Skip to main content

Advertisement

SpringerLink
Log in

Prognostic factors for biologic therapy in kidney cancer

  • Published:
Current Urology Reports Aims and scope Submit manuscript

Abstract

Renal cell cancer is resistant to most forms of therapy. Cytokine therapy with either interleukin-2 or interferon-α yields the best results, with response rates from 10% to 20%. Therapy is not without toxicity, which means that the majority of patients treated with cytokines suffer toxicity without any therapeutic benefit. Recent endeavors have tried to find new ways to identify responders to cytokine therapy. Prognostic factors, such as good performance status, lack of anemia, normal calcium, normal lactate dehydrogenase, and prior nephrectomy, correlate with an increased likelihood of responding to cytokine therapy. Recent studies have examined whether altered subpopulations of lymphocytes, the presence of eosinophils, or altered levels of cytokines can predict response to cytokine therapy. Although prior nephrectomy does correlate with improved survival while the patient is receiving cytokine therapy, it is unclear if this is due to a significant alteration in the tumor’s response to cytokine or some unrelated benefit from surgery. Further studies are needed to confirm the current immune parameters and disease characteristics that suggest a better response to cytokine therapy.

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

Similar content being viewed by others

References and Recommended Reading

  1. Amato RJ: Chemotherapy for renal cell carcinoma. Semin Oncol 2000, 27:177–186.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Fairlamb DJ: Spontaneous regression of metastases of renal cancer: a report of two cases including the first recorded regression following irradiation of a dominant metastasis and review of the world literature. Cancer 1981, 47:2102–2106.

    Article  PubMed  CAS  Google Scholar 

  4. Marcus SG, Choyke PL, Reiter R, et al.: Regression of metastatic renal cell carcinoma after cytoreductive nephrectomy. J Urol 1993, 150(pt 1):463–466.

    PubMed  CAS  Google Scholar 

  5. Balch CM, Riley LB, Bae YJ, et al.: Patterns of human tumor-infiltrating lymphocytes in 120 human cancers. Arch Surg 1990, 125:200–205.

    PubMed  CAS  Google Scholar 

  6. Holan V, Kohno K, Minowada J: Natural human interferonalpha augments interleukin-2 production by a direct action on the activated IL-2-producing T cells. J Interferon Res 1991, 11:319–325.

    PubMed  CAS  Google Scholar 

  7. Trinchieri G, Matsumoto-Kobayashi M, Clark SC, et al.: Response of resting human peripheral blood natural killer cells to interleukin 2. J Exp Med 1984, 160:1147–1169.

    Article  PubMed  CAS  Google Scholar 

  8. Motzer RJ, Mazumdar M, Bacik J, et al.: Effect of cytokine therapy on survival for patients with advanced renal cell carcinoma. J Clin Oncol 2000, 18:1928–1935. This paper demonstrates that both nephrectomy and cytokine therapy have a survival benefit over that of the natural benefit from improved prognostic factors.

    PubMed  CAS  Google Scholar 

  9. Wirth MP: Immunotherapy for metastatic renal cell carcinoma. Urol Clin North Am 1993, 20:283–295.

    PubMed  CAS  Google Scholar 

  10. Vogelzang NJ, Lipton A, Figlin RA: Subcutaneous interleukin-2 plus interferon alfa-2a in metastatic renal cancer: an outpatient multicenter trial. J Clin Oncol 1993, 11:1809–1816.

    PubMed  CAS  Google Scholar 

  11. Fossa SD: Interferon in metastatic renal cell carcinoma. Semin Oncol 2000, 27:187–193.

    PubMed  CAS  Google Scholar 

  12. Canobbio L, Rubagotti A, Miglietta L, et al.: Prognostic factors for survival in patients with advanced renal cell carcinoma treated with interleukin-2 and interferon-alpha. J Cancer Res Clin Oncol 1995, 121:753–756.

    Article  PubMed  CAS  Google Scholar 

  13. Fossa SD, Kramar A, Droz JP: Prognostic factors and survival in patients with metastatic renal cell carcinoma treated with chemotherapy or interferon-alpha. Eur J Cancer 1994, 9:1310–1314.

    Article  Google Scholar 

  14. Fossa S, Jones M, Johnson P, et al.: Interferon-alpha and survival in renal cell cancer. Br J Urol 1995, 76:286–290.

    Article  PubMed  CAS  Google Scholar 

  15. Lissoni P, Barni S, Ardizzoia A, et al.: Prognostic factors of the clinical response to subcutaneous immunotherapy with interleukin-2 alone in patients with metastatic renal cell carcinoma. Oncology 1994, 51:59–62.

    Article  PubMed  CAS  Google Scholar 

  16. Elson PJ, Witte RS, Trump DL: Prognostic factors for survival in patients with recurrent or metastatic renal cell carcinoma. Cancer Res 1988, 48(pt 1):7310–7313.

    PubMed  CAS  Google Scholar 

  17. Motzer RJ, Bacik J, Murphy BA, Mazumdar M: Interferon-α as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol, in press.

  18. Palmer PA, Vinke J, Philip T, et al.: Prognostic factors for survival in patients with advanced renal cell carcinoma treated with recombinant interleukin-2. Ann Oncol 1992, 3:475–480.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  20. Sato K, Tsuchiya N, Sasaki R, et al.: Increased serum levels of vascular endothelial growth factor in patients with renal cell carcinoma. Jpn J Cancer Res 1999, 90:874–879.

    PubMed  CAS  Google Scholar 

  21. Dosquet C, Coudert MC, Lepage E, et al.: Are angiogenic factors, cytokines, and soluble adhesion molecules prognostic factors in patients with renal cell carcinoma? Clin Cancer Res 1997, 3(pt 1):2451–2458.

    PubMed  CAS  Google Scholar 

  22. Jacobsen J, Rasmuson T, Grankvist K, Ljungberg B: Vascular endothelial growth factor as prognostic factor in renal cell carcinoma. J Urol 2000, 163:343–347.

    Article  PubMed  CAS  Google Scholar 

  23. Fischer C, Georg C, Kraus S, et al.: CD44s, E-cadherin and PCNA as markers for progression in renal cell carcinoma. Anticancer Res 1999, 19:1513–1517.

    PubMed  CAS  Google Scholar 

  24. Kamel D, Turpeenniemi-Hujanen T, Vahakangas K, et al.: Proliferating cell nuclear antigen but not p53 or human papillomavirus DNA correlates with advanced clinical stage in renal cell carcinoma. Histopathology 1994, 25:339–347.

    Article  PubMed  CAS  Google Scholar 

  25. Reuter VE, Presti JCJr: Contemporary approach to the classification of renal epithelial tumors. Semin Oncol 2000, 27:124–137.

    PubMed  CAS  Google Scholar 

  26. Tomera KM, Farrow GM, Lieber MM: Sarcomatoid renal carcinoma. J Urol 1983, 130:657–659.

    PubMed  CAS  Google Scholar 

  27. Ro JY, Ayala AG, Sella A, et al.: Sarcomatoid renal cell carcinoma: clinicopathologic. A study of 42 cases. Cancer 1987, 59:516–526.

    Article  PubMed  CAS  Google Scholar 

  28. Wu J, Caliendo G, Hu XP, Dutcher JP: Impact of histology on the treatment outcome of metastatic or recurrent renal cell carcinoma. Med Oncol 1998, 15:44–49.

    PubMed  CAS  Google Scholar 

  29. Dupere S, Obiri N, Lackey A, et al.: Patterns of cytokines released by peripheral blood leukocytes of normal donors and cancer patients during interleukin-2 activation in vitro. J Biol Response Mod 1990, 9:140–148.

    PubMed  CAS  Google Scholar 

  30. Rini BI, Vogelzang NJ: Prognostic factors in renal carcinoma. Semin Oncol 2000, 27:213–220.

    PubMed  CAS  Google Scholar 

  31. Lauerova L, Dusek L, Spurny V, et al.: Relation of prenephrectomy CD profiles and serum cytokines to the disease outcome and response to IFN-alpha/IL-2 therapy in renal cell carcinoma patients. Oncol Rep 2001, 8:685–692. This paper identifies changes in lymphocyte populations following nephrectomy and prior to cytokine therapy that predict an increased likelihood of responding to cytokines.

    PubMed  CAS  Google Scholar 

  32. Molto L, Carballido J, Manzano L, et al.: Immunological changes in peripheral blood mononuclear cells of patients with metastatic renal cell carcinoma after low doses of subcutaneous immunotherapy with IFN-alpha-2b and IL-2. J Immunother 1999, 22:260–267. This paper identifies changes in peripheral blood monocyte populations before and after cytokine therapy that predict an increased likelihood of responding to cytokines.

    Article  PubMed  CAS  Google Scholar 

  33. Moroni M, Porta C, De Amici M, et al.: Eosinophils and C4 predict clinical failure of combination immunotherapy with very low dose subcutaneous interleukin-2 and interferon in renal cell carcinoma patients. Haematologica 2000, 85:298–303. This paper suggests that the blood level of eosinophils can identify which patients are more likely to respond to cytokine therapy.

    PubMed  CAS  Google Scholar 

  34. Fiorentino DF, Bond MW, Mosmann TR: Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 1989, 170:2081–2095.

    Article  PubMed  CAS  Google Scholar 

  35. Buelens C, Verhasselt V, De Groote D, et al.: Interleukin-10 prevents the generation of dendritic cells from human peripheral blood mononuclear cells cultured with interleukin-4 and granulocyte/macrophage-colony-stimulating factor. Eur J Immunol 1997, 27:756–762.

    Article  PubMed  CAS  Google Scholar 

  36. Wittke F, Hoffmann R, Buer J, et al.: Interleukin 10 (IL-10): an immunosuppressive factor and independent predictor in patients with metastatic renal cell carcinoma. Br J Cancer 1999, 79:1182–1184. This paper identifies IL-10 as another prognostic factor in predicting response to cytokine therapy.

    Article  PubMed  CAS  Google Scholar 

  37. Flanigan RC: Role of surgery in patients with metastatic renal cell carcinoma. Semin Urol Oncol 1996, 14:227–229.

    PubMed  CAS  Google Scholar 

  38. Motzer RJ, Russo P: Systemic therapy for renal cell carcinoma. J Urol 2000, 163:408–417.

    Article  PubMed  CAS  Google Scholar 

  39. Rackley R, Novick A, Klein E, et al.: The impact of adjuvant nephrectomy on multimodality treatment of metastatic renal cell carcinoma. J Urol 1994, 152(pt 1):1399–1403.

    PubMed  CAS  Google Scholar 

  40. Atkins MB, Sparano J, Fisher RI, et al.: Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. J Clin Oncol 1993, 11:661–670.

    PubMed  CAS  Google Scholar 

  41. Fisher RI, Coltman CA Jr, Doroshow JH, et al.: Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. A phase II clinical trial. Ann Intern Med 1988, 108:518–523.

    PubMed  CAS  Google Scholar 

  42. Bennett RT, Lerner SE, Taub HC, et al.: Cytoreductive surgery for stage IV renal cell carcinoma. J Urol 1995, 154:32–34.

    Article  PubMed  CAS  Google Scholar 

  43. Walther MM, Yang JC, Pass HI, et al.: Cytoreductive surgery before high dose interleukin-2 based therapy in patients with metastatic renal cell carcinoma. J Urol 1997, 158:1675–1678.

    Article  PubMed  CAS  Google Scholar 

  44. Motzer RJ, Russo P, Nanus DM, Berg WJ: Renal cell carcinoma. Curr Probl Cancer 1997, 21:185–232.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  46. Fallick ML, McDermott DF, LaRock D, et al.: Nephrectomy before interleukin-2 therapy for patients with metastatic renal cell carcinoma. J Urol 1997,158:1691–1695.

    Article  PubMed  CAS  Google Scholar 

  47. Figlin R, Gitlitz B, Franklin J, et al.: Interleukin-2-based immunotherapy for the treatment of metastatic renal cell carcinoma: an analysis of 203 consecutively treated patients. Cancer J Sci Am 1997, 3(suppl:1):S92-S97.

    PubMed  Google Scholar 

  48. Flanigan RC, Yonover PM: The role of radical nephrectomy in metastatic renal cell carcinoma. Semin Urol Oncol 2001, 19:98–102. Presentation of the first randomized trial exploring the role of cytoreductive nephrectomy prior to IFN-α in metastatic disease.

    PubMed  CAS  Google Scholar 

  49. Tannock IF: Cytoreduction nephrectomy in metastatic renal cancer: the results of Southwest Oncology Group Trial 8949 [commentary]. J Clin Oncol. 2000, 18(suppl):39S-42S. An excellent analysis of the data presented on the randomized Southwest Oncology Group Trial 8949, which examined the role of radical nephrectomy prior to radiation in the metastatic setting.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 510, 10021, New York, NY, USA

    Beverly J. Drucker MD, PhD

Authors
  1. Beverly J. Drucker MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Drucker, B.J. Prognostic factors for biologic therapy in kidney cancer. Curr Urol Rep 3, 31–36 (2002). https://doi.org/10.1007/s11934-002-0008-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11934-002-0008-5

Keywords

Search

Navigation