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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 1/2015

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

Authors: 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

Published in: Cancer Chemotherapy and Pharmacology | Issue 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 SUVmax (+22 %; p = 0.006) and SUVmean (+20 %; p = 0.001) were observed. Significant increases relative to peak axitinib concentration were observed at day 2 withdrawal for SUVmax and SUVmean, with no further significant increase from day 2 to day 7 of withdrawal. No significant change in SUVmax or SUVmean 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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Metadata
Title
Pharmacodynamic study of axitinib in patients with advanced malignancies assessed with 18F-3′deoxy-3′fluoro-l-thymidine positron emission tomography/computed tomography
Authors
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
Publication date
01-07-2015
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 1/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-015-2779-7

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