Der Internist

, Volume 52, Issue 6, pp 756–764

Moderne Pharmakotherapie des malignen Melanoms

Arzneimitteltherapie
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Zusammenfassung

Das maligne Melanom weist weltweit die höchste Inzidenzzunahme auf und zählt in Deutschland derzeit zu den 10 häufigsten Tumorentitäten. Die Heilungschancen sind in frühen Erkrankungsstadien gut. Bei eingetretener Fernmetastasierung ist die Prognose ungünstig und eine Therapie immer palliativ. Diese palliative Therapie stützt sich bis dato auf die Säulen der Tumorchirurgie, der Chemo- bzw. Immuntherapie und der Strahlentherapie. Das zunehmende Verständnis der Tumorbiologie und -immunologie, der pathophysiologischen Mechanismen des Tumorstromas und die neuen Erkenntnisse auf molekularpathologischer Ebene haben zu einem individualisierten Therapieansatz geführt. Die Entwicklung zielgerichteter Substanzen bietet in naher Zukunft die Aussicht auf eine bessere Versorgungssituation von Melanompatienten.

Schlüsselwörter

Malignes Melanom Palliative Therapie Immuntherapie Zielgerichtete Therapie Kinaseinhibitoren 

State-of-the-art pharmacotherapy of malignant melanoma

Abstract

The incidence of malignant melanoma continues to rise steadily and is one of the 10 most frequent solid tumors in Germany. Cure rates in early clinical stages are high. However, in case of distant metastasis treatment is palliative by operative, radiological und chemo(immuno)therapeutical means. All therapeutic interventions have until now not shown any clear influence on overall survival. The increasing knowledge of tumor biology, tumor immunology, the pathophysiological mechanisms of the tumor stroma and of molecularbiological understanding of melanoma have led the way to an individual treatment approach. Targeted therapy of melanoma has achieved impressive clinical response in clinical studies and has risen expectations for improving medical care for melanoma-patients in the near future.

Keywords

Malignant melanoma Palliative therapy Immunotherapy Targeted therapy Kinase inhibitors 

Literatur

  1. 1.
    Balch CM, Gershenwald JE, Soong SJ et al (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206PubMedCrossRefGoogle Scholar
  2. 2.
    Brose MS, Volpe P, Feldman M et al (2002) BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 62:6997–7000PubMedGoogle Scholar
  3. 3.
    Chambers CA, Kuhns MS, Egen J et al (2001) CTLA-4-mediated inhibition in regulation of T cell response: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol 19:565–594PubMedCrossRefGoogle Scholar
  4. 4.
    Curtin JA, Fridlyand J, Kageshita T et al (2005) Distinct sets of genetic alterations in melanoma. N Engl J Med 353:2135–2147PubMedCrossRefGoogle Scholar
  5. 5.
    Fecher LA, Cummings SD, Keefe MJ et al (2007) Toward a molecular classification of melanoma. J Clin Oncol 25:1606–1620PubMedCrossRefGoogle Scholar
  6. 6.
    Flaherty K, Puzanov I, Kim KB et al (2010) Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 363:809–819PubMedCrossRefGoogle Scholar
  7. 7.
    Garbe C, Schadendorf D, Stolz W et al (2008) Kurzleitlinie – Malignes Melanom der Haut. J Dtsch Dermatol Ges 6 (Suppl 1):S9–S15PubMedCrossRefGoogle Scholar
  8. 8.
    Hauschild A, Weichenthal M, Knuth R et al (2010) Efficacy of low-dose interferon α2a 18 versus 60 months of treatment in patients with primary melanoma of >1,5 mm tumor thickness: results of a randomized phase III DeCOG trial. J Clin Oncol 28:841–846PubMedCrossRefGoogle Scholar
  9. 9.
    Hodi FS, Friedlander P, Corless CL et al (2008) Major response to imatinib mesylate in KIT-mutated melanoma. J Clin Oncol 26:2046–2051PubMedCrossRefGoogle Scholar
  10. 10.
    Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723PubMedCrossRefGoogle Scholar
  11. 11.
    LoRusso PM, Krishnamurthi SS, Rinehart JJ et al (2010) Phase I pharmacokinetic and pharmacodynamic study of the oral MAPK/ERK kinase inhibitor PD-0325901 in patients with advanced cancers. Clin Cancer Res 16:1924–1937PubMedCrossRefGoogle Scholar
  12. 12.
    Mocellin S, Pasquali S, Rossi CR et al (2010) Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis. J Natl Cancer Inst 102:493–501PubMedCrossRefGoogle Scholar
  13. 13.
    O’Day SJ, Hamid O, Urba WJ (2007) Targeting cytotoxic T-lymphozyte antigen-4 (CTLA-4). A novel strategy for the treatment of melanoma and other malignancies. Cancer 110:2614–2627CrossRefGoogle Scholar
  14. 14.
    Roeder C, Schuler-Thurner B, Berchtold S et al (2005) MAGE-A3 is a frequent tumor antigen of metastasized melanoma. Arch Dermatol Res 296:314–319PubMedCrossRefGoogle Scholar
  15. 15.
    Ugurel S, Schadendorf D, Pföhler C et al (2006) In vitro drug sensitivity predicts response and survival after individualized sensitivity-directed chemotherapy in metastatic melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group. Clin Cancer Res 12:5454–5463PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Klinik für Dermatologie, Venerologie und AllergologieHauttumorzentrum am Westdeutschen Tumorzentrum EssenEssenDeutschland

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