title: 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.
authors.affiliation: Department of Medical Oncology, Oita University, Hasama-machi, Yufu, Oita, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hirashima
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Ukihide
authors.initials: U
authors.lastname: Tateishi
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Mototaka
authors.initials: M
authors.lastname: Miyake
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Horita
authors.forename: Kohei
authors.initials: K
authors.lastname: Akiyoshi
authors.forename: Atsuo
authors.initials: A
authors.lastname: Takashima
authors.forename: Natsuko
authors.initials: N
authors.lastname: Okita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahari
authors.forename: Takako
authors.initials: T
authors.lastname: Nakajima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D003287:Contrast Media; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin