Front-line bevacizumab in serous epithelial ovarian cancer: biomarker analysis of the FINAVAST trial.
BACKGROUND
Potential tissue and serum biomarkers were assessed for predicting efficacy of bevacizumab in ovarian cancer (OC).


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.


CONCLUSIONS
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.
Karihtala
Peeter
P
Department of Oncology and Radiotherapy, P.O. Box 22, FIN-90029 Oulu University Hospital, Finland. peeter.karihtala@oulu.fi.
Mäenpää
Johanna
J
Turpeenniemi-Hujanen
Taina
T
Puistola
Ulla
U
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000097:blood / Q000378:metabolism; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage; D040262:Receptors, Vascular Endothelial Growth Factor / Q000097:blood / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D016190:Carboplatin; D040262:Receptors, Vascular Endothelial Growth Factor; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D017239:Paclitaxel