Assessment of Sunitinib-Induced Toxicities and Clinical Outcomes Based on Therapeutic Drug Monitoring of Sunitinib for Patients With Renal Cell Carcinoma

The benefit of pharmacokinetic assessment of sunitinib remains unknown. We reported that patients with total sunitinib (sunitinib + its active metabolite SU12662) >= 100 ng/mL showed high incidence of Grade >= 3 toxicities and worsening clinical outcomes. Thus, pharmacokinetic assessment of sunitinib could be helpful for dose optimization. Background: Sunitinib has been approved for the treatment of metastatic renal cell carcinoma (RCC). Sunitinib pharmacokinetics shows a large interpatient variability. Patients and Methods: A retrospective, observational clinical study of 21 patients with RCC was performed. Sunitinib was administered for 4 weeks of a 6-week cycle for the first cycle. We evaluated the association of sunitinib-induced toxicities and clinical outcomes with the trough total sunitinib concentration in a steady state during the first cycle. Results: The median total sunitinib concentration was 91.8 ng/mL (range, 49.8-205 ng/mL). There was an association between total sunitinib concentration and the severity of thrombocytopenia, anorexia, and fatigue. Patients with >= 100 ng/mL total sunitinib (n = 8), compared with patients with < 100 ng/mL (n = 13), had a greater incidence of Grade >= 3 toxicities (6 patients [75.0%] vs. 3 patients [23.1%]). Patients with < 100 ng/mL total sunitinib had significantly longer time to treatment failure (TTF) and progression-free survival (PFS) time than patients with >= 100 ng/mL (median TTF, 590 vs. 71 days; P = .04; median PFS, 748 vs. 238 days; P = .02). Conclusion: Results of this study suggest that therapeutic drug monitoring of sunitinib could be useful for avoiding severe toxicities. Dose reduction might be needed, especially when the total sunitinib concentration is >= 100 ng/mL, to avoid unnecessary early discontinuation of treatment.