Effect of dasatinib on blood concentrations of sunitinib and adverse events in a patient with metastatic renal cell carcinoma treated with sunitinib: A case report.

The combined use of sunitinib and other tyrosine kinase inhibitors (TKIs) is discouraged because of the increased risk of adverse events (AEs). Furthermore, plasma sunitinib levels are affected by drugs that affect CYP3A4 activity; therefore, caution should be exercised when using CYP3A4 inhibitors. In the present study, a 59-year-old Japanese man with metastatic renal cell carcinoma (RCC) was diagnosed with chronic myeloid leukemia (CML) while on sunitinib treatment and was simultaneously treated with sunitinib and dasatinib, a multi-TKI used for CML with moderate CYP3A4 inhibitory activity. The trough levels of sunitinib and N-desethyl sunitinib were 63.7 and 13.7 ng/ml, respectively, with sunitinib 50 mg/day alone. While grade 2 hand-foot skin reactions and grade 2 diarrhea were observed after starting dasatinib, the trough levels of sunitinib and N-desethyl sunitinib were stable, and dasatinib levels were lower than the reference range. Because of the risk of severe AEs, the doses of sunitinib and dasatinib were temporarily reduced or suspended. Ultimately, they were maintained at 87.5 and 83.3% of their initial doses, respectively, with no severe AEs observed. The patient achieved a complete cytogenetic response for CML on day 154 after starting dasatinib treatment; however, RCC metastasis was observed on day 186, leading to a switch from sunitinib to axitinib. This suggests that dasatinib did not significantly affect the plasma levels of sunitinib. A dose reduction at the start of combination therapy is advisable, increasing the dose while monitoring AEs may safely provide sufficient therapeutic intensity.