Front-line bevacizumab in serous epithelial ovarian cancer: biomarker analysis of the FINAVAST trial

Anticancer Res. 2010 Mar;30(3):1001-6.

Abstract

Background: Potential tissue and serum biomarkers were assessed for predicting efficacy of bevacizumab in ovarian cancer (OC).

Patients and methods: Twenty patients with OC received chemotherapy alone (control group) or in combination with bevacizumab (study group) in this non-randomised study. Pre- and post-treatment serum concentrations of vascular endothelial growth factor (VEGF), 8-hydroxydeoxyguanosine (8-OHdG) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured in all patients. In addition, immunohistochemical expressions VEGF receptors (R1, R2), hypoxia-inducible factor 1alpha (HIF-1 alpha), matrix metalloproteinases (-2, -9) and TIMP-2 were analysed in tumours from bevacizumab-treated patients.

Results: 8-OHdG and HIF-1alpha immunostainings were more highly expressed among patients with progression-free survival (PFS) >23 months than in patients with PFS <12 months. Similarly, MMP-9 was more frequently highly expressed in those with long versus short PFS. Serum VEGF concentrations decreased substantially in all bevacizumab-treated patients versus only 20% of the control group.

Conclusion: Our results indicate differences in MMP-9 and HIF-1alpha expression in relation to duration of PFS and effects on serum VEGF when bevacizumab is used in combination with chemotherapy.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine / analogs & derivatives
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism*
  • Carboplatin / administration & dosage
  • Female
  • Guanine / analogs & derivatives
  • Guanine / blood
  • Guanine / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / blood
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunohistochemistry
  • Matrix Metalloproteinase 2 / blood
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / blood
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / surgery
  • Paclitaxel / administration & dosage
  • Receptors, Vascular Endothelial Growth Factor / blood
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Tissue Inhibitor of Metalloproteinase-1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Guanine
  • 8-oxo-7,8-dihydrodeoxyguanine
  • 8-Hydroxy-2'-Deoxyguanosine
  • Carboplatin
  • Receptors, Vascular Endothelial Growth Factor
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Paclitaxel