title: Paclitaxel and bevacizumab as first line combined treatment in patients with metastatic breast cancer: the Hellenic Cooperative Oncology Group experience with biological marker evaluation.
abstract: BACKGROUND
  Randomized studies have shown that bevacizumab combined with taxane-based regimens increases response rates and prolongs progression-free survival (PFS) of patients with metastatic breast cancer (MBC). However predictive or prognostic biological markers that identify the appropriate target population, thus improving the cost-effectiveness ratio of this treatment, are still needed.
  
  
  METHODS
  Retrospectively, 124 patients with MBC treated either with paclitaxel 90 mg/m² weekly x12 plus bevacizumab 10 μg/kg every 2 weeks or 15 μg/kg every 3 weeks (85 patients) or paclitaxel 175 mg/m² plus bevacizumab 15 μg/kg every 3 weeks for 6 cycles (36 patients) were identified. Additionally, the prognostic significance of a panel of key biological markers was evaluated centrally by immunohistochemistry (IHC) in 88 evaluable patients.
  
  
  RESULTS
  More than two thirds of the patients completed chemotherapy, as planned. The response rate was almost identical (55.3% vs. 55.6%) in the patients treated with weekly or 3-weekly paclitaxel, respectively. After a median follow-up time of 23 months, the median PFS of the study population was 13 months, while median survival had not yet been reached. Common severe adverse events were neutropenia (33%), neuropathy (18.6%) and metabolic disturbances (17.6%). The incidence of hypertension of all grades was 28.1%. High expression of vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3) was associated with clinical response, while high expression of VEGFR1 was associated with poor survival.
  
  
  CONCLUSIONS
  The safety and activity of the combination of bevacizumab with paclitaxel given either weekly or 3-weekly in patients with MBC is confirmed.
authors.affiliation: Department of Medical Oncology, "Papageorgiou" Hospital, Ring Road, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. fountzil@auth.gr
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: Helen P
authors.initials: HP
authors.lastname: Kourea
authors.forename: Mattheos
authors.initials: M
authors.lastname: Bobos
authors.forename: Despina
authors.initials: D
authors.lastname: Televantou
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kotoula
authors.forename: Christos
authors.initials: C
authors.lastname: Papadimitriou
authors.forename: Konstantinos T
authors.initials: KT
authors.lastname: Papazisis
authors.forename: Eleni
authors.initials: E
authors.lastname: Timotheadou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Efstratiou
authors.forename: Angelos
authors.initials: A
authors.lastname: Koutras
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: Christos
authors.initials: C
authors.lastname: Christodoulou
authors.forename: Gerassimos
authors.initials: G
authors.lastname: Aravantinos
authors.forename: Dimosthenis
authors.initials: D
authors.lastname: Miliaras
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Petraki
authors.forename: Christos N
authors.initials: CN
authors.lastname: Papandreou
authors.forename: Pavlos
authors.initials: P
authors.lastname: Papakostas
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Bafaloukos
authors.forename: Dimitra
authors.initials: D
authors.lastname: Repana
authors.forename: Evangelia
authors.initials: E
authors.lastname: Razis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.forename: Athanassios M
authors.initials: AM
authors.lastname: Dimopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D017239:Paclitaxel