Pharmacokinetic parameters from 3‐Tesla DCE‐MRI as surrogate biomarkers of antitumor effects of bevacizumab plus FOLFIRI in colorectal cancer with liver metastasis

Abstract

Bevacizumab (BV) is an antivascular endothelial growth factor antibody. When administered with other chemotherapeutic drugs, BV-combined regimens prolong survival of colorectal cancer patients. We conducted a phase II trial to confirm the pharmacokinetic parameters from 3-Tesla dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as surrogate biomarkers of BV + FOLFIRI regimen efficacy in colorectal cancer with liver metastases. DCE-MRI was performed before treatment, on the seventh day after first treatment and every 8 weeks thereafter using a 3-Tesla MRI system. DCE-MRI parameters-area under the contrast concentration versus time curve at 90 and 180 s (AUC90 and AUC180, respectively) after contrast injection, and volume transfer constant of contrast agents (K(trans) and K(ep) ) were calculated from liver metastases. Fifty-eight liver metastases were analyzed. Univariate analysis revealed that a decrease in K(trans) ratios (ΔK(trans) ), K(ep) ratios (ΔK(ep) ), AUC90 ratios (ΔAUC90) and AUC180 ratios (ΔAUC180) correlated with higher response (all p < 0.0001) and longer time to progression (TTP) (ΔK(trans) : p = 0.001; ΔK(ep) : p = 0.004; ΔAUC90: p = 0.006; ΔAUC180: p < 0.0001). Multivariate analysis showed that ΔAUC180 was correlated with higher response (p = 0.009), and ΔK(trans) and ΔAUC180 were correlated with longer TTP (ΔK(trans) : p = 0.001; ΔAUC180: p = 0.024). ΔK(trans) and ΔAUC180 are pharmacodynamic biomarkers of the blood perfusion of BV + FOLFIRI. Our data suggest that ΔK(trans) and ΔK(ep) can predict response to chemotherapy at 1 week. Changes in 3-Tesla DCE-MRI parameters confirmed the potential of these biomarkers of blood perfusion as surrogate predictors of response and TTP.