Development of new effective drugs for therapy of metastatic melanoma (BRAF/MEK inhibitors, PD1/CTLA4 blockers) requires additional studies of the optimal sequence of their use. But in many cases the duration of the effect of these medicinal products is limited by time even in their sequential use. This literature review considers a possibility of repeated indication of BRAF/ MEK inhibitors after progression on them in various clinical settings. The potential use of such approach is illustrated by two own clinical observations.

Pharmaceutical therapy of hepatocellular carcinoma represents a major clinical issue of debate in modern oncology. Until now, Sorafenib remains the only option for the management of locally advanced and metastatic hepatocellular carcinomas, which increases the overall survival of patients. In the absence of alternative treatment, the oncologist understanding of the place, time, the strategic goal and tactical objectives of the pharmaceutical therapy of hepatocellular carcinoma at different stages of cancer is of great importance. The article considers the practical aspects of the Sorafenib therapy of hepatocellular cancer in various clinical situations, and proposes algorithms of accompanying therapy for the underlying liver pathology. It presents the results of Regorafenib therapy, a new multi-kinase inhibitor, which significantly increases survival in the second line therapy of sorafenib-resistant hepatocellular  carcinoma. The options  of  pharmaceutical therapy for hepatocellular  carcinoma using cytotoxic and molecular-directed medicines, prospects of modern immunotherapy are discussed.

Advances in the treatment of disseminated patients with non-small cell lung cancer are directly linked to targeted therapy. Patients with activating mutations in the gene for the receptor of epidermal growth factor  (EGFR) in appointing them in the first line EGFR tyrosine kinase inhibitors (EGFR TKI) of the first and second generations have a significant preference for immediate efficacy and time to progression. In addition, patients with a deletion in exon 19 of EGFR receiving afatinib, overall survival reached 30 months, which is statistically higher compared to standard chemotherapy. However, during the 10–12 months developing acquired resistance to targeted drugs. The main reason which in 60% of cases is a mutation Т790М. Osimertinib – TKI third-generation proved to be highly effective  in these  patients. To clarify the mechanism of resistance requires repeated molecular genetic testing. Thus, you need to re-biopsy the tumor, optimally from the source of progression. Unfortunately, it is not always possible and an alternative may be a liquid biopsy. Only such an individual approach can provide a choice of optimum treatment tactics and improve patient survival.

Angiogenesis   has  become  an  important  target  in  the  treatment  of  solid  tumors  and  anti-angiogenic   agents   are a  promising  approach  to  cancer  therapy.  Ramucirumab, an  anti-angiogenic   agent   specifically  targeting  vascular endothelial  growth factor receptor-2  (VEGFR-2). In April 2014, the FDA approved ramucirumab as a single  agent  or in combination with paclitaxel  for treatment of advanced gastric or gastroesophageal junction adenocarcinoma (GC) that has progressed on or after prior fluoropyrimidine – or platinumcontaining chemotherapy based on data of REGARD and RAINBOW trials.

We evaluated the progression free (PFS), overall survival (OS) and safety of ramucirumab in patients (pts) with advanced GC in routine clinical practice From June 2016  to 20 Sep 2017  40 pts with advanced GC were treated with ramucirumab in the second line treatment as single  agent (8 pts) or in combination with paclitaxel  (26 pts) in N.N.Blokhin National medical research center of oncology.

Median PFS (MPFS) and median OS (MOS) was 1,8  and 7,6 mons for monotherapy group. For combination group MPFS was 5,02  mons, MOS was not reached. Ramucirumab had an acceptable safety profile Our data are similar to the data of REGARD and RAINBOW trials.

The HannaH study showed that neoadjuvante-adjuvant subcutaneous and intravenous trastuzumab have similar efficacy and tolerability in patients with early HER2-positive breast cancer. The analysis of the results of the subcutaneous and intravenous trastuzumab usage in  Russian population showed  the favorable association between tpCR anf EFS. tpCR achiviement is associated with clinical benefit in HER2 positive breast cancer. For patients with difficult venous access who do not require intravenous chemotherapy currently, Subcutaneous trastuzumab allows  to receive effective treatment without the risk of complications, which involves catheterization of a Central vein.

A reasonable strategy for drug therapy of non-small-cell lung cancer  (NSCLC) with activating mutations of EGFR is the use of tyrosine kinase inhibitors (TKI) in front-line therapy, providing a two-fold increase in life expectancy for patients with metastatic or locally advanced form of the disease. The results of several randomized trials determined and proved the role of Afatinib, the selective irreversible inhibitor of protein kinase receptors of the ErbB family, which  consists in the following positions: a verifiable increase in progression-free period (PFP) as front-line metastatic EGFR-mutated NSCLC as compared to chemotherapy, regardless of the EGFR gene mutation type; the advantage in respect of overall survival (OS) as front-line therapy with frequent EGFR gene mutation in NSCLC, with Del19 in particular (OS increase by more than 1 year in comparison with chemotherapy); the advantage in progression-free survival (PFS), treatment  time duration (TTD) as well as in objective response rate (ORR) in comparison with Gefitinib against metastatic EGFR-mutated NSCLC; therapeutic efficacy against brain metastasis and many rare mutations; dose adjustment of Afinitib with a view of its tolerability is an effective measure to decrease the drug-induced toxicity rate without affecting its therapeutic efficacy. This article also presents the results of clinical and economic research of the response and benefit of comparable drugs (Afatinib, Gefitinib and Erlotinib) for treatment of patients with NSCLC in the Russian Federation and the results of minor studies demonstrating the new opportunities of Afinitib and its combinations with other «partners». In particular, the efficiency of Afinitib use in the treatment of patients with HER2-mutated lung cancer is provided. In addition, the safety and efficacy of combinations of Afatinib + Bevacizumab and Afatinib + Cetuximab after the formation of acquired resistance to TKI is also noted, which can be used as a therapeutic option in case of Т790М mutation. Current controversial issues concerning the effectiveness of this drug with the new and other rare mutations, the allegedly incomplete cross-resistance against the previous two drugs of this group, lack of information about the therapeutic benefit of Afinitib in case of discordancy of the primary tumor and its metastasis call for further clinical research studies and refinement of diagnostic tests and systems.

A clinical case of trastuzumab emtansine in therapy line 4 in patient with metastatic HER2positive breast cancer is provided. After 10  courses of targeted therapy by the drug a complete  response to the therapy was obtained. By results of PET CT conducted in the period from December 2015  to September 2017 the complete response is preserved.

Over the course of the past couple of decades, we have witnessed some significant improvements in the treatment of metastatic colorectal cancer: the emergence of novel targeted drugs and a differentiated approach to their administration, the extension of indications for surgical resection for liver and lungs metastases has resulted in the increased life expectancy among patients in this group. Nevertheless, chemotherapy remains the treatment of choice for colon cancer. In this paper, we discuss new approaches to the use of chemotherapy on stages III and IV of colorectal cancer.

Therapy of CRPC is one of the most difficult problems in oncourology. Until now the optimal consequence of use of drugs in CRPC is not determined.

Study objective: evaluation of effectiveness  of sequential  therapeutic schemes  in progression of m-CRPC: cytotoxic (Docetaxel) or second-line hormonal therapy (Abiraterone) after previous treatment by an analogue of prolonged action somatostatin (Octreotide-depo) and without it.

Materials and methods: the study design included 4 groups of patients (170 subjects). The first two groups included patients who received initial therapy by Octreotide-Depo 30 mg before chemotherapy and second line hormone therapy, compared to two groups of primary chemical and hormone therapy indicated after progression of m-CRPC.

Results: the number of patients in whom the reduction of PSA concentration, process stabilization, tolerability profile were analogous in groups receiving Docetaxel as the first-line therapy and in the group after administration of Octreotide-depo. Analogous data were registered in groups who administered Abiraterone.

Conclusion: the analysis of the therapeutic results didn’t demonstrate any significant differences in groups that received Docetaxel or Abiraterone as the second-line therapy after administration of Octreotide-Depo with groups of patients with received first-line cytotoxic or hormone therapy, which means lack of resistance after application of the prolonged action somatropin analogue to  subsequent schemes of anti-tumour therapy, which allows delaying the dates of the second line chemical or hormonal therapy of CRPC.

Modern first-line therapy programs can cure about 80% of patients with classical Hodgkin lymphoma at any stage  of the disease, but 10-30% of patients is refractory and need to continue treatment. The treatment standard for relapsed or refractory forms of classical Hodgkin lymphoma is the second-line chemotherapy with high-dose consolidation under the protection of autologous blood stem cells, but the efficacy of such therapy does not exceed 50% for the entire group of refractory patients. The release of target drugs specific for Berezovsky-Reed-Sternberg tumor cells opens up new prospects for the treatment of classical Hodgkin lymphoma. The article reviews the studies of the use of a new target drug Brentuximab Vedotin for the treatment of relapsed and refractory forms of classical Hodgkin lymphoma.

The use of proteasome inhibitors and immunomodulatory drugs in the clinical practice has contributed to the significant improvement in survival for patients with multiple myeloma over the past decades. Alongside this, due to the recurrent course of the disease, there is a need to introduce new classes of drugs to clinical practice. In 2015,  the FDA (USA) approved two monoclonal  antibodies  for use  in  patients  with  relapsed  multiple  myeloma,  and  immunotherapy has  rapidly become indispensable  in the management of such patients. The article presents an analysis of the published data regarding the mechanism of action, safety and clinical efficacy of daratumumab, a human monoclonal antibody that targets CD38 tumor protein, for the  treatment  of patients  with multiple  myeloma. In Russia, daratumumab is registered  (RU LP-004367  of 07.07.2017) and is indicated as monotherapy for patients with relapsed or refractory multiple myeloma, who have received prior therapies, incuding proteasome  inhibitors and immunomodulatory drugs. Daratumumab demonstrated  an excellent safety profile. In the context of daratumumab therapy, the moderate-grade infusion-related reactions occurring mostly during the  first infusion  are the  main adverse  events.  Daratumumab-based combination  therapies  are currently under active evaluation in patients with relapsed and newly diagnosed myeloma.

The purpose of our study is to evaluate our own experience in the use of low molecular weight heparins, in particular bemiparin, in a group of patients with an increased risk of venous thromboembolic events undergoing major surgery for esophageal and gastric cancer. The study presents a comparative analysis of these groups and short-term results of the use of bemiparin in cancer patients.

Chemotherapy regimen AС (doxorubicin and cyclophosphamide) is the most often used in adjuvant chemotherapy of breast cancer. AC regimen is high emetogenic.

Objective – to evaluate the effectiveness of the combination of aprepitant, ondansetron and dexamethasone for the prevention of nausea and vomiting in patients with breast cancer receiving chemotherapy regimen AC.

Materials and methods: 82 female patients with breast cancer received adjuvant chemotherapy regimen AC: doxorubicin 60 mg/ m², cyclophosphamide 600 mg/m²  in day 1, each 21 day 4 cycle. Patients received an triple-therapy regimen (aprepitant 125 mg p.o. in day 1, 80 mg in days 2 and 3, ondansetron 8 mg i.v. in 1 day, dexamethasone 12 mg i.v.in 1 day, then to 8 mg/day p.o. in days 2–4)  for prevention of nausea and vomiting.

Results: During the first cycle of chemotherapy in acute phase (0-24  hours from the start of chemotherapy) complete control of nausea and vomiting was achieved at 72 (87.8%) patients. During delayed phase (25-120 hours from the start of chemotherapy) complete control achieved at 56 (68.3%)patients . 57.3% of patients had complete control of nausea and vomiting during all 4 cycles.

Efficacy of posaconazole for prophylaxis was evaluated in 77 chemotherapy cycles in 59 patients with acute myeloid leukemia (AML) aged 39 (17–62) years from 2012  till 2017. Posaconazole was given in oral suspension 200 mg three times a day after meal during chemotherapy cycle or on 1st  day after the cycle. Administration of posaconazole predominated in patients with de novo AML (84.5%) on 1st induction cycles (66.3%). Neutropenia was present in all patients with median duration of 22 days. Median duration of prophylaxis was 21  (2–57)  days. Posaconazole prophylaxis was interrupted in 28  (36.4%) of 77 cases, mainly due to diarrhea (28.6%). In 17 (61%) of 28 cases prophylaxis was resumed within a median of 3 days. In 72 (93.5%) of cases duration of posaconazole prophylaxis was ≥ 7 days, in 5 (6.5%) cases < 7 days. Efficacy of prophylaxis was evaluated in cases of posaconazole duration ≥ 7 days. Invasive pulmonary aspergillosis (probable) was in 2 (2.7%) of 72 cases. Administration of posaconazole with duration ≥ 7 days was in 46 cases on chemotherapy cycle, in 26 cases – on first day after the cycle. Patients using Posaconazole after a course of chemotherapy in comparison with patients receiving the drug in the first days of the course had significantly less interruptions of prophylaxis (11,5% vs 41,3%, p=0.009) and a reduction in duration of Posaconazole using (19 days vs 27 days, p=0.007).One case of invasive aspergillosis was registered in each group.

We confirmed the  efficacy of posaconazole  for prophylaxis of invasive mycoses  in patients  with AML. Administration of posaconazole prophylaxis on first day after the end of chemotherapy cycle results in saving of drug by reducing duration of posaconazole using by 8 days and does not increase the incidence of invasive mycoses.

Breast cancer in men is 100 times less common than in women. The principles of treatment of breast cancer in men are still based on knowledge obtained during the treatment of women with a similar pathology. The article reviews 67 cases of all breast cancer stages  in men. The majority (50.7%) of all patients who initiated therapy had stage  III-IV tumors. In most cases,  the  patients  had  an  infiltrating ductal  carcinoma (52.2%). The combination  and  complex  treatment  methods accounted for 53.6% of all cases. The radical mastectomy (89.6%) was the most frequent method of operative intervention. 29 patients (43.3%) received preoperative chemotherapy. 36 patients received adjuvant treatment. The adjuvant treatment comprised chemotherapy (29 patients), and subsequently was supplemented with antihormonal therapy in patients with receptor-positive tumors. The anthracycline-containing chemotherapy was the most prevalent among treatment regimens (72.4%). In 7 patients with a locally diffused process, the treatment was supplemented with radiotherapy. 72.2% of patients had a clinically significant estrogen receptor (RE) expression in the tumor and 61% of patients had a progesterone receptor (RP) expression. 85.0% of patients with stages  I-IIA breast cancers showed the relatively high 5-year survival rates, and 67.5% of patients with stage IIB cancers showed 5-year survival. The survival rates for stages III and IV cancer were 18.1% and 16.6%, respectively.

The typical treatment of ameloblastoma is by surgery. The result of the procedure nevertheless  does  not always lead to complete healing of the sickness but to a recurrence during the post-operative period. It has been reported by a number of authors that the recurrence of the condition is influenced by a number of factors such as the kind of surgical intervention, the histological variant of the ameloblastoma and the incomplete removal of the tumor. The purpose of this research is to study the incidence of recurrence of ameloblastoma after surgery, taking into consideration type of surgery and size of the tumor. A study of 76 cases of ameloblastoma with different histological structures was undertaken in the laboratory of pathological anatomy of Central Research Institute of Dental and Maxillofacial Surgery. Data such as the recurrence of the disease and tumors size was collected, registered and analysed. The size of the tumors was expressed in conventional units. The analysis showed that basal cell and plexiform variants of ameloblastoma are often relate to cases with aggressive clinical courses. The tendency to the recurrence of the disease was also observed in the follicular and acanthomatous variants. According to the results of this study, cases of peripheral variants of ameloblastoma have the best prognosis.

Pl-VEGF165 (Neovasculgen) is a new genotherapeutic drug for treatment of chronic lower limb ischemia.  It is registered in Russia and underwent effectiveness assessment in clinical trial. Objective of this study is to report results of the economical modeling study to compare long-term effectiveness and costs of the treatment. The comparison show that the treatment with this drug allows to decrease number of amputations by 6.5 fold and increase quality adjusted length of life by 2.6 QALYs. Summary  costs were lower with new drug by 574 thousand rubles with lifelong modeling and by 353 thousand rubles in first 5 years.