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01.07.2015 | Original Article

Pharmacodynamic study of axitinib in patients with advanced malignancies assessed with ¹⁸F-3′deoxy-3′fluoro-l-thymidine positron emission tomography/computed tomography

verfasst von: Justine Yang Bruce, Peter Colin Scully, Lakeesha L. Carmichael, Jens C. Eickhoff, Scott B. Perlman, Jill Marie Kolesar, Jennifer L. Heideman, Robert Jeraj, Glenn Liu

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2015

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Abstract

Purpose

Rapid disease progression associated with increased tumor proliferation has been observed during withdrawal of anti-angiogenic therapy. We characterize the dynamics of withdrawal flare for axitinib.

Methods

Thirty patients with metastatic solid malignancies received axitinib for 2 weeks, followed by a 1-week drug holiday. Twenty patients suitable for PET imaging received scans with ¹⁸F-3′deoxy-3′fluoro-l-thymidine (FLT), a marker of proliferation. Plasma VEGF and axitinib pharmacokinetic levels were also assessed at specified time points.

Results

During axitinib withdrawal, significant increases in both SUV_max (+22 %; p = 0.006) and SUV_mean (+20 %; p = 0.001) were observed. Significant increases relative to peak axitinib concentration were observed at day 2 withdrawal for SUV_max and SUV_mean, with no further significant increase from day 2 to day 7 of withdrawal. No significant change in SUV_max or SUV_mean was observed during the treatment period, relative to baseline. VEGF concentration significantly increased when on drug (p < 0.001) and decreased back to a level indistinguishable from baseline by day 7 of drug washout (p = 0.448). No correlation between change in VEGF and change in imaging metrics was observed.

Conclusions

A significant increase in tumor proliferation was observed during withdrawal of axitinib therapy, and this flare occurred within 2 days of axitinib withdrawal. An exploratory analysis indicated that this flare may be associated with poor clinical outcome.

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Titel: Pharmacodynamic study of axitinib in patients with advanced malignancies assessed with 18F-3′deoxy-3′fluoro-l-thymidine positron emission tomography/computed tomography
verfasst von: Justine Yang Bruce
Peter Colin Scully
Lakeesha L. Carmichael
Jens C. Eickhoff
Scott B. Perlman
Jill Marie Kolesar
Jennifer L. Heideman
Robert Jeraj
Glenn Liu
Publikationsdatum: 01.07.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 1/2015
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2779-7

Springer Medizin

Pharmacodynamic study of axitinib in patients with advanced malignancies assessed with ¹⁸F-3′deoxy-3′fluoro-l-thymidine positron emission tomography/computed tomography