Cancer UrologyCancer UrologyОнкоурология1726-97761996-1812Publishing House ABV Press14510.17650/1726-9776-2013-9-1-28-33DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCERДИАГНОСТИКА И ЛЕЧЕНИЕ ОПУХОЛЕЙ МОЧЕПОЛОВОЙ СИСТЕМЫ. Рак почкиSEQUENTIAL TARGETED THERAPY FOR DISSEMINATED KIDNEY CANCERПОСЛЕДОВАТЕЛЬНАЯ ТАРГЕТНАЯ ТЕРАПИЯ ПРИ ДИССЕМИНИРОВАННОМ РАКЕ ПОЧКИMatveevV. B.МатвеевВ. Б.
Russian Federation

Department of Urology

Отделение урологии

mivolkova@rambler.ruVolkovaM. I.ВолковаМ. И.
Russian Federation

Department of Urology

Отделение урологии

mivolkova@rambler.ruN.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, MoscowФГБУ «РОНЦ им. Н.Н. Блохина» РАМН, Москва300320139128332907201429072014https://oncourology.abvpress.ru/oncur/article/view/145

Targeted therapy is a standard treatment in advanced renal cell carcinoma. Stabilization is an expected response to targeted therapy. The main goal of targeted therapy is to improve progression-free survival. This purpose is served through the sequential use of targeted agents. First-line therapy agents in the good and intermediate MSKCC prognostic groups are antiangiogenic ones such as bevacizumab, sunitinib, sorafenib, pazopanib; in the poor MSKCC prognostic group treatment of choice is an mTOR inhibitor temsirolimus. The antiangiogenic agent axitinib and the mTOR inhibitor everolimus were proved to be effective as second-line therapy. Axitinib administration after anti-VEGF drugs is associated with cumulative toxicity. The efficacy of axitinib in sorafenib-refractory renal cell carcinoma has not been proven. So everolimus remains the agent of choice for second-line targeted therapy. The effect of repeated antiangiogenic therapy may be anticipated after everolimus therapy.

 

renal cell carcinomasecond-line targeted therapyeverolimusaxitinibпочечно-клеточный рактаргетная терапия 2-й линииэверолимусакситиниб1. Матвеев В.Б., Волкова М.И. Рак почки. РМЖ 2007;(14):1094–9.Матвеев В.Б., Волкова М.И. Рак почки. РМЖ 2007;(14):1094–9.2. Ljungberg B., Cowan N., HanburyD.C. et al. Guidelines on Renal Cell Carcinoma. European Association of Urology 2012; p. 36–39.Ljungberg B., Cowan N., HanburyD.C. et al. Guidelines on Renal Cell Carcinoma. European Association of Urology 2012; p. 36–39.3. Motzer R.J., Hutson T.E., Tomczak P. et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356(2):115–24.Motzer R.J., Hutson T.E., Tomczak P. et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356(2):115–24.4. 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 Dec;370(9605):2103–11.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 Dec;370(9605):2103–11.5. Rini B.I., Halabi S., Rosenberg J.E. et al. Bevacizumab plus interferon alfa compared with interferon alfamonotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J ClinOncol 2008;26:5422–8.Rini B.I., Halabi S., Rosenberg J.E. et al. Bevacizumab plus interferon alfa compared with interferon alfamonotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J ClinOncol 2008;26:5422–8.6. Escudier B., Szczylik C., Eisen T. et al. Randomized phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC) [abstract LBA4510]. Proc Am Soc Clin Oncol 2005;23.Escudier B., Szczylik C., Eisen T. et al. Randomized phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC) [abstract LBA4510]. Proc Am Soc Clin Oncol 2005;23.7. Sternberg C.N., Davis I.D., Mardiak J. et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010;28(6):1061–8.Sternberg C.N., Davis I.D., Mardiak J. et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010;28(6):1061–8.8. Hudes G., Carducci M., Tomczak P. et al. Temsirolimus, Interferon alfa, or Both for Advanced Renal-Cell Carcinoma. N Engl J Med 2007;356 (22):2271–81.Hudes G., Carducci M., Tomczak P. et al. Temsirolimus, Interferon alfa, or Both for Advanced Renal-Cell Carcinoma. N Engl J Med 2007;356 (22):2271–81.9. Tamaskar I., Dhillon J., Pili R. Resistance to angiogenesis inhibitors in renal cell carcinoma. Clin Adv Hematol Oncol 2011;9(2):101–10.Tamaskar I., Dhillon J., Pili R. Resistance to angiogenesis inhibitors in renal cell carcinoma. Clin Adv Hematol Oncol 2011;9(2):101–10.10. Porta C., Procopio G., Cartenì G. et al. Sequential use of sorafenib and sunitinib in advanced renal-cell carcinoma (RCC): an Italian multicentre retrospective analysis of 189 patient cases. BJUI 201;108:250–7.Porta C., Procopio G., Cartenì G. et al. Sequential use of sorafenib and sunitinib in advanced renal-cell carcinoma (RCC): an Italian multicentre retrospective analysis of 189 patient cases. BJUI 201;108:250–7.11. Tamaskar I., Garcia J.A., Elson P. et al. Antitumor effects of sunitinib or sorafenib in patients with metastatic renal cell carcinoma who received prior antiangiogenic therapy. J Urol 2008;179(1):81–6.Tamaskar I., Garcia J.A., Elson P. et al. Antitumor effects of sunitinib or sorafenib in patients with metastatic renal cell carcinoma who received prior antiangiogenic therapy. J Urol 2008;179(1):81–6.12. Richter S., Piper C., Pfister D.A. et al. Long-term therapy with sunitinib and sorafenib in patients with metastasizing renal cell carcinoma. J Clin Oncol 2011;29 (suppl 7; abstr 407).Richter S., Piper C., Pfister D.A. et al. Long-term therapy with sunitinib and sorafenib in patients with metastasizing renal cell carcinoma. J Clin Oncol 2011;29 (suppl 7; abstr 407).13. Zimmermann K., Schmittel A., Steiner U. et al. Sunitinib treatment for patients with advanced clear-cell renal-cell carcinoma after progression on sorafenib. Oncology 2009;76(5):350–4.Zimmermann K., Schmittel A., Steiner U. et al. Sunitinib treatment for patients with advanced clear-cell renal-cell carcinoma after progression on sorafenib. Oncology 2009;76(5):350–4.14. Eichelberg C., Heuer R., Chun F.K. et al. Sequential use of the tyrosine kinase inhibitors sorafenib and sunitinib in metastatic renal cell carcinoma: a retrospective outcome analysis. EurUrol 2008;54(6):1373–8.Eichelberg C., Heuer R., Chun F.K. et al. Sequential use of the tyrosine kinase inhibitors sorafenib and sunitinib in metastatic renal cell carcinoma: a retrospective outcome analysis. EurUrol 2008;54(6):1373–8.15. Choueiri T.K., Plantade A., Elson P. et al. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. JCO 2008;26(1);127–131.Choueiri T.K., Plantade A., Elson P. et al. Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma. JCO 2008;26(1);127–131.16. Dudek A.Z., Zolnierek J., Dham A. et al. Sequential therapy with sorafenib and sunitinib in renal cell carcinoma. Cancer. 2009;115(1):61–7.Dudek A.Z., Zolnierek J., Dham A. et al. Sequential therapy with sorafenib and sunitinib in renal cell carcinoma. Cancer. 2009;115(1):61–7.17. Sablin M.P., Negrier S., Ravaud A. et al. Sequential sorafenib and sunitinib for renal cell carcinoma. J Urol. 2009;182(1):29–34.Sablin M.P., Negrier S., Ravaud A. et al. Sequential sorafenib and sunitinib for renal cell carcinoma. J Urol. 2009;182(1):29–34.18. Rini B.I., Escudier B., Tomczak P.Axitinib versus sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC): Results of phase III AXIS trial. J Clin Oncol 2011;29 (suppl; abstr 4503).Rini B.I., Escudier B., Tomczak P.Axitinib versus sorafenib as second-line therapy for metastatic renal cell carcinoma (mRCC): Results of phase III AXIS trial. J Clin Oncol 2011;29 (suppl; abstr 4503).19. Escudier B., Loomis A.K., Kaprin A. et al. Association of single nucleotide polymorphisms (SNPs) inVEGF pathway genes with progression-free survival (PFS) and blood pressure (BP) in metastatic renal cell carcinoma (mRCC) in the phase 3 trial of axitinib versus sorafenib (AXISTrial). Eur J Cancer 2011;47(Suppl 1):abstr 7103.Escudier B., Loomis A.K., Kaprin A. et al. Association of single nucleotide polymorphisms (SNPs) inVEGF pathway genes with progression-free survival (PFS) and blood pressure (BP) in metastatic renal cell carcinoma (mRCC) in the phase 3 trial of axitinib versus sorafenib (AXISTrial). Eur J Cancer 2011;47(Suppl 1):abstr 7103.20. Pfizer Inc. FDA Oncologic Drugs Advisory Committee Briefing Document (NDA 202324). Axitinib (AG-013736) For the Treatment of Patients With Advanced Renal Cell Carcinoma. 2011. Available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/ucm282 284.htm.Pfizer Inc. FDA Oncologic Drugs Advisory Committee Briefing Document (NDA 202324). Axitinib (AG-013736) For the Treatment of Patients With Advanced Renal Cell Carcinoma. 2011. Available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/ucm282 284.htm.21. Motzer R.J., Escudier B.J., Oudard S. et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebocontrolled phase III trial. Lancet 2008;372(9637):449–56.Motzer R.J., Escudier B.J., Oudard S. et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebocontrolled phase III trial. Lancet 2008;372(9637):449–56.22. Calvo E., Escudier B., Motzer R.J. et al. Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur J Cancer 2012;48(3):333–9.Calvo E., Escudier B., Motzer R.J. et al. Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur J Cancer 2012;48(3):333–9.23. Oudard S., Thiam R., Fournier L.S. et al. Optimisation of the tumour response threshold in patients treated with everolimus for metastatic renal cell carcinoma: Analysis of response and progression-free survival in the RECORD-1 study. Eur J Canc 2012;48:1512–8.Oudard S., Thiam R., Fournier L.S. et al. Optimisation of the tumour response threshold in patients treated with everolimus for metastatic renal cell carcinoma: Analysis of response and progression-free survival in the RECORD-1 study. Eur J Canc 2012;48:1512–8.24. Blesius A., Beuzelink B., Chevreau C. Are TKIs still active in patients treated with TKI and everolimus? Experience from 36 patients treated in France in the RECORD 1 trial. ESMO 2010 (abstr 4179).Blesius A., Beuzelink B., Chevreau C. Are TKIs still active in patients treated with TKI and everolimus? Experience from 36 patients treated in France in the RECORD 1 trial. ESMO 2010 (abstr 4179).25. Di Lorenzo G., Buonerba C., Federico P. et al. Third-line sorafenib after sequential therapy with sunitinib and mTOR inhibitors in metastatic. Ren Cell Carc 2010;58:62.Di Lorenzo G., Buonerba C., Federico P. et al. Third-line sorafenib after sequential therapy with sunitinib and mTOR inhibitors in metastatic. Ren Cell Carc 2010;58:62.26. Gruenwald V., Seidel C., Fenner M. Antitumor activity of tyrosine kinase inhibitors (TKI) after failure of RAD001 in metastatic renal cell carcinoma (mRCC). Genitourinary Cancers Symposium 2010. Abstr. 414. Available at: http://www.asco.org/ascov2/Meetings/Abstracts.Gruenwald V., Seidel C., Fenner M. Antitumor activity of tyrosine kinase inhibitors (TKI) after failure of RAD001 in metastatic renal cell carcinoma (mRCC). Genitourinary Cancers Symposium 2010. Abstr. 414. Available at: http://www.asco.org/ascov2/Meetings/Abstracts.