Pharmacodynamic study of axitinib in patients with advanced malignancies assessed with F-3′deoxy-3′fluoro- l-thymidine positron emission tomography/computed tomography.

Autor: Bruce, Justine, Scully, Peter, Carmichael, Lakeesha, Eickhoff, Jens, Perlman, Scott, Kolesar, Jill, Heideman, Jennifer, Jeraj, Robert, Liu, Glenn
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Zdroj: Cancer Chemotherapy & Pharmacology; Jul2015, Vol. 76 Issue 1, p187-195, 9p
Abstrakt: Purpose: 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. Methods: 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-3′deoxy-3′fluoro- l-thymidine (FLT), a marker of proliferation. Plasma VEGF and axitinib pharmacokinetic levels were also assessed at specified time points. Results: During axitinib withdrawal, significant increases in both SUV (+22 %; p = 0.006) and SUV (+20 %; p = 0.001) were observed. Significant increases relative to peak axitinib concentration were observed at day 2 withdrawal for SUV and SUV, with no further significant increase from day 2 to day 7 of withdrawal. No significant change in SUV or SUV 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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