Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial.
Lancet
; 374(9707): 2055-2063, 2009 Dec 19.
Article
em En
| MEDLINE
| ID: mdl-20004966
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.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 majorobjectives:
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 233 ratio (tamoxifenCAF-TCAFT) 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.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.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.FUNDING:
National Cancer Institute (US National Institutes of Health).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
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Neoplasias da Mama
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Adenocarcinoma
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Antineoplásicos Hormonais
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Linfonodos
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article