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Неоперабельный гепатоцеллюлярный рак: новые возможности и перспективы терапии
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Abdurakhmanov D.T., Breder V.V., Bolotina L.V. et al. Unresectable hepatocellular carcinoma: new opportunities and prospects for therapy. Journal of Modern Oncology. 2019; 21 (2): 10–16. DOI: 10.26442/18151434.2019.2.190410
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Ключевые слова: гепатоцеллюлярный рак, цирроз печени, скрининг, мультидисциплинарный подход, классификация BCLC, системная терапия гепатоцеллюлярного рака, исследование REFLECT, ленватиниб.
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Hepatocellular carcinoma (HCC) is the most common liver malignancy and ranks sixth for cancer prevalence and fourth place among the causes of cancer mortality. Despite the improvement of diagnostic techniques, the diagnosis of HCC is still determined in the late stages. The absence of screening programs in groups of risk of HCC (cirrhosis) and the late diagnosis of HCC show the mortality rate exceeds incidence rate in the Russian Federation. It is important to improve the diagnostic methods for early detection of HCC and to use the multidisciplinary approach in diagnosis and treatment of HCC in association with different specialists (hepatologist, oncologist, chemotherapist, surgeon, transplantologist, interventional radiologist). Systemic therapy should be used in all patients with unresectable HCC and compensated liver function. Since 2007 sorafenib has represented the only approved drug for treatment of unresectable HCC. In 2017, according to the results of REFLECT trial lenvatinib was registered for the treatment of unresectable HCC in the first line therapy. For the first time in the last 10 years the efficiency of lenvatinib application in comparison with sorafenib was practically the same, concerning the overall survival rate. Lenvatinib also demonstrated the statistically significant and clinically meaningful benefit in terms of improvement of survival without progression, the time to progression and frequency of objective response rate compared with sorafenib.
Key words: hepatocellular carcinoma, cirrhosis of the liver, screening, a multidisciplinary approach, BCLC staging classification, systemic therapy for hepatocellular carcinoma, REFLECT trial, lenvatinib.
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20. Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378–90.
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23. Cheng AL, Kang YK, Lin DY et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013; 31: 4067–75.
24. Johnson PJ, Qin S, Park JW et al. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study. J Clin Oncol 2013; 31: 3517–24.
25. Cainap C, Qin S, Huang WT et al. Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol 2015; 33: 172–9.
26. Zhu AX, Rosmorduc O, Evans TR et al. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2015; 33: 559–66.
27. FDA website: https://www.fda.gov
28. Инструкция по медицинскому применению препарата ленватиниб. Регистрационный номер: ЛП-003398 (с изменениями от 26.02.2019 г.) http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=a063c935-a9a8-4919-959e-5b36280eb082&t
[Instruktsiia po meditsinskomu primeneniiu preparata lenvatinib. Registratsionnyi nomer: LP-003398 (s izmeneniiami ot 26.02.2019 g.) http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=a063c935-a9a8-4919-959e-5b36280eb082&t (in Russian).]
29. Kudo M, Finn RS, Qin S et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018; 391 (10126): 1163–73.
30. NCCN Guidelines Version 2.2019 – March 6 2019. Hepotocellular carcinoma. https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_g...
31. Alsina A et al. Subsequent Anticancer Medication Following First-line Lenvatinib: A Post Hoc Responder. Analysis From the Phase 3 REFLECT Study in Unresectable Hepatocellular Carcinoma. Presented at ASCO GI 2019.
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1. Zlokachestvennye novoobrazovaniia v Rossii v 2017 godu (zabolevaemost' i smertnost'). Pod red. A.D.Kaprina, V.V.Starinskogo, G.V.Petrovoi. Moscow, 2018 (in Russian).
2. Breder V.V., Bazin I.S., Borisov V.I. et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu pervichnogo raka pecheni. Zlokachestvennye opukholi. 2016; 4 (Spetsvyp. 2): 292–9 (in Russian).
3. GLOBOCAN 2018; IACR, WHO, 2018; http://gco.iarc.fr/today
4. Sostoianie onkologicheskoi pomoshchi naseleniiu Rossii v 2017 god. Pod red. A.D.Kaprina, V.V.Starinskogo, G.V.Petrovoi. Moscow, 2018. http://www.oncology.ru/service/statistics/condition/2017.pdf (in Russian).
5. Breder V.V., Kosyrev V.Iu., Kudashkin N.E., Laktionov K.K. Gepatotselliuliarnyi rak v Rossiiskoi Federatsii kak sotsial'naia i meditsinskaia problema. Med. sovet. 2016; 10: 10–20 (in Russian).
6. Komova A.G., Maevskaia M.V., Ivashkin V.T. Rasprostranennost' diffuznykh zabolevanii pecheni v Moskve. Klin. perspektivy gastroenterologii, gepatologii. 2014; 5: 3–8 (in Russian).
7. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018; 69: 182–236.
8. Hina Arif-Tiwari, Bobby Kalb, Surya Chundru et al. MRI of hepatocellular carcinoma: an update of current practices. Diagn Interv Radiol 2014; 20: 209–21.
9. Solomon R. Contrast-induced acute kidney injury: is there a risk after intravenous contrast? Clin J Am Soc Nephrol 2008; 3: 1242–3.
10. Nahon P, Bourcier V, Layese R et al. Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications. Gastroenterology 2017; 152 (1):142–56.
11. Ioannou GN, Green PK, Berry Kr. J Hepatol 2018; 68: 25–32.
12. Page A, Zunirah A, Ravi S, Singal AK. Hepatitis C Virus and Hepatocellular Carcinoma: A Narrative Review. J Clin Transl Hepatol 2018; 6 (1): 79–84.
13. Alyaa HA, Entethar MH. Diagnosis of liver tumor from CT images using digital image processing. Int J Sci Engineer Res 2015; 6 (Issue 1): 685–9.
14. Bolog N, Andreisek G, Oancea I, Mangrau A. CT and MR imaging of hepatocellular carcinoma. J Gastrointestin Liver Dis 2011; 20 (2): 181–9.
15. Sang Hyun Choi et al. J Hepatol 2016; 64 (5): 1099–107.
16. LI-RADS version 2018, American college of Radiology.
17. Petkau VV, Shabunina LA, Bessonova EN. Primary malignant tumors of liver: the results of observationof patients been registered in Sverdlovsk Region in 2016. Malignant Tumours 2018; 1: 61–5.
18. Vitale A, Morales RR, Zanus G et al. Barcelona Clinic Liver Cancer staging and transplant survival benefit for patients with hepatocellular carcinoma: a multicentre, cohort study, Lancet Oncol 2011; 12 (7): 654–62. DOI: 10.1016/S1470-2045(11)70144-9
19. Breder V.V. et al. Klinicheskie rekomendatsii "Rak pecheni (pechenochnokletochnyi)". Assotsiatsiia onkologov Rossii (AOR), dlia vzroslykh. Versiia 2017: http://oncology-association.ru/files/clinical-guidelines_adults/rak_pecheni.pdf (in Russian).
20. Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378–90.
21. Cheng AL, Kang YK, Chen Z et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10: 25–34.
22. Kudo M. Molecular targeted agents for hepatocellular carcinoma: current status and future perspectives. Liver Cancer 2017; 6: 101–12.
23. Cheng AL, Kang YK, Lin DY et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013; 31: 4067–75.
24. Johnson PJ, Qin S, Park JW et al. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study. J Clin Oncol 2013; 31: 3517–24.
25. Cainap C, Qin S, Huang WT et al. Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol 2015; 33: 172–9.
26. Zhu AX, Rosmorduc O, Evans TR et al. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2015; 33: 559–66.
27. FDA website: https://www.fda.gov
28. Instruktsiia po meditsinskomu primeneniiu preparata lenvatinib. Registratsionnyi nomer: LP-003398 (s izmeneniiami ot 26.02.2019 g.) http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=a063c935-a9a8-4919-959e-5b36280eb082&t (in Russian).
29. Kudo M, Finn RS, Qin S et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018; 391 (10126): 1163–73.
30. NCCN Guidelines Version 2.2019 – March 6 2019. Hepotocellular carcinoma. https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_g...
31. Alsina A et al. Subsequent Anticancer Medication Following First-line Lenvatinib: A Post Hoc Responder. Analysis From the Phase 3 REFLECT Study in Unresectable Hepatocellular Carcinoma. Presented at ASCO GI 2019.
1 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
2 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Россия;
3 Московский научно-исследовательский онкологический институт им. П.А. Герцена – филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России, Москва, Россия;
4 ГБУЗ СО «Свердловский областной онкологический диспансер», Екатеринбург, Россия
*abdjamal@mail.ru
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Dzhamal T. Abdurakhmanov*1, Valerii V. Breder2, Larisa V. Bolotina3, Vladislav Iu. Kosyrev1,2, Bela M. Medvedeva2, Vladislav V. Petkau4
1 I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
2 N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russia;
3 P.A. Herzen Moscow Research Institute of Oncology – branch of National Medical Research Center for Radiology, Moscow, Russia;
4 Sverdlovsk Regional Oncology Dispensary, Yekaterinburg, Russia
*abdjamal@mail.ru