Clinical implications of pharmacokinetics of sunitinib malate and N-desethyl-sunitinib plasma concentrations for treatment outcome in metastatic renal cell carcinoma patients.

In this study, we examined the association between the pharmacokinetics (PK) level of sunitinib malate (SU) and its metabolite N-desethyl-sunitinib (DSU) in terms of adverse events (AEs) and clinical outcomes in patients with metastatic renal cell carcinoma (mRCC). The PK of sunitinib (SU and DSU) was examined in 26 patients (20 men and 6 women) with mRCC. The associations between SU/DSU C0 and AE occurrence, best response rate, time to treatment failure, progression-free survival (PFS), and overall survival (OS) were investigated. Occurrence of grade 1 or higher hand-foot syndrome and thrombocytopenia ( p = 0.002 and 0.024, respectively) was associated with a high concentration before morning intake (C0) level of SU. Low C0 levels of DSU were significantly associated with drug discontinuation due to disease progression ( p = 0.035). Patients with DSU C0 level higher than 15.0 ng/mL showed a tendency toward increased PFS (61 weeks vs 12 weeks, p = 0.004) and OS (36 months vs 8 months, p = 0.040). The C0 level of SU and SU + DSU were not associated with prognosis. The higher level of C0 of SU may predict developing AEs and DSU C0 >15.0 ng/mL may lead to better prognosis of patients treated with sunitinib. PK of sunitinib may be useful for determining adequate dosages and prevention of severe AEs. Further studies are required to establish the utility of the PK of sunitinib in patients with mRCC.