro, P. Pronzato, P. Bruzzi, and M. Venturini Re: Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte Colony-Stimulating Factors During Breast Cancer Adjuvant Chemotherapy J Natl Cancer Inst, July 4, 2007; 99(13): 1050 - 1051. [Full Text] [PDF]
|
|
|
|
|
|
A. U. Buzdar Adjuvant Chemotherapy for High-Risk Operable Breast Cancer J. Clin. Oncol., May 1, 2007; 25(13): 1642 - 1644. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Walshe, N. Denduluri, and S. M. Swain Amenorrhea in Premenopausal Women After Adjuvant Chemotherapy for Breast Cancer J. Clin. Oncol., December 20, 2006; 24(36): 5769 - 5779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. U. Lin, R. Gelman, and E. P. Winer Dose Density in Breast Cancer: A Simple Message? J Natl Cancer Inst, December 7, 2005; 97(23): 1712 - 1714. [Full Text] [PDF]
|
|