【文章名】Pharmacokinetic parameters from 3-Tesla DCE-MRI as surrogate biomarkers of antitumor effects of bevacizumab plus FOLFIRI in colorectal cancer with liver metastasis
Pharmacokinetic parameters from 3-Tesla DCE-MRI as surrogate biomarkers of antitumor effects of bevacizumab plus FOLFIRI in colorectal cancer with liver metastasis
[摘要]：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 (Ktrans and Kep) were calculated from liver metastases. Fifty-eight liver metastases were analyzed. Univariate analysis revealed that a decrease in Ktrans ratios (?Ktrans), Kep ratios (?Kep), AUC90 ratios (?AUC90) and AUC180 ratios (?AUC180) correlated with higher response (all p < 0.0001) and longer time to progression (TTP) (?Ktrans: p = 0.001; ?Kep: p = 0.004; ?AUC90: p = 0.006; ?AUC180: p < 0.0001). Multivariate analysis showed that ?AUC180 was correlated with higher response (p = 0.009), and ?Ktrans and ?AUC180 were correlated with longer TTP (?Ktrans: p = 0.001; ?AUC180: p = 0.024). ?Ktrans and ?AUC180 are pharmacodynamic biomarkers of the blood perfusion of BV + FOLFIRI. Our data suggest that ?Ktrans and ?Kep 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.
