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Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer.

AbstractBACKGROUND:
Chemotherapy regimens that combine anthracyclines and taxanes result in improved disease-free and overall survival among women with operable lymph-node-positive breast cancer. The effectiveness of concurrent versus sequential regimens is not known.
METHODS:
We randomly assigned 5351 patients with operable, node-positive, early-stage breast cancer to receive four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel (sequential ACT); four cycles of doxorubicin and docetaxel (doxorubicin-docetaxel); or four cycles of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT). The primary aims were to examine whether concurrent ACT was more effective than sequential ACT and whether the doxorubicin-docetaxel regimen would be as effective as the concurrent-ACT regimen. The secondary aims were to assess toxic effects and to correlate amenorrhea with outcomes in premenopausal women.
RESULTS:
At a median follow-up of 73 months, overall survival was improved in the sequential-ACT group (8-year overall survival, 83%) as compared with the doxorubicin-docetaxel group (overall survival, 79%; hazard ratio for death, 0.83; P=0.03) and the concurrent-ACT group (overall survival, 79%; hazard ratio, 0.86; P=0.09). Disease-free survival was improved in the sequential-ACT group (8-year disease-free survival, 74%) as compared with the doxorubicin-docetaxel group (disease-free survival, 69%; hazard ratio for recurrence, a second malignant condition, or death, 0.80; P=0.001) and the concurrent-ACT group (disease-free survival, 69%; hazard ratio, 0.83; P=0.01). The doxorubicin-docetaxel regimen showed noninferiority to the concurrent-ACT regimen for overall survival (hazard ratio, 0.96; 95% confidence interval, 0.82 to 1.14). Overall survival was improved in patients with amenorrhea for 6 months or more across all treatment groups, independently of estrogen-receptor status.
CONCLUSIONS:
Sequential ACT improved disease-free survival as compared with doxorubicin-docetaxel or concurrent ACT, and it improved overall survival as compared with doxorubicin-docetaxel. Amenorrhea was associated with improved survival regardless of the treatment and estrogen-receptor status. (ClinicalTrials.gov number, NCT00003782.)
AuthorsSandra M Swain, Jong-Hyeon Jeong, Charles E Geyer Jr, Joseph P Costantino, Eduardo R Pajon, Louis Fehrenbacher, James N Atkins, Jonathan Polikoff, Victor G Vogel, John K Erban, Priya Rastogi, Robert B Livingston, Edith A Perez, Eleftherios P Mamounas, Stephanie R Land, Patricia A Ganz, Norman Wolmark
JournalThe New England journal of medicine (N Engl J Med) Vol. 362 Issue 22 Pg. 2053-65 (Jun 03 2010) ISSN: 1533-4406 [Electronic] United States
PMID20519679 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright2010 Massachusetts Medical Society
Chemical References
  • Taxoids
  • Docetaxel
  • Doxorubicin
  • Cyclophosphamide
Topics
  • Adenocarcinoma (drug therapy, mortality, surgery)
  • Amenorrhea (chemically induced)
  • Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
  • Breast Neoplasms (drug therapy, mortality, surgery)
  • Chemotherapy, Adjuvant
  • Cyclophosphamide (administration & dosage)
  • Docetaxel
  • Doxorubicin (administration & dosage)
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Premenopause
  • Survival Analysis
  • Taxoids (administration & dosage)

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