Journal article
Pharmacodynamic study of axitinib in patients with advanced malignancies assessed with F-18-3'deoxy-3'fluoro-L-thymidine positron emission tomography/computed tomography
Cancer chemotherapy and pharmacology, Vol.76(1), pp.187-195
07/01/2015
DOI: 10.1007/s00280-015-2779-7
PMCID: PMC4499265
PMID: 26021741
Abstract
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.
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 F-18-3'deoxy-3'fluoro-l-thymidine (FLT), a marker of proliferation. Plasma VEGF and axitinib pharmacokinetic levels were also assessed at specified time points.
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.
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.
Details
- Title: Subtitle
- Pharmacodynamic study of axitinib in patients with advanced malignancies assessed with F-18-3'deoxy-3'fluoro-L-thymidine positron emission tomography/computed tomography
- Creators
- Justine Yang Bruce - University of Wisconsin Carbone Cancer CenterPeter Colin Scully - Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USALakeesha L. Carmichael - Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53792 USAJens C. Eickhoff - Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53792 USAScott B. Perlman - Univ Wisconsin, Dept Radiol, Ctr Clin Sci, Madison, WI 53792 USAJill Marie Kolesar - Univ Wisconsin, Dept Pharm, Madison, WI 53792 USAJennifer L. Heideman - Univ Wisconsin, Carbone Canc Ctr, Ctr Clin Sci, Madison, WI 53705 USARobert Jeraj - Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USAGlenn Liu - Univ Wisconsin, Carbone Canc Ctr, Dept Med, Madison, WI 53705 USA
- Resource Type
- Journal article
- Publication Details
- Cancer chemotherapy and pharmacology, Vol.76(1), pp.187-195
- DOI
- 10.1007/s00280-015-2779-7
- PMID
- 26021741
- PMCID
- PMC4499265
- NLM abbreviation
- Cancer Chemother Pharmacol
- ISSN
- 0344-5704
- eISSN
- 1432-0843
- Publisher
- Springer Nature
- Number of pages
- 9
- Grant note
- 133-PRJ17VG / Pfizer T32GM008349 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) T32CA009206 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 5T32CA009206 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 07/01/2015
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695793602771
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