open access

Vol 6, No 1 (2010)
Review paper
Published online: 2010-05-06
Get Citation

Has the knowledge of molecular biology of renal cancer already the practical value for an oncologist? The search for predictive factors for new drugs

Piotr Potemski
Onkol. Prak. Klin 2010;6(1):14-20.

open access

Vol 6, No 1 (2010)
REVIEW ARTICLES
Published online: 2010-05-06

Abstract

For many years renal cancer has been regarded as a neoplasm refractory to chemotherapy and immunotherapy with interferon a or interleukin 2 remained the only modestly effective form of systemic treatment available. Advances in molecular biology of renal cancer and understanding the role of function loss of VHL gene in cancerogenesis and tumour progression gave reason for using therapy with bevacizumab, multikinase inhibitors or mTOR kinase inhibitors in disseminated disease. Sunitinib prolongs overall survival when compared with interferon in patients who fulfill criteria of favourable or intermediate risk category, whereas temsirolimus has the same effect in a high risk category. However, so far in renal cancer molecular predictive factors for new drugs have not been recognized. In particular, serum concentration of vascular endothelial growth factor (VEGF) failed to show any predictive value for treatment with bevacizumab or multikinase inhibitors. As only the minority of treated patients truly benefit from targeted therapy, in the process of patient selection for novel therapies a practicing oncologist must take into account all available clinical factors like: performance status, histological type, Motzer’s risk category, age, history of nephrectomy, sites of metastases, and co-morbidities.

Abstract

For many years renal cancer has been regarded as a neoplasm refractory to chemotherapy and immunotherapy with interferon a or interleukin 2 remained the only modestly effective form of systemic treatment available. Advances in molecular biology of renal cancer and understanding the role of function loss of VHL gene in cancerogenesis and tumour progression gave reason for using therapy with bevacizumab, multikinase inhibitors or mTOR kinase inhibitors in disseminated disease. Sunitinib prolongs overall survival when compared with interferon in patients who fulfill criteria of favourable or intermediate risk category, whereas temsirolimus has the same effect in a high risk category. However, so far in renal cancer molecular predictive factors for new drugs have not been recognized. In particular, serum concentration of vascular endothelial growth factor (VEGF) failed to show any predictive value for treatment with bevacizumab or multikinase inhibitors. As only the minority of treated patients truly benefit from targeted therapy, in the process of patient selection for novel therapies a practicing oncologist must take into account all available clinical factors like: performance status, histological type, Motzer’s risk category, age, history of nephrectomy, sites of metastases, and co-morbidities.
Get Citation

Keywords

renal cancer; predictive factors; bevacizumab; multikinase inhibitors; mTOR kinase inhibitors

About this article
Title

Has the knowledge of molecular biology of renal cancer already the practical value for an oncologist? The search for predictive factors for new drugs

Journal

Oncology in Clinical Practice

Issue

Vol 6, No 1 (2010)

Article type

Review paper

Pages

14-20

Published online

2010-05-06

Bibliographic record

Onkol. Prak. Klin 2010;6(1):14-20.

Keywords

renal cancer
predictive factors
bevacizumab
multikinase inhibitors
mTOR kinase inhibitors

Authors

Piotr Potemski

References (23)
  1. 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(3): 688–696.
  2. Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. Lancet. 1999; 353(9146): 14–17.
  3. Coppin C, Porzsolt F, Awa A, et al. Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev. 2005; 1: CD001425.
  4. Flanigan RC, Mickisch G, Sylvester R, et al. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. 2004; 171(3): 1071–1076.
  5. Motzer RJ, Bacik J, Murphy BA, et al. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002; 20(1): 289–296.
  6. Negrier S, Perol D, Ravaud A, et al. French Immunotherapy Intergroup. Medroxyprogesterone, interferon alfa-2a, interleukin 2, or combination of both cytokines in patients with metastatic renal carcinoma of intermediate prognosis: results of a randomized controlled trial. Cancer. 2007; 110(11): 2468–2477.
  7. Sükösd F, Kuroda N, Beothe T, et al. Deletion of chromosome 3p14.2-p25 involving the VHL and FHIT genes in conventional renal cell carcinoma. Cancer Res. 2003; 63(2): 455–457.
  8. Gnarra JR, Tory K, Weng Y, et al. Mutations of the VHL tumour suppressor gene in renal carcinoma. Nat Genet. 1994; 7(1): 85–90.
  9. Escudier B, Pluzanska A, Koralewski P, et al. AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007; 370(9605): 2103–2111.
  10. Rini BI, Halabi S, Rosenberg JE, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol. 2008; 26(33): 5422–5428.
  11. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007; 356(2): 115–124.
  12. Patil S, Figlin RA, Hutson TE, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009; 27(22): 3584–3590.
  13. Escudier B, Eisen T, Stadler WM, et al. TARGET Study Group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007; 356(2): 125–134.
  14. Escudier B, Eisen T, Stadler WM, et al. Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009; 27(20): 3312–3318.
  15. Hudes GR, Carducci MA, Choueiri TK, et al. Global ARCC Trial. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007; 356(22): 2271–2281.
  16. Hudes GR. Targeting mTOR in renal cell carcinoma. Cancer. 2009; 115(10 Suppl): 2313–2320.
  17. Motzer RJ, Escudier B, Oudard S, et al. RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008; 372(9637): 449–456.
  18. Wysocki P, Krzemieniecki K, Drosik K, et al. Obecne możliwości leczenia zaawansowanego raka nerkowokomórkowego. Onkol Prakt Klin. 2009; 5: 181–188.
  19. Escudier BJ, Bellmunt J, Negrier S, et al. Final results of the phase III, randomized, double-blind AVOREN trial of first-line bevacizumab (BEV) + interferon-a2a (IFN) in metastatic renal cell carcinoma (mRCC). J. Clin. Oncol. 2009; 27(supl. 15S): abstr. 5020.
  20. Rini BI, Halabi S, Rosenberg J, et al. 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. 2009; 27(supl. 18S): abstr. LBA5019.
  21. Escudier B, Szczylik C, Hutson TE, et al. Randomized phase II trial of first-line treatment with sorafenib versus interferon Alfa-2a in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009; 27(8): 1280–1289.
  22. Schneider BP, Wang M, Radovich M, et al. ECOG 2100. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008; 26(28): 4672–4678.
  23. Haas N, Manola J, Pins M, et al. ECOG 8802: Phase II trial of doxorubicin (Dox) and gemcitabine (Gem) in metastatic renal cell carcinoma (RCC) with sarcomatoid features. J. Clin. Oncol. 2009; 27(supl. 15S): abstr. 5038.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Wydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl