Currently in Russia drugs a new class - immunological synapse modulators (ISM) – appear, the most effective among which are PD-1 blockers. Pembrolizumab is an effective antineoplastic drug, which is a monoclonal antibody blocking the PD-1 signaling molecule on cytotoxic lymphocytes, inhibiting the immune response. Pembrolizumab can be used successfully in the first and subsequent lines of treatment of metastatic melanoma regardless of the presence of activating mutations in the BRAF gene and other molecular markers. Recommended mode of application at the present time is 2 mg/kg intravenously every 3 weeks long before the development of intolerance or overt disease progression. In the present review information is systemized on the effectiveness and safety of using pembrolizumab in patients with metastatic melanoma, is given in a variety of clinical trials and retrospective observations.

Today, the role of the genetic factor in the etiology of ovarian cancer is unquestionable. Genetic disorders in low-differentiated serous adenocarcinoma of ovaries in about 50 per cent of cases occur in the form of a lack of homologous DNA reparation. About 2/3 of these cases are associated with mutations in BRCA genes. The use of PARP inhibitors is a promising direction in the treatment of BRCA-mutated ovarian cancer, and a number of studies have proven their advantage. But because they are used in supporting mode, one of the basic requirements for this group of drugs is the toxicity profile. The most common complications in taking PARP-inhibitors are nausea, fatigue, vomiting, anaemia, thrombocytopenia. Olaparib has the lowest toxicity range of all the PARP inhibitors known today in the treatment of ovarian cancer.

The article deals with the new oral target drug Palbociclib and its place in estrogen-receptor therapy, a positive HER2-negative metastatic breast cancer. Until recently, the consistent endocrine therapy was the primary treatment for the patients of this subgroup, as it significantly improved clinical outcomes of the disease. However, in the vast majority of cases, the tumor demonstrated the acquired, and sometimes the original, hormone resistance, which sooner or later led to failure of treatment and to the progress of the disease. Discovery of the role of cycline- dependent kinases (CDK) in the activation of the tumor proliferation and the subsequent creation of the first inhibitor, CDK 4 and 6 types of Palbociclib, led to a fundamental change in the situation: The results of the clinical examination of the combinations of Palbociclib with Letrozole or Fulvestrantom showed doubling of the median survival rate without the disease progress compared to single hormonal therapy. This strategy called Therapy of Breakthroughs combines proven efficiency, good tolerability, maintains a high quality of life and should be used in patients with an al-positive HER2-negative metastatic breast cancer.

The tyrosine kinase inhibitors (TKIs) of the epidermal receptor growth factor (EGFR) such as gefitinib, erlotinib and afatinib, are the standard first-line therapy in locally advanced and metastatic non-small cell lung cancer (NSCLC) with frequent mutations of the EGFR gene. These drugs are more effective from the point of view of frequency response (FR) and survival without progression (SWP), less toxic and better tolerated than the standard two-component chemotherapy based on platinum drugs. The most frequent adverse events (AE) are gastrointestinal (GI) (diarrhea and stomatitis/mucositis) and dermatological (rash, dry skin and paronychia). They are usually mild, but in some cases symptoms can be moderate and more severity and have a negative impact on quality of life (QOL) of the patient and can require dose adjustment or discontinuation of treatment. Management of AEs, including preventive measures, supportive therapy, temporary cancellation and a reduction in the dose of the drug is important. Recommendations for the prevention and treatment of dermatological toxicity (rash, dry skin and paronychia) and toxicity for the gastrointestinal tract (diarrhoea, stomatitis and mucositis) related to therapy TKI-EGFR are developed. These guidelines describe in detail supportive therapy, the temporary discontinuation of the treatment and reducing the dose of the drug for KTI-EGFR.

The advances in molecular biology have had a considerable influence on the medicinal treatment of patients with small cell lung cancer (NSCLC). The discovery of targets and development of drugs for molecular-targeted action improved the results of therapy of a specific group of patients. Translocation (rearrangeable) gene ROS-1 is quite rare – only in 1.7 percent of NSCLC patients. In addition to the genetic characteristics of the tumor, there are a number of morphological features that differentiate these patients from the general population. The most important is the fact that ROS-1 positive patients were very sensitive to crizotinib-tyrosine kinase inhibitor of ALK, MET and ROS1. Immediate effectiveness and long-term results of the use of crizotinib in this category of patients was even higher than the ALK translocation in the tumor. Therefore, it is advisable for patients, particularly with adenocarcinoma of the lung, in the absence of EGFR mutation and ALK to conduct molecular-genetic testing to determine ROS1. Individual approach to the choice of treatment strategy, timely correction of undesirable effects can greatly extend the life of NSCLC patients and improve its quality.

Pancreatic cancer is characterized by its aggressive behaviour and high metastatic potential, and in most cases the disease is detected in inoperable stages. The main method of treatment of locally advanced and metastatic pancreatic cancer is chemotherapy. Until recently, gemcitabine monotherapy was considered the standard of chemotherapy; until the moment when more effective regimens of combination chemotherapy (FOLFIRINOX and the combination of nab-paclitaxel plus gemcitabine) were included in clinical practice. Application of these chemotherapy regimens is limited by their relatively high toxicity, which makes their use impossible in fragile patients and in patients with serious concomitant pathology. The article highlights criteria for choosing the best regimen of combination chemotherapy based on the assessment of patient’s condition, the possibility to manage side effects of chemotherapy, and the molecular and biological characteristics of the tumor.

The review considers information about the efficacy and safety of Ixabepilone as a monotherapy and as a component of combination therapy for advanced breast cancer. Successful treatment of metastatic breast cancer is often confounded by resistance to chemotherapy, in particular anthracyclines and taxanes. The limited number of effective treatment options for patients with more aggressive biological subtypes, such as triple-negative metastatic breast cancer, is especially important. A therapy clinically proven to be effective in this subtype would be of great value. Ixabepilone, a novel synthetic lactam analog of epothilone B, demonstrated better clinical outcomes in metastatic disease, particularly in triple-negative breast cancer and “intensivelytreated” variant. Most recently, studies have shown the activity of ixabepilone in the neoadjuvant setting, suggesting a role for this drug in primary disease.

Gastric cancer is one of the leading causes of death among all cancers in Russia. Progression-free and overall survival cannot be drastically changed by current therapeutic approaches. There is a strong need in new drugs for that disease. Teysuno has demonstrated its efficacy in treatment of advanced gastric cancer and some other cancers. The more drugs we obtain for clinical practice the more opportunities we can offer for these patients.

Venous thromboembolism (VTE) is a common complication in patients with malignant disease. Cancer-associated thrombosis is a major cause of morbidity and mortality in patients with cancer. Several risk factors for developing venous thrombosis usually coexist in cancer patients including surgery, hospital admissions and immobilization, the presence of an indwelling central catheter, chemotherapy. Effective prophylaxis and treatment of VTE reduced morbidity and mortality, and improved quality of life. Low-molecular-weight heparin (LMWH) is preferred as an effective and safe means for prophylaxis and treatment of VTE.

Androgen deprivation therapy (ADT) is used in the treatment of prostate cancer metastatic cancer (PC) since the first description of its hormone dependence in 1941. After receiving the results of a TAX 327 study in 2004, the drug from the taxanes - docetaxel became the main cytostatic agent in the treatment of the castration resistant prostate cancer (CRPC). In a recently published
study CHAARTED it was shown for the first time that the combination of ADT with docetaxel in men with hormone-sensitive metastatic prostate cancer (HSMPC) showed the advantage in the total survival rate by 13.6 months compared to the independent ADT. Similar results were obtained in the STAMPEDE study of men with local-distrubuted and metastatic PC with initial long ADT. A combination of six docetaxel courses with ADT in men starting long-term ADT demonstrated the same advantage by the survival rate parameter compared to the standard ADT by 10 months. Based on the reliability of the treatment results obtained by a new combination of a cytostatic and hormonal product, docetaxel in addition to ADT should be regarded as the basic initial therapy for men with the first identified hormone-sensitive PC, as reflected in the practical recommendations on the treatment of malignant tumours (RUSSCO) 2016 and the recommendations of the European Association of Urologists, 2017.

Our surveillance was performed for 358 patients with locally advanced and disseminated prostate gland cancer who were treated by analogues of LHRH. Patients in group 1 (n = 222) received treatment with a LHRH analogue, and patients in group 2 (n = 136) received treatment with 75 mg Buserelin-depo 3. Experience has shown that the use of the Buserelin-Depot drug results in a regression of the average PSA value: Up to 36.05 ng/ml in 2 months, up to 12.35 ng/ml - in four months, up to 3.3 ng/ml - in six months. The drug ensures a steady decrease in the level of testosterone in the blood serum to the castration level already in a month after the start of treatment, a decrease in prostate gland volume (from 57.3 to 40.45 cc 3 by month 6 of treatment (-29.4%)). A number of patients have experienced a decrease in the need for analgesics and thus an increase in the activity status. The obtained data are comparable to those in the group of patients receiving other analogues of LHRH.

Prostate cancer initially responds to androgen-deprivation therapy, but most patients eventually develop a castration-resistant form of disease. Enzalutamid is the superselective inhibitor of the androgen receptor (AR), which blocks several stages of the AR signal path. The drug showed significant effectiveness in the treatment of metastatic castration-resistant prostate cancer (MCRPC) in both the first line therapy and the second line therapy after the previous cytotoxic therapy of Docetaxel. To ensure optimum treatment, it is important to understand the impact of Enzalutamide in the context of other therapies, as recent studies have shown that cross-resistance occurs between and within classes of drugs. Mutations and AR splice-variants also affect prostate cancer. Future treatment strategies, including enzalutamide, should take into account the previous level of exposure to taxanes or anti-androgen therapy and the existence of variants of AR that may affect efficiency.

This article provides a critical overview of the methods of optical diagnosis of muscular and non-invasive bladder cancer (BC), describes the technologies available so far, their advantages and disadvantages, and reviews the assessment of their effectiveness, both clinical and economic. The results are based on the work of leading scientific societies, such as the European Association of Urology (EAU), the European Organization for Research and Treatment of cancer (EORTC), Сlinical Research Office of the Endourological Society (Croes), etc.

In recent years several therapeutic options have been developed that significantly improve the survival of patients with metastatic treatment-resistant prostate gland cancer (mCRPC). The presence of several active agents gives oncologists an unprecedented opportunity to adapt their choices to the clinical characteristics of each patient, to each treatment line, but at the same time raises the problem of determining the optimal therapeutic sequence for the individual. Due to evolution of the therapeutic strategy, difficulty of the process of the therapy dynamics evaluation and variability of the clinical disease aspects the multi-disciplinary approach currently acquires the primary importance. This article presents the views and recommendations of the expert of the Interdisciplinary Group (Milan, Italy) on the use of Radium-223 in men with mCRPC.

The clinic-rentgenological differential diagnosis is difficult especially in case of localized mediastinal disease. Just detailed histological diagnosis allows making a right tactic decision and choosing effective therapy. Furthermore, some indolent B-cell lymphomas and T-cell lymphomas can arise in mediastinum. Mediastinal tumors are frequent in young adults, and most of these neoplasms are lymphoproliferative disorders. The spectrum of mediastinal lymphoma is broad. The most often of them are large B-cell lymphomas: classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma and mediastinal grey zone lymphoma.

Purpose of the study. To obtain experience with ibrutinib in patients with chronic lymphocytic leukemia (CLL) in everyday clinical practice.

Material and methods. 20 patients with refractory or relapsed CLL were included in the study during the period from October 2015 to January 2016. Immunophenotyping, cytogenetic and molecular tests of peripheral blood samples were performed for all patients. Patients took ibrutinib at dose of 420 mg once daily for a year or until progression. The effectiveness of treatment was assessed by overall response rate, complete response and overall survival.

Results. The overall response rate was 100%. The overall survival rate at 14 months was 80%. The complete response rate at 14 months after initiation of therapy was 60%. The primary effect was observed in lymph nodes, while changes in the hemogram occurred later. The medicine was well tolerated. Patients who stopped ibrutinib therapy therapy due to complications, restarted treatment at full dose after resolving.

Conclusion. Ibrutinib is a highly effective medicine for patients with refractory or relapsed CLL, including those from the highrisk group, but it is not a «salvage therapy» and is not effective at terminal states. Ibrutinib can be considered as a «bridge» for young patients who are candidates for allogeneic bone marrow transplantation.

The study included 108 patients with B-cell lymphoma which had complication with invasive aspergillosis, 57 patients with Hodgkin lymphoma (HL) and 51 patients with non-Hodgkin lymphoma (NHL). All patients in both groups received chemotherapy before the development of invasive aspergillosis, 73% of patients with HL and 67% patients with NHL received chemotherapy for induction and consolidation of remission. The main predictive factors for IA in patients with HL and NHL were: prolonged lymphocytopenia (70% vs 48%), agranulocytosis (64% vs 71%), use of glucocorticosteroids as part of treatment protocol (61% vs 85%), presence of B – symptoms (63% vs 48%), respectively. In most cases nosocomial invasive aspergillosis was diagnosed in both groups: 65% vs 83% respectively. We identified etiological agents in Hodgkin and non-Hodgkin lymphoma patients: A. fumigatus (50% vs 39%), A. niger (43% vs 33%) and A. flavus (7% vs 8%). The lungs were involved in 100% cases, in group with NHL patients 6% had combined lesions in lungs and other organs and different types of tissues. Clinical manifestation of IA was nonspecific in both groups: fever – 83% vs 76%, cough – 75% vs 59%, respiratory insufficiency – 50% vs 40%, respectively. CT-signs of IA were also nonspecific in both groups: infiltrative (75% vs 66%), focal changes (61% vs 63%), and «ground-glass opacity» (28% vs 31%), respectively. In most cases patients were treated with voriconazole in both patients (88% vs 98%). Overall 12-weeks survival in patients with Hodgkin lymphoma and invasive aspergillosis was 84%, in patients with non-Hodgkin lymphoma and invasive aspergillosis – 81%.

The article covers the results of clinical application of a domestic drug based on recombinant tumor necrosis factor-alphathymosin-alpha1 (Refnot) in 20 patients with metastatic skin melanoma. Refnot was administered at a dose of 100 000 IU subcutaneously 1–5 days every week, the cycle 3 or 4 weeks. During the therapy the levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) were determined in patients serum before therapy, every 3 or 4 weeks of treatment until disease progression. In patients with stabilization of the disease showed a decreasing level of VEGF and FGF. In the case of the detection of the progression level of VEGF and FGF have.

Ovarian suppression (OS) is an effective therapy in hormone-sensitive breast cancer. Oophorectomy and ovarian irradiation have historically been used to achieve the goal of ovarian ablation. Luteinizing hormone releasing hormone (LHRH) analogues have largely supplanted surgical and radiation-based approaches because of less side effects and a lower likelihood of permanent amenorrhea, with the potential for restoration of fertility. LHRH analogues goserelin, buserelin, leuprorelin are equally effective. Buserelin is economically attractive.

Adjuvant endocrine therapy of premenopausal patients with ER+ breast cancer typically consists in administration of tamoxifen for 5 years. However, in cases of high risk of disease recurrence there is a need to suppress (inhibit) function of the ovaries as the main generators of estrogen stimulating growth and progression of the disease, typically using agonists of gonadotropinreleasing hormone. As a result of the onset of drug-induced menopause it becomes possible to use with GnRH agonists not only tamoxifen but also aromatase inhibitors with enhanced antineoplastic activity.

Given the high number of patient survival rates with Hodgkin lymphoma (HL), most modern studies are focused on strategies to reduce the toxicity of treatment. The objectives of this study were to assess the early toxicity of the protocols DAL-HD (German working group for study and treatment of leukaemia in children) and SPbLH (St. Petersburg group on treatment of Hodgkin Lymphoma in children) compatible by effectiveness used in therapy of HL in children and adolescents. The study includes 143 HL patients aged between 3 and 18 (median-11.6 years), who received treatment from 1993 to 2015 under the following programs: DAL-HD-versions 87 and 90 and original research protocol SPBLH-05. Analysis of the direct toxicity of polychemotherapy (PCT) showed that the therapy according to DAL-HD protocol has a more pronounced emetogenicity and myelotoxicity than the SPbLH protocol. The most pronounced complications of PCT have been recorded in high-risk patients treated by DAL-HD program (hematotoxicity degree 3-4, dyspeptic syndrome with hypotrophy development). By reducing the combined doses of anthracycline antibiotics and alkylating agents, therapy by SPbLH protocol is accompanied by less pronounced side effects while maintaining a high level of common and relapsed survival. Thus, risk-adapted SPbLH programme can be recommended for the treatment of children and adolescents suffering from HL.

The article is based on the concept of framing, as described in the works of the Nobel Prize laureate D. Kahneman and A. Tverski. The purpose of work is acquaintance physicians and health care managers with the effect of framing in medicine The essence of effect of framing is expounded. The examples of decision- making in medical practice and the organization of medical care on the basis of effect of framing are given. Emphasized influence of the formulation on the choice of the solution. Dependence of effect of framing is indicated on System of 1 cogitative activity. The question of moral and ethical aspect of framing in medical practice is discussed.