Adjuvant chemotherapy in older women with early-stage breast cancer Journal Article


Authors: Muss, H. B.; Berry, D. A.; Cirrincione, C. T.; Theodoulou, M.; Mauer, A. M.; Kornblith, A. B.; Partridge, A. H.; Dressler, L. G.; Cohen, H. J.; Becker, H. P.; Kartcheske, P. A.; Wheeler, J. D.; Perez, E. A.; Wolff, A. C.; Gralow, J. R.; Burstein, H. J.; Mahmood, A. A.; Magrinat, G.; Parker, B. A.; Hart, R. D.; Grenier, D.; Norton, L.; Hudis, C. A.; Winer, E. P.
Article Title: Adjuvant chemotherapy in older women with early-stage breast cancer
Abstract: BACKGROUND: Older women with breast cancer are underrepresented in clinical trials, and data on the effects of adjuvant chemotherapy in such patients are scant. We tested for the noninferiority of capecitabine as compared with standard chemotherapy in women with breast cancer who were 65 years of age or older. METHODS: We randomly assigned patients with stage I, II, IIIA, or IIIB breast cancer to standard chemotherapy (either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide plus doxorubicin) or capecitabine. Endocrine therapy was recommended after chemotherapy in patients with hormone-receptor-positive tumors. A Bayesian statistical design was used with a range in sample size from 600 to 1800 patients. The primary end point was relapse-free survival. RESULTS: When the 600th patient was enrolled, the probability that, with longer follow-up, capecitabine therapy was highly likely to be inferior to standard chemotherapy met a prescribed level, and enrollment was discontinued. After an additional year of follow-up, the hazard ratio for disease recurrence or death in the capecitabine group was 2.09 (95% confidence interval, 1.38 to 3.17; P<0.001). Patients who were randomly assigned to capecitabine were twice as likely to have a relapse and almost twice as likely to die as patients who were randomly assigned to standard chemotherapy (P=0.02). At 3 years, the rate of relapse-free survival was 68% in the capecitabine group versus 85% in the standard-chemotherapy group, and the overall survival rate was 86% versus 91%. Two patients in the capecitabine group died of treatment-related complications; as compared with patients receiving capecitabine, twice as many patients receiving standard chemotherapy had moderate-to-severe toxic effects (64% vs. 33%). CONCLUSIONS: Standard adjuvant chemotherapy is superior to capecitabine in patients with earlystage breast cancer who are 65 years of age or older. (ClinicalTrials.gov number, NCT00024102.) Copyright © 2009 Massachusetts Medical Society.
Keywords: survival; cancer chemotherapy; cancer survival; controlled study; treatment response; aged; aged, 80 and over; survival analysis; survival rate; major clinical study; clinical trial; fatigue; neutropenia; cancer recurrence; cisplatin; doxorubicin; fluorouracil; cancer combination chemotherapy; diarrhea; skin manifestation; capecitabine; cancer adjuvant therapy; comparative study; disease free survival; chemotherapy, adjuvant; methotrexate; cancer staging; outcome assessment; follow up; antineoplastic agent; neoplasm staging; metastasis; controlled clinical trial; multiple cycle treatment; neoplasm recurrence, local; breast cancer; anemia; antimetabolites, antineoplastic; leukopenia; mucosa inflammation; nausea; randomized controlled trial; thrombocytopenia; antineoplastic combined chemotherapy protocols; cyclophosphamide; pathology; breast neoplasms; cancer mortality; cancer hormone therapy; febrile neutropenia; kaplan-meiers estimate; chemotherapy induced emesis; drug fatality; disease severity; early cancer; multicenter study; tumor recurrence; adjuvant chemotherapy; thrombosis; breast tumor; neoplasm metastasis; drug derivative; patient compliance; receptors, estrogen; kaplan meier method; embolism; estrogen receptor; progesterone receptor; trastuzumab; drug dose increase; deoxycytidine; antineoplastic antimetabolite; cmf protocol; cmf regimen
Journal Title: New England Journal of Medicine
Volume: 360
Issue: 20
ISSN: 0028-4793
Publisher: Massachusetts Medical Society  
Date Published: 2009-05-01
Start Page: 2055
End Page: 2065
Language: English
DOI: 10.1056/NEJMoa0810266
PUBMED: 19439741
PROVIDER: scopus
PMCID: PMC3082436
DOI/URL:
Notes: --- - "Cited By (since 1996): 42" - "Export Date: 30 November 2010" - "CODEN: NEJMA" - "Source: Scopus"
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MSK Authors
  1. Clifford Hudis
    850 Hudis
  2. Larry Norton
    587 Norton