PTU - Polskie Towarzystwo Urologiczne
list of articles:

New strategies in treatment of patients with metastatic renal cell carcinoma
Article published in Urologia Polska 2007/60/4.


Jakub Żołnierek, Piotr Wysocki, Paweł Nurzyński
Klinika Onkologii Centralnego Szpitala Klinicznego MON, Wojskowy Instytut Medyczny w Warszawie
Zakład Immunologii Nowotworów, Katedra Biotechnologii Medycznej, Uniwersytet Medyczny, Wielkopolskie Centrum Onkologii w Poznaniu


kidney, renal cell cancer, targeted therapy, thyrosine kinase inhibitor, VEGF


As renal cell carcinoma appears to be resistant to conventional treatment modalities there is a strong need for development of new drugs to be used in therapy of patients with this malingancy. Immunotherapy, typically based on subcutaneous injections of interferon alfa in Poland offers results far from satisfactory. Introduction of advanced techniques of molecular biology into the practice helped to establish the potent role of membrane receptors for growth factors, especially its component with activity of thyrosine kinases in growth, proliferation, invasion and forming of metastatic lesions. These molecules became therapeutic targets. Nowadays it seems thyrosine kinases inhibitors are drugs of choice. Cytokines remain alternative for new agents and targeted therapy is a basement of second line treatments for patients who failed to benefit from immunotherapy. The most investigated and advanced in clinical trials process are Nexavar (sorafenib, BAY 439006), Sutent (sunitinib, SU 011248), Torisel (temsirolimus, CCI 779) oraz Avastin (bevacizumab).
The first and the second have already been formally approved for treatment of patients with renal cell carcinoma. Torisel has only approval of American FDA and can not be used in European Union yet.
The article is a short review of literature with special attention paid to clinical data. As clear cell renal carcinoma is the most frequent histology of kidney cancer and most clinical trials protocols allowed recruitment of patients with such diagnosis, data provided below refers to clear cell type. To date no recommendation for treatment of patients with non-clear cell type exists.


  1. Stebbing J, Gore M: The current stasus of interferon-alfa treatment in advanced
  2. renal cancer. BJU International 2001, 132, 87, 599-601.
  3. Steineck G, Strander H, Barbin BE: Recombinant Leucocyte IFN alpha 2a and medroxyprogesteron in advanced renal cell carcinoma. Acta Oncol 1990, 29, 155-162.
  4. Kriegmair M, Oberneder R, Hofstetter A et al: Interferon alpha and vinblastine
  5. versus medroxyprogesterone acetate in the treatment of metastatic renal cell carcinoma. Urology 1995, 45, 758-762.
  6. Beghini A, Larizza L, Cairoli R et al: C-Kit activating mutations and mast cell proliferation in human leukemia. Blood 1998, 92, 701-703.
  7. Cherrington JM, Strawn LM, Shawver LK: New paradigms for treatment of cancer: the role of anti-angiiogenesis agents. Adv Cancer Res 2000, 79, 1-38.
  8. Ferrara N: Molecular and biological properties of vascular endothelial growth factor. J Molec Med 1999, 77, 527-543.
  9. Fukumura D, Xavier R, Sugiura T et al: Tumor induction of VEGF promoter activity in stromal cells. Cell 1998, 94, 715-725.
  10. Gale NW, Yancopoulos GD: Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev 1999, 13, 1055-1066.
  11. Gilliand DG, Gfiffin JD: Role of FLT3 in leukemia. Curr Opin Hematol 2002, 9, 274-281.
  12. Hanahan D, Weinberg RA: The hallmarks of cancer. Cell 2000, 100, 57-70.
  13. Heinrich MC, Blanke CD, Druker BJ et al: Inhibition of KIT tyrosine kinase activity: A novel molecular approach to the treatment of KIT-possitive malignacies.
  14. J Clin Oncol 2002, 20, 1692-1703.
  15. Heinrich MC, Corless CL, Duensing A et al: PDGFR activating mutations in gastrointesitnal stromal tumors. Science 2003, 299, 708-710.
  16. Laird AD, Christensen JG, Li G et al: SU6668 inhibits FLK-1/KDR and PDGFRbeta in vivo, resulting in rapid apoptosis of tumor vasculature ant tumor regression in mice. FASEB J 2002, 16, 681-690.
  17. Plate KH, Breier G, Farrel CL et al: Platelet-derived growth factor receptor beta in induced during tumor development and upregulated during tumor progression
  18. in endothelial cells in human gliomas. Lab Invest 1992, 67, 529-534.
  19. Reilly JT. Class III receptor tyrosine kinases: Role in leukaemogenesis. Br J Haematol 2002, 116, 744-757.
  20. Schlessinger J, Ullrich A: Growth factor signaling by receptor tyrosine kinases. Neuron 1992, 9, 383-391.
  21. Shimizu A, O’Brien KP, Sjoblom T et al: The dermatofibrosarcoma protuberans-
  22. associated collagen type I alpha 1/plated-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer Res 1999, 59, 3719-3723.
  23. Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med 1971, 285, 1182-1186.
  24. Ferrara N, Davis-Smyth T: The biology of vascular endothelial growth factor. Endoc Rev 1997, 18, 4-25.
  25. Eisen T: Renewed hope for patients with advanced renal cell cancer: Cindirella comes of age. EJC 2005, 41, 1106-1108.
  26. Raymond E, Faivre S, Vera K: Final results of phase I and pharmacokinetic study of SU11248, a novel multi- target tyrosine kinase inhibitor, in patients with advanced cancers. Proc Am Soc Clin Oncol 2003, 22, 192 (Abstract 769).
  27. Rosen L, Mulay M, Long J: Phase I trial of SU 11248, a novel tyrosine kinase inhibitor in advanced solid tumors. Proc Am Soc Clin Oncol 2003, 22, 191 (Abstract 765).
  28. Motzer RJ et al: Sunitinib in Patients with Metastatic Renal Cell Cancer. JAMA, June 7, 2006 Vol 295, No. 21.
  29. Motzer RJ, Hutson TE, Tomczak P et al: Sunitinib versus Interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007, 356, 115-124.
  30. Escudier B, Szczylik C, Eisen T et al: Randomized Phase III trial of the multi-
  31. kinase inhibitor sorafenib (BAY 43-9906) in patients with advanced renal cell carcinoma (RCC). European Journal of Cancer Supplements Vol. 3, No. 2, 2005, p. 226.
  32. Escudier B, Eisen T, Stadler WM et al: TARGET group. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007, 356, 125-134.
  33. Szczylik C, Demkow T, Staehler M et al: Randomized phase II trial of first-line treatment with sorafenib versus interferon in patients with advanced renal cell carcinoma: Final results. ASCO 2007, abstract 5025.
  34. Hudes G, Carducci M, Tomczak P et al: Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007, 356, 2271-2281.
  35. Yang JC, Haworth L, Sherry RM et al: A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003, 349, 427-434.
  36. Escudier B, Koralewski P, Pluzanska A: A randomized, controlled, double-blind phase III study (AVOREN) of bevacizumab/interferon-α2a vs placebo/interferon-
  37. α2a as first-line therapy in metastatic renal cell carcinoma. ASCO 2007, abstract 3. str str str str str
  38. Halbert RJ, Figlin RA, Atkins MB,et al: Treatment of patients with metastatic renal cell cancer. A RAND appropriateness panel. Cancer 2006, 107/10, 2375-2383.
  39. Motzer RJ, Mazumdar M, Bacik J et al: Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 1999, 17, 2530-2540.
  40. Motzer RJ, Bacik J, Schwartz LH et al: Prognostic factors for survival in previously treated patients with advanced renal cell carcinoma. J Clin Oncol 2004, 22, 454-63.


Jakub Żołnierek
Klinika Onkologii CSK MON
ul. Szaserów 128
00-909 Warszawa
tel. (022) 610 30 98