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.
Boccardo
Francesco
F
National Cancer Research Institute and the University of Genoa Largo Rosanna Benzi 10, IT-16132 Genoa, Italy. fboccardo@unige.it
Amadori
Dino
D
Guglielmini
Pamela
P
Sismondi
Piero
P
Farris
Antonio
A
Agostara
Biagio
B
Gambi
Angelo
A
Catalano
Giuseppina
G
Faedi
Marina
M
Rubagotti
Alessandra
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D015999:Multivariate Analysis; D017239:Paclitaxel / Q000008:administration & dosage*; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
D015251:Epirubicin; D014747:Vinblastine; D003520:Cyclophosphamide; D017239:Paclitaxel; D000077235:Vinorelbine; D005472:Fluorouracil; D008727:Methotrexate