Epirubicin followed by cyclophosphamide, methotrexate and 5-fluorouracil versus paclitaxel followed by epirubicin and vinorelbine in patients with high-risk operable breast cancer.

OBJECTIVE: Breast cancer patients with >3 involved nodes (N+) have a poor outcome. Chemotherapy (CT), alone or combined with endocrine therapy (ET) in hormone receptor (HOR)-positive patients, is the standard for these women. However, there are still questions surrounding the optimal adjuvant CT regimen. METHODS: 244 patients with >3 N+ were randomized to receive either four 3-weekly courses of epirubicin (E: 100 mg/m(2), day 1) followed by four 4-weekly cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF: 600, 40, 600 mg/m(2), days 1, 8: n = 122) or four 3-weekly courses of paclitaxel (T: 175 mg/m(2), day 1) followed by four 3-weekly cycles of epirubicin and vinorelbine (E: 75 mg/m(2), day 1; V: 25 mg/m(2), days 1, 8: n = 122). After CT, tamoxifen (plus an LH-RH analog in menstruating women) was given to all HOR-positive patients over a period of 5 years. Overall survival (OS) was the primary end point. Relapse-free survival (RFS) and toxicity were secondary end points. RESULTS: At a median follow-up time of 102 months (range 3-146), OS and RFS did not differ significantly between groups (E-CMF vs. T-EV: OS, HR 0.94, 95% CI 0.59-1.48, p = 0.8; RFS, HR 0.86, 95% CI 0.57-1.29, p = 0.45). The lack of any difference between assigned treatments was confirmed by multivariate analysis (E-CMF vs. T-EV: RFS, HR 0.98, 95% CI 0.64-1.48, p = 0.9). The 2 regimens showed different toxicity profiles. In fact, significantly more women assigned to E-CMF were affected by stomatitis (p = 0.001) while significantly more women in the T-EV group developed peripheral neuropathy (p < 0.0001) and musculoskeletal disorders (p < 0.0001). However, side effects were moderate and manageable and no toxic death occurred in either arm of the study. CONCLUSIONS: T-EV was safe and moderately toxic but was not superior to E-CMF.

Phase III randomized multicenter study on the effects of adjuvant CMF in patients with node-negative, rapidly proliferating breast cancer: twelve-year results and retrospective subgroup analysis.

The randomized multicenter study on rapidly proliferating breast cancer, assessed according to thymidine labelling index (TLI), was activated at the end of the 1980s. The present work investigated whether and to what degree the short-term advantages observed from adjuvant CMF (cyclophosphamide, methotrexate, 5-fluorouracil) were maintained at a longer follow-up. Two hundred and eighty-one patients with node-negative and high TLI tumors were randomized to receive six cycles of CMF or no further treatment. At a median follow-up of 12 years, CMF produced a 25% and 20% relative reduction in relapse and death cumulative incidence, respectively. A breakdown analysis identified a subgroup of patients with intermediate proliferating tumors for whom a 70% and 73% reduction in relapse and death was observed in the intention-to-treat population. An even higher reduction of 80% and 84% in relapse and death was seen for the patients who had received the full CMF dose. We identified a subgroup of patients with intermediate proliferating tumors in whom the high benefit obtained from adjuvant CMF was maintained at a long-term follow up.