1. From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy
- Author
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Vittorina Zagonel, Maria Giulia Zampino, Carla Codecà, Pina Ziranu, Nicoletta Pella, Gerardo Rosati, M. Libertini, Domenico Germano, Bruno Daniele, Pietro Sozzi, Luigi Cavanna, Mariaelena Casagrande, Antonio Zizzi, Roberto Labianca, Alberto Zaniboni, Sara Lonardi, Mario Scartozzi, Stefano Cascinu, Riccardo Giampieri, Eleonora Lai, Marco Puzzoni, Daris Ferrari, Laura Demurtas, Valeria Pusceddu, 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., Codeca, C., Libertini, M., Puzzoni, M., Labianca, R., Cascinu, S., and Scartozzi, M.
- Subjects
0301 basic medicine ,Oncology ,Placental growth factor ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,Circulating biomarkers ,Colorectal cancer ,FGF2 ,bevacizumab ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,Folinic acid ,angiogenesis ,0302 clinical medicine ,Internal medicine ,medicine ,Progression-free survival ,business.industry ,circulating biomarkers ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,VEGF ,Colon cancer ,Irinotecan ,Regimen ,030104 developmental biology ,colon cancer ,PlGF ,030220 oncology & carcinogenesis ,FOLFIRI ,Angiogenesis ,business ,medicine.drug - Abstract
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&mdash, HR: 0.73, 95% Confidence Interval&mdash, 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&ndash, 1.33, p = 0.35). Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels&rsquo, early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy.
- Published
- 2020