References

medsovet

Медицинский Совет

Meditsinskiy sovet = Medical Council

2079-701X2658-5790

REMEDIUM GROUP Ltd.

10.21518/2079-701X-2018-19-90-94

medsovet-2753

Research Article

Онкоурология

Oncourology

Пазопаниб в терапии распространенного почечноклеточного рака

Pazopanib in the treatment of advanced renal cell carcinoma

Волкова

М. И.

Volkova

M. I.

д.м.н., в.н.с. отделения урологии

Ольшанская

А. С.

Olshanskaya

A. S.

аспирант кафедры онкологии

ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, МоскваРоссияBlokhin Russian Medical Research Centre of Oncology of the Ministry of Health of Russia, MoscowRussian Federation

ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова», МоскваРоссияPirogov Russian National Research Medical University, MoscowRussian Federation

2018

11112018

0199094

2018

Волкова М.И., Ольшанская А.С.

Volkova M.I., Olshanskaya A.S.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.med-sovet.pro/jour/article/view/2753

Пазопаниб – пероральный мультикиназный ингибитор, применяемый при распространенном раке почки в большинстве стран мира. Пазопаниб блокирует рецепторы тирозинкиназ, участвующих в опухолевом ангиогенезе и пролиферации, включая VEGF, фактор роста, исходящий из тромбоцитов (PDGF), и фактор роста стволовых клеток c-Kit, что приводит к ингибированию ангиогенеза, роста и пролиферации опухолевых клеток. В клинических испытаниях пазопаниб демонстрировал преимущество в БПВ по сравнению с плацебо у ранее не леченных больных и пациентов, получавших цитокины, а также отсутствие ущерба БПВ по сравнению с сунитинибом в первой линии терапии светлоклеточного ПКР групп хорошего и промежуточного прогноза. Кроме того, пазопаниб продемонстрировал лучший профиль безопасности, чем сунитиниб. Результаты применения пазопаниба в широкой клинической практике согласуются с данными рандомизированных исследований, подтверждая высокую эффективность данного препарата в сочетании с хорошей переносимостью даже у пациентов, не соответствующих общепринятым критериям включения в клинические испытания.

Pazopanib is an oral multitargeted tyrozine kinase inhibitor that is used in advanced renal cancer in most countries of the world. Pazopanib inhibits tyrosine kinase receptors involved in tumor angiogenesis and proliferation, including VEGF, platelet-derived growth factor (PDGF) and stem cell growth factor receptor c-Kit, which leads to inhibiting angiogenesis, growth and proliferation of tumor cells. In clinical trials, pazopanib demonstrated improvement of progression-free survival (PFS) versus placebo in previously untreated patients and patients treated with cytokines, as well as the absence of worsening PFS versus sunitinib in the first-line therapy of clear cell RCC in the good- and intermediate prognosis groups. In addition, pazopanib demonstrated a better safety profile than sunitinib. The results of use of pazopanib in broad clinical practice are consistent with data from randomized trials that confirms the high efficacy combined with good tolerability of this drug even in patients who do not meet the generally accepted criteria for the inclusion in clinical trials.

пазопанибсорафенибсунитинибакситиниббевацизумабэверолимусдиссеминированный почечно-клеточный рактаргетная терапиявыживаемость

pazopanibsorafenibsunitinibaxitinibbevacizumabeverolimusdisseminated renal cell carcinomatargeted therapysurvival

References1

National Comprehensive Cancer Network (2018) In: NCCN clinical practice guidelines in oncology (NCCN Guidelines®) Kidney Cancer. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.

National Cancer Institute. (2017) Surveillance, epidemiology, and end results program. In: National Comprehensive Cancer Network (ed.), NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Kidney Cancer v1. 2017. Bethesda, MD: National Cancer Institute, Surveillance Systems Branch.

Flanigan R.C., Mickisch G., Sylvester R., Tangen C., Van Poppel H., Crawford E.D. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. 2004 Mar; 171(3): 1071-6.

Motzer R.J., Escudier B., McDermott D.F. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015; 373: 1803-1813.

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, doubleblind phase III trial. Lancet. 2007 Dec; 370(9605): 2103–11.

Rini B.I., Halabi S., Rosenberg J.E., Stadler W.M., Vaena D.A., Archer L. et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol. 2010; 28: 2137- 2143.

Figlin R.A., Hutson T.E., Tomczac P. et al. Overall survival with sunitinib versus interferon alfa as first-line treatment in metastatic renal-cell carcinoma. ASCO Annual Meeting Proceedings 2008. J Clin Oncol. 2008; 26(Suppl.): abstr 5024.

Motzer R.J., Hutson T.E., Cella D. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22; 369(8): 722-31.

Sternberg C.N., Davis I.D., Mardiak J., Szczylik C., Lee E., Wagstaff J. et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010; 28: 1061-1068.

Hudes G., Carducci M., Tomczak P., Dutcher J., Figlin R., Kapoor A. et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007; 356:2271-2281.

Escudier B., Eisen T., Stadler W.M., Szczylik C., Oudard S., Staehler M. 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: 3312-3318.

Motzer R.J., Escudier B., Oudard S., Hutson T.E., Porta C., Bracarda S. et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008; 372: 449-456.

Rini B.I., Escudier B.J., Michaelson M.D., Negrier S., Gore M.E., Oudard S., Clark J., Tarazi J.C., Rosbrook B., Kim S., Motzer R.J. Phase III AXIS trial for second-line metastatic renal cell carcinoma (mRCC): Effect of prior first-line treatment duration and axitinib dose titration on axitinib efficacy. J Clin Oncol. 2012 Feb 10; 30(5_suppl): 354.

Носов Д.А., Воробьев Н.А., Гладков О.А., Матвеев В.Б., Русаков И.Г., Харкевич Г.Ю. Практические рекомендации по диагностике и лечению почечно-клеточного рака. Злокачественные опухоли. 2016, 4 (спецвып. 2): 333–337

Nosov DA, Vorobev NA, Gladkov OA, Matveev VB, Rusakov IG, Kharkevich GYu. Practical guidelines for the diagnosis and treatment of renal cell cancer. Zlokachestvennye Opukholi. 2016, 4 (special issues 2): 333–337.

Pick A., Nystrom K. Pazopanib for the treatment of metastatic renal cell carcinoma. Clin Ther. 2012, 34: 511–520.

Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, et al. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J. Clin. Oncol. 2014; 32: 1412–1418.

Sternberg C., Hawkins R., Wagstaff J., Salman P., Mardiak J., Barrios C., et al. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013; 49: 1287–1296.

Sternberg C., Davis I., Deen K., Sigal E., Hawkins R. An open-label extension study to evaluate safety and efficacy of pazopanib in patients with advanced renal cell carcinoma. Oncology. 2014; 87: 342–350.

Mitchell C., Parikh O. Factors involved in treatment preference in patients with renal cancer: pazopanib versus sunitinib. Patient Prefer Adherence. 2014; 8: 503–511.

Cella D., Hackshaw M., Diaz J., Huang C., Deen K., Crescenzo R., et al. Quality of life (QoL) among patients with renal cell carcinoma (RCC) treated with pazopanib versus sunitinib in the COMPARZ study. J Clin Oncol. 2013; 31(Suppl. 6): abstr. 346.

Beaumont J., Diaz J., Deen K., McCann L., Powles T., Hackshaw M., et al. Q-TWiST analysis of patients with metastatic renal cell carcinoma (mRCC) randomized to pazopanib (PAZ) or sunitinib (SUN). J Clin Oncol. 2014; 32(Suppl. 5): abstr. 4581.

Heng D.Y., Choueiri T.K., Rini B.I., Lee J., Yuasa T., Pal S.K., et al. Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials. Ann. Oncol. 2014; 25: 149–154.

Mao F.J., Rini B.I. The ineligible patient: how to treat patients not included in clinical studies. World J. Urol. 2014; 32: 9–18.

Matrana M., Bathala T., Campbell M.T., Duran C., Shetty A., Teegavarapu P., et al. Outcomes of unselected patients with metastatic clear-cell renal cell carcinoma treated with first-line pazopanib therapy followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors or mammalian target of rapamycin inhibitors: a single institution experience. BJU Int. 2016; 118: 264–271.

Galvis V., Chow S., Lawrence D., Hawkins R. Clinical practice outcomes of patients treated with pazopanib for metastatic renal cell cancer (mRCC) – 6 year experience at a referral centre in Manchester, UK. Eur J Cancer. 2013; 49 (Suppl. 2): abstr. 2763.

Ruiz-Morales J.M., Swierkowski M., Wells J.C., Fraccon A.P., Pasini F., Donskov F., et al. First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: results from the Inter national Metastatic Renal Cell Carcinoma Database Consortium. Eur. J. Cancer. 2016; 65: 102–108.

Hurwitz H.I., Dowlati A., Saini S., Savage S., Suttle A.B., Gibson D.M., et al. Phase I trial of pazopanib in patients with advanced cancer. Clin. Cancer Res. 2009; 15: 4220–4227.

Hutson T.E., Davis I.D., Machiels J.P., De Souza P.L., Rottey S., Hong B. F., et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 2010; 28: 475–480.

Pérez-Valderrama B., Arranz Arija J.A., Rodríguez Sánchez A., Pinto Marín A., Borrega García P., Castellano Gaunas D.E., et al. Validation of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model for first-line pazopanib in metastatic renal carcinoma: the Spanish Oncologic Genitourinary Group (SOGUG) SPAZO study. Ann. Oncol. 2016; 27: 706–711.

Porta C., Tortora G., Larkin J., Hutson T. Management of poor-risk metastatic renal cell carcinoma: current approaches, the role of temsirolimus and future directions. Future Oncol. 2016; 12: 533–549.

Kim J.M., Park S.H., Lee J., Lee S., Lee S.J., Lim H.Y. A Korean multi-center, real-world, retrospective study of first-line pazopanib in unselected patients with metastatic renal clear-cell carcinoma. BMC Urol. 2016; 16: 46.

Park J.Y., Lee J.L., Baek S., Eo S.H., Go H., Ro J.Y., et al. Sarcomatoid features, necrosis, and grade are prognostic factors in metastatic clear cell renal cell carcinoma with vascular endothelial growth factor-targeted therapy. Hum. Pathol. 2014; 45: 1437–1444.

Beuselinck B., Lerut E., Wolter P., Dumez H., Berkers J., Van Poppel H., et al. Sarcomatoid dedifferentiation in metastatic clear cell renal cell carcinoma and outcome on treatment with anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors: a retrospective analysis. Clin. Genitourin. Cancer. 2014; 12: e205–e214.

Costello B.A., Zhang B., Lohse C.M., Boorjian S.A., Cheville J., Leibovich B.C., et al. Outcomes of patients with sarcomatoid renal cell carcinoma: the Mayo Clinic experience [abstract]. J. Clin. Oncol. 2014; 31(Suppl. 6): abs.359. 2013 Genitourinary Cancers Symposium.

Matrana M.R., Ng C., Rao P., Lim Z.D., Tannir N.M. Chromophobe renal cell carcinoma with sarcomatoid dedifferentiation treated with pazopanib: a case report. Clin. Genitourin Cancer. 2011; 9: 137–139

Stukalin I., Wells C., Fraccon A.P., Pasini F., Porta C., Moreira R.B., et al. Fourth-line targeted therapy in metastatic renal cell carcinoma (mRCC): results from the International mRCC Database Consortium (IMDC). 2017 Genitourinary Cancers Symposium. J. Clin. Oncol. 2017; 35(Suppl. 6S): abs. 498.

Vera-Badillo F.E., Templeton A., Ocana A., de Gouveia P., Aneja P., Knox J.J., et al. Response to systemic therapy in non-clear cell renal cell carcinomas: a systematic review and metaanalysis. J. Clin. Oncol. 2014; 32(Suppl. 4): abs. 425.

The authors declare that there are no conflicts of interest present.