TY - JOUR
T1 - Concurrent vs sequential adjuvant chemotherapy and hormone therapy in breast cancer
T2 - A multicenter randomized phase III trial
AU - Bedognetti, Davide
AU - Sertoli, Mario Roberto
AU - Pronzato, Paolo
AU - Del Mastro, Lucia
AU - Venturini, Marco
AU - Taveggia, Paola
AU - Zanardi, Elisa
AU - Siffredi, Guido
AU - Pastorino, Simona
AU - Queirolo, Paola
AU - Gardin, Giovanni
AU - Wang, Ena
AU - Monzeglio, Clara
AU - Boccardo, Francesco
AU - Bruzzi, Paolo
PY - 2011/10/19
Y1 - 2011/10/19
N2 - Conclusion Background The most appropriate timing of chemotherapy and hormone therapy administration is a critical issue in early breast cancer patients. The purpose of our study was to compare the efficacy of concurrent vs sequential administration of adjuvant chemotherapy and tamoxifen.Conclusion Methods Women with node-positive primary breast cancer were randomly assigned to receive tamoxifen (20 mg/d for 5 years) during (concurrent arm) or after (sequential arm) adjuvant chemotherapy. Chemotherapy consisted of alternating regimens of cyclophosphamide, epidoxorubicin, and 5-fluorouracil and cyclophosphamide, methotrexate, and 5-fluorouracil every 21 days for a total of 12 cycles. The primary endpoint was overall survival (OS), and secondary endpoints were toxic effects and disease-free survival (DFS). No provision for interim analyses was made in the original study protocol. Survival curves were estimated by the Kaplan-Meier method. Multivariable Cox regression models, adjusted for age, menopausal status, tumor stage, and lymph node and hormone receptor status, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.Conclusion Results From 1985 to 1992, 431 patients were randomly assigned and studied according to the intention-to-treat principle. After a maximum of 15.4 years of follow-up (median 12.3 years), the estimated actuarial 10-year OS was equivalent for the two study arms (concurrent arm: 111 patients, 66%, 95% CI = 59% to 72%; sequential arm: 114 patients, 65%, 95% CI = 59% to 72%, P =. 86). No differences in DFS and toxic effects were evident. Four interim analyses were performed, but no alpha error adjustment was necessary because of the largely negative Results of this final analysis (sequential vs concurrent arm: HR of death = 1.06, 95% CI = 0.78 to 1.44, P =. 76; HR of relapse = 1.16, 95% CI = 0.88 to 1.52, P =. 36).Conclusion Conclusion sNo statistically significant differences in OS, DFS, and toxic effects between concurrent and sequential adjuvant chemo-and hormone therapies were observed. Our study does not support the superiority of one schedule of chemo-and hormone-therapy administration over the other. However, because of the limited statistical power of the study, these Results must be considered with caution.
AB - Conclusion Background The most appropriate timing of chemotherapy and hormone therapy administration is a critical issue in early breast cancer patients. The purpose of our study was to compare the efficacy of concurrent vs sequential administration of adjuvant chemotherapy and tamoxifen.Conclusion Methods Women with node-positive primary breast cancer were randomly assigned to receive tamoxifen (20 mg/d for 5 years) during (concurrent arm) or after (sequential arm) adjuvant chemotherapy. Chemotherapy consisted of alternating regimens of cyclophosphamide, epidoxorubicin, and 5-fluorouracil and cyclophosphamide, methotrexate, and 5-fluorouracil every 21 days for a total of 12 cycles. The primary endpoint was overall survival (OS), and secondary endpoints were toxic effects and disease-free survival (DFS). No provision for interim analyses was made in the original study protocol. Survival curves were estimated by the Kaplan-Meier method. Multivariable Cox regression models, adjusted for age, menopausal status, tumor stage, and lymph node and hormone receptor status, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.Conclusion Results From 1985 to 1992, 431 patients were randomly assigned and studied according to the intention-to-treat principle. After a maximum of 15.4 years of follow-up (median 12.3 years), the estimated actuarial 10-year OS was equivalent for the two study arms (concurrent arm: 111 patients, 66%, 95% CI = 59% to 72%; sequential arm: 114 patients, 65%, 95% CI = 59% to 72%, P =. 86). No differences in DFS and toxic effects were evident. Four interim analyses were performed, but no alpha error adjustment was necessary because of the largely negative Results of this final analysis (sequential vs concurrent arm: HR of death = 1.06, 95% CI = 0.78 to 1.44, P =. 76; HR of relapse = 1.16, 95% CI = 0.88 to 1.52, P =. 36).Conclusion Conclusion sNo statistically significant differences in OS, DFS, and toxic effects between concurrent and sequential adjuvant chemo-and hormone therapies were observed. Our study does not support the superiority of one schedule of chemo-and hormone-therapy administration over the other. However, because of the limited statistical power of the study, these Results must be considered with caution.
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U2 - 10.1093/jnci/djr351
DO - 10.1093/jnci/djr351
M3 - Article
C2 - 21921285
AN - SCOPUS:80054933718
VL - 103
SP - 1529
EP - 1539
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 20
ER -