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

Hirashima, Yoshinori; Yamada, Yasuhide; Tateishi, Ukihide; Kato, Ken; Miyake, Makito; Horita, Yuki; Kasuga, Akiyoshi; Takashima, Atsuo; Okita, Natsuko; Takahari, Daisuke; Nakajima, Takako Eguchi; Hamaguchi, Tetsuya; Shimada, Yasuhiro; Shirao, Kuniaki

doi:10.1002/ijc.26282

Cited by 59 publications

(35 citation statements)

References 29 publications

(33 reference statements)

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“…This finding suggests that DCE-MRI K trans response may be a potential marker of disease control during nintedanib treatment. Importantly, the results mirror those in the overall phase I population and support other data suggesting DCE-MRI as a potentially useful surrogate marker for defining the pharmacological response to angiogenesis inhibitors in CRC [26,34,46,47]. …”

Section: Discussionsupporting

confidence: 81%

Vascular effects, efficacy and safety of nintedanib in patients with advanced, refractory colorectal cancer: a prospective phase I subanalysis

et al. 2014

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BackgroundNintedanib is a potent, oral angiokinase inhibitor that targets VEGF, PDGF and FGF signalling, as well as RET and Flt3. The maximum tolerated dose of nintedanib was evaluated in a phase I study of treatment-refractory patients with advanced solid tumours. In this preplanned subanalysis, the effect of nintedanib on the tumour vasculature, along with efficacy and safety, was assessed in 30 patients with colorectal cancer (CRC).MethodsPatients with advanced CRC who had failed conventional treatment, or for whom no therapy of proven efficacy existed, were treated with nintedanib ranging from 50–450 mg once-daily (n = 14) or 150–250 mg twice-daily (n = 16) for 28 days. After a 1-week rest, further courses were permitted in the absence of progression or undue toxicity. The primary objective was the effect on the tumour vasculature using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and expressed as the initial area under the DCE-MRI contrast agent concentration–time curve after 60 seconds (iAUC60) or the volume transfer constant between blood plasma and extravascular extracellular space (Ktrans).ResultsPatients received a median of 4.0 courses (range: 1–13). Among 21 evaluable patients, 14 (67%) had a ≥40% reduction from baseline in Ktrans and 13 (62%) had a ≥40% decrease from baseline in iAUC60, representing clinically relevant effects on tumour blood flow and permeability, respectively. A ≥40% reduction from baseline in Ktrans was positively associated with non-progressive tumour status (Fisher’s exact: p = 0.0032). One patient achieved a partial response at 250 mg twice-daily and 24 (80%) achieved stable disease lasting ≥8 weeks. Time to tumour progression (TTP) at 4 months was 26% and median TTP was 72.5 days (95% confidence interval: 65–114). Common drug-related adverse events (AEs) included nausea (67%), vomiting (53%) and diarrhoea (40%); three patients experienced drug-related AEs ≥ grade 3. Four patients treated with nintedanib once-daily had an alanine aminotransferase and/or aspartate aminotransferase increase ≥ grade 3. No increases > grade 2 were seen in the twice-daily group.ConclusionsNintedanib modulates tumour blood flow and permeability in patients with advanced, refractory CRC, while achieving antitumour activity and maintaining an acceptable safety profile.

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Section: Discussionsupporting

confidence: 81%

Vascular effects, efficacy and safety of nintedanib in patients with advanced, refractory colorectal cancer: a prospective phase I subanalysis

et al. 2014

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“…63 Perfusion MR imaging in patients receiving bevacizumab-based chemotherapy for colorectal cancer metastases to liver revealed that a decrease in K trans and k ep ratios correlated with treatment response as early as 1 week after therapy. 96 …”

Section: Perfusion Mr Imagingmentioning

confidence: 99%

Multiparametric MR Imaging in Abdominal Malignancies

Luna

Pahwa

Bonini³

et al. 2016

Magnetic Resonance Imaging Clinics of North America

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“…This gradient represents the density of vascularization within the neoplasia, as demonstrated in several studies [19,[27][28][29][30][31]. A recent study showed that the enhancement gradient in a baseline CT-SCAN correlates with radiological responses to anti-angiogenic therapy [32].…”

Section: Ct-scan Behind Evaluation Of Efficacy: Radiology Predictor Fmentioning

confidence: 89%

Bevacizumab-based neoadjuvant chemotherapy for colorectal cancer liver metastases: Pitfalls and helpful tricks in a review for clinicians

Pietrantonio

Orlandi

Inno

et al. 2015

Critical Reviews in Oncology/Hematology

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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

Cited by 59 publications

References 29 publications

Vascular effects, efficacy and safety of nintedanib in patients with advanced, refractory colorectal cancer: a prospective phase I subanalysis

Vascular effects, efficacy and safety of nintedanib in patients with advanced, refractory colorectal cancer: a prospective phase I subanalysis

Multiparametric MR Imaging in Abdominal Malignancies

Bevacizumab-based neoadjuvant chemotherapy for colorectal cancer liver metastases: Pitfalls and helpful tricks in a review for clinicians

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