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.
|Number of pages||8|
|Journal||Cancer Chemotherapy and Pharmacology|
|State||Published - Dec 1 2016|
Bibliographical noteFunding Information:
This clinical trial was funded by a Pfizer Investigator-Initiated Research Grant (PI: Liu) (WS1610530) as well as a Prostate Cancer Foundation Young Investigator Award (MSN133051). This trial was conducted within the Cancer Therapy Discovery and Development (CTD2) research program with support from the Translational Imaging Research Working Group (TIRWG) at the UW Carbone Cancer Center.
© 2016, Springer-Verlag Berlin Heidelberg.
- Anti-angiogenic therapy
- FLT PET
- Tumor cell proliferation
- Tyrosine kinase inhibitor
ASJC Scopus subject areas
- Cancer Research
- Pharmacology (medical)