Annals of Oncology 14:833-842, 2003
© 2003 European Society for Medical Oncology
Original Paper |
Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group
1 Hospital Universitario San Carlos, Madrid; 2 Hospital Arnau de Vilanova, Valencia; 3 Hospital Vall d’Hebron, Barcelona; 4 Hospital Reina Sofia, Cordoba; 5 Hospital General Universitario, Alicante; 6 Hospital Universitario San Juan, Alicante; 7 Hospital General Universitario, Valencia; 8 Hospital General Universitario, Elche; 9 Hospital La Fe, Valencia; 10 Department of Biostatistics, GEICAM, Madrid, Spain
Received 17 February 2003; revised 28 March 2003; accepted 31 March 2003
Background:
The purpose of this study was to determine the relative efficacy of doxorubicin versus methotrexate in combination with intravenous cyclophosphamide and 5-fluorouracil (FAC versus CMF) as adjuvant chemotherapy for operable breast cancer.
Patients and methods:
Over a 4-year period, 985 women undergoing curative surgery for breast cancer (T1–3 N0–2 M0, stage I–IIIA, UICC) from nine hospitals were stratified with respect to axillary node involvement (node positive versus node negative) and randomized to receive either FAC (500/50/500/m2) every 3 weeks for six cycles or CMF (600/60/600/m2) every 3 weeks for six cycles.
Results:
The relative dose intensities of FAC and CMF were 87% and 85% of planned doses, respectively. Unadjusted data indicated a non-significant trend towards better results with FAC. In the prospectively formed subset of node-negative patients, disease-free survival and overall survival were statistically superior in the FAC treatment arm (P = 0.041 and 0.034, respectively), but this advantage was not seen in the subset of node-positive patients, probably because of a difference in the percentage of patients with four or more positive nodes. Adjusting data for size of treatment effect and potential interactions (number of positive nodes, tumor size, treatment center), the overall relative risk (RR) of disease recurrence and death were significantly lower with FAC treatment (RR 1.2, P = 0.03, and RR 1.3, P = 0.05, respectively). This result was mainly due to the difference observed in the node-negative patient population. Toxicity was mild: FAC induced more alopecia, emesis, mucositis and cardiotoxicity; this last was of clinical concern, but was infrequent and manageable. CMF induced more conjunctivitis and weight gain. There were no toxic deaths.
Conclusions:
Doxorubicin in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil is superior to methotrexate in combination with day 1 i.v. cyclophosphamide and 5-fluorouracil as adjuvant chemotherapy for operable breast cancer. A treatment effect is particularly evident in the node-negative patients. Although the clinical toxicity of FAC is greater than that of CMF, the levels were manageable and clinically acceptable.
Key words: adjuvant chemotherapy, anthracyclines, operable breast cancer
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Martin, A. Rodriguez-Lescure, A. Ruiz, E. Alba, L. Calvo, M. Ruiz-Borrego, B. Munarriz, C. A. Rodriguez, C. Crespo, E. de Alava, et al. Randomized Phase 3 Trial of Fluorouracil, Epirubicin, and Cyclophosphamide Alone or Followed by Paclitaxel for Early Breast Cancer J Natl Cancer Inst, June 4, 2008; 100(11): 805 - 814. [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]
|
|
|
|
 |
|
 A. Goldhirsch, W. C. Wood, R. D. Gelber, A. S. Coates, B. Thurlimann, H. -J. Senn, and Panel Members Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007 Ann. Onc., July 1, 2007; 18(7): 1133 - 1144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Colozza, E. de Azambuja, F. Cardoso, C. Bernard, and M. J. Piccart Breast cancer: achievements in adjuvant systemic therapies in the pre-genomic era. Oncologist, February 1, 2006; 11(2): 111 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. F. Hutchins, S. J. Green, P. M. Ravdin, D. Lew, S. Martino, M. Abeloff, A. P. Lyss, C. Allred, S. E. Rivkin, and C. K. Osborne Randomized, Controlled Trial of Cyclophosphamide, Methotrexate, and Fluorouracil Versus Cyclophosphamide, Doxorubicin, and Fluorouracil With and Without Tamoxifen for High-Risk, Node-Negative Breast Cancer: Treatment Results of Intergroup Protocol INT-0102 J. Clin. Oncol., November 20, 2005; 23(33): 8313 - 8321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gluck Adjuvant Chemotherapy for Early Breast Cancer: Optimal Use of Epirubicin Oncologist, November 1, 2005; 10(10): 780 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Alliot Weekly Epirubicin Plus Tamoxifen Versus Tamoxifen Alone As Adjuvant Treatment of Operable, Node-Positive, Elderly Breast Cancer Patients J. Clin. Oncol., June 20, 2005; 23(18): 4237 - 4238. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Martin, T. Pienkowski, J. Mackey, M. Pawlicki, J.-P. Guastalla, C. Weaver, E. Tomiak, T. Al-Tweigeri, L. Chap, E. Juhos, et al. Adjuvant Docetaxel for Node-Positive Breast Cancer N. Engl. J. Med., June 2, 2005; 352(22): 2302 - 2313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Fisher, J.-H. Jeong, S. Anderson, and N. Wolmark Treatment of Axillary Lymph Node-Negative, Estrogen Receptor-Negative Breast Cancer: Updated Findings From National Surgical Adjuvant Breast and Bowel Project Clinical Trials J Natl Cancer Inst, December 15, 2004; 96(24): 1823 - 1831. [Abstract] [Full Text] [PDF]
|
|