Journal article
F-18-FLT PET/CT imaging in patients with advanced solid malignancies treated with axitinib on an intermittent dosing regimen
Cancer chemotherapy and pharmacology, Vol.78(6), pp.1245-1252
12/01/2016
DOI: 10.1007/s00280-016-3183-7
PMCID: PMC5209788
PMID: 27817059
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.
Details
- Title: Subtitle
- F-18-FLT PET/CT imaging in patients with advanced solid malignancies treated with axitinib on an intermittent dosing regimen
- Creators
- Matthew Scarpelli - Wisconsin Institutes for DiscoveryJustine Yang Bruce - University of Wisconsin Carbone Cancer CenterLakeesha Carmichael - University of Wisconsin–MadisonJens Eickhoff - University of Wisconsin–MadisonJill Kolesar - University of Wisconsin Carbone Cancer CenterScott Perlman - University of Wisconsin–MadisonRobert Jeraj - University of Wisconsin–MadisonGlenn Liu - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- Cancer chemotherapy and pharmacology, Vol.78(6), pp.1245-1252
- Publisher
- Springer Nature
- DOI
- 10.1007/s00280-016-3183-7
- PMID
- 27817059
- PMCID
- PMC5209788
- ISSN
- 0344-5704
- eISSN
- 1432-0843
- Number of pages
- 8
- Grant note
- P30CA014520 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) MSN133051 / Prostate Cancer Foundation Translational Imaging Research Working Group (TIRWG) at the UW Carbone Cancer Center WS1610530 / Pfizer Investigator-Initiated Research Grant
- Language
- English
- Date published
- 12/01/2016
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695792902771
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