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Introduction. Hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm of the liver. During the early stages, HCC is asymptomatic, which makes X-ray examination a particularly important diagnostic tool. According to WHO data, the mortality rate from HCC was 782,000 in 2018. HCC is associated with a number of risk factors: a high viral load, liver cirrhosis, detected HBeAg and elevated serum HBsAg levels. Inhibitors of tyrosine kinase receptors increase the overall survival and progression-free survival rates in patients with metastatic HCC. In this article, we conduct an analysis of results of the REFLECT study obtained for Russian patients by the Republican Clinical Oncological Dispensary, Ufa.Materials and methods. The experimental group included 9 patients (52.9%) receiving Lenvatinib. The control group included 8 patients (47.1%)) underwent therapy with Sorafenib at a dose of 800 mg per day 7 (41.17%) patients had a history of chronic hepatitis, of which hepatitis B and chronic hepatitis C was confirmed in 6 and 1 cases, respectively.Results and discussion. Over the period from 2017 up to the present, progression-free survival was observed in three patients (17.6%), of which 2 and 1 received Lenvatinib and Sorafenib, respectively. Overall survival was 10.5 months. The median overall survival rate in the experimental and control groups was 9.8 and 11.2 months, respectively. These parameters are considered comparable, provided that the sample was small.Conclusions. The use of Lenvatinib demonstrated the efficacy comparable to that of Sorafenib in terms of the overall survival rate in patients with inoperable HCC. Lenvatinib allowed statistically and clinically significant improvement in the progression-free survival and time to progression to be achieved.

С открытием патогенетических путей развития метастатического почечно-клеточного рака (МПКР) и появлением таргетных препаратов прогноз течения заболевания и выживаемость этой группы больных значительно улучшились. Резистентность и непереносимость препаратов, развивающиеся при длительной терапии, индуцируют проведение новых клинических исследований и поиск новых препаратов и схем лечения. В статье обсуждаются результаты исследований эффективности и переносимости сорафениба как в первой, так и во второй линиях лечения МПКР.

Aim. To assess the pharmacoeconomic feasibility of including lenvatinib in the list of vital and essential drugs (VED) and the state program for providing to the necessary drugs to treat patients with differentiated radioiodine-resistant thyroid cancer. Materials and methods. The design of the study is a retrospective analysis of the literature data. Methods of pharmacoeconomic analysis - cost analysis, budget impact analysis, cost-effectiveness analysis. Results. The replacement of sorafenib with lenvatinib when included in the VED list and the state program for providing the necessary medicines for the treatment of patients with differentiated radioiodine-resistant thyroid cancer will reduce the burden on the program budget. At the size of the target group of 100 people for 3 years, the savings will amount to 43.95 million rubles. The total reduction in the load on the budget will be 11.8%. The results obtained are resistant to an increase in the price of lenvatinib by 19.0% and a decrease in the price of sorafenib by 52%. The average cost of therapy for 1 patient with differentiated radioiodine-resistant thyroid cancer for 1 year with the use of lenvatinib in the first line is 36.0% lower than with sorafenib. The savings for 1 year is 334 911 rubles on the patient. In terms of «cost-effectiveness», the drug lenvatinib dominates sorafenib. The CER value per patient for the year using lenvatinib is 48.7% lower than with sorafenib. Conclusion. From the pharmacoeconomic point of view, the use of lenvatinib in the first line of therapy of radioiodide-differentiated thyroid cancer is preferred in comparison with the use of sorafenib. The inclusion of lenvatinib in the list of vital and essential drugs and the state program for providing the necessary drugs is pharmacoeconomically feasible.

Glomerular damage and proteinuria are important pathophysiological signs of chronic kidney disease. This study provides data obtained using a model developed based on the use of the anti-cancer drug sorafenib. Sorafenib is a tyrosine kinase inhibitor that acts through the signaling pathway associated with vascular endothelial growth factor and is widely used to treat various types of cancer. Sorafenib, on the other hand, causes serious side effects in patients, including the development of chronic kidney disease. This study was aimed at using the nephrotoxic properties of sorafenib to model chronic kidney disease in rats. We showed that rats treated with sorafenib for 8 weeks along with a diet high in salt (8% NaCl) develop hypertension with high systolic blood pressure of 80 mmHg, proteinuria with an increase in protein content of 75% higher, and a 4-fold increase in glomerular damage compared to the control group. In case of damage to the renal glomeruli caused by sorafenib, the level of transcripts that are involved in the synthesis of key glomerular proteins such as nephrine, podocin, synaptopodin and subplanin is significantly reduced. Also, when studying this model, activation of the endothelial-mesenchymal transition is observed. In the group of rats treated with sorafenib, the mRNA level for the WT-1 endothelial cell marker was reduced by 20%, while the concentration of the Col III, FSP-1, α-SMA and vimentin mesenchymal cell markers increased by 2–3 times. Thus, we developed a preclinical model of chronic kidney disease, expressed in damage to the renal glomeruli. We also demonstrated that glomerular damage in this model is associated with decreased expression of key structural glomerular proteins and activation of the endothelial-mesenchymal transition of the kidneys. [ABSTRACT FROM AUTHOR]