Skip to main content

Advertisement

SpringerLink
Log in

Predictive factors for response to treatment in patients with advanced renal cell carcinoma

  • REVIEW
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Introduction The analysis of predictive factors of response may aid in predicting which patients with advanced renal cell carcinoma (RCC) would be good candidates for systemic treatments. Materials and methods The expression of several biomarkers was retrospectively analyzed using immunohistochemistry (IHC), as well as 2 analytical variables in 135 patients with advanced RCC treated with cytokines (CK) and/or new targeted drugs (NTD). Results 67 patients were treated solely with NTD and 68 with CK (23 also received NTD). Univariate analysis: HIF1α did not correlate significantly with response to these drugs. Overexpression of CAIX was associated with more responses (%) to NTD (64.7 vs. 21.1; p = 0.004) and CK (22.6 vs. 0; p = 0.038). PTEN demonstrated predictive value of response to sunitinib (70.8 vs. 34.1; p = 0.005). p21 was associated with a lower response to sunitinib (35.9 vs. 65.4; p = 0.025). Thrombocytosis was not significantly associated with response to NTD, although it was with CK (0 vs. 20; p = 0.017). Neutrophilia correlated with a lower response to NTD (29.6 vs. 57.5; p = 0.045), although not with CK. Multivariate analysis: Overexpression of CAIX was an independent predictor of significantly higher response to NTD and CK; OR = 8.773 (p < 0.001). Conclusions Our findings highlight the usefulness of CAIX in selecting patients with advanced RCC as candidates for systemic treatment. PTEN and p21 may be important in predicting response to sunitinib. Thrombocytosis and neutrophilia correlate well with response to CK and NTD, respectively.

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Godley PA, Ataga KI (2000) Renal cell carcinoma. Curr Opin Oncol 12:260–264

    Article  PubMed  CAS  Google Scholar 

  2. Jemal A, Murria T, Ward E, Samuels A, Tiwari RC (2005) Cancer statistics. Cancer J Clin 55:10–30

    Article  Google Scholar 

  3. McLaughlin JK, Lipworth L (2000) Epidemiologic aspects of renal cell cancer. Semin Oncol 27:115–123

    PubMed  CAS  Google Scholar 

  4. Greenlee RT, Murray T, Bolden S et al (2000) Cancer statistics Cancer J Clin 50.

  5. Vinels P, Alavanja M, Buffer P et al (2004) Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 96:99–106

    Article  Google Scholar 

  6. Maclurem WW (1990) A case control study of diet and risk of renal adenocarcinoma. Epidemiology 1:430

    Article  Google Scholar 

  7. Hunt JD, van der Hel OL, McMillan GP et al (2005) Renal cell carcinoma en relation to cigarette smoking: meta-analysis of 24 studies. Int J Cancer 114:101–108

    Article  PubMed  CAS  Google Scholar 

  8. Bergstrom A, Hsich CC, Lindbland P et al (2001) Obesity and renal cell cancer: a quantitative review. Br J Cancer 85:984–990

    Article  PubMed  CAS  Google Scholar 

  9. Bergstrom A, Pisani P, Tenet V et al (2001) Overweight as an avoidable cause of cancer in Europe. Int J Cancer 91:421–430

    Article  PubMed  CAS  Google Scholar 

  10. Calle EE, Kaasks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4:579–591

    Article  PubMed  CAS  Google Scholar 

  11. Wolchok JD, Motzer RJ (2000) Management of renal cell carcinoma. Oncology 14:29–34

    PubMed  CAS  Google Scholar 

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

    Article  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. 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 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  17. 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 metastatic renal cell carcinoma (mRCC). J Clin Oncol 27:15s (suppl; abstr 5020)

    Google Scholar 

  18. Motzer RJ, Escudier B, Oudard S, RECORD-1. Study Group et al (2008) Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372(9637):449–456

    Article  PubMed  CAS  Google Scholar 

  19. 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(6):1061–1068

    Article  PubMed  CAS  Google Scholar 

  20. Bui MH, Seligson D, Han KR et al (2003) Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: Implications for prognosis and therapy. Clin Cancer Res 9:802–811

    PubMed  CAS  Google Scholar 

  21. Hager M, Haufe H, Kemmerling R et al (2007) PTEN expression in renal cell carcinoma and oncocytoma and prognosis. Pathology 39:482–485

    Article  PubMed  CAS  Google Scholar 

  22. Bozhurt SU, Avan E, Bolukbasi F et al (2009) Immunohistochemical expression of SPARC is correlated with recurrence, survival and malignant potential in meningiomas. APMIS 117(9):651–659

    Article  Google Scholar 

  23. Zoblec I, Steele R, Terracciano L et al (2007) Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol 60(10):1112–1116

    Article  Google Scholar 

  24. Youden WJ (1950) Index for rating diagnostic tests. Cancer 3(1):32–35

    Article  PubMed  CAS  Google Scholar 

  25. Miller AB, Hooqstraten B, Staquet M et al (1958) Reporting results of cancer treatment. Cancer 47:207–214

    Article  Google Scholar 

  26. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observation. J Am Stat Assoc 53:457–481

    Article  Google Scholar 

  27. Motzer RJ, Mazumdar M, Bacik J et al (1999) Survival and prognostic factors stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17(8):2530–2540

    PubMed  CAS  Google Scholar 

  28. Motzer RJ, Bacik J, Murphy BA et al (2002) Interferon-α as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:286–296

    Google Scholar 

  29. Mekhail TM, Abou-Jawde RM, BouMerhi G et al (2005) Validation and extension of the Memorial Sloan-Kettering Prognostic Factors Model for Survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 23:832–841

    Article  PubMed  Google Scholar 

  30. Unruh A, Ressel A, Mohamed HG et al (2003) The hypoxia-inducible factor-1 is a negative factor for tumor therapy. Oncogene 22:3213–3220

    Article  PubMed  CAS  Google Scholar 

  31. Brugarolas J (2007) Renal-cell carcinoma-molecular pathways and therapies. N Engl J Med 356:185–187

    Article  PubMed  CAS  Google Scholar 

  32. Patel PH, Chadalavada RS, Ishill NM et al (2008) Hypoxia-inducible factor (HIF) 1α and 2α levels in cell lines and human tumor predicts response to sunitinib in renal cell carcinoma (RCC). J Clin Oncol 26 (abstr. 5008)

    Google Scholar 

  33. Bui MH, Seligson D, Han KR et al (2003) Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: Implications for prognosis and therapy. Clin Cancer Res 9:802–811

    PubMed  CAS  Google Scholar 

  34. Patard J-J, Fergelot P, Karakiewicz PI et al (2008) Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma. Int J Carncer 123:395–400

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  36. Klatte T, Zomorodian N, Kabbinavar FF et al (2007) Prospective evaluation of carbonic anhydrase IX (CAIX) as a molecular marker in metastatic renal cell carcinoma. J Clin Oncol 25 (abstr. 5112)

    Google Scholar 

  37. Signoretti S, Regan M, Atkins M (2008) Carbonic anhydrase IX as a predictive biomarker of response to kidney cancer therapy. BJU Int 101(Suppl 4):31–35

    Article  PubMed  CAS  Google Scholar 

  38. Choueiri TK, Regan MM, Brick AJ et al (2008) Carbonic anhydrase IX (CAIX) and pathologic features as predictors of outcome in patients with metastatic renal cell carcinoma receiving VEGF-targeted therapy. ASCO Annual Meeting J Clin Oncol 26(Suppl 20):16042

    Google Scholar 

  39. Choueiri TK, Vaziri SA, Rini I et al (2007) Use of Von-Hippel Lindau (VHL) mutation status to predict objective response to vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma (RCC). ASCO Annual Meeting Proceedings Part I. J Clin Oncol 25:5012

    Google Scholar 

  40. Fan Y, Borowsky AD, Weiss RH (2003) An antisense oligodeoxynucleotide to p21 (Waf1/Cip1) causes apoptosis in human breast cancer cells. Mol Cancer Ther 2:773

    Google Scholar 

  41. Weiss RH (2003) p21 Waf1/Cip1 as a therapeutic target in breast and other cancers. Cancer Cell 4:425

    Google Scholar 

  42. Hollen CW, Henthorn J, Koziol JA et al (1992) Serum interleukin-6 levels in patients with thrombocytosis. Leuk Lymphoma 8:235–241

    Google Scholar 

  43. Donskov F, Von der Maase H (2006) Impact of immune parameters on long-term survival in metastatic renal cell carcinoma. J Clin Oncol 24:1997–2005

    Google Scholar 

Download references

Acknowledgements

The authors wish to thank Pablo Martinez-Camblor for his help with the statistics and Aurora Astudillo for the laboratory analyses. We are grateful to Pfizer SA (Madrid, Spain) for providing logistics support.

Funding

The study was not funded.

Conflict of interest

None

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Hospital Universitario Central de Asturias, C/ Celestino Villamil s/n, 33006, Oviedo, Asturias, Spain

    Carolina Muriel López, Emilio Esteban, Pablo Pardo, Jose Pablo Berros, Marta Izquierdo, Guillermo Crespo, Paula J. Fonseca & Miguel Sanmamed

  2. Department of Pathology, Hospital Universitario Central de Asturias, C/ Celestino Villamil s/n, 33006, Oviedo, Asturias, Spain

    Aurora Astudillo

  3. Department of Statistics, Hospital Universitario Central de Asturias, C/ Celestino Villamil s/n, 33006, Oviedo, Asturias, Spain

    Pablo Martínez-Camblor

Authors
  1. Carolina Muriel López
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emilio Esteban
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aurora Astudillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pablo Pardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jose Pablo Berros
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marta Izquierdo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guillermo Crespo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Paula J. Fonseca
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Miguel Sanmamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pablo Martínez-Camblor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carolina Muriel López.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Muriel López, C., Esteban, E., Astudillo, A. et al. Predictive factors for response to treatment in patients with advanced renal cell carcinoma. Invest New Drugs 30, 2443–2449 (2012). https://doi.org/10.1007/s10637-012-9836-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-012-9836-4

Keywords

Search

Navigation