Skip to main content
SpringerLink
Log in

Adjuvante Therapie des Melanoms

Von unspezifischen Immunstimulanzien in die Gegenwart

Adjuvant therapy of melanoma

From non-specific immune stimulants into the future

  • Leitthema
  • Published:
Der Hautarzt Aims and scope Submit manuscript

Zusammenfassung

Vier Jahrzehnte klinischer und Grundlagenforschung haben eine solide Basis für rationale Entscheidungen bei Melanompatienten geschaffen, denen wir trotz steigender Inzidenz einen relativen und absoluten Rückgang der Mortalität verdanken. Entscheidend hierfür sind jedoch im wesentlichen die primäre und sekundäre Prävention, nicht die Therapie. Bemühungen, das Schicksal durch eine hoch dosierte Immunmodulation und/oder Zytostatikatherapie günstig zu beeinflussen, schlugen bisher fehl. Ob die von Kirkwood et al. 2001 inaugurierte hoch dosierte Interferon-α-Therapie die Heilungsraten nachhaltig verbessern kann, wird derzeit kontrovers diskutiert: Weiterentwicklungen wie die Behandlung mit rekombinanten Zytokinen, speziell IL-2, GM-CSF, spezifischen Blockaden der neoplastischen Signaltransduktion oder auch Vakzinierungen stehen derzeit im Mittelpunkt der Forschung. In Zukunft wird es aber entscheidend sein, eine hoch individualisierte Therapie, gestützt auf molekulargenetisch definierte, spezifische Prognose- und Risikokriterien gezielt einzusetzen. Ein undifferenzierter breiter Einsatz wäre auch wegen der zunehmenden Rationierung der finanziellen Ressourcen nicht mehr zu bewältigen.

Abstract

Four decades of clinical and basic research have laid a solid base for clinicians to choose the best possible treatment for patients with melanoma. There has been a relative and absolute decrease in mortality despite increasing incidence. However, this decline in mortality is primarily the result of programs for primary and secondary prevention, not therapeutic advances. Conventional and high-dose immunomodulatory regimens and cytostatic therapy have failed to improve the prognosis. Whether the high-dose interferon-α therapy introduced by Kirkwood et al. 2001 can produce sustainable improvement in cure rate is controversial. Further developments such as treatment with recombinant cytokines (especially IL-2 and GM-CSF), specific blockade of neoplastic signal transduction and vaccination are the central issues in current research. In the future the task will be to offer an highly individualized therapy plan, based on specific prognostic and risk criteria defined in molecular genetic parameters. Indiscriminate use of newer therapeutic approaches is simply not affordable in this age of shrinking financial resources for health care.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literaturverzeichnis

  1. Balch CM, Hersey P (1988) Heutiger Stand der adjuvanten Therapie. In: Balch CM, Milton GW, Shaw HM et al. (Hrsg) Hautmelanome. Diagnose, Therapie und weltweite Ergebnisse. Springer, Berlin Heidelberg New York, S 192–212

  2. Balch CM, Buzaid AC, Soong SJ et al. (2001) Final version of the American Joint Committee on Cacer staging system for cutaneous melanoma. J Clin Oncol 15: 3535–3648

    Google Scholar 

  3. Cameron DA, Cornbleet MC, MacKie RM et al. (2001) Adjuvant interferon alpha 2b in high risk melanoma – the Scottish study. Br J Cancer 84: 1146–1149

    Article  PubMed  Google Scholar 

  4. Cascinelli N, Belli F, MacKie RM et al. (2001) Effect of long-term adjuvant therapy with interferon alpha-2a in patients with regional node metastases from cutaneous melanoma: a randomized trial. Lancet 358: 866–869

    Article  PubMed  Google Scholar 

  5. Creagan ET, Dalton RJ, Ahmann DL et al. (1995) Randomized, surgical adjuvant clinical trial of recombinant interferon alfa-2a in selected patients with malignant melanoma. J Clin Oncol 13: 2776–2783

    PubMed  Google Scholar 

  6. Eggermont AM, Suciu S, MacKie R et al. (2005) Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952): randomized controlled trial. Lancet 366: 1189–1196

    Article  PubMed  Google Scholar 

  7. Garbe C, Hauschild A, Linse R et al. (2002) Adjuvant treatment of patients with cutaneous melanoma and regional node metastasis with low dose interferon or interferon plus DTIC versus observation alone. Preliminary evaluation of a randomized multicenter DeCOG trial. Melanoma Res 12: A13–A14

    Google Scholar 

  8. Garbe C, Hauschild A, Volkenandt M et al. (2006) Kurzleitlinie: Malignes Melanom der Haut. JDDG 4: 344–349

    Article  PubMed  Google Scholar 

  9. Garbe C, Hauschild A, Volkenandt M et al. (2006) Kutanes Melanom. In: Garbe C, Albers P, Beckmann MW et al. (Hrsg) Kurzgefasste interdisziplinäre Leitlinien 2006. Zuckschwerdt, München Wien New York, S 278–286

  10. Grob JJ, Dreno B, de la Salmoniere P et al. (1998) Randomized trial of interferon alpha-2b as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. Lancet 351: 1905–1910

    Article  PubMed  Google Scholar 

  11. Hancock BW, Wheatley K, Harris S et al. (2004) Adjuvant interferon in high-risk melanoma: the AIM HIGH Study – United Kingdom Coordinating Committee on Cancer Research randomized study of adjuvant low-dose extended-duration interferon alfa-2a in high-risk resected malignant melanoma. J Clin Oncol 22: 53–61

    Article  PubMed  Google Scholar 

  12. Hauschild A, Eiling S, Lischner S et al. (2001) Sicherheitsabstände bei der Melanomexzision: Vorschläge basierend auf kontrollierten klinischen Studien. Hautarzt 52: 1003–1010

    Article  PubMed  Google Scholar 

  13. Hauschild A, Weichenthal M, Balda BR et al. (2003) Prospective-randomized trial of interferon alfa-2b and interleukin-2 as adjuvant treatment for resected intermediate- and high-risk primary melanoma without clinical detectable node metastasis. J Clin Oncol 21: 2883–2888

    Article  PubMed  Google Scholar 

  14. Hill GJ, Moss SE, Golomb FM et al. (1981) DTIC and combination therapy for melanoma, III: DTIC surgical adjuvant study COG protocol 7040. Cancer 47: 2556–2562

    Article  PubMed  Google Scholar 

  15. Karg C, Garbe C, Orfanos CE (1990) Chemotherapie des malignen Melanoms – aktueller Stand. Hautarzt 41: 56–65

    PubMed  Google Scholar 

  16. Kirkwood JM, Strawderman MH, Ernstorff MS et al. (1996) Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma. The Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 14: 7–17

    PubMed  Google Scholar 

  17. Kirkwood JM, Ibrahim JG, Sondak VK et al. (2000) High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E 1690. J Clin Oncol 18: 2444–2458

    PubMed  Google Scholar 

  18. Kirkwood JM, Ibrahim JG, Sosman JA et al. (2001) High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIb-III melanoma: results of intergroup trial E 1694. J Clin Oncol 19: 2370–2380

    PubMed  Google Scholar 

  19. Kleeberg UR, Suciu S, Brocker EB et al. (2004) Final results of the EORTC 18871/DKG 80–1 randomized phase III trial: rIFN-α2b versus rIFN-γ versus ISCADOR M® versus observation after surgery in melanoma patients with either high-risk primary (thickness>3 mm) or regional lymph node metastasis. Eur J Cancer 40: 390–402

    Article  PubMed  Google Scholar 

  20. Koops HS, Vaglini M, Suciu S et al. (1998) Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. J Clin Oncol 16: 2906–2912

    PubMed  Google Scholar 

  21. Lens MB, Dawes M (2002) Interferon alfa therapy for malignant melanoma: a systematic review of randomized controlled trials. J Clin Oncol 20: 1818–1825

    Article  PubMed  Google Scholar 

  22. Meyskens FL, Kopecky K, Samson M et al. (1990) Recombinant human interferon gamma: adverse effects in high-risk stage I and II cutaneous malignant melanoma. J Natl Cancer Inst 82: 1071

    PubMed  Google Scholar 

  23. Pehamberger H, Soyer HP, Steriner A et al. (1998) Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group. J Clin Oncol 16: 1425–1429

    PubMed  Google Scholar 

  24. Spitler LE, Grossbard ML, Ernsthoff MS et al. (2000) Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony stimulating factor. J Clin Oncol 18: 1614–1621

    PubMed  Google Scholar 

  25. Stadler R, Luger T, Bieber T et al. (2006) Long-term survival benefit after adjuvant treatment of cutaneous melanoma with Dacarbazine and low dose natural interferon alpha: a controlled, randomized, multicenter trial. Acta Oncol 45: 389–399

    Article  PubMed  Google Scholar 

  26. Veronesi U, Adamus J, Aubert C (1982) A randomized trial of adjuvant chemotherapy and immunotherapy in cutaneous melanoma. N Engl J Med 307: 913–916

    PubMed  Google Scholar 

  27. Wheatley K, Ives N, Hancock B et al. (2003) Does adjuvant interferon alpha for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomized trials. Cancer Treat Rep 29: 241–252

    Article  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor weist auf eine Verbindung mit folgender Firma/Firmen hin: A. Hauschild ist Studienleiter in Projekten, die von den Firmen Hoffmann-La-Roche (Roferon A®), Essex Pharma (Intron A®) und Viragen Inc. (Multiferon®) finanziert wurden bzw. werden.

Author information

Authors and Affiliations

  1. Internistisch-onkologische Gemeinschaftspraxis, Hamburg-Altona

    U. R. Kleeberg

  2. Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Schittenhelmstraße 7, 24105 , Kiel

    A. Hauschild

Authors
  1. A. Hauschild
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. U. R. Kleeberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Hauschild.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hauschild, A., Kleeberg, U.R. Adjuvante Therapie des Melanoms. Hautarzt 57, 764–772 (2006). https://doi.org/10.1007/s00105-006-1196-6

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00105-006-1196-6

Schlüsselwörter

Keywords

Search

Navigation