title: Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer--8-year results of the Breast International Group 02-98 phase III trial.
abstract: Background In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease-free survival (DFS) with docetaxel. We present results at 8-year median follow-up and exploratory analyses within biologically defined subtypes. Methods Patients were randomly assigned to one of four treatments: (i) sequential control: doxorubicin (A) (75 mg/m(2)) × 4 →classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF); (ii) concurrent control: doxorubicin, cyclophosphamide (AC)(60/600 mg/m(2)) × 4 →CMF; (iii) sequential docetaxel: A (75 mg/m(2)) × 3 → docetaxel (T) (100 mg/m(2)) × 3 → CMF and (iv) concurrent docetaxel: AT(50/75 mg/m(2)) × 4 →CMF. The primary comparison evaluated docetaxel efficacy regardless of the schedule. Exploratory analyses were undertaken within biologically defined subtypes. Results Two thousand eight hundred and eighty-seven patients were enrolled. After 93.4 months of median follow-up, there were 916 DFS events. For the primary comparison, there was no significant improvement in DFS from docetaxel [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.80-1.05, P = 0.187]. In secondary comparisons, sequential docetaxel significantly improved DFS compared with sequential control (HR = 0.81, 95% CI = 0.67-0.99, P = 0.036), and significantly improved DFS (HR = 0.84, 95% CI = 0.72-0.99, P = 0.035) and overall survival (OS) (HR = 0.79, 95% CI = 0.65-0.98, P = 0.028) compared with concurrent doxorubicin-docetaxel. Luminal-A disease had the best prognosis. HRs favored addition of sequential docetaxel in all subtypes, except luminal-A; but this observation was not statistically supported because of limited numbers. Conclusion With further follow-up, the sequential docetaxel schedule resulted in significantly better OS than concurrent doxorubicin-docetaxel, and continued to show better DFS than sequential doxorubicin-based control.
authors.affiliation: Sandro Pitigliani Medical Oncology Unit, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Oakman
authors.forename: P A
authors.initials: PA
authors.lastname: Francis
authors.forename: J
authors.initials: J
authors.lastname: Crown
authors.forename: E
authors.initials: E
authors.lastname: Quinaux
authors.forename: M
authors.initials: M
authors.lastname: Buyse
authors.forename: E
authors.initials: E
authors.lastname: De Azambuja
authors.forename: M
authors.initials: M
authors.lastname: Margeli Vila
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.forename: B
authors.initials: B
authors.lastname: Nordenskjöld
authors.forename: R
authors.initials: R
authors.lastname: Jakesz
authors.forename: B
authors.initials: B
authors.lastname: Thürlimann
authors.forename: J
authors.initials: J
authors.lastname: Gutiérrez
authors.forename: V
authors.initials: V
authors.lastname: Harvey
authors.forename: L
authors.initials: L
authors.lastname: Punzalan
authors.forename: P
authors.initials: P
authors.lastname: Dell'orto
authors.forename: D
authors.initials: D
authors.lastname: Larsimont
authors.forename: I
authors.initials: I
authors.lastname: Steinberg
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.forename: M
authors.initials: M
authors.lastname: Piccart-Gebhart
authors.forename: G
authors.initials: G
authors.lastname: Viale
authors.forename: A
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008207:Lymphatic Metastasis; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate