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Aktuelle Urol 2011; 42(4): 242-246
DOI: 10.1055/s-0031-1271548
Originalarbeit

© Georg Thieme Verlag KG Stuttgart ˙ New York

Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms

Interdisciplinary Recommendations for the Treatment of Metastatic Renal Cell CarcinomaK. Miller1 , L. Bergmann2 , J. Gschwend3 , U. Keilholz4
  • 1Klinik für Urologie, Charité – Universitätsmedizin Berlin
  • 2MedizinischeKlinik II, J. W. Goethe-Universität Frankfurt / Main
  • 3Urologische Klinik und Poliklinik der Technischen Universität München Klinikum rechts der Isar
  • 4Medizinische Klinik III, Charité – Universitätsmedizin Berlin
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Publikationsverlauf

Publikationsdatum:
30. Juni 2011 (online)

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Zusammenfassung

Mit der Einführung zielgerichteter Substanzen hat die Therapie des metastasierten Nierenzellkarzinoms einen Paradigmenwechsel erfahren: Der Einsatz von Zytokinen als langjährige Standardtherapie rückte in den Hintergrund, neue Medikamente wie Sunitinib, Sorafenib, Bevacizumab und Temsirolimus haben sich als Behandlungsstandard etabliert. Vor kurzem wurde das therapeutische Spektrum durch Everolimus und Pazopanib erweitert. Welche Kriterien beim Einsatz dieser Medikamente zu berücksichtigen sind und welche Fragen auf Basis der aktuellen Stu­dienlage noch unbeantwortet bleiben, war Gegenstand einer Konsensuskonferenz. Das interdisziplinäre Board knüpfte an Therapieempfehlungen aus dem Jahr 2010 an [1]. Das Ergebnis der Diskussion wird hier in Form von Thesen zusammengefasst. 

Abstract

With the introduction of targeted drug therapies, a paradigm shift for the treatment of metastatic renal cell carcinoma has taken place. New compounds like sunitinib, sorafenib, bevacizumab and temsirolimus have become established as new therapeutic standards to replace the use of cytokines as standard therapy. Recently, these substances have been complemented by everolimus and pazopanib. An interdisciplinary consensus conference was held to discuss which criteria to consider when using these drugs (treatment sequence) and what questions remain unanswered based on the current study situation (open questions). Results from the 2009 conference provided the basis for the 2010 meeting. The results of the 2010 conference are presented as short theses. 

Schlüsselwörter

Nierenzellkarzinom - Metastasen - medikamentöse Therapie

Key words

renal cell cancer - metastases - medical treatment

Literatur

  • 1 Miller K, Bergmann L, Jäger E et al. Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms.  Aktuel Urol. 2010;  41 193-196
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 2 Robert-Koch-Institut und. Krebs in Deutschland 2005 / 2006. Häufigkeiten und Trends. 7. Ausgabe 2010
    Google Scholar
  • 3 Bukowski R M, Negrier S, Elson P et al. Prognostic factors in patients with advanced renal cell carcinoma: development of an international kidney cancer working group.  Clin Cancer Res. 2004;  10 6310-6314
    CrossrefPubMedGoogle Scholar
  • 4 Coppin C, Porzsolt F, Kumpf J et al. Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev; 2005 (1) CD001425
    Google Scholar
  • 5 Motzer R J, Bacik J, Murphy B A et al. Interferon-alpha as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma.  J Clin Oncol. 2002;  20 289-296
    CrossrefPubMedGoogle Scholar
  • 6 Motzer R J, Hutson T E, Tomczak P et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.  N Engl J Med. 2007;  356 115-124
    CrossrefPubMedGoogle Scholar
  • 7 Motzer R J, Hutson T E, Tomczak P et al. Overall survival and updated ­results for sunitinib compared with interferon alpha in patients with metastatic renal cell carcinoma.  . 2009;  27 3584-3590
    PubMedGoogle Scholar
  • 8 Escudier B, Pluzanska A, Koralewski P et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial.  Lancet. 2007;  370 2103-2111
    CrossrefPubMedGoogle Scholar
  • 9 Sternberg C, Davis I D, Mardiak J et al. Pazopanib in Locally Advanced or Metastatic Renal Cell Carcinoma: Results of a Randomized Phase III Trial.  J Clin Oncol. 2010;  38 1061-1068
    PubMedGoogle Scholar
  • 10 Sternberg C N, Hawkins R E, Szczylik C et al. Randomized, double-blind phase III study of pazopanib in patients with advanced/metastatic renal cell carcinoma (mRCC): Final overall survival (OS) results.  Ann Oncol. 2010;  21 viii10
    CrossrefPubMedGoogle Scholar
  • 11 NICE .http://http://www.nice.org.uk/nicemedia/live/12032/52299/52299.pdf 2010
  • 12 NCT00720941. http://(www.clinicaltrials.gov)
    Google Scholar
  • 13 Hudes G, Carducci M, Tomczak P et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.  N Engl J Med. 2007;  356 2271-2281
    CrossrefPubMedGoogle Scholar
  • 14 Motzer R J, Michaelson M D, Hutson T E et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma (mRCC): updated efficacy and safety results and further analysis of prognostic factors.  Eur J Cancer. 2007;  5 301s
    PubMedGoogle Scholar
  • 15 Escudier B, Eisen T, Stadler W M et al. Sorafenib in advanced clear-cell renal-cell carcinoma.  N Engl J Med. 2007;  356 125-134
    CrossrefPubMedGoogle Scholar
  • 16 Motzer R, Escudier B, Oudard S RECORD-1 Study Group et al.,. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, ran­domised, placebo-controlled phase III trial.  Lancet. 2008;  372 449-456
    CrossrefPubMedGoogle Scholar
  • 17 Gore M E, Szczylik C, Porta C et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial.  Lancet Oncol. 2009;  10 757-763
    CrossrefPubMedGoogle Scholar
  • 18 Rosenberg J E, Michaelson M D, Redman B G et al. Sunitinib therapy for patients with metastatic renal cell carcinoma: updated results of two phase II trials and prognostic factor analysis for survival. ASCO 2007 Poster 5095
    Google Scholar
  • 19 George D J, Michaelson M D, Rosenberg J E et al. Sunitinib in patients with cytokine-refractory metastatic renal cell carcinoma (mRCC).  Eur J Cancer. 2007;  5 304
    PubMedGoogle Scholar
  • 20 Atzpodien J, Kirchner H, Jonas U et al. Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).  J Clin Oncol. 2004;  22 1188-1194
    CrossrefPubMedGoogle Scholar
  • 21 McDermott D F, Regan M M, Clark J I et al. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma.  J Clin Oncol. 2005;  23 133-141
    CrossrefPubMedGoogle Scholar
  • 22 Negrier S, Escudier B, Lasset C et al. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Francais d'Immunotherapie.  N Engl J Med. 1998;  338 1272-1278
    CrossrefPubMedGoogle Scholar
  • 23 Pyrhonen S, Salminen E, Ruutu M et al. Prospective randomized trial of interferon alfa-a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer.  J Clin Oncol. 1999;  17 2859-2867
    PubMedGoogle Scholar
  • 24 Ratain M J, Eisen T, Stadler W M et al. Phase II placebo-controlled randomized discontinuation trial of Sorafenib in patients with metastatic renal cell carcinoma.  J Clin Oncol. 2006;  24 2505-2512
    CrossrefPubMedGoogle Scholar
  • 25 Yang J C, Haworth L, Sherry R M et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer.  N Engl J Med. 2003;  349 427-434
    CrossrefPubMedGoogle Scholar
  • 26 Yang J C, Sherry R M, Steinberg S M et al. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer.  J Clin Oncol. 2003;  21 3127-3132
    CrossrefPubMedGoogle Scholar
  • 27 Beck J, Bajetta E, Escudier B et al. A large open-label non-comparative phase III study of the multi-targeted kinase inhibitor Sorafenib in ­European patients with advanced renal cell carcinoma. ECCO 2007; Abstract 4506
    Google Scholar
  • 28 Dutcher J P, Szczylik C, Tannir N et al. Correlation of survival with tumor histology, age, and prognostic risk group for previously untreated patients with advanced renal cell carcinoma (advRCC) receiving temsirolimus (TEMSR) or interferon-alpha (IFN).  J Clin Oncol. 2007;  25 18
    PubMedGoogle Scholar
  • 29 Choueiri T K, Plantade A, Elson P et al. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma.  J Clin Oncol. 2008;  26 127-131
    CrossrefPubMedGoogle Scholar
  • 30 ClinicalTrials.gov Identifier. NCT00979966
    Google Scholar
  • 31 ClinicalTrials.gov Identifier. NCT00688753
    Google Scholar
  • 32 Pfizer Pharma GmbH .Fachinformation TORISEL® 25 mg Konzentrat. 2010
    Google Scholar
  • 33 Pfizer Pharma GmbH .Fachinformation SUTENT® 12,5 / 25 / 37,5 / 50 mg Hartkapseln. 2010
    Google Scholar
  • 34 Roche Pharma AG .Fachinformation AVASTIN®. 2010
    Google Scholar
  • 35 Roche Pharma AG .Fachinformation ROFERON®-A 18 Mio. I.E. / 0,6 ml Patrone mit Injektionslösung. 2010
    Google Scholar
  • 36 GlaxoSmithKline GmbH .Fachinformation VOTRIENT® 200 / 400 mg Filmtabletten. 2010
    Google Scholar
  • 37 Gore M E, Griffin C, Hancock B et al. Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04 / EORTC GU 30012): an open-label randomised trial.  Lancet. 2010;  375 641-648
    CrossrefPubMedGoogle Scholar
  • 38 Bukowski R M, Eisen T, Szczylik W M et al. Final results of the randomized phase III trial of Sorafenib in advanced renal cell carcinoma: Survival and biomarker analysis. ASCO2007.  J Clin Oncology. 2007;  25 5023
    PubMedGoogle Scholar
  • 39 Bayer Schering Pharma AG .Fachinformation NEXAVAR® 200 mg Filmtabletten. 2010
    Google Scholar
  • 40 Rini B I, Hutson T E, Elson P et al. Phase II Study of Sorafenib in patients with mRCC refractory to Sunitinib or Bevacizumab. ASCO GU 2008
    Google Scholar
  • 41 Tamaskar I, Garcia J A et al. Antitumor effects of sunitinib or Sorafenib in patients with metastatic renal cell carcinoma who received prior antiangiogenic therapy.  J Urol. 2008;  179 81-86
    PubMedGoogle Scholar
  • 42 Di Lorenzo G, Buonerba C, Federico P et al. Phase II Study of Sorafenib in Patients With Sunitinib-Refractory Metastatic Renal Cell Cancer.  J Clin Oncol. 2009;  27 4469-4474
    CrossrefPubMedGoogle Scholar
  • 43 Shepard D R, Rini B I, Garcia A et al. A multicenter prospective trial of sorafenib in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) refractory to prior sunitinib or bevacizumab.  J Clin Oncol. 2008;  26 280
    PubMedGoogle Scholar
  • 44 Rini B I, Wilding G, Hudes G et al. Phase II Study of Axitinib in Sorafenib-Refractory Metastatic Renal Cell Carcinoma.  JCO. 2009;  27 4462-4468
    CrossrefPubMedGoogle Scholar
  • 45 Sablin M P, Negrier S, Ravaud A et al. Sequential sorafenib and sunitinib for renal cell carcinoma.  J Urol. 2009;  182 29-34
    CrossrefPubMedGoogle Scholar
  • 46 Grünwald V, Fenner M, Seidel C et al. Antitumor activity of sequen­tial treatment with tyrosine kinase inhibitors (TKI) after failure of RAD001 in metastatic renal cell carcinoma (mRCC).  J Clin Oncol. 2010;  28
    PubMedGoogle Scholar
  • 47 Flanigan R C, Mickisch G, Sylvester R et al. Cytoreductive nephrectomy in patients with metastatic renal cancer:a combined analysis.  J Urol. 2004;  171 1071-1076
    CrossrefPubMedGoogle Scholar
  • 48 CinicalTrials.gov Identifier. NCT00930033
    Google Scholar
  • 49 Johannsen M, Flörcken, A, Bex A et al. Can tyrosine kinase inhibitors be discontinued in patients with metastatic renal cell carcinoma and a complete response to treatment? A multicentre, retrospective analysis.  Eur Urol. 2009;  55 1430-1438
    CrossrefPubMedGoogle Scholar
  • 50 ClinicalTrials.gov Identifier. NCT00619268
    Google Scholar
  • 51 Hainsworth J D, Spigel D R, Burris H A et al. Phase II trial of bevacizumab and everolimus in patients with advanced renal cell carcinoma.  J Clin Oncol. 2010;  28 2131-2136
    CrossrefPubMedGoogle Scholar
  • 52 Karakiewicz P I, Suardi N, Jeldres C et al. Neoadjuvant sutent induction therapy may effectively down-stage renal cell carcinoma a trial thrombi.  Eur Urol. 2008;  53 845-848
    CrossrefPubMedGoogle Scholar
  • 53 Baccala Jr A, Hedgepath R, Kaouk J et al. Pathological evidence of necrosis in recurrent renal mass following treatment with sunitinib.  Int J Urol. 2007;  14 1095-1097
    CrossrefPubMedGoogle Scholar
  • 54 Heng D Y, Rini B Y, Garci J et al. Prolonged complete responses and near-complete responses to sunitinib in metastatic renal cell carcinoma.  Clin Genitourin Cancer. 2007;  5 446-451
    CrossrefPubMedGoogle Scholar
  • 55 Atzpodien J, Schmitt E, Gertenbach U et al. Adjuvant treatment with interleukin-2-and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumournephrectomy: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).  Br J Cancer. 2005;  92 843-846
    CrossrefPubMedGoogle Scholar

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Prof. Dr. med. K. Miller

Charité – Urologische Klinik und Hochschulambulanz

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12200 Berlin

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