title: A randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer.
abstract: The sequential doxorubicin --> CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF x 6 cycles (CMF); (b) doxorubicin x 4 cycles followed by CMF x 6 cycles (A --> CMF); (c) CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (CMF --> GT); and (d) doxorubicin x 4 cycles followed by CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (A --> CMF --> GT). The study used a 2 x 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A --> CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A --> CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556-0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555-0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54-1.32). A --> CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients.
authors.affiliation: Department Molecular and Clinical Oncology and Endocrinology, University Federico II, Via S Pansini 5, Napoli 80131, Italy.
authors.forename: S
authors.initials: S
authors.lastname: De Placido
authors.forename: M
authors.initials: M
authors.lastname: De Laurentiis
authors.forename: M
authors.initials: M
authors.lastname: De Lena
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.forename: A
authors.initials: A
authors.lastname: Paradiso
authors.forename: M
authors.initials: M
authors.lastname: D'Aprile
authors.forename: G
authors.initials: G
authors.lastname: Pistillucci
authors.forename: A
authors.initials: A
authors.lastname: Farris
authors.forename: M G
authors.initials: MG
authors.lastname: Sarobba
authors.forename: S
authors.initials: S
authors.lastname: Palazzo
authors.forename: L
authors.initials: L
authors.lastname: Manzione
authors.forename: V
authors.initials: V
authors.lastname: Adamo
authors.forename: S
authors.initials: S
authors.lastname: Palmeri
authors.forename: F
authors.initials: F
authors.lastname: Ferraù
authors.forename: R
authors.initials: R
authors.lastname: Lauria
authors.forename: C
authors.initials: C
authors.lastname: Pagliarulo
authors.forename: G
authors.initials: G
authors.lastname: Petrella
authors.forename: G
authors.initials: G
authors.lastname: Limite
authors.forename: R
authors.initials: R
authors.lastname: Costanzo
authors.forename: A R
authors.initials: AR
authors.lastname: Bianco
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D017273:Goserelin / Q000008:administration & dosage*; D006801:Humans; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D013629:Tamoxifen / Q000008:administration & dosage*
chemical_list: D013629:Tamoxifen; D017273:Goserelin; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate