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Erschienen in: Cancer Chemotherapy and Pharmacology 6/2016

05.11.2016 | Original Article

18F-FLT PET/CT imaging in patients with advanced solid malignancies treated with axitinib on an intermittent dosing regimen

verfasst von: Matthew Scarpelli, Justine Yang Bruce, Lakeesha Carmichael, Jens Eickhoff, Jill Kolesar, Scott Perlman, Robert Jeraj, Glenn Liu

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 6/2016

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Abstract

Purpose

This study utilizes FLT PET/CT imaging to characterize changes in tumor cell proliferation and vasculature during intermittent treatment with VEGR-TKI axitinib.

Methods

Patients with metastatic solid malignancies underwent 3-week treatment cycles with axitinib (7 and 5 mg BID for safety and pharmacodynamic cohorts, respectively). Cycles consisted of 2 weeks of treatment (dosing period) followed by a 1-week treatment break (washout period). Patients in the pharmacodynamic cohort had up to six FLT PET/CT scans (three scans in each cycle 1 and cycle 3) and had plasma VEGF concentrations measured at imaging timepoints. Changes in tumor SUVs and VEGF within and across drug cycles were investigated.

Results

Eight patients enrolled in the safety cohort where it was determined 7 mg axitinib was not tolerable due to severe adverse events, including three patients who experienced significant hypertension and thrombovascular effects. Sixteen patients enrolled in the pharmacodynamic cohort demonstrated significant decreases in SUVs and increases in VEGF during dosing periods. This was followed by significant increases in SUVs and decreases in VEGF during drug washout periods. No significant differences in SUVs or VEGF were found when comparing cycle 1 with cycle 3. A mixed effects model demonstrated significant negative correlation between SUV and VEGF.

Conclusions

Response to axitinib included diminished FLT uptake during dosing periods followed by increased FLT uptake during drug washout periods. These changes were not different when comparing treatment cycle 1 versus cycle 3, suggesting that the pharmacodynamic effect of intermittent axitinib is similar across multiple drug cycles.
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Metadaten
Titel
18F-FLT PET/CT imaging in patients with advanced solid malignancies treated with axitinib on an intermittent dosing regimen
verfasst von
Matthew Scarpelli
Justine Yang Bruce
Lakeesha Carmichael
Jens Eickhoff
Jill Kolesar
Scott Perlman
Robert Jeraj
Glenn Liu
Publikationsdatum
05.11.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 6/2016
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-016-3183-7

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