18F-FLT PET/CT imaging in patients with advanced solid malignancies treated with axitinib on an intermittent dosing regimen.
OBJECTIVE
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.
Department of Medical Physics, Wisconsin Institute for Medical Research, University of Wisconsin, Room 1005, 1111 Highland Ave, Madison, WI, 53705, USA.
Matthew
M
Scarpelli
Division of Hematology/Oncology, Department of Medicine, Wisconsin Institute for Medical Research, University of Wisconsin, Room 7105, 1111 Highland Ave, Madison, WI, 53705, USA. jybruce@medicine.wisc.edu.|University of Wisconsin Carbone Cancer Center, University of Wisconsin, 600 Highland Ave, Madison, WI, 53792, USA. jybruce@medicine.wisc.edu.
Justine Yang
JY
Bruce
Department of Biostatistics and Medical Informatics, K6/422 Clinical Science Center, University of Wisconsin, MC 4675, 600 Highland Ave, Madison, WI, 53792, USA.
Lakeesha
L
Carmichael
University of Wisconsin Carbone Cancer Center, University of Wisconsin, 600 Highland Ave, Madison, WI, 53792, USA.|Department of Biostatistics and Medical Informatics, K6/422 Clinical Science Center, University of Wisconsin, MC 4675, 600 Highland Ave, Madison, WI, 53792, USA.
Jens
J
Eickhoff
University of Wisconsin Carbone Cancer Center, University of Wisconsin, 600 Highland Ave, Madison, WI, 53792, USA.|Department of Pharmacy, K4/554 Clinical Science Center, University of Wisconsin, 600 Highland Ave, Madison, WI, 53792, USA.
Jill
J
Kolesar
University of Wisconsin Carbone Cancer Center, University of Wisconsin, 600 Highland Ave, Madison, WI, 53792, USA.|Department of Radiology, Clinical Science Center, University of Wisconsin, 600 Highland Ave, Box 3252, Madison, WI, 53792, USA.
Scott
S
Perlman
Department of Medical Physics, Wisconsin Institute for Medical Research, University of Wisconsin, Room 1005, 1111 Highland Ave, Madison, WI, 53705, USA.|University of Wisconsin Carbone Cancer Center, University of Wisconsin, 600 Highland Ave, Madison, WI, 53792, USA.
Robert
R
Jeraj
Department of Medical Physics, Wisconsin Institute for Medical Research, University of Wisconsin, Room 1005, 1111 Highland Ave, Madison, WI, 53705, USA.|Division of Hematology/Oncology, Department of Medicine, Wisconsin Institute for Medical Research, University of Wisconsin, Room 7105, 1111 Highland Ave, Madison, WI, 53705, USA.|University of Wisconsin Carbone Cancer Center, University of Wisconsin, 600 Highland Ave, Madison, WI, 53792, USA.
Glenn
G
Liu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077784:Axitinib; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D007191:Indazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D015224:Dideoxynucleosides; D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000077784:Axitinib; C002854:alovudine
Anti-angiogenic therapy; Axitinib; FLT PET; Pharmacodynamic; Tumor cell proliferation; Tyrosine kinase inhibitor; VEGF