Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer - PubMed (original) (raw)

Clinical Trial

. 2011 Apr 12;104(8):1262-9.

doi: 10.1038/bjc.2011.85. Epub 2011 Mar 15.

C Cremolini, A Fioravanti, P Orlandi, L Salvatore, G Masi, T Di Desidero, B Canu, M Schirripa, P Frumento, A Di Paolo, R Danesi, A Falcone, G Bocci

Affiliations

Clinical Trial

F Loupakis et al. Br J Cancer. 2011.

Abstract

Background: The identification of molecular and genetic markers to predict or monitor the efficacy of bevacizumab (BV) represents a key issue in the treatment of metastatic colorectal cancer (mCRC).

Methods: Plasma levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble VEGF receptor 2 (sVEGFR-2) and thrombospondin-1 (TSP-1) were assessed by ELISA assay at different time points in a cohort of 25 patients enroled in a phase II trial of GONO-FOLFOXIRI plus BV as first-line treatment of mCRC. VEGF: -2578A/C, -1498C/T, -1154A/G, -634C/G and 936C/T; and VEGFR-2: -604A/G, +1192C/T and +1719A/T, polymorphisms were assessed in a total of 54 patients.

Results: Treatment with GONO-FOLFOXIRI plus BV determined a prolonged and significant reduction in plasma free, biologically active VEGF concentration. Interestingly, VEGF concentrations remained lower than at baseline also at the time of PD. Conversely, PlGF levels increased during the treatment if compared with baseline, suggesting a possible role in tumour resistance; moreover, sVEGFR-2 increased at the time of PD, as well as TSP-1. No association of assessed polymorphisms with outcome was found.

Conclusion: Our study suggested the possible mechanisms of resistance to combined therapy in those patients with a progressive disease to be tested in ongoing phase III randomised studies.

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Figures

Figure 1

Figure 1

Comparisons between immunodepleted plasma VEGF levels at different time points (A) and correlation between baseline (d1) and d15 VEGF levels (B). Columns and bars, mean values ±s.d., respectively.

Figure 2

Figure 2

Comparisons between PlGF (A), sVEGFR-2 (B) and TSP-1 (C) plasma concentrations at different time points. Columns and bars, mean values ±s.d., respectively.

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