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Pharmacokinetic parameters from 3‐Tesla DCE‐MRI as surrogate biomarkers of antitumor effects of bevacizumab plus FOLFIRI in colorectal cancer with liver metastasis
Author(s) -
Hirashima Yoshinori,
Yamada Yasuhide,
Tateishi Ukihide,
Kato Ken,
Miyake Mototaka,
Horita Yosuke,
Akiyoshi Kohei,
Takashima Atsuo,
Okita Natsuko,
Takahari Daisuke,
Nakajima Takako,
Hamaguchi Tetsuya,
Shimada Yasuhiro,
Shirao Kuniaki
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26282
Subject(s) - bevacizumab , folfiri , medicine , colorectal cancer , metastasis , pharmacokinetics , nuclear medicine , cancer , area under the curve , chemotherapy , oncology , irinotecan
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 (Δ K trans ), K ep ratios (Δ K ep ), AUC90 ratios (ΔAUC90) and AUC180 ratios (ΔAUC180) correlated with higher response (all p < 0.0001) and longer time to progression (TTP) (Δ K trans : p = 0.001; Δ K 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 Δ K trans and ΔAUC180 were correlated with longer TTP (Δ K trans : p = 0.001; ΔAUC180: p = 0.024). Δ K trans and ΔAUC180 are pharmacodynamic biomarkers of the blood perfusion of BV + FOLFIRI. Our data suggest that Δ K trans and Δ K 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.

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