Pharmacokinetic/Pharmacodynamic Analysis of a Hemodialyzed Patient Treated with 25 mg of Sunitinib

Sunitinib has been approved for the treatment of advanced and/or metastatic renal cell carcinoma (RCC). Information on the dosage adjustment of sunitinib for patients undergoing hemodialysis is limited. Especially, efficacy and tolerance of sunitinib at a low dose in such patients are not fully understood. Thus, we examined the effect of hemodialysis on the pharmacokinetics, safety and efficacy of 25 mg of sunitinib. The patient was a 66-year-old man diagnosed with RCC and undergoing hemodialysis. He was treated with sunitinib at 25 mg daily for 4 weeks of a 6-week cycle. There were little differences in the AUC(0-24 h) of sunitinib and its major active metabolite SU12662 on day 17 (on hemodialysis) and day 18 (off hemodialysis) of the first cycle. The total sunitinib concentration (sunitinib and SU12662) was approximately 50 ng/ml at a steady state in every cycle. The patient's genotype was wild type for ABCG2 421C>A, which is associated with increased sunitinib exposure. In the following two cycles of sunitinib, computed tomography scan showed a partial response of the lung metastasis. During the first cycle, the patient developed grade 2 thrombocytopenia and leukocytopenia. After four cycles of treatment, the patient developed grade 3 fatigue and the sunitinib treatment was discontinued. Our patient on hemodialysis could be safely and effectively treated with 25 mg of sunitinib, and a total sunitinib concentration of about 50 ng/ml was maintained. The pharmacokinetics of sunitinib and SU12662 were rarely affected by hemodialysis. Therapeutic drug monitoring could be helpful during sunitinib therapy, especially in a specific population.