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From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy

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Medical Oncology Unit, University Hospital and Università Politecnica delle Marche, 60126 Ancona, Italy
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Medical Oncology Unit, University Hospital and University of Cagliari, 09042 Monserrato, Italy
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Medical Oncology Unit, Ospedale G. Rummo, 82100 Benevento, Italy
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Medical Oncology Unit, Azienda Ospedaliera San Paolo, 20142 Milano, Italy
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Medical Oncology Unit 1, Istituto Oncologico Veneto-IRCCS, 35128 Padova, Italy
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Medical Oncology Unit, Fondazione Poliambulanza, 25124 Brescia, Italy
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Medical Oncology Unit, Ospedale di Piacenza, 29121 Piacenza Italy
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Medical Oncology Unit, Ospedale San Carlo, 85100 Potenza, Italy
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Medical Oncology Unit, Azienda Ospedaliero Universitaria Santa Maria della Misericordia, 33100 Udine, Italy
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Gastrointestinal Medical Oncology Unit and Neuroendocrine Tumors, Istituto Europeo di Oncologia-IRCCS, 20141 Milano, Italy
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Medical Oncology Unit, Nuovo Ospedale degli Infermi, 13900 Biella, Italy
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Medical Oncology Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
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IRCCS San Raffaele Scientific Institute Hospital, 20132 Milan, Italy
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1330; https://doi.org/10.3390/cancers12051330
Received: 2 April 2020 / Revised: 16 May 2020 / Accepted: 18 May 2020 / Published: 22 May 2020
(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)
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. View Full-Text
Keywords: colon cancer; bevacizumab; FGF2; PlGF; VEGF; angiogenesis; circulating biomarkers colon cancer; bevacizumab; FGF2; PlGF; VEGF; angiogenesis; circulating biomarkers
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Giampieri, R.; Ziranu, P.; Daniele, B.; Zizzi, A.; Ferrari, D.; Lonardi, S.; Zaniboni, A.; Cavanna, L.; Rosati, G.; Casagrande, M.; Pella, N.; Demurtas, L.; Zampino, M.G.; Sozzi, P.; Pusceddu, V.; Germano, D.; Lai, E.; Zagonel, V.; Codecà, C.; Libertini, M.; Puzzoni, M.; Labianca, R.; Cascinu, S.; Scartozzi, M. From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy. Cancers 2020, 12, 1330.

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