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Metastasiertes Nierenzellkarzinom

Bestimmung der Plasmaspiegel der Tyrosinkinaseinhibitoren Sunitinib, Sorafenib und Pazopanib

Metastasized renal cell carcinoma

Measurement of plasma levels of the tyrosine kinase inhibitors sunitinib, sorafenib and pazopanib

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Zusammenfassung

Hintergrund

In der Sequenztherapie des metastasierten Nierenzellkarzinoms (mNZK) wird u. a. die Gruppe der Tyrosinkinaseinhibitoren (TKI) eingesetzt. Diese Arbeit präsentiert eine Machbarkeitsstudie zur Bestimmung der Plasmaspiegel von Sunitinib, Sorafenib und Pazopanib mittels Tandemmassenspektrometrie im klinischen Alltag.

Methode

Das untersuchte Patientenkollektiv umfasste 23 Patienten, die aufgrund eines mNZK mit Sunitinib (n = 16), Sorafenib (n = 3) oder Pazopanib (n = 4) behandelt wurden. Untersuchungsmaterial waren 100 μl einer Plasmaprobe. Die Proben wurden mittels Flüssigchromatographie (LC) getrennt, die Plasmakonzentration der TKI dann mittels Tandemmassenspektrometrie (MS/MS) ermittelt.

Ergebnisse

Es waren Plasmaspiegel aller Substanzen messbar, die Ergebnisse waren reproduzierbar. Die Proben waren bei 4 °C 1 Woche lagerungsstabil. Die maximal nachgewiesenen Plasmaspiegel lagen bei 99 ng/ml (Sunitinib), 9,8 μg/ml (Sorafenib) und 63 μg/ml (Pazopanib). Spiegelschwankungen der TKI waren analog zu Dosisänderungen oder Behandlungspausen nachweisbar.

Schlussfolgerung

Die Messung der Plasmaspiegel von TKI mittels LC-MS/MS ist möglich. Zur Klärung der Frage, ob Schwellenwerte für Nebenwirkungen oder Therapieansprechen existieren und welchen Stellenwert und Nutzen dieses Verfahrens im klinischen Alltag haben kann, müssen weitere klinische Studien angeschlossen werden.

Abstract

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.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. C. Keil, L. Götze, P. Olbert, R. Hofmann, W.A. Nockher und A. Hegele geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Klinik für Urologie und Kinderurologie, Universitätsklinikum Gießen und Marburg, Standort Marburg, Philipps-Universität Marburg, Baldingerstraße, 35043, Marburg, Deutschland

    C. Keil, P. Olbert, R. Hofmann & A. Hegele

  2. Institut für Laboratoriumsmedizin und Pathobiochemie, Molekulare Diagnostik, Universitätsklinikum Gießen und Marburg, Standort Marburg, Marburg, Deutschland

    L. Götze & W.A. Nockher

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  1. C. Keil
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  2. L. Götze
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  3. P. Olbert
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  4. R. Hofmann
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  5. W.A. Nockher
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  6. A. Hegele
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Correspondence to C. Keil.

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C. Keil und A. Hegele haben gleichberechtigte Autorenschaft.

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Keil, C., Götze, L., Olbert, P. et al. Metastasiertes Nierenzellkarzinom. Urologe 54, 811–818 (2015). https://doi.org/10.1007/s00120-014-3711-1

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  • DOI: https://doi.org/10.1007/s00120-014-3711-1

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