title: Taxanes with anthracyclines as first-line chemotherapy for metastatic breast carcinoma.
abstract: BACKGROUND
  The magnitude of the benefit of adding taxanes to anthracyclines in first-line chemotherapy for metastatic breast carcinoma is still unclear. The authors performed a pooled analysis as well as a meta-analysis of all Phase III trials, to determine whether the combination of anthracyclines plus taxanes provided an advantage over standard anthracyclines-based regimens.
  
  
  METHODS
  All Phase III peer-reviewed published or presented trials were considered eligible. A pooled analysis (Method A) and a literature-based meta-analysis (Method B) were accomplished, and event-based relative risk ratios (RR(A-B)) with 95% confidence intervals were derived. Both analyses were performed to examine for significant differences in time to disease progression (TTP), overall response rate (ORR), overall survival (OS), complete response rate (CR), neutropenia, and febrile neutropenia (FN). For both analyses, a heterogeneity test was applied.
  
  
  RESULTS
  Seven trials (2805 patients) were gathered. When data were pooled and plotted, significant differences in favor of taxanes were seen for ORR (RR(A-B) 1.21, P<0.001), CR (RR(A) 2.04; RR(B) 1.81, P<0.001), even though they caused a significant increase in neutropenia (RR(A) 1.19; RR(B) 1.15, P<0.001) and FN (RR(A) 2.82; RR(B) 3.44, P<0.001). A borderline significance in favor of taxanes was seen in TTP (RR(A) 1.10, P=0.05; RR(B) 1.06, P=0.07). A nonsignificant trend for taxanes was found in OS. No significant heterogeneity (except for neutropenia, P<0.01) was observed.
  
  
  CONCLUSIONS
  The adjunction of taxanes to anthracyclines in first-line chemotherapy for metastatic breast carcinoma yielded a significant benefit in activity (ORR, CR), a slight advantage in TTP, and a trend in OS, although with a significant cost in hematologic toxicity.
authors.affiliation: Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy. emiliobria@yahoo.it
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Felici
authors.forename: William P
authors.initials: WP
authors.lastname: Peters
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nisticò
authors.forename: Barbara
authors.initials: B
authors.lastname: Vanni
authors.forename: Federica
authors.initials: F
authors.lastname: Cuppone
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Edmondo
authors.initials: E
authors.lastname: Terzoli
mesh_terms: D018943:Anthracyclines / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002986:Clinical Trials as Topic; D006801:Humans; D016019:Survival Analysis; D043823:Taxoids / Q000009:adverse effects
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D043823:Taxoids