Skip to main content

Advertisement

SpringerLink
Log in

Treatment of metastatic renal cell carcinoma

  • Mini Review
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To review the treatment of metastatic renal cell carcinoma (RCC), including the use of new targeted therapies.

Methods

A search of MEDLINE (1966 to August 2008) and American Society of Clinical Oncology Meeting abstracts (2005 to May 2008) was preformed using the search terms bevacizumab, everolimus, interferon-alfa (IFN-α), interleukin-2 (IL-2), sorafenib, sunitinib, temsirolimus, and RCC. Articles most pertinent to the treatment of metastatic RCC are reviewed.

Results

The treatment of metastatic RCC has undergone a paradigm shift over the past 5 years from biologic response modifiers to new targeted therapies. Historically, response rates for the biological response modifiers, aldesleukin (IL-2), and IFN-α were approximately 15%. Recently, three targeted agents, sorafenib, sunitinib, and temsirolimus have been approved for the treatment of RCC. Additionally, bevacizumab has been investigated and shown to increase progression free survival in RCC. IL-2 remains the only agent to induce complete, durable remissions; however, many patients are not eligible for this therapy. Newer agents (sorafenib, sunitinib, and temsirolimus) have shown to be superior to IFN-α or placebo and bevacizumab combined with IFN-α has shown activity when compared to IFN-α alone. Unlike IL-2, the greatest benefit obtained with targeted therapies is in achieving stable disease (SD). Despite their benefit, targeted therapies have never been compared with each other in clinical trials and choosing the most appropriate agent remains challenging. To date, the optimal sequence or combination of treatments has not been defined; however, everolimus has recently demonstrated activity in patients progressing on targeted therapy.

Conclusions

IL-2 remains the most active regimen in inducing complete responses; however, its use is accompanied by substantial morbidity and is limited to those with a good performance status. Targeted therapies are also efficacious in the treatment of RCC, with the major benefit being induction of SD. Future research will better define the sequencing of therapies, as well as, explore the activity of novel combination regimens.

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

Fig. 1

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E et al (2008) Cancer Statistics, 2008. CA Cancer J Clin 58:71–96

    Article  PubMed  Google Scholar 

  2. National Cancer Care Network (2008) Kidney cancer V.1.2008. www.nccn.org/professionals/physician_gls/PDF/kidney.pdf. Accessed 1 March 2008

  3. Kim HL, Seligson D, Liu X et al (2005) Using tumor markers to predict the survival of patients with metastatic renal cell carcinoma. J Urol 173:1496–1501

    Article  PubMed  CAS  Google Scholar 

  4. Mancuso A, Sternberg CN (2005) New treatments for metastatic kidney cancer. Can J Urol 12(Suppl 1):66–70

    PubMed  Google Scholar 

  5. Cohen HT, McGovern FJ (2005) Renal-cell carcinoma. N Engl J Med 353:2477–2490

    Article  PubMed  CAS  Google Scholar 

  6. National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch (2008) Surveillance, Epidemiology and End Results (SEER) Program Stat Database. www.seer.cancer.gov. Accessed 3 Mar 2008

  7. Motzer RJ, Mazumdar M, Bacik J et al (1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17:2530–2540

    PubMed  CAS  Google Scholar 

  8. Motzer RJ, Bacik J, Mazumdar M (2004) Prognostic factors for survival of patients with stage IV renal cell carcinoma: Memorial Sloan-Kettering Cancer Center experience. Clin Cancer Res 10:6302S–6303S

    Article  PubMed  CAS  Google Scholar 

  9. Yagoda A, Abi-Rached B, Petrylak D (1995) Chemotherapy for advanced renal-cell carcinoma: 1983–1993. Semin Oncol 22:42–60

    PubMed  CAS  Google Scholar 

  10. Fyfe G, Fisher RI, Rosenberg SA et al (1995) Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 13:688–696

    PubMed  CAS  Google Scholar 

  11. Fisher RI, Rosenberg SA, Fyfe G (2000) Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am 6(Suppl 1):S55–S57

    PubMed  Google Scholar 

  12. Product information (2007) Proleukin (aldesleukin). Novartis Pharmaceuticals Corporation, East Hanover

    Google Scholar 

  13. Yang JC, Sherry RM, Steinberg SM et al (2003) Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 21:3127–3132

    Article  PubMed  CAS  Google Scholar 

  14. Mcdermott DF, Regan MM, Clark JI et al (2005) 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 23:133–141

    Article  PubMed  CAS  Google Scholar 

  15. Fossa SD (2000) Interferon in metastatic renal cell carcinoma. Semin Oncol 27:187–193

    PubMed  CAS  Google Scholar 

  16. Minasian LM, Motzer RJ, Gluck L et al (1993) Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol 11:1368–1375

    PubMed  CAS  Google Scholar 

  17. Quesada JR (1989) Role of interferons in the therapy of metastatic renal cell carcinoma. Urology 34(Suppl 4):80–83

    Article  PubMed  CAS  Google Scholar 

  18. Pyrhonen S, Salminen E, Ruutu M et al (1999) Prospective randomized trial of interferon alfa-2a plus vinblastine versus vinblastine alone in patients with advanced renal cell cancer. J Clin Oncol 17:2859–2867

    PubMed  CAS  Google Scholar 

  19. Ritchie A, Griffiths G, Parmar M et al (1999) Interferon-α and survival in metastatic renal cell carcinoma: early results of a randomized controlled trial. Lancet 353:14–17

    Article  CAS  Google Scholar 

  20. Coppin C, Porzsolt F, Autenrieth M, Kumpf J, Coldman A, Wilt T (2004) Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev (3):CD001425. doi: 10.1002/14651858.CD001425.pub2

  21. Product information (2008) Intron-A (interferon-α2b). Shering Corporation, Kenilworth

    Google Scholar 

  22. Mancuso A, Sternberg CN (2006) New treatment approaches in metastatic renal cell carcinoma. Curr Opin Urol 16:337–341

    Article  PubMed  Google Scholar 

  23. Product information (2008) Nexavar (sorafenib). Bayer Pharmaceuticals Corporation, West Haven

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  25. Gollob JA, Rathmell WK, Richmond TM et al (2007) Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer. J Clin Oncol 25:3288–3295

    Article  PubMed  CAS  Google Scholar 

  26. Ryan CW, Goldman BH, Lara PN Jr et al (2007) Sorafenib with interferon alfa-2b as first-line treatment of advanced renal carcinoma: a phase II study of the Southwest Oncology Group. J Clin Oncol 25:3296–3301

    Article  PubMed  CAS  Google Scholar 

  27. Szczylik C, Demkow T, Staehler M et al (2007) Randomized phase II trial of first-line treatment with sorafenib versus interferon in patients with advanced renal cell carcinoma: final results. J Clin Oncol 25(Suppl 18) (abstract 5025)

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

    Article  PubMed  CAS  Google Scholar 

  29. Figlin R, Hutson TE, Tomczak P et al (2008) Overall survival with sunitinib versus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC). J Clin Oncol 26(Suppl 18) (abstract 5024)

  30. Motzer RJ, Michaelson MD, Redman BG et al (2006) Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 24:16–24

    Article  PubMed  CAS  Google Scholar 

  31. Motzer RJ, Michaelson MD, Rosenberg J et al (2007) Sunitinib efficacy against advanced renal cell carcinoma. J Urol 178:1883–1887

    Article  PubMed  CAS  Google Scholar 

  32. 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  PubMed  CAS  Google Scholar 

  33. Escudier B, Pluzanska A, Koralewski P et al (2007) 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 

  34. Rini BI, Halabi S, Rosenberg J et al (2008) A phase III trial of bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in metastatic renal cell carcinoma. In: Genitourinary cancer symposium, American Society of Clinical Oncology, San Francisco (abstract 350). http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=54&abstractID=20357. Accessed 17 Apr 2008

  35. Yang JC, Haworth L, Sherry RM et al (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427–434

    Article  PubMed  CAS  Google Scholar 

  36. Product information (2008) Sutent (sunitinib). Pfizer, Inc, New York

    Google Scholar 

  37. Pouessel D, Culine S (2008) High frequency of intracerebral hemorrhage in metastatic renal carcinoma patients with brain metastases treated with tyrosine kinase inhibitors targeting vascular endothelial growth factor receptor. Eur Urol 53:376–381

    Article  PubMed  CAS  Google Scholar 

  38. Porta C, Paglino C, Imarisio I (2008) Re: Pouessel D, Culine S. High frequency of intracerebral hemorrhage in metastatic renal carcinoma patients with brain metastases treated with tyrosine kinase inhibitors targeting vascular endothelial growth factor receptor. Eur Urol 53:1092–1093 (comment)

    Google Scholar 

  39. Wu S, Chen JJ, Kudelka A et al (2008) Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncol 9:117–123

    Article  PubMed  CAS  Google Scholar 

  40. Chu TF, Rupnick MA, Kerkela R et al (2007) Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 370:2011–2019

    Article  PubMed  CAS  Google Scholar 

  41. Yang CH, Lin WC, Chuang CK et al (2008) Hand-foot skin reaction in patients treated with sorafenib: a clinicopathological study of cutaneous manifestations due to multitargeted kinase inhibitor therapy. Br J Dermatol 158:592–596

    Article  PubMed  CAS  Google Scholar 

  42. Rosenbaum SE, Wu S, Newman MA et al (2008) Dermatological reactions to the multitargeted tyrosine kinase inhibitor sunitinib. Support Care Cancer 16:557–566

    Article  PubMed  CAS  Google Scholar 

  43. Product information (2007) Torisel (temsirolimus). Wyeth Pharmaceuticals Inc, Philadelphia

    Google Scholar 

  44. Product information (2008) Avastin (bevacizumab). Genentech, Inc, San Francisco

    Google Scholar 

  45. Genentech (2008) Important drug warning subject: microangiopathic hemolytic anemia (MAHA) in patients treated with Avastin® (bevacizumab) and sunitinib malate. http://www.fda.gov/medwatch/safety/2008/MAHA_DHCP.pdf. Accessed 1 Sept 2008

  46. Tamaskar I, Garcia JA, Elson P et al (2008) Antitumor effects of sunitinib or sorafenib in patients with metastatic renal cell carcinoma who received prior antiangiogenic therapy. J Urol 179:81–86

    Article  PubMed  CAS  Google Scholar 

  47. Drabkin HA, Figlin R, Stadler WM et al (2007) The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: Safety and efficacy in patients with prior bevacizumab treatment. J Clin Oncol 25(Suppl 18) (abstract 5041)

  48. George DJ, Michaelson MD, Rosenberg J et al (2007) Phase II trial of sunitinib in bevacizumab-refractory metastatic renal cell carcinoma (mRCC): updated results and analysis of circulating biomarkers. J Clin Oncol 25(Suppl 18) (abstract 5035)

  49. Feldman DR, Ginsberg MS, Baum C et al (2008) Phase I trial of bevacizumab plus sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol 26(Suppl 18) (abstract 5100)

  50. Sosman JA, Flaherty KT, Atkins MB et al (2008) Updated results of phase I trial of sorafenib (S) and bevacizumab (B) in patients with metastatic renal cell cancer (mRCC). J Clin Oncol 26(Suppl 18) (abstract 5011)

  51. Merchan JR, Liu G, Fitch T et al (2007) Phase I/II trial of CCI-779 and bevacizumab in stage IV renal cell carcinoma: phase I safety and activity results. J Clin Oncol 25(Suppl 18) (abstract 5034)

  52. Ratain MJ, Eisen T, Stadler WM et al (2006) Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 24:2505–2512

    Article  PubMed  CAS  Google Scholar 

  53. Choueiri TK, Plantade A, Elson P et al (2008) Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. J Clin Oncol 26:127–131

    Article  PubMed  CAS  Google Scholar 

  54. Stadler WM, Figlin R, Ernstoff MS et al (2007) The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: safety and efficacy in patients with non-clear cell renal cell carcinoma. J Clin Oncol 25(Suppl 18) (abstract 5036)

  55. Dutcher JP, Wilding G, Hudes GR et al (2008) Sequential axitinib (AG-013736) therapy of patients (pts) with metastatic clear cell renal cell cancer (RCC) refractory to sunitinib and sorafenib, cytokines and sorafenib, or sorafenib alone. J Clin Oncol 26(Suppl 18) (abstract 5127)

  56. Rini BI, Wilding G, Hudes G et al (2007) Axitinib (AG-013736; AG) in patients (pts) with metastatic renal cell cancer (RCC) refractory to sorafenib. J Clin Oncol 25(Suppl 18) (abstract 5032)

  57. Hutson TE, Davis ID, Machiels JP et al (2007) Pazopanib (GW786034) is active in metastatic renal cell carcinoma (RCC): interim results of a phase II randomized discontinuation trial (RDT). J Clin Oncol 25 (Suppl 18) (abstract 5031)

  58. Ravaud A, Gardner R, Hawkins R et al (2006) Efficacy of lapatinib in patients with high tumor EGFR expression: results of a phase III trial in advanced renal cell carcinoma. J Clin Oncol 24(Suppl 18) (abstract 4502)

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

    Article  PubMed  CAS  Google Scholar 

  60. LaGow B (ed) (2008) Red book. Thompson Healthcare, Montvale

    Google Scholar 

  61. Klatte M, Zomorodian N, Kabbinavar FF, Belldegrun AS, Pantuck AJ (2007) Prospective evaluation of carbonic anhydrase IX (CAIX) as a molecular marker in metastatic renal cell carcinoma. J Clin Oncol 25 (Suppl 18) (abstract 5112)

Download references

Conflict of interest statement

None.

Author information

Authors and Affiliations

  1. Department of Pharmacy Services, Karmanos Cancer Center, 4100 John R, Detroit, MI, 48201, USA

    David J. Reeves & Chin Y. Liu

Authors
  1. David J. Reeves
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chin Y. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David J. Reeves.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reeves, D.J., Liu, C.Y. Treatment of metastatic renal cell carcinoma. Cancer Chemother Pharmacol 64, 11–25 (2009). https://doi.org/10.1007/s00280-009-0983-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-009-0983-z

Keywords

Search

Navigation