PDF herunterladen
TumorDiagnostik & Therapie 2014; 35(5): 280-285
DOI: 10.1055/s-0034-1384891
Thieme Onkologie aktuell
© Georg Thieme Verlag KG Stuttgart · New York

Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms

Interdisciplinary Recommendations for the Treatment of Metastatic Renal Cell Carcinoma
K. Miller
1   Klinik für Urologie, Charité – Universitätsmedizin Berlin
,
L. Bergmann
2   Medizinische Klinik II, J. W. Goethe-Universität Frankfurt/Main
,
J. Gschwend
3   Urologische Klinik und Poliklinik der Technischen Universität München Klinikum rechts der Isar
,
U. Keilholz
4   Medizinische Klinik II, Charité – Universitätsmedizin Berlin
,
M. Kuczyk
5   Klinik für Urologie und onkologische Urologie der Medizinischen Hochschule Hannover
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
15. August 2014 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Zusammenfassung

Patienten mit metastasiertem Nierenzellkarzinom (mRCC) haben eine lebensbegrenzende Prognose. Die Zielsetzung der Therapie ist daher in der Regel palliativ. Dennoch konnten in den letzten Jahren deutliche Fortschritte erreicht werden. Die Immuntherapie mit Zytokinen in der palliativen Situation ist zunehmend durch neue zielgerichtete Substanzen abgelöst worden. Sunitinib, die Kombination Bevacizumab+Interferon-alpha, Pazopanib sowie Temsirolimus sind für die Erstlinie beim mRCC zugelassen. Sunitinib und Pazopanib haben eine Zulassung auch für die Zweitlinientherapie – für Pazopanib ist diese auf den Einsatz nach Zytokinen beschränkt. Everolimus (nach TKI-Therapie) und Sorafenib (nach Zytokintherapie) sind weitere Substanzen, die in der Zweitlinientherapie zur Verfügung stehen. Neu zugelassen wurde Axitinib, es kann nach Versagen einer Sunitinib- oder Zytokintherapie eingesetzt werden. Zur Frage nach der optimalen Sequenz gibt es erste Studienergebnisse aus einer Phase III Studie. Welche Kriterien einer Therapieentscheidung zugrundgelegt werden sollten, wurde im Rahmen eines Expertenmeetings unter Berücksichtigung der 2012 publizierten Daten diskutiert. Wie in den Vorjahren war es auch diesmal das Ziel des interdisziplinären Expertengesprächs, gemeinsame Therapieempfehlungen auf Basis der publizierten Daten und der eigenen klinischen Erfahrung zu erarbeiten und für den Praxisalltag abzuleiten. Das interdisziplinäre Board knüpfte an Therapieempfehlungen aus dem Jahr 2012 an [1]. Die Publikation fasst die Ergebnisse der Diskussion zusammen und enthält einen aktuellen Therapiealgorithmus.

Abstract

Patients with metastatic renal cell carcinoma have a life-limiting prognosis. Therefore, the aim of therapy is normally palliative care. Nevertheless, substantial achievements have been made in the past years. Cytokines as long-term standard therapy have been more and more replaced by new targeted therapies. Sunitinib, the combination of bevacizumab+interferon alfa, pazopanib and temsirolimus are now approved for first-line therapy. Sunitinib and pazopanib can also be applied as second-line options – for pazopanib the use is restricted to cases of cytokine failure. Everolimus (after TKI therapy) and sorafenib (after cytokines) are other compounds available for second-line therapy. In addition, axitinib was recently approved for second-line therapy after failure of sunitinib or cytokines. For questions regarding the optimal sequence, first study results are now available from the phase III trial. The purpose of an interdisciplinary expert meeting held in 2012 was to debate upon which criteria should influence the therapy decision. The members discussed several aspects of treating patients with the disease. Results from the 2011 conference provided the basis for the 2012 meeting [1]. As in previous years, the experts intended to provide common recommendations for clinical practice. The results of the 2012 conference are presented as short theses and a current therapy algorithm.

Schlüsselwörter

Nierenzellkarzinom - Metastasen - medikamentöse Therapie

Key words

renal cell cancer - metastases - targeted therapy
 

  • Literatur

  • 1 Miller K, Bergmann L, Gschwend J et al. Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms. Aktuel Urol 2013; 45-49
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 2 Kaatsch P, Spix C, Katalinic A et al. Krebs in Deutschland 2007/2008. In Berlin: Robert Koch-Institut & Gesellschaft der epidemiologischen Krebsregister in Deutschland e. V.; 2012
    Google Scholar
  • 3 Corgna E, Betti M, Gatta G et al. Renal cancer. Crit Rev Oncol Hematol 2007; 64: 247-262
    CrossrefPubMedGoogle Scholar
  • 4 Motzer RJ, Hutson TE, Tomczak P et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma (mRCC): updated efficacy and safety results and further analysis of prognostic factors. New Engl J Med 2007; 356: 115-124
    CrossrefPubMedGoogle Scholar
  • 5 Sternberg CN, Davis ID, Mardiak J et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010; 28: 1061-1068
    CrossrefPubMedGoogle Scholar
  • 6 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
  • 7 Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356: 125-134
    CrossrefPubMedGoogle Scholar
  • 8 Motzer RJ, Hutson TE, Tomczak P et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 2009; 27: 3584-3590
    CrossrefPubMedGoogle Scholar
  • 9 Sternberg CN, Hawkins R, 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. In: ESMO. ed. 2010. LBA22
    Google Scholar
  • 10 Hutson TE, Davis ID, Machiels JP et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol 2010; 28: 475-480
    CrossrefPubMedGoogle Scholar
  • 11 Motzer RJ, Bacik J, Murphy BA et al. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002; 20: 289-296
    CrossrefPubMedGoogle Scholar
  • 12 Bukowski RM, Negrier S, Elson P. Prognostic factors in patients with advanced renal cell carcinoma: development of an international kidney cancer working group. Clin Cancer Res 2004; 10: 6310S-6314S
    CrossrefPubMedGoogle Scholar
  • 13 Coppin C, Porzsolt F, Autemrieth M et al. Immunotherapy for advanced renal cell cancer In: The Cochran Library. John Wiley & Sons, Ltd; 2008: 1-88
    Google Scholar
  • 14 Motzer R, Hutson T, Reeves J et al. Randomized, open-label, phase III trial of Pazopanib versus sunitinib in first treatment of patients with metastatic renal cell carcinoma (mRCC): results of the COMPARZ trial. In: ESMO. ed. 2012. LBA8_PR
    Google Scholar
  • 15 Hudes G, Carducci MA, Tomczak P et al. Temsirolimus, Interferon alfs, or both for advanced renal-cell carcinoma. New Engl J Med 2007; 356: 2271-2281
    CrossrefPubMedGoogle Scholar
  • 16 Motzer R. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma (mRCC): updated efficacy and safety results and further analysis of prognostic factors. 2007 301
    PubMedGoogle Scholar
  • 17 Rini B. Axitinib versus sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC): Results of phase III AXIS trial. J Clin Oncol 2011; 29
    PubMedGoogle Scholar
  • 18 Motzer RJ, Escudier B, Oudard S 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
  • 19 Gore ME, 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
  • 20 Rosenberg J, Michaelson MD, Redman BG et al. Sunitinib therapy for patients with metastatic renal cell carcinoma: updated results of two phase II trials and prognostic factor analysis for survival. In 2008; 5095
    PubMedGoogle Scholar
  • 21 George D, Michaelson M, Rosenberg J. Sunitinib in patients with cytokine-refractory metastatic renal cell carcinoma (mRCC). Eur J Cancer 2007; 5: 304s
    PubMedGoogle Scholar
  • 22 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
  • 23 McDermott DF, Regan MM, Clark JI 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
  • 24 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
  • 25 Pyrhonen S, Salminen E, Ruutu M et al. Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol 1999; 17: 2859-2867
    PubMedGoogle Scholar
  • 26 Ratain MJ, Eisen T, Stadler WM 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
  • 27 Yang JC, Haworth L, Sherry RM 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
  • 28 Yang JC, Sherry RM, Steinberg SM 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
  • 29 Beck J, Bajetta E, Escudier B. A large open-label non-comparative phase III study of the multi-targeted kinase inhibitor Sorafenib in European patients with advanced renal cell carcinoma. In: ECCO. ed. 2007. 4506.
    Google Scholar
  • 30 Dutcher J, 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 (adv RCC) receiving temsirolimus (TEMSR) or interferon-alpha (IFN). J Clin Oncol 2007; 25: 5033
    PubMedGoogle Scholar
  • 31 Choueiri TK, 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
  • 32 Motzer R, Nosov D, Eisen T et al. Tivozanib versus sorafenib as initial targeted therapy for patients with advanced renal cell carcinoma: Results from a phase III randomized, open-label, multicenter trial. In: J Clin Oncol. 2012
    PubMedGoogle Scholar
  • 33 AVEO and Astellas Report FDA . Oncologic Drug Advisory Committee Votes Tivozanib Application Did Not Demonstrate Favorable Benefit-to-Risk Evaluation in Treatment of Advanced Renal Cell Carcinoma. Press release 5 2 2013; http://investor.aveooncology.com/phoenix.zhtml?c=219651&p=irol-newsArticle&ID=1814508& highlight=
    PubMedGoogle Scholar
  • 34 Torisel ® 30 mg Konzentrat und Verdünnungsmittel zur Herstellung einer Infusionslösung In: Berlin: Pfizer Pharma GMBH; 2013
  • 35 Fachinformation SUTENT ® 12,5/25/37,5/50 mg Hartkapsel In: Berlin: Pfizer Pharma GmbH; 2013
  • 36 Fachinformation AVASTIN® In Grenzach-Wyhlen: Roche Pharma AG; 2013
  • 37 Fachinformation ROFERON®-A 18 Mio. I. E./0,6 ml Patrone mit Injektionslösung In Grenzach-Wyhlen: Roche Pharma AG; 2013
  • 38 Fachinformation VOTRIENT® 200/400 mg Filmtabletten In München: GlaxoSmithKline GmbH; 2013
  • 39 Bukowski R, Eisen T, Szczylik C et al. Final results of the randomized phase III trial of sorafenib in advanced renal cell carcinoma: Survival and biomarker analysis. In: J Clin Oncol 2007;
    PubMedGoogle Scholar
  • 40 Tamaskar I, Garcia JA, Elson P 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 discussion 86
    PubMedGoogle Scholar
  • 41 Rini B, Hutson T, Elson P. Phase II Study of Sorafenib in patients with mRCC refractory to Sunitinib or Bevacizumab. In: ASCO. ed. 2008. 346.
    Google Scholar
  • 42 Motzer R, Escudier B, Oudard S. RAD001 vs. placebo in patients with metastatic renal cell carcinoma (RCC) after progression on VEGFR-TKI therapy: Results from a randomized, double-blind, multicenter Phase-III study. In: J Clin Oncol. 2008
    PubMedGoogle Scholar
  • 43 Motzer R. Record-3: Phase II randomized trial comparing sequential first-line everolimus (EVE) and second-line sunitinib (SUN) vs. first-line SUN and second-line EVE in patients with metastatic renal cell carcinoma (mRCC). In: J Clin Oncol 2013;
    PubMedGoogle Scholar
  • 44 Rini BI, Escudier B, Tomczak P et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011; 378: 1931-1939
    CrossrefPubMedGoogle Scholar
  • 45 Proskorovsky I, Benedict A, Negrier S et al. Axitinib (axi) and everolimus (eve) in the treatment (tx) of sunitinib-refractory (su-r) patients (pts) with metastatic renal cell carcinoma (mRCC): results of a simulated TX comparison (stc) analyses. In: ESMO. ed. 2012. 843P
    Google Scholar
  • 46 Rini BI, Wilding G, Hudes G et al. Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. J Clin Oncol 2009; 27: 4462-4468
    CrossrefPubMedGoogle Scholar
  • 47 Di Lorenzo G, Carteni G, Autorino R 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
  • 48 Grünwald V, Fenner M, Seidel C. Antitumor activity of sequential treatment with tyrosine kinase inhibitors (TKI) after failure of RAD001 in metastatic renal cell carcinoma (mRCC). J Clin Oncol 2010; 28s: e15132
    PubMedGoogle Scholar
  • 49 Flanigan RC, 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
  • 50 Johannsen M, Florcken 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
  • 51 Hainsworth JD, Spigel DR, Burris 3rd HA 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 PI, Suardi N, Jeldres C et al. Neoadjuvant sutent induction therapy may effectively down-stage renal cell carcinoma atrial thrombi. Eur Urol 2008; 53: 845-848
    CrossrefPubMedGoogle Scholar
  • 53 Tobert CM, Uzzo RG, Wood CG et al. Adjuvant and neoadjuvant therapy for renal cell carcinoma: A survey of the Society of Urologic Oncology. Urol Oncol. 2012
    PubMedGoogle Scholar
  • 54 Choueiri M, Tannir N, Jonasch E. Adjuvant and neoadjuvant therapy in renal cell carcinoma. Curr Clin Pharmacol 2011; 6: 144-150
    CrossrefPubMedGoogle Scholar
  • 55 Bex A, Jonasch E, Kirkali Z et al. Integrating surgery with targeted therapies for renal cell carcinoma: current evidence and ongoing trials. Eur Urol 2010; 58: 819-828
    CrossrefPubMedGoogle Scholar
  • 56 Jonasch E, Wood CG, Matin SF et al. Phase II presurgical feasibility study of bevacizumab in untreated patients with metastatic renal cell carcinoma. J Clin Oncol 2009; 27: 4076-4081
    CrossrefPubMedGoogle Scholar
  • 57 Thomas AA, Rini BI, Stephenson AJ et al. Surgical resection of renal cell carcinoma after targeted therapy. J Urol 2009; 182: 881-886
    CrossrefPubMedGoogle Scholar
  • 58 Cowey CL, Amin C, Pruthi RS et al. Neoadjuvant clinical trial with sorafenib for patients with stage II or higher renal cell carcinoma. J Clin Oncol 2010; 28: 1502-1507
    CrossrefPubMedGoogle Scholar
  • 59 Atzpodien J, Schmitt E, Gertenbach U et al. Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). British Journal of Cancer 2005; 92: 843-846
    CrossrefPubMedGoogle Scholar