Pharmacodynamic study of axitinib in patients with advanced malignancies assessed with 18F-3′deoxy-3′fluoro-l-thymidine positron emission tomography/computed tomography
| Autor: | P Scully, Lakeesha Carmichael, Jill M. Kolesar, Justine Yang Bruce, Scott B. Perlman, Jens C. Eickhoff, Jennifer Heideman, Robert Jeraj, Glenn Liu |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Vascular Endothelial Growth Factor A Fluorine Radioisotopes Cancer Research medicine.medical_specialty Indazoles Axitinib Pharmacology toxicology Toxicology Multimodal Imaging Article Neoplasms medicine Humans Pharmacology (medical) In patient L-thymidine Protein Kinase Inhibitors Aged Positron Emission Tomography-Computed Tomography Pharmacology business.industry Imidazoles Middle Aged Rapid disease progression Dideoxynucleosides Substance Withdrawal Syndrome Pharmacodynamic Study Oncology Positron-Emission Tomography Pharmacodynamics Disease Progression Female Radiology Radiopharmaceuticals Tomography X-Ray Computed business Nuclear medicine medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 76:187-195 |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | 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 (18)F-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. |
| Databáze: | OpenAIRE |
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