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Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial.
- Source :
-
Lancet (London, England) [Lancet] 2009 Dec 19; Vol. 374 (9707), pp. 2055-2063. Date of Electronic Publication: 2009 Dec 10. - Publication Year :
- 2009
-
Abstract
- Background: Tamoxifen is standard adjuvant treatment for postmenopausal women with hormone-receptor-positive breast cancer. We assessed the benefit of adding chemotherapy to adjuvant tamoxifen and whether tamoxifen should be given concurrently or after chemotherapy.<br />Methods: We undertook a phase 3, parallel, randomised trial (SWOG-8814, INT-0100) in postmenopausal women with hormone-receptor-positive, node-positive breast cancer to test two major objectives: whether the primary outcome, disease-free survival, was longer with cyclophosphamide, doxorubicin, and fluorouracil (CAF) given every 4 weeks for six cycles plus 5 years of daily tamoxifen than with tamoxifen alone; and whether disease-free survival was longer with CAF followed by tamoxifen (CAF-T) than with CAF plus concurrent tamoxifen (CAFT). Overall survival and toxicity were predefined, important secondary outcomes for each objective. Patients in this open-label trial were randomly assigned by a computer algorithm in a 2:3:3 ratio (tamoxifen:CAF-T:CAFT) and analysis was by intention to treat of eligible patients. Groups were compared by stratified log-rank tests, followed by Cox regression analyses adjusted for significant prognostic factors. This trial is registered with ClinicalTrials.gov, number NCT00929591.<br />Findings: Of 1558 randomised women, 1477 (95%) were eligible for inclusion in the analysis. After a maximum of 13 years of follow-up (median 8.94 years), 637 women had a disease-free survival event (tamoxifen, 179 events in 361 patients; CAF-T, 216 events in 566 patients; CAFT, 242 events in 550 patients). For the first objective, therapy with the CAF plus tamoxifen groups combined (CAFT or CAF-T) was superior to tamoxifen alone for the primary endpoint of disease-free survival (adjusted Cox regression hazard ratio [HR] 0.76, 95% CI 0.64-0.91; p=0.002) but only marginally for the secondary endpoint of overall survival (HR 0.83, 0.68-1.01; p=0.057). For the second objective, the adjusted HRs favoured CAF-T over CAFT but did not reach significance for disease-free survival (HR 0.84, 0.70-1.01; p=0.061) or overall survival (HR 0.90, 0.73-1.10; p=0.30). Neutropenia, stomatitis, thromboembolism, congestive heart failure, and leukaemia were more frequent in the combined CAF plus tamoxifen groups than in the tamoxifen-alone group.<br />Interpretation: Chemotherapy with CAF plus tamoxifen given sequentially is more effective adjuvant therapy for postmenopausal patients with endocrine-responsive, node-positive breast cancer than is tamoxifen alone. However, it might be possible to identify some subgroups that do not benefit from anthracycline-based chemotherapy despite positive nodes.<br />Funding: National Cancer Institute (US National Institutes of Health).<br /> (Copyright 2009 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adenocarcinoma mortality
Adult
Aged
Antibiotics, Antineoplastic administration & dosage
Antimetabolites, Antineoplastic administration & dosage
Antineoplastic Agents, Alkylating administration & dosage
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Breast Neoplasms mortality
Chemotherapy, Adjuvant
Cyclophosphamide administration & dosage
Disease-Free Survival
Doxorubicin administration & dosage
Female
Fluorouracil administration & dosage
Humans
Lymphatic Metastasis
Middle Aged
Postmenopause
Receptors, Estrogen analysis
Receptors, Progesterone analysis
Adenocarcinoma drug therapy
Antineoplastic Agents, Hormonal administration & dosage
Breast Neoplasms drug therapy
Lymph Nodes pathology
Tamoxifen administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1474-547X
- Volume :
- 374
- Issue :
- 9707
- Database :
- MEDLINE
- Journal :
- Lancet (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 20004966
- Full Text :
- https://doi.org/10.1016/S0140-6736(09)61523-3