Download PDF
Aktuelle Urol 2015; 46(02): 151-157
DOI: 10.1055/s-0035-1547281
Übersicht
© 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
,
C. Doehn
3   Urologikum Lübeck
,
V. Grünwald
4   Klinik für Urologie und onkologische Urologie der Medizinischen Hochschule Hannover
,
J. Gschwend
5   Urologische Klinik und Poliklinik der Technischen Universität München Klinikum rechts der Isar
,
M. Kuczyk
4   Klinik für Urologie und onkologische Urologie der Medizinischen Hochschule Hannover
› Author Affiliations
Further Information

Publication History

Publication Date:
21 April 2015 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Patienten mit metastasiertem Nierenzellkarzinom (mRCC) haben eine lebensbegrenzende Prognose. Die Zielsetzung der Therapie ist daher in der Regel palliativ. Dennoch konnten durch die Einführung zielgerichteter Therapien deutliche Fortschritte erreicht werden. Die Immuntherapie mit Zytokinen in der palliativen Situation ist durch die neuen 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. Axitinib 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 2014 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 2014 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 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 administered as second-line options – for pazopanib the use is restricted to the event of cytokine failure. Everolimus (after TKI therapy) und sorafenib (after cytokines) are other compounds now available for second-line therapy. In addition, axitinib was 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 2014 was to debate about which criteria should influence the therapy decision. The members discussed several aspects of treating patients with the disease. Results from the 2012 conference provided the basis for the 2014 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 - zielgerichtete Therapie - operative Therapie

Key words

Renal cell cancer - Metastases - Targeted Therapy - Surgery
 

  • Literatur

  • 1 Miller K, Bergmann L, Gschwend J et al. Interdisziplinäre Empfehlungen zur Behandlung des metastasierten Nierenzellkarzinoms. Aktuel Urol 2014; 45: 39-44
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Kaatsch P, Spix C, Hentschel S et al. Krebs in Deutschland 2009/2010 – 9. Ausgabe, 2013. In: Edition Robert Koch-Institut 2013
    PubMedGoogle Scholar
  • 3 Corgna E, Betti M, Gatta G et al. Renal cancer. Crit Rev Oncol Hemat 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. New 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, Davis ID, Mardiak J et al. Randomized, double-blind phase III study of Pazopanib in patients with advanced/metastatic renal cell carcinoma (MRCC): final overall survival (OS) results. ESMO 2010; Abstract LBA22
    PubMedGoogle 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. Clinical Cancer Research 2004; 10: 6310S-6314S
    CrossrefPubMedGoogle Scholar
  • 13 Coppin C, Porzsolt F, Autemrieth M. Immunotherapy for advanced renal cell cancer In The Cochran Library, Edition John Wiley & Sons, Ltd. 2008; 1-88
    PubMedGoogle 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. ESMO 2012; abstract #LBA8_PR
    PubMedGoogle Scholar
  • 15 Hudes G, Carducci MA, Tomczak P et al. Temsirolimus, Interferon alfa, 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. 2008; abstract #5095
    PubMedGoogle Scholar
  • 21 George D, Michaelson M, Rosenberg J et al. 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. New 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. New 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 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
    PubMedGoogle 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 (18S): 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 Tannir N, Jonasch E, Altinmakas E et al. Everolimus versus sunitinib prospective evaluation in metastatic non-clear cell renal cell carcinoma (The ESPN Trial): A multicenter randomized phase 2 trial. ASCO 2014; 32 (suppl; abstr 4505)
    PubMedGoogle Scholar
  • 33 Vera-Badillo FE, Templeton AJ, Duran I et al. Systemic Therapy for Non-clear Cell Renal Cell Carcinomas: A Systematic Review and Meta-analysis. Eur Urol 2014;
    PubMedGoogle Scholar
  • 34 Angevin E, Lopez-Martin JA, Lin CC et al. Phase I study of dovitinib (TKI258), an oral FGFR, VEGFR, and PDGFR inhibitor, in advanced or metastatic renal cell carcinoma. In Clin Cancer Res, Edition United States 2013; 1257-1268
    PubMedGoogle Scholar
  • 35 Molina AM, Lin X, Korytowsky B et al. Sunitinib objective response in metastatic renal cell carcinoma: Analysis of 1059 patients treated on clinical trials. Eur J Cancer 2014; 50: 351-358
    CrossrefPubMedGoogle Scholar
  • 36 Sridhar SS, Mackenzie MJ, Hotte SJ et al. A phase II study of cediranib (AZD 2171) in treatment naive patients with progressive unresectable recurrent or metastatic renal cell carcinoma. A trial of the PMH phase 2 consortium. Invest New Drugs 2013; 31: 1008-1015
    CrossrefPubMedGoogle Scholar
  • 37 Escudier B, Szczylik C, Porta C et al. Treatment selection in metastatic renal cell carcinoma: expert consensus. Nat Rev Clin Oncol 2012; 9: 327-337
    CrossrefPubMedGoogle Scholar
  • 38 Bergmann L, Beck J, Bothe K et al. Treatment algorithm for metastatic renal cell carcinoma–recommendations based on evidence and clinical practice. In Oncol Res Treat, Edition Netherlands 2014; 136-141
    PubMedGoogle Scholar
  • 39 Motzer RJ, Hutson TE, McCann L et al. Overall Survival in Renal-Cell Carcinoma with Pazopanib versus Sunitinib. New Engl J Med 2014; 370: 1769-1770
    CrossrefPubMedGoogle Scholar
  • 40 Motzer R, Barrios CH, Kim TM et al. Record-3: Phase II randomized trial comparing sequential first-line everolimus (EVE) and second-line sunitinib (SUN) versus first-line SUN and second-line EVE in patients with metastatic renal cell carcinoma (mRCC). ASCO. J Clin Oncol 2013; 31 (suppl; abstr 4504)
    PubMedGoogle Scholar
  • 41 Fachinformation TORISEL® 30 mg Konzentrat und Verdünnungsmittel zur Herstellung einer Infusionslösung. Stand: Juli 2013 Pfizer Pharma GMBH, Berlin
    PubMed
  • 42 Escudier B, Porta C, Bono P et al. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol 2014; 32: 1412-1418
    CrossrefPubMedGoogle Scholar
  • 43 Rini BI, Zhou M, Aydin H et al. Identification of prognostic genomic markers in patients with localized clear cell renal cell carcinoma (ccRCC). ASCO. J Clin Oncol 2010; 28 (suppl; abstr 4501)
    PubMedGoogle Scholar
  • 44 Motzer RJ, Hutson TE, Cella D et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. New Engl J Med 2013; 369: 722-731
    CrossrefPubMedGoogle Scholar
  • 45 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. ASCO. J Clin Oncol 25 2007; (suppl; abstr 5023)
    PubMedGoogle Scholar
  • 46 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
  • 47 Rini B, Hutson T, Elson P. Phase II Study of Sorafenib in patients with mRCC refractory to Sunitinib or Bevacizumab. ASCO 2008; abstract #346
    PubMedGoogle Scholar
  • 48 Motzer R, Escudier B, Oudard S et al. 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. ASCO, J Clin Oncol 2008; 26 (suppl; abstr LBA5026)
    PubMedGoogle Scholar
  • 49 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
  • 50 Eichelberg C, Goebell PJ, Vervenne WL et al. Updated overall survival, multivariate, and Q-TWiST analyses of a randomized, sequential, open-label study (SWITCH) to evaluate the efficacy and safety of sorafenib (So)-sunitnib (Su) versus Su-So in the treatment of metastatic renal cell cancer. ESMO 2014; Abstract 835p
    PubMedGoogle Scholar
  • 51 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
  • 52 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; 28s: e15132
    PubMedGoogle Scholar
  • 53 Sabbatini R, Ortega C, Procopio G et al. Metastatic renal cell carcinoma: how to make the best sequencing decision after withdrawal for intolerance to a tyrosine kinase inhibitor. Future Oncol 2013; 9: 831-843
    CrossrefPubMedGoogle Scholar
  • 54 Stenner-Liewen F, Grünwald V, Greil R et al. The clinical potential of temsirolimus in second or later lines of treatment for metastatic renal cell carcinoma. Expert review of anticancer therapy 2013; 13: 1021-1033
    CrossrefPubMedGoogle Scholar
  • 55 Buchler T, Bortlicek Z, Poprach A et al. Efficacy of everolimus in second- and third-line therapy for metastatic renal cell carcinoma: a registry-based analysis. Urol Oncol 2014; 32: 569-575
    CrossrefPubMedGoogle Scholar
  • 56 Oudard S, Gross Goupil M, Geoffrois L. 816PD Clinical activity of sunitinib rechallenge in metastatic renal cell carcinoma (MCRR) – results of the resume study. Ann Oncol 2014; 25 (Suppl. 04) iv283-iv284
    CrossrefPubMedGoogle Scholar
  • 57 Blesius A, Beuzelink B, Chevreau C et al. Are TKIs still active in patients treated with TKI and everolimus? Experience from 36 patients treated in France in the RECORD 1trial. ESMO 2010; Abstract
    PubMedGoogle Scholar
  • 58 Calvani N, Morelli F, Chiuri V et al. Prolonged exposure to tyrosine kinase inhibitors or early use of everolimus in metastatic renal cell carcinoma: are the two options alike?. Med Oncol 2013; 30: 578
    CrossrefPubMedGoogle Scholar
  • 59 Rini BI, Escudier B, Tomczak P. Axitinib vs. Sorafenibas Second-line Therapy for Metastatic Renal Cell Carcinoma: Results of the Phase 3 AXIS Trial. ASCO 2011; 20 (suppl; abstr 4503)
    PubMedGoogle Scholar
  • 60 Rexer H. Third-line-Therapie beim metastasierten Nierenzellkarzinom. Urologe 2011; 50: 1319-1321
    CrossrefPubMedGoogle Scholar
  • 61 Maute L, Grünwald V, Weikert S et al. Therapy of mRCC beyond mTOR-inhibition in clinical practice: results of a retrospective analysis. J Cancer Res Clin Oncol 2014; 140: 823-827
    CrossrefPubMedGoogle Scholar
  • 62 Fachinformation TORISEL® 30 mg Konzentrat und Verdünnungsmittel zur Herstellung einer Infusionslösung. Stand: Juli 2013 Pfizer Pharma GmbH, Berlin
    PubMed
  • 63 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
  • 64 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
  • 65 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
  • 66 Rini BI, Bellmunt J, Clancy J et al. Randomized phase III trial of temsirolimus and bevacizumab versus interferon alfa and bevacizumab in metastatic renal cell carcinoma: INTORACT trial. In J Clin Oncol, Edition United States 2014; 752-759
    PubMedGoogle Scholar
  • 67 Ravaud A, Gross-Goupil M, Bellmunt J. Combination therapy in metastatic renal cell cancer. Semin Oncol 2013; 40: 472-481
    CrossrefPubMedGoogle Scholar
  • 68 Yuki H, Kamai T, Kubota K et al. Axitinib for preoperative downstaging of renal cell carcinoma with sarcomatoid differentiation and direct invasion of the duodenum and inferior vena cava: a case report. In Onco Targets Ther, Edition New Zealand 2014; 289-295
    PubMedGoogle Scholar
  • 69 Sassa N, Kato M, Funahashi Y et al. Efficacy of pre-surgical axitinib for shrinkage of inferior vena cava thrombus in a patient with advanced renal cell carcinoma. In Jpn J Clin Oncol, Edition England 2014; 370-373
    PubMedGoogle Scholar
  • 70 Karam JA, Devine CE, Urbauer DL et al. Phase 2 Trial of Neoadjuvant Axitinib in Patients with Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma. Eur Urol 2014;
    PubMedGoogle Scholar
  • 71 Kats-Ugurlu G, Oosterwijk E, Muselaers S et al. Neoadjuvant sorafenib treatment of clear cell renal cell carcinoma and release of circulating tumor fragments. Neoplasia 2014; 16: 221-228
    CrossrefPubMedGoogle Scholar
  • 72 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
  • 73 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
  • 74 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
  • 75 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