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

Medical Oncology Unit, University Hospital and Università Politecnica delle Marche, 60126 Ancona, Italy
Medical Oncology Unit, University Hospital and University of Cagliari, 09042 Monserrato, Italy
Medical Oncology Unit, Ospedale G. Rummo, 82100 Benevento, Italy
Medical Oncology Unit, Azienda Ospedaliera San Paolo, 20142 Milano, Italy
Medical Oncology Unit 1, Istituto Oncologico Veneto-IRCCS, 35128 Padova, Italy
Medical Oncology Unit, Fondazione Poliambulanza, 25124 Brescia, Italy
Medical Oncology Unit, Ospedale di Piacenza, 29121 Piacenza Italy
Medical Oncology Unit, Ospedale San Carlo, 85100 Potenza, Italy
Medical Oncology Unit, Azienda Ospedaliero Universitaria Santa Maria della Misericordia, 33100 Udine, Italy
Gastrointestinal Medical Oncology Unit and Neuroendocrine Tumors, Istituto Europeo di Oncologia-IRCCS, 20141 Milano, Italy
Medical Oncology Unit, Nuovo Ospedale degli Infermi, 13900 Biella, Italy
Medical Oncology Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
IRCCS San Raffaele Scientific Institute Hospital, 20132 Milan, Italy
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1330;
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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MDPI and ACS Style

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.

AMA Style

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 MG, 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(5):1330.

Chicago/Turabian Style

Giampieri, Riccardo; Ziranu, Pina; Daniele, Bruno; Zizzi, Antonio; Ferrari, Daris; Lonardi, Sara; Zaniboni, Alberto; Cavanna, Luigi; Rosati, Gerardo; Casagrande, Mariaelena; Pella, Nicoletta; Demurtas, Laura; Zampino, Maria G.; Sozzi, Pietro; Pusceddu, Valeria; Germano, Domenico; Lai, Eleonora; Zagonel, Vittorina; Codecà, Carla; Libertini, Michela; Puzzoni, Marco; Labianca, Roberto; Cascinu, Stefano; Scartozzi, Mario. 2020. "From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy" Cancers 12, no. 5: 1330.

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