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Kutane Nebenwirkungen der medikamentösen Tumortherapie mit BRAF- und MEK-Inhibitoren

Cutaneous side effects of anti-tumor therapy with BRAF and MEK inhibitors

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Zusammenfassung

Hintergrund

BRAF- und MEK-Inhibitoren sind neu entwickelte, zielgerichtete Substanzen. Sie werden in der Therapie bösartiger Tumoren wie dem malignen Melanom eingesetzt.

Nebenwirkungen

Kutane Nebenwirkungen sind bei beiden Substanzklassen häufig. Dazu gehören entzündliche Nebenwirkungen wie makulopapulöse und papulopustulöse Exantheme, Hand-Fuß-Syndrome, Pannikulitiden, Paronychien, Photosensitivierung und Radiosensitivierung. Als Klasseneffekt der BRAF-Inhibitoren sind Keratinozyten- und Melanozytenproliferationen zu nennen, die sich als palmoplantare Kallus-artige Hyperkeratosen (im Rahmen des Hand-Fuß-Syndroms), Verruca- oder Akanthom-artige Knoten, follikuläre Hyperkeratosen, Morbus-Grover-artige Hyperkeratosen oder Keratoakanthome bzw. Plattenepithelkarzinome äußern können. Bei den Melanozytenproliferationen handelt es sich um die Entwicklung atypischer melanozytärer Nävi mit Übergang in Zweitmelanome. Darüber hinaus sind Haarveränderungen und eine Xerosis cutis bekannt.

Schlussfolgerung

Die Durchführung einer Therapie mit BRAF- und MEK-Inhibitoren verlangt eine engmaschige dermatologische Betreuung. Dieser Beitrag fasst die typischen Nebenwirkungen an Haut und Hautanhangsgebilden sowie und deren Management zusammen.

Abstract

Background

BRAF and MEK inhibitors are new targeted therapies which are used in the treatment of malignancies, in particular of malignant melanoma.

Side effects

Cutaneous side effects are common during the treatment with both types of inhibitors. These side effects include inflammatory reactions such as maculopapular and papulopustular exanthema, hand-foot syndrome, panniculitis, paronychia, photo- and radio-sensitization. As a class effect, BRAF-inhibitors induce proliferative disorders of keratinocytes and melanocytes, such as palmoplantar hyperkeratosis (as part of the hand-foot syndrome), verruciform and acanthoma-like lesions, follicular and Grover disease-like hyperkeratoses, keratoacanthomas, squamous cell carcinomas and atypical melanocytic nevi with transition to secondary melanomas. Furthermore, hair alterations and xerosis are possible.

Conclusions

Treatment with BRAF and MEK inhibitors requires close dermatologic monitoring of the patient. This manuscript summarizes the most frequent cutaneous side effects and their management.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. R. Gutzmer erhielt Vortragshonorare, Projektunterstützung, Honorare für Beratungstätigkeit und Kongressunterstützung von Roche, GSK und Novartis. J.C. Hassel erhielt Vortragshonorare, Honorare für Beratungstätigkeit und Kongressunterstützung von Roche und GSK. K.C. Kähler erhielt Vortragshonorare, Honorare für Beratungstätigkeit und Kongressunterstützung von Roche und GSK. C. Loquai erhielt Vortragshonorare, Honorare für Beratungstätigkeit und Kongressunterstützung von Roche. R. Mössner erhielt Vortragshonorare, Projektunterstützung, Honorare für Beratungstätigkeit oder Kongressunterstützung von Roche und Novartis. S. Ugurel erhielt Vortragshonorare und Projektunterstützung von BMS, Medac und Roche. L. Zimmer erhielt Vortragshonorare, Honorare für Beratungstätigkeit und Kongressunterstützung von Roche, GSK und Novartis. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Klinik für Dermatologie, Allergologie und Venerologie, Hauttumorzentrum Hannover (HTZH), Medizinische Hochschule Hannover, Ricklinger Str. 5, 30449, Hannover, Deutschland

    R. Gutzmer

  2. Klinik für Dermatologie, Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg, Heidelberg, Deutschland

    J.C. Hassel

  3. Klinik für Dermatologie und Venerologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland

    K.C. Kähler

  4. Hautklinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Deutschland

    C. Loquai

  5. Klinik für Dermatologie, Universitätsmedizin Göttingen, Göttingen, Deutschland

    R. Mössner

  6. Klinik für Dermatologie, Venerologie und Allergologie, Julius-Maximilians-Universität Würzburg, Würzburg, Deutschland

    S. Ugurel

  7. Klinik für Dermatologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Deutschland

    L. Zimmer

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  1. R. Gutzmer
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  2. J.C. Hassel
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  8. Für Komitee „Kutane Nebenwirkungen“ ADO der das ADO
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Correspondence to R. Gutzmer.

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Gutzmer, R., Hassel, J., Kähler, K. et al. Kutane Nebenwirkungen der medikamentösen Tumortherapie mit BRAF- und MEK-Inhibitoren. Hautarzt 65, 582–589 (2014). https://doi.org/10.1007/s00105-013-2733-8

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