Serial measurements of serum PDGF-AA, PDGF-BB, FGF2, and VEGF in multiresistant ovarian cancer patients treated with bevacizumab.

Anders Jakobsen,Karina Steffensen,Christine Madsen,Dorte Olsen,Parvin Adimi,Maja Smerdel,Marianne Waldstrøm,Ivan Brandslund

doi:10.1186/1757-2215-5-23

Anders Jakobsen, Karina Steffensen + Show 6 more

Open Access

https://doi.org/10.1186/1757-2215-5-23

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Abstract

IntroductionAnti-VEGF treatment has proven effective in recurrent ovarian cancer. However, the identification of the patients most likely to respond is still pending. It is well known that the angiogenesis is regulated by several other pro-angiogenic proteins, e.g. the platelet - derived growth factor (PDGF) system and the fibroblast growth factor (FGF) system. These other signaling pathways may remain active or become upregulated during anti-VEGF treatment.The aim of the present study was to investigate if potential changes of PDGF-BB, PDGF-AA, and FGF2 before and during bevacizumab treatment had predictive value for early progression or survival. Furthermore, we wanted to investigate the importance of serum VEGF in the same cohort.MethodsThis study included 106 patients with chemotherapy-resistant epithelial ovarian cancer who were treated with single agent bevacizumab as part of a biomarker protocol. Patients were evaluated for response by the Response Evaluation Criteria In Solid Tumors (RECIST) and/ or Gynecologic Cancer Intergroup (GCIG) CA125 criteria. Serum samples were collected at baseline and prior to each treatment. FGF2, PDGF-BB, PDGF-AA were quantified simultaneously using the Luminex system, and VEGF-A was measured by ELISA. Eighty-eight baseline samples were avaliable for FGF2, PDGF-BB, PDGF-AA analysis, and 93 baseline samples for VEGF.ResultsHigh baseline serum VEGF was related to poor overall survival. Furthermore, high serum PDGF-BB and FGF2 was of prognostic significance. None of the markers showed predictive value, neither at baseline level nor during the treatment.

Highlights

Anti-vascular endothelial growth factor (VEGF) treatment has proven effective in recurrent ovarian cancer
High serum platelet - derived growth factor (PDGF)-BB and FGF2 was of prognostic significance
At time of referral for bevacizumab treatment, patients had received a median of 4 different chemotherapy regimens, but most of them were still in a good performance stage (PS 0/1 87%)

Summary

Introduction

Anti-VEGF treatment has proven effective in recurrent ovarian cancer. It is well known that the angiogenesis is regulated by several other pro-angiogenic proteins, e.g. the platelet - derived growth factor (PDGF) system and the fibroblast growth factor (FGF) system. These other signaling pathways may remain active or become upregulated during anti-VEGF treatment. Data presented at ASCO (American Society of Clinical Oncology) 2012 illustrated a clear improvement in progression-free survival (PFS) for platinum-resistant ovarian cancer patients treated with combined chemotherapy and bevacizumab compared to patients only treated with chemotherapy [10] (the AURELIA study). There is an obvious need for validated biomarkers [11,12,13] as a rational basis for patient selection

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