Concurrent vs sequential adjuvant chemotherapy and hormone therapy in breast cancer: A multicenter randomized phase III trial

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 -