Head and Neck TumorsHead and Neck TumorsОпухоли головы и шеи2222-14682411-4634Publishing House ABV Press12710.17650/2222-1468-2012-0-4-19-25DIAGNOSIS AND TREATMENT OF HEAD AND NECK TUMORSДИАГНОСТИКА И ЛЕЧЕНИЕ ОПУХОЛЕЙ ГОЛОВЫ И ШЕИROLE OF TARGETED THERAPY IN THE COMBINATION TREATMENT OF PATIENTS WITH KIDNEY CANCER AND METASTATIC BRAIN INVOLVEMENTРОЛЬ ТАРГЕТНОЙ ТЕРАПИИ В КОМПЛЕКСНОМ ЛЕЧЕНИИ БОЛЬНЫХ РАКОМ ПОЧКИ С МЕТАСТАТИЧЕСКИМ ПОРАЖЕНИЕМ ГОЛОВНОГО МОЗГАNaskhletashviliD. R.НасхлеташвилиД. Р.
Russian Federation
nas-david@yandex.ruGorbunovaV. A.ГорбуноваВ. А.
Russian Federation
BekyashevA. Kh.БекяшевА. Х.
Russian Federation
KarakhanV. B.КараханВ. Б.
Russian Federation
MoskvinaE. A.МосквинаЕ. А.
Russian Federation
ProzorenkoE. V.ПрозоренкоЕ. В.
Russian Federation
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, MoscowФГБНУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН, МоскваГБОУ ДПО «Российская медицинская академия последипломного образования» Минздрава России, МоскваN.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, MoscowФГБНУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН, Москва150420122419251904201519042015Copyright ©; 2012, Naskhletashvili D.R., Gorbunova V.A., Bekyashev A.K., Karakhan V.B., Moskvina E.A., Prozorenko E.V.Copyright ©; 2012, Насхлеташвили Д.Р., Горбунова В.А., Бекяшев А.Х., Карахан В.Б., Москвина Е.А., Прозоренко Е.В.2012Naskhletashvili D.R., Gorbunova V.A., Bekyashev A.K., Karakhan V.B., Moskvina E.A., Prozorenko E.V.Насхлеташвили Д.Р., Горбунова В.А., Бекяшев А.Х., Карахан В.Б., Москвина Е.А., Прозоренко Е.В.https://creativecommons.org/licenses/by/4.0https://ogsh.abvpress.ru/jour/article/view/127

In patients with kidney cancer (KC), the rate of metastatic brain involvement is 2-11%, is steadily growing, and is one of the important reasons for treatment failures in these patients. Surgery and radiotherapy, including radiosurgery, must be considered as optimal treatments for patients with KC and brain metastases. Systemic drug therapy has recently played a more and more increasing role in the treatment of patients with a progressive brain tumor process. At the same time, there are no exact pharmacokinetic data on drugs registered for the treatment of disseminated KC in respect to their concentration in the human central nervous when they are used in therapeutic doses. On the basis of the data of the literature review and the results of the authors’ studies, it may be concluded that while none of the target agents has still shown any significant advantage over others in treating KC patients with brain metastases. All the drugs have demonstrated their ability to achieve a clinical and X-ray verified objective effect (as stabilizations in most cases) in treating brain metastases. The most data are available on the therapeutic efficacy of sunitinib and sorafenib. In case of progressive brain tumor process, drug treatment should be individually discussed in each situation in accordance with standard approaches to treating patients with disseminated KC. 

kidney cancerbrain metastasestargeted therapyрак почкиметастазы в головном мозгетаргетная терапия1. Ammirati M., Cobbs C.S., Linskey M.E. et al. The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2010;96:85−96.Ammirati M., Cobbs C.S., Linskey M.E. et al. The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2010;96:85−96.2. Besse B., Lasserre S.F., Compton P. et al. Bevacizumab safety in patients with central nervous system metastases. Clin Cancer Res 2010;16:269−78.Besse B., Lasserre S.F., Compton P. et al. Bevacizumab safety in patients with central nervous system metastases. Clin Cancer Res 2010;16:269−78.3. Choueiri T.K., Duh M.S., Clement J. et al. Angiogenesis inhibitor therapies for metastatic renal cell carcinoma: effectiveness, safety and treatment patterns in clinical practice-based on medical chart review. BJU Int 2009;105:1247−54.Choueiri T.K., Duh M.S., Clement J. et al. Angiogenesis inhibitor therapies for metastatic renal cell carcinoma: effectiveness, safety and treatment patterns in clinical practice-based on medical chart review. BJU Int 2009;105:1247−54.4. Culine S., Bekradda M., Kramar A. et al. Prognostic factors for survival in patients with brain metastases from renal cell carcinoma. Cancer 1998;83:2548−53.Culine S., Bekradda M., Kramar A. et al. Prognostic factors for survival in patients with brain metastases from renal cell carcinoma. Cancer 1998;83:2548−53.5. Dalhaung A., Haukland E., Nieder C. Leptomeningeal carcinomatosis from renal cell cancer: treatment attempt with radiation and sunitinib. World J Surg Oncol 2010;8:36.Dalhaung A., Haukland E., Nieder C. Leptomeningeal carcinomatosis from renal cell cancer: treatment attempt with radiation and sunitinib. World J Surg Oncol 2010;8:36.6. Elfiky A.A., Cho D.C., McDermott D.F. et al. Predictors of response to sequential sunitinib and the impact of prior VEGF-targeted drug washout in patients with metastatic clear cell renal carcinoma. Urol Oncol 2010; doi:10.1016/j. urolonc.2010.01.008; [Epub ahead of print].Elfiky A.A., Cho D.C., McDermott D.F. et al. Predictors of response to sequential sunitinib and the impact of prior VEGF-targeted drug washout in patients with metastatic clear cell renal carcinoma. Urol Oncol 2010; doi:10.1016/j. urolonc.2010.01.008; [Epub ahead of print].7. Escudier B., Bellmut J., Negrier S. et al. Phase III trial of bevacizumab plus interferon alpha-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 2010; 28:2144−50.Escudier B., Bellmut J., Negrier S. et al. Phase III trial of bevacizumab plus interferon alpha-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J Clin Oncol 2010; 28:2144−50.8. Escudier B., Eisen T., Stadler W.M. et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cell cancer global evaluation trial. J Clin Oncol 2009;27:3312−8.Escudier B., Eisen T., Stadler W.M. et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cell cancer global evaluation trial. J Clin Oncol 2009;27:3312−8.9. Feldman D.R., Baum M.S., Ginsberg M.S. et al. Phase 1 trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. Genitourinary Cancer 2009;27:1432−9.Feldman D.R., Baum M.S., Ginsberg M.S. et al. Phase 1 trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. Genitourinary Cancer 2009;27:1432−9.10. Gleave M.E., Elhilali M., Fradet Y. et al. Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. New Engl J Med 1998;338:1265−71.Gleave M.E., Elhilali M., Fradet Y. et al. Interferon gamma-1b compared with placebo in metastatic renal-cell carcinoma. New Engl J Med 1998;338:1265−71.11. Gore M.E., Hariharan S., Porta C. et al. Sunitinib in metastatic renal carcinoma patients with brain metastases. Cancer 2011; 117:501−9.Gore M.E., Hariharan S., Porta C. et al. Sunitinib in metastatic renal carcinoma patients with brain metastases. Cancer 2011; 117:501−9.12. Guirgis L.M., Yang J.C., White D.E. et al. Safety and efficacy of high dose IL-2 therapy in patients with brain metastasis. J Immunother 2002;25:82−7.Guirgis L.M., Yang J.C., White D.E. et al. Safety and efficacy of high dose IL-2 therapy in patients with brain metastasis. J Immunother 2002;25:82−7.13. Haznedar J., Patyna S., Bello C.L. et al. Single and multiple dose disposition kinetics of sunitinib malate, a multitargeted receptor tyrosine kinase inhibitor: comparative plasma kinetics in non-clinical species. Cancer Chemother Pharmacol 2009;64:691−706.Haznedar J., Patyna S., Bello C.L. et al. Single and multiple dose disposition kinetics of sunitinib malate, a multitargeted receptor tyrosine kinase inhibitor: comparative plasma kinetics in non-clinical species. Cancer Chemother Pharmacol 2009;64:691−706.14. Helgason H.H., Mallo H.A., Droogendijk H. et al. Brain metastases in patients with renal cell cancer new targeted treatment. J Clin Oncol 2008;26:152−4.Helgason H.H., Mallo H.A., Droogendijk H. et al. Brain metastases in patients with renal cell cancer new targeted treatment. J Clin Oncol 2008;26:152−4.15. Hu S., Chen Z., Franke R. et al. Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res 2009;15:6062−9.Hu S., Chen Z., Franke R. et al. Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res 2009;15:6062−9.16. Hudes G., Carducci M., Tomczak P. et al. Temsirolimus, interferon alpha, or both for advanced renal cell carcinoma. New Engl J Med 2007;456:2271−81.Hudes G., Carducci M., Tomczak P. et al. Temsirolimus, interferon alpha, or both for advanced renal cell carcinoma. New Engl J Med 2007;456:2271−81.17. Iwamoto F.M., Lamborn K.R., Robins I.H. et al. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06−02). Neuro Oncol 2010;12:855−61.Iwamoto F.M., Lamborn K.R., Robins I.H. et al. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06−02). Neuro Oncol 2010;12:855−61.18. Kim A., McCully C., Cruz R. et al. The plasma and cerebrospinal fluid pharmacokinetics of sorafenib after intravenous administration in non-human primates. Invest New Drugs 2010; doi:10.1007/s10637-010-9585-1; [Epub ahead of print].Kim A., McCully C., Cruz R. et al. The plasma and cerebrospinal fluid pharmacokinetics of sorafenib after intravenous administration in non-human primates. Invest New Drugs 2010; doi:10.1007/s10637-010-9585-1; [Epub ahead of print].19. Kirchner H., Strumberg D., Bahl A. et al. Patient based strategy for systemic treatment of metastatic renal cell carcinoma. Expert Rev Anticancer Ther 2010;10:585−96.Kirchner H., Strumberg D., Bahl A. et al. Patient based strategy for systemic treatment of metastatic renal cell carcinoma. Expert Rev Anticancer Ther 2010;10:585−96.20. Kuhn J.G., Chang S.M., Wen P.Y. et al. Pharmacokinetic and tumor distribution characteristics of temsirolimus in patients with recurrent malignant glioma. Clin Cancer Res 2007;13:7401−6.Kuhn J.G., Chang S.M., Wen P.Y. et al. Pharmacokinetic and tumor distribution characteristics of temsirolimus in patients with recurrent malignant glioma. Clin Cancer Res 2007;13:7401−6.21. Lagas J.S., van Waterschoot R.A., Sparidans R.W. et al. Breast cancer resistance protein and p-glycoprotein limit sorafenib brain accumulation. Molec Cancer Ther 2010;9:319−26.Lagas J.S., van Waterschoot R.A., Sparidans R.W. et al. Breast cancer resistance protein and p-glycoprotein limit sorafenib brain accumulation. Molec Cancer Ther 2010;9:319−26.22. Larkin J., Gore M. Is advanced renal cell carcinoma becoming a chronic disease? Lancet 2010;376:574−5.Larkin J., Gore M. Is advanced renal cell carcinoma becoming a chronic disease? Lancet 2010;376:574−5.23. Lukas R.V., Chmura S., Nicholas M.K. Management of central nervous system metastases from renal cancer. Emerg Cancer Therap 2011;2:157−68.Lukas R.V., Chmura S., Nicholas M.K. Management of central nervous system metastases from renal cancer. Emerg Cancer Therap 2011;2:157−68.24. Massard C., Zonierek J., Gross-Goupil M. et al. Incidence of brain metastases in renal cell carcinoma treated with sorafenib. Ann Oncol 2010; 21:1027−31.Massard C., Zonierek J., Gross-Goupil M. et al. Incidence of brain metastases in renal cell carcinoma treated with sorafenib. Ann Oncol 2010; 21:1027−31.25. Medioni J., Cojocarasu O., Belcaceres J.L. et al. Complete cerebral response with sunitinib for metastatic renal cell carcinoma. Ann Oncol 2007;18:1282−3.Medioni J., Cojocarasu O., Belcaceres J.L. et al. Complete cerebral response with sunitinib for metastatic renal cell carcinoma. Ann Oncol 2007;18:1282−3.26. Motzer R.J., Hutson T.E., Tomczak P. et al. Sunitinib versus interferon alpha in metastatic renal cell carcinoma. New Engl J Med 2007;356:115−24.Motzer R.J., Hutson T.E., Tomczak P. et al. Sunitinib versus interferon alpha in metastatic renal cell carcinoma. New Engl J Med 2007;356:115−24.27. Motzer R.J., Escudier B., Oudard S. et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 2010;116:4256−65.Motzer R.J., Escudier B., Oudard S. et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 2010;116:4256−65.28. Muacevic A., Siebels M., Tonn J.C. et al. Treatment of brain metastases in renal cell carcinoma: radiotherapy, radiosurgery, or surgery? World J Urol 2005;23:180−4.Muacevic A., Siebels M., Tonn J.C. et al. Treatment of brain metastases in renal cell carcinoma: radiotherapy, radiosurgery, or surgery? World J Urol 2005;23:180−4.29. Muldoon L.L., Soussain C., Jahnke K. et al. Chemotherapy delivery issues in central nervous system malignancy: a reality check. J Clin Oncol 2007;25:2295−305.Muldoon L.L., Soussain C., Jahnke K. et al. Chemotherapy delivery issues in central nervous system malignancy: a reality check. J Clin Oncol 2007;25:2295−305.30. Murata J.I., Sawamura Y., Terasaka S. et al. Complete response of a large brain metastasis of renal cell cancer to interferon-alpha: case report. Surg Neurol 1999;51:289−91.Murata J.I., Sawamura Y., Terasaka S. et al. Complete response of a large brain metastasis of renal cell cancer to interferon-alpha: case report. Surg Neurol 1999;51:289−91.31. Nicholas M.K., Lukas R. Immunologic privilege and the brain. In: Arnason B.G., ed. NeuroImmune Biology: The Brain and Host Defense, Vol. 9. London, UK: Elsevier; 2010. P. 169−181.Nicholas M.K., Lukas R. Immunologic privilege and the brain. In: Arnason B.G., ed. NeuroImmune Biology: The Brain and Host Defense, Vol. 9. London, UK: Elsevier; 2010. P. 169−181.32. O’Reilly T., McSheehy P., Kawai R. et al. Comparative pharmacokinetics of RAD001 (everolimus) in normal and tumor-bearing rodents. Cancer Chemother Pharmacol 2010;54:625−39.O’Reilly T., McSheehy P., Kawai R. et al. Comparative pharmacokinetics of RAD001 (everolimus) in normal and tumor-bearing rodents. Cancer Chemother Pharmacol 2010;54:625−39.33. Ranze O., Hoffman E., Distelrath A. et al. Renal cell cancer presented with leptomeningeal carcinomatosis effectively treated with sorafenib. Onkologie 2007; 30:450−1.Ranze O., Hoffman E., Distelrath A. et al. Renal cell cancer presented with leptomeningeal carcinomatosis effectively treated with sorafenib. Onkologie 2007; 30:450−1.34. Saitoh H. Distant metastases from renal carcinoma. Cancer 1988;48:1487−91.Saitoh H. Distant metastases from renal carcinoma. Cancer 1988;48:1487−91.35. Samlowski W.E., Majer M., Boucher K.M. et al. Multidisciplinary treatment of brain metastases derived from clear cell renal cancer incorporating stereotactic radiosurgery. Cancer 2008; 113:2539−48.Samlowski W.E., Majer M., Boucher K.M. et al. Multidisciplinary treatment of brain metastases derived from clear cell renal cancer incorporating stereotactic radiosurgery. Cancer 2008; 113:2539−48.36. Shuch B., LaRochelle J.C., Klatte T. et al. Brain metastasis from renal cell carcinoma: presentation, recurrence, and survival. Cancer 2008;113;1641−8.Shuch B., LaRochelle J.C., Klatte T. et al. Brain metastasis from renal cell carcinoma: presentation, recurrence, and survival. Cancer 2008;113;1641−8.37. Shukla S., Robey R.W., Bates S.E. et al. Sunitinib (Sutent, SU11248), a smallmolecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters p-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos 2009; 37:359−65.Shukla S., Robey R.W., Bates S.E. et al. Sunitinib (Sutent, SU11248), a smallmolecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters p-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos 2009; 37:359−65.38. Sperduto P.W., Chao S.T., Sneed P.K. et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4259 patients. Int J Radiat Oncol Biol Phys 2010; 77:655−61.Sperduto P.W., Chao S.T., Sneed P.K. et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4259 patients. Int J Radiat Oncol Biol Phys 2010; 77:655−61.39. Stadler W.M., Figlin R.A., McDermott D.F. et al. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer 2010;116:1272−9.Stadler W.M., Figlin R.A., McDermott D.F. et al. Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America. Cancer 2010;116:1272−9.40. 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;28:1061−8.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;28:1061−8.41. Thibault F., Billemont B., Rixe O. Regression of brain metastases of renal cell carcinoma with antiangiogenic therapy. J Neurooncol 2008;86:243−4.Thibault F., Billemont B., Rixe O. Regression of brain metastases of renal cell carcinoma with antiangiogenic therapy. J Neurooncol 2008;86:243−4.42. Valcamonico F., Ferrari V., Amoroso V. et al. Long lasting successful cerebral response with sorafenib in advanced renal cell carcinoma. J Neurooncol 2009; 91:47−50.Valcamonico F., Ferrari V., Amoroso V. et al. Long lasting successful cerebral response with sorafenib in advanced renal cell carcinoma. J Neurooncol 2009; 91:47−50.43. Vogl U.M., Bojic M., Lamm W. et al. Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma. BMC Cancer 2010;10:480.Vogl U.M., Bojic M., Lamm W. et al. Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma. BMC Cancer 2010;10:480.44. Vredenburgh J.J., Cloughesy T., Samant M. et al. Corticosteroid use in patients with glioblastoma at first or second relapse treated with bevacizumab in the BRAIN study. Oncologist 2010;15:1329−34.Vredenburgh J.J., Cloughesy T., Samant M. et al. Corticosteroid use in patients with glioblastoma at first or second relapse treated with bevacizumab in the BRAIN study. Oncologist 2010;15:1329−34.45. Yamanaka K., Gohji K., Hara I. et al. Clinical study of renal cell carcinoma with brain metastasis. Int J Urol 1998;5:124−8.Yamanaka K., Gohji K., Hara I. et al. Clinical study of renal cell carcinoma with brain metastasis. Int J Urol 1998;5:124−8.46. Zeng H., Li X., Yao J. et al. Multifocal brain metastases in clear cell renal cell carcinoma with complete response to sunitinib. Urol Int 2009;83:482−5.Zeng H., Li X., Yao J. et al. Multifocal brain metastases in clear cell renal cell carcinoma with complete response to sunitinib. Urol Int 2009;83:482−5.