Concurrent vs sequential adjuvant chemotherapy and hormone therapy in breast cancer: A multicenter randomized phase III trial Full Text
Journal of the National Cancer Institute, 10/15/2011  Clinical Article

Bedognetti D et al. – No 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. Because of the limited statistical power of the study, these results must be considered with caution.

• 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
• Primary endpoint was OS, and secondary endpoints were toxic effects and DFS
• No provision for interim analyses was made in original study protocol
• Survival curves estimated by 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 HRs and 95% CIs
• All statistical tests were 2-sided

• 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 2 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
• 4 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)