[Metastasized renal cell carcinoma. Measurement of plasma levels of the tyrosine kinase inhibitors sunitinib, sorafenib and pazopanib].

BACKGROUND: Several tyrosine kinase inhibitors (TKI) are used in the treatment of metastasized renal cell carcinoma (mRCC). This article presents a feasibility study for the measurement of plasma levels of sunitinib, sorafenib and pazopanib using liquid chromatography tandem mass spectrometry (LC-MS/MS). METHODS: A total of 23 patients suffering from mRCC under treatment with sunitinib (n=16), sorafenib (n=3) and pazopanib (n=4) were included. Plasma samples (100 µl) were separated by liquid chromatographic analysis and the plasma levels of the TKIs determined by tandem mass spectrometry. RESULTS: The plasma levels of sunitinib, sorafenib and pazopanib were measurable and the results reproducible. During storage of the plasma samples for 1 week at 4°C no significant decrease of the initial concentration was found. The highest plasma levels detected were 99 ng/ml for sunitinib, 9.8 µg/ml for sorafenib and 63 µg/ml for pazopanib. We could show variability in plasma levels according to changes in dosage of TKIs or during treatment-free intervals. CONCLUSION: Measurement of TKI plasma levels using LC-MS/MS is feasible. Further clinical studies have to be conducted to examine if there are any threshold levels for the incidence of adverse events or response to treatment.