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Defining risk status in the first-line treatment of metastatic renal cell carcinoma

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Abstract

Targeted agents, such as sunitinib, have significantly improved the prognosis of patients with metastatic renal cell carcinoma (mRCC) and are now well-established treatment options for these patients. Several pre-treatment clinical features have been associated with shorter survival, and identification of these prognostic factors has led to the development of risk models, such as the Memorial Sloan-Kettering Cancer Center (MSKCC) model. These risk models can be used to stratify patients according to their risk status. The risk status of patients can have important implications for their response to different treatment strategies; therefore, risk models enable treatment to be tailored for individual patients. In the MSKCC model, patients are stratified into one of three groups according to defined risk factors: favourable, intermediate or poor risk. The MSKCC model is well established and has been used to stratify patients in many clinical studies with targeted agents. However, some studies have used modified criteria which can make it difficult to make direct comparisons between studies. This can have important implications when selecting the most appropriate treatment for individual patients. In this review the rationale for establishing risk status is discussed and the practical application of risk models to aid the selection of appropriate first-line treatments is examined. Additionally, the evidence supporting the use of targeted agents in patients with mRCC according to their risk status is reviewed.

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References

  • Bhojani N, Jeldres C, Patard JJ et al (2008) Toxicities associated with the administration of sorafenib, sunitinib, and temsirolimus and their management in patients with metastatic renal cell carcinoma. Eur Urol 53:917–930

    Article  CAS  PubMed  Google Scholar 

  • Coppin C, Porzsolt F, Awa A et al (2005) Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev (1):CD001425

  • Dutcher JP, Szczylik C, Tannir N et al (2007) 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 25(18S Part 1):243 s (Abstract 5033)

  • Escudier B, Koralewski P, Pluzanska A et al (2007a) A randomized, controlled, double-blind phase III study (AVOREN) of bevacizumab/interferon-α2a vs placebo/interferon-α2a as first-line therapy in metastatic renal cell carcinoma. J Clin Oncol 25(18S Part 1):2 s (Abstract 3)

  • Escudier B, Eisen T, Stadler WM et al (2007b) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134

    Article  CAS  PubMed  Google Scholar 

  • Escudier B, Pluzanska A, Koralewski P et al (2007c) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111

    Article  PubMed  Google Scholar 

  • Escudier BJ, Bellmunt J, Negrier S et al (2009) Final results of the phase III, randomized, double-blind AVOREN trial of first-line bevacizumab (BEV) + interferon-α2a (IFN) in metastaric renal cell carcinoma (mRCC). J Clin Oncol 27:Abstr 5020 (Oral presentation)

  • Ferlay J, Autier P, Boniol M et al (2007) Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 18:581–592

    Article  CAS  PubMed  Google Scholar 

  • Gore ME, Szczylik C, Porta C et al (2009) Safety and efficacy of sunitinib with subpopulation analysis in an expanded-access trial of metastatic renal cell carcinoma. Lancet Oncol 10:757–763

    Article  CAS  PubMed  Google Scholar 

  • Heng DY, Xie W, Regan MM et al (2009) Prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF)-targeted agents: results from a large multicenter study. J Clin Oncol 27 5 s (suppl; abstr 5041)

  • Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281

    Article  CAS  PubMed  Google Scholar 

  • Janzen NK, Kim HL, Figlin RA et al (2003) Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am 30:843–852

    Article  PubMed  Google Scholar 

  • Lilleby W, Fossa SD (2005) Chemotherapy in metastatic renal cell cancer. World J Urol 23:175–179

    Article  CAS  PubMed  Google Scholar 

  • Ljungberg B, Hanbury DC, Kuczyk MA et al (2009) Guidelines on renal cell carcinoma (2009). European Association of Urology http://www.uroweb.org/fileadmin/tx_eauguidelines/2009/Full/RCC.pdf

  • Motzer RJ, Bander NH, Nanus DM (1996) Renal-cell carcinoma. N Engl J Med 335:865–875

    Article  CAS  PubMed  Google Scholar 

  • Motzer RJ, Bacik J, Murphy BA et al (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289–296

    Article  CAS  PubMed  Google Scholar 

  • Motzer RJ, Figlin R, Hutson TE et al (2007a) Sunitinib versus interferon-alfa (IFN-α) as first-line treatment of metastatic renal cell carcinoma (mRCC): updated results and analysis of prognostic factors. Oral presentation at the Annual Meeting of American Society of Clinical Oncology (ASCO), Chicago, June 1–5, 2007 (Abstract 5024)

  • Motzer RJ, Hutson TE, Tomczak P et al (2007b) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124

    Article  CAS  PubMed  Google Scholar 

  • Motzer RJ, Michaelson MD, Hutson TE et al (2007c) Sunitinib versus interferon-alfa (IFN-á) as first-line treatment of metastatic renal cell carcinoma (mRCC): updated efficacy and safety results and further analysis of prognostic factors. Poster presentation at: the 14th European Cancer Conference, Barcelona, Spain, September 23–27, 2007

  • Motzer RJ, Bukowski RM, Figlin RA et al (2008a) Prognostic nomogram for sunitinib in patients with metastatic renal cell carcinoma. Cancer 113:1552–1558

    Article  CAS  PubMed  Google Scholar 

  • Motzer RJ, Escudier B, Oudard S et al (2008b) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372:449–456

    Article  CAS  PubMed  Google Scholar 

  • Motzer RJ, Hutson TE, Tomczak P et al (2009) Overall survival and updated results for sunitinib versus interferon alfa in first-line treatment of patients with metastatic renal cell carcinoma. J Clin Oncol 27:3584–3590

    Article  CAS  PubMed  Google Scholar 

  • National Comprehensive Cancer Network (2009) NCCN clinical practice guidelines in oncology: kidney cancer v.2.2010. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp

  • Parkin DM, Bray F, Ferlay J et al (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  • Patil S, Ishill NM, Deluca J et al (2008) Trends in memorial Sloan-Kettering cancer center risk group distribution according to treatment year for patients with metastatic renal cell carcinoma (mRCC). J Clin Oncol 26 (May 20 suppl):(Abstract 5092)

  • Pfizer Inc (2009a) SUTENT, Summary of product characteristics, October 2009

  • Pfizer Inc (2009b) Torisel, Summary of product characteristics. September 2009

  • Porta C, Szczylik C (2009) Tolerability of first-line therapy for metastatic renal cell carcinoma. Cancer Treat Rev 35:297–307

    Article  CAS  PubMed  Google Scholar 

  • Porta C, Bellmunt J, Eisen T et al (2010) Treating the individual: the need for a patient-focused approach to the management of renal cell carcinoma. Cancer Treat Rev 36:16–23

    Article  PubMed  Google Scholar 

  • Rabinovitch RA, Zelefsky MJ, Gaynor JJ et al (1994) Patterns of failure following surgical resection of renal cell carcinoma: implications for adjuvant local and systemic therapy. J Clin Oncol 12:206–212

    CAS  PubMed  Google Scholar 

  • Ravaud A (2009) How to optimise treatment compliance in metastatic renal cell carcinoma with targeted agents. Ann Oncol 20(Supplement 1):i7–i12

    Article  PubMed  Google Scholar 

  • Rini BI, Tamaskar I, Shaheen P et al (2007) Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst 99:81–83

    Article  CAS  PubMed  Google Scholar 

  • Rini BI, Halabi S, Rosenberg JE et al (2008) CALGB 90206: a phase III trial of bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in metastatic renal cell carcinoma. Oral presentation at the American Society of Clinical Oncology Genitourinary Cancers Symposium, San Francisco, California, USA, February 14–16, 2008

  • Rini BI, Halabi S, Rosenberg JE et al (2008b) Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 26:5422–5428

    Article  CAS  PubMed  Google Scholar 

  • Rini BI, Halabi S, Rosenberg J et al (2009) Bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in patients with metastatic renal cell carcinoma: Results of overall survival for CALGB 90206. J Clin Oncol 27:Abstr LBA5019 (oral presentation)

  • Roche Products Ltd (2009) Avastin® (bevacizumab). Summary of product characteristics. August 2009

  • Schmidinger M, Zielinski CC, Vogl UM et al (2008) Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 26:5204–5212

    Article  PubMed  Google Scholar 

  • Stadler WM, Figlin RA, McDermott DF et al (2010) Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer 116:1272–1280

    Article  CAS  PubMed  Google Scholar 

  • Sternberg CN, Davis ID, Mardiak J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061–1068

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Editorial support was provided by Caroline Masterman at ACUMED® (Tytherington, UK) and was funded by Pfizer, Inc.

Conflict of interest statement

Dr Schmidinger has received honoraria for lectures from Pfizer, Roche, Wyeth and Novartis. Dr Zielinski has received honoraria for lectures from Roche.

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Correspondence to Manuela Schmidinger.

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Schmidinger, M., Zielinski, C.C. Defining risk status in the first-line treatment of metastatic renal cell carcinoma. J Cancer Res Clin Oncol 136, 961–968 (2010). https://doi.org/10.1007/s00432-010-0901-0

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