From central to sentral (Serum angiogenesis central): Circulating predictive biomarkers to anti-VEGFR therapy

R. Giampieri, P. Ziranu, B. Daniele, A. Zizzi, D. Ferrari, S. Lonardi, A. Zaniboni, L. Cavanna, G. Rosati, M. Casagrande, N. Pella, L. Demurtas, M.G. Zampino, P. Sozzi, V. Pusceddu, D. Germano, E. Lai, V. Zagonel, C. Codecà, M. LibertiniM. Puzzoni, R. Labianca, S. Cascinu, M. Scartozzi

Research output: Contribution to journalArticlepeer-review


Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab. Methods: First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PlGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8). Results: Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio—HR: 0.73, 95% Confidence Interval—CI: 0.43-1.27, p = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46–1.33, p = 0.35). Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels’ early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
Issue number5
Publication statusPublished - 2020


  • Angiogenesis
  • Bevacizumab
  • Circulating biomarkers
  • Colon cancer
  • FGF2
  • PlGF
  • VEGF
  • B Raf kinase
  • bevacizumab
  • fibroblast growth factor 2
  • fluorouracil
  • folinic acid
  • interleukin 8
  • irinotecan
  • K ras protein
  • monocyte chemotactic protein 3
  • placental growth factor
  • scatter factor
  • stromal cell derived factor 1
  • vasculotropin A
  • vasculotropin inhibitor
  • adult
  • aged
  • Article
  • cancer prognosis
  • cancer survival
  • carcinogenesis
  • controlled study
  • disease marker
  • drug efficacy
  • drug safety
  • enzyme linked immunosorbent assay
  • exploratory research
  • female
  • human
  • major clinical study
  • male
  • metastatic colorectal cancer
  • overall survival
  • progression free survival


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