Variations in serum concentrations of sunitinib and its metabolites in patients receiving long-term sunitinib treatment

The blood concentrations of some tyrosine kinase inhibitors are known to decrease with long-term administration. We evaluated the variability in the serum concentrations of sunitinib and its metabolites in patients receiving long-term sunitinib treatment.

This study prospectively recruited patients who received sunitinib for metastatic renal cell carcinoma at the Showa University Hospital between March 2020 and January 2022. Bivariate correlations between the serum concentration/dose (C/D) ratios of sunitinib and its metabolites (i.e., N-desethyl sunitinib and sunitinib N-oxide) and treatment duration were evaluated using Pearson’s correlation coefficient.

Seven patients were enrolled, and 79 blood samples were collected. Among six patients who received sunitinib for > 1 year, three showed a decreasing trend in the C/D ratio of sunitinib (Pt1: r = -0.608, p = 0.047; Pt2: r = -0.555, p = 0.077; Pt6: r = -0.590, p = 0.073). In these patients, the median annual decrease in the C/D ratio of sunitinib was 55.8% (26.5–63.2%). Additionally, two of the three patients also showed a decrease in the C/D ratio of N-desethyl sunitinib. The ratio of N-desethyl sunitinib/sunitinib concentration at baseline and the end of follow-up was similar between the C/D-decreased and C/D-non-decreased groups.

This study showed that the C/D ratio of sunitinib decreased by half over time in half of the patients who received long-term sunitinib treatment despite continuing the same dose. Therefore, serum concentrations of sunitinib and its metabolites should be monitored periodically in patients receiving long-term treatment to prevent decrease in serum sunitinib concentrations.