Updated Survival Analysis after a Median Follow-up of 12 Years of an Anthracycline-Containing Adjuvant Prospective Multicentre, Randomised Phase III Trial on Dose-Dense Chemotherapy in Primary Node-Positive, High-Risk Breast Cancer Patients.

PURPOSE: Although dose-dense (dd) chemotherapy plays a fundamental role in the treatment of breast cancer (BC), a variety of trials have presented divergent survival results. Here, we present data of patients with more than 3 positive axillary lymph nodes (+aLN) receiving dd chemotherapy after a median follow-up period of 12.3 years. METHODS: In the years 1996-2000, 231 patients with invasive BC, ≥pN2a and no evidence of distant metastases were recruited to receive treatment A, i.e. dd 3 × epirubicin (E, 90 mg/m2) + paclitaxel (P, 175 mg/m2) every 2 weeks (q2w) followed by 3 × cyclophosphamide (C)/methotrexate/5-fluorouracil (CMF, 600/40/600 mg/m2, q2w), or treatment B, i.e. 4 × E + C (C, 600 mg/m2) q3w followed by 3 × CMF q3w. RESULTS: 113 patients in arm A and 113 patients in arm B were analysed after an updated median follow-up of 12.3 years. The median age was 55 years, with a median number of 6 +aLN, 50.4% had a T2 and 79.2% hormone receptor-positive BC. The disease-free survival (DFS) rate was 53.1% in arm A and 42.5% in arm B (adjusted p = 0.027). The overall survival (OS) rate was 54.9% in arm A and 48.7% in arm B (adjusted p = 0.058). In the multivariable analysis, the tumour burden was a significant predictor for DFS and OS. CONCLUSION: The adjuvant use of dd chemotherapy led to a statistically significant improvement of DFS after a follow-up of 12.3 years.

Dose-dense adjuvant chemotherapy for node-positive breast cancer in women 60 years and older: feasibility and tolerability in a subset of patients in a randomized trial.

To evaluate the feasibility and tolerability of dose-dense adjuvant chemotherapy for older patients with node-positive breast cancer, a retrospective subset analysis compared dose delays and dose reductions for women aged > or = 60 years with those of younger women. Patients were randomized to a dose-dense (DD, 14-day cycle) or conventional-schedule (CS, 21-day cycle) regimen. DD patients (n = 104; 25 aged > or = 60 years) received epirubicin 90 mg/m2 plus paclitaxel 175 mg/m2 (four cycles), then cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2 and fluorouracil 600 mg/m2 (CMF 600/40/600) (three cycles), plus filgrastim 5 microg/kg per day in every cycle. CS patients (n = 107; 27 aged > or = 60 years) received epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 (four cycles), then CMF 600/40/600 (three cycles), plus filgrastim if required. Delays were more common in older patients in both the DD and CS groups (DD, 17% versus 6%; CS, 11% versus 6%), as were Grades 3-4 leukopenia (26% versus 12%) and neutropenia (33% versus 25%). All older DD and 89% of older CS patients received all seven chemotherapy cycles, with 99% of cycles at full dose. This study demonstrates that a dose-dense regimen combining epirubicin and paclitaxel can be administered to patients > or = 60 years of age with a tolerable safety profile.