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Pharmacodynamic parameters from 3-tesla dynamic contrast-enhanced magnetic resonance imaging as surrogate biomarkers of antitumor effect of bevacizumab plus FOLFIRI in colorectal cancer with liver metastasis.
Background: Bevacizumab (BV) is an anti-vascular endothelial growth factor antibody. When administered with other chemotherapeutic drugs, BV combined regimen prolongs survival of colorectal cancer patients. We conducted in a phase II trial to confirm the pharmacodynamic parameters from 3-Tesla dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as surrogate biomarkers of the blood perfusion of BV+FOLFIRI in colorectal cancer with liver metastases. Methods: We enrolled 17 patients with colorectal cancer who had liver metastases. The patients received BV+FOLFIRI regimen as second-line treatment. DCE-MRI was performed before treatment, 7 days post-treatment and every 8 weeks using a 3-Tesla MRI system. DCE-MRI parameters, namely, area under the contrast concentration versus time curve 90 and 180 seconds (AUC90 and AUC180, respectively) after contrast injection, and volume transfer constant of contrast agents (Ktrans and Kep) were calculated from liver metastases. Results: Fifty-eight liver metastases were analyzed. Univariate analysis revealed that a decrease in Ktrans ratios (ΔKtrans), Kep ratios (ΔKep), AUC90 ratios (ΔAUC90), and AUC180 ratios (ΔAUC180) correlated with higher response (P < 0.0001, all) and longer time to progression (TTP) (ΔKtrans: P = 0.001, ΔKep: P = 0.004, ΔAUC90: P = 0.006, ΔAUC180: P < 0.0001). Multivariate analysis showed that ΔAUC180 correlated with higher response (P = 0.009), and ΔKtrans and ΔAUC180 with longer TTP (ΔKtrans: P = 0.001, ΔAUC180: P = 0.024). Conclusions: ΔKtrans and ΔAUC180 are pharmacodynamic biomarkers of the blood perfusion of BV+FOLFIRI. Our data suggest that ΔKtrans and ΔKep can predict response to chemotherapy in one week. Changes in 3-Tesla DCE-MRI parameters showed the potential of these biomarkers of blood perfusion as surrogate predictors of response and TTP.
Abstracts by Y. Hirashima:
Phase II trial of paclitaxel and nedaplatin in patients with advanced/recurrent uterine cervical cancer: A Kansai Clinical Oncology Group study.Meeting: 2011 ASCO Annual Meeting | Abstract No: 5102Category: Gynecologic Cancer - Uterine Cancer
New analysis of the hypertension mechanism in bevacizumab-treated patients using 3-tesla dynamic contrast-enhanced magnetic resonance imaging.Meeting: 2011 Gastrointestinal Cancers Symposium | Abstract No: 450