Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Treatment for renal cancer: are we beyond the cytokine era?

Nature Clinical Practice Urology volume 3, pages 478–484 (2006)Cite this article

Abstract

Cytokines have been the mainstay of treatment for metastatic renal cancer for the past 20 years. Response rates of patients treated with these agents are low, and toxicity is high, but there is evidence from large multicenter randomized trials that indicate that there are survival benefits with interferon-based immunotherapy. A large number of new small molecule inhibitors are emerging that have caused considerable interest in the oncology community. The evidence for benefit from these compounds is based on small studies, using progression-free survival as an end-point. New compounds may provide an improvement in survival for patients with metastatic renal cancer; however, any trial of these agents should be tested against established, standard cytokine therapy.

Key Points

  • Inteferon-α-based immunotherapy is a toxic treatment but carries a consistent survival advantage for patients with metastatic renal cell carcinoma (RCC) reported from four randomized placebo-controlled trials

  • Interleukin-2-based immunotherapy is more toxic than inteferon-α-based immunotherapy, but offers highly selected patients with metastatic RCC the best chance of a durable complete response

  • Small molecule inhibitors are targeted agents shown to have activity in RCC and have caused considerable excitement due to their reported increased tolerability and response rates

  • As yet, little evidence has been published reporting overall survival outcomes in patients treated with small molecule inhibitors

  • Two clinical trials have reported improved outcomes for patients receiving small molecule inhibitors when compared with immunotherapy

  • The role of small molecule inhibitors in combination with cytokine therapy, cytoreductive nephrectomy, and non-clear cell histology has yet to be established

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Coppin C et al. (2005) Immunotherapy for advanced renal cell cancer. The Cochrane Database of Systematic Reviews, Issue 1, Art. No CD001425

  2. Dorr RT (1993) Interferon-α in malignant and viral disease. Drugs 45: 177–211

    Article  CAS  Google Scholar 

  3. Steineck G et al. (1990) Recombinant leukocyte interferon alpha-2a and medroxyprogesterone in advanced renal cell carcinoma. A randomized trial. Acta Oncol 29: 155–162

    Article  CAS  Google Scholar 

  4. Kriegmair M et al. (1995) Interferon alfa and vinblastine versus medroxyprogesterone acetate in the treatment of metastatic renal cell carcinoma. Urology 45: 758–762

    Article  CAS  Google Scholar 

  5. Pyrhonen S 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

    Article  CAS  Google Scholar 

  6. Medical Research Council Renal Cancer Collaborators (1999) Interferon-α and survival in metastatic renal carcinoma: early results of a randomized controlled trial. Lancet 353: 14–17

  7. Mickisch GHJ et al. (2001) Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet 358: 966–970

    Article  CAS  Google Scholar 

  8. Flanigan RC et al. (2001) Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 345: 1655–1659

    Article  CAS  Google Scholar 

  9. Elson PJ et al. (1988) Prognostic factors for survival in patients with recurrent or metastatic renal cell carcinoma. Cancer Res 48: 7310–7313

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Negrier S et al. (2002) Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d'Immunotherapie. Ann Oncol 13: 1460–1468

    Article  CAS  Google Scholar 

  12. Negrier S et al. (2005) Do cytokines improve survival in patients with metastatic renal cell carcinoma (MRCC) of intermediate prognosis? Results of the prospective randomized PERCY Quattro trial [abstract]. J Clin Oncol 23 (suppl): 4511

    Article  Google Scholar 

  13. Bromwich E et al. (2004) The systemic inflammatory response, performance status and survival in patients undergoing alpha-interferon treatment for advanced renal cancer. Br J Cancer 91: 1236–1238

    Article  CAS  Google Scholar 

  14. Blay JY et al. (1994) Pretreatment serum CRP and response to interleukin-2. Br J Cancer 69: 200–201

    Article  CAS  Google Scholar 

  15. Fyfe G 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

    Article  CAS  Google Scholar 

  16. Yang JC 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  CAS  Google Scholar 

  17. McDermott DF 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  CAS  Google Scholar 

  18. Vogelzang NJ et al. (1993) Subcutaneous interleukin-2 plus interferon alfa-2a in metastatic renal cancer: an outpatient multicenter trial. J Clin Oncol 11: 1809–1816

    Article  CAS  Google Scholar 

  19. Negrier S et al. (1998) Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. N Engl J Med 338: 1272–1278

    Article  CAS  Google Scholar 

  20. Negrier S et al. (2006) Is intravenous (iv) IL2 superior to subcutaneous (sc) IL2 in good prognosis patients (pts) with metastatic renal cell carcinoma (MRCC) receiving a combination of IL2 and alpha interferon (IFN)? Results of the prospective randomized PERCY Duo trial [abstract]. J Clin Oncol 24 (suppl): 4536

    Google Scholar 

  21. Upton MP et al. (2005) Histological parameters of renal cell carcinoma response to interleukin-2 based therapy. J Immunother 28: 488–495

    Article  CAS  Google Scholar 

  22. Atkins M et al. (2005) Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer. Clin Cancer Res 11: 3714–3721

    Article  CAS  Google Scholar 

  23. Atzpodien J et al. (2001) IL-2 in combination with IFN-alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial. Br J Cancer 85: 1130–1136

    Article  CAS  Google Scholar 

  24. Gleave M et al. (1998) Interferon gamma-1b compared with placebo in metastatic renal cell carcinoma. N Engl J Med 338: 1265–1271

    Article  CAS  Google Scholar 

  25. Escudier B et al. (2005) Randomized Phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC) [abstract]. J Clin Oncol 23 (suppl): 4510

    Article  Google Scholar 

  26. Rini B et al. (2005) AG-013736, a multi-targeted tyrosine kinase receptor inhibitor, demonstrates anti-tumour activity in a phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC) [abstract]. J Clin Oncol 23 (suppl): 4509

    Article  Google Scholar 

  27. Motzer RJ et al. (2004) SU011248, a novel tyrosine kinase inhibitor, shows antitumour activity in second-line therapy for patients with metastatic renal cell carcinoma: results of a phase 2 trial [abstract]. J Clin Oncol 22 (suppl): 4500

    Article  Google Scholar 

  28. Ratain MJ et al. (2005) Final findings from a Phase II, placebo-controlled, randomised discontinuation trial (RDT) of sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC) [abstract]. J Clin Oncol 23 (suppl): 4544

    Article  Google Scholar 

  29. Eisen T et al. (2006) Randomized phase III trial of sorafenib in advanced renal cell carcinoma (RCC): impact of crossover on survival [abstract]. J Clin Oncol 24 (suppl): 4524

    Google Scholar 

  30. Hudes G et al. (2006) A phase 3, randomized, 3-arm study of temsirolimus (TEMSR) or interferon-alpha (IFN) or the combination of TEMSR + IFN in the treatment of first-line, poor-risk patients with advanced renal cancer (adv RCC) [abstract]. J Clin Oncol 24 (suppl): LBA4

    Google Scholar 

  31. Motzer RJ et al. (2006) Phase III randomized trial of sunitinib malate (SU11248) versus interferon-alfa (IFN-a) as first-line systemic therapy for patients with metastatic renal cell carcinoma (mRCC) [abstract]. J Clin Oncol 24 (suppl): LBA3

    Google Scholar 

  32. Flaherty K (2005) Close-up on new ECOG trial: how it could define paradigm for combination targeted therapy. Kidney Cancer Journal. 3: 14–21

    Google Scholar 

  33. Rini BI et al. (2004) Practice and progress in kidney cancer: methodology for novel drug development. J Urol 171: 2115–2121

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Fellow in Urology,

    Sara Ramsey & Michael Aitchison

  2. Consultant Urologist with the North Glasgow NHS Trust at the Department of Urology, Gartnavel General Hospital, Glasgow, UK

    Sara Ramsey & Michael Aitchison

Authors
  1. Sara Ramsey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Aitchison
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sara Ramsey.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ramsey, S., Aitchison, M. Treatment for renal cancer: are we beyond the cytokine era?. Nat Rev Urol 3, 478–484 (2006). https://doi.org/10.1038/ncpuro0581

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpuro0581

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing