В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

Aranose is an original cytostatic, synthesized in the Russian Cancer Research Center, belongs to the class of nitrosourea derivatives (this class of drugs also including streptozotocin). In preclinical trials, Aranose has shown its activity in neuroendocrine tumors (NETs). Prospective clinical studies have confirmed high efficacy and good tolerability of the drug in different lines of treatment of patients with NET G1 and G2. Median PFS while Aranose treatment in a single mode or in combination with capecitabine, doxorubicin and temozolomide did not differ significantly (15.3 vs 15.8, 15.3 and 17.9 months, respectively, p = 0.791). After updating the histological classification and highlighting the prognostically unfavorable subgroup of NET G3, a prospective single-center clinical study of Aranose in the first line of NET G3 therapy was conducted. The standard dosage regimen of the drug was used: 500 mg/m 2 from the first to the third days, a cycle of 21 days. On average, patients received nine courses of Aranose chemotherapy, but in case of an increase in the radiological response treatment continued until disease progression or unacceptable toxicity. Median PFS in the Aranose group was 12 months, in the group of patients receiving capecitabine and oxaliplatin combination – 5 months, in capecitabine and temozolomide combination – 7 months, in the etoposide with cisplatin or carboplatin group only 4 months. The frequency of objective responses in the Aranose group was 37 % (10/27), no complete responses were recorded. Disease stabilization was achieved in 40.7 % (11/27), thus, the frequency of disease control was 77.7 % (21/27). Disease control was maintained after 6 months or more in 63 % of patients.

Aim. The main objective of the prospective multicentre observational study is to describe adverse events occurred during treatment with aflibercept plus FOLFIRI therapy in real life practice. In despite of broad use of aflibercept in Federal oncological centers, this regimen is still perceived by healthcare professionals (HCPs) as having worse safety profile in comparison with other antiangiogenic agents. Taking into account limited experience of using aflibercept in Russia it s critically important to evaluate and document adverse events occurred with treatment in aflibercept plus FOLFIRI regimen in patients with metastatic colorectal cancer (mCRC) in real-life practice. Methods. The physician selection was performed as a random process. Twenty sites with experience in treatment of mCRC patients were selected. The investigators were encouraged to enroll all patients meeting eligibility criteria in consecutive manner. Total number of included patients into the study patient was 101. Data were evaluable for 91 patients. 14 of 91 (15.4 %) patients didn ’t meet inclusion criteria and were excluded from the per protocol analysis: 10 patients didn ’t receive oxaliplatin within the last line of therapy preceding inclusion into the study and in 4 patients progression occurred more than 6 months after the end of adjuvant therapy. Results. Overall, 265 treatment emergent adverse events (TEAEs) occurred in the 77 patients analysed per protocol. In total, 23 grade 3 and 5 grade 4 TEAEs were reported by 16 and 4 patients, respectively. The most common TEAEs were nausea (68 events in 31 [40.3 %j patients), diarrhea (43 events in 25 [32.5 %j patients), hypertension (36 in 20 [26.0 %] patients), neutropenia (29 events in J5 [J9.5 %] patients), asthenia (28 events in 12 [15.6 %]patients). Three cases of grade 1-2 stomatitis were reported in 2 (2.6 %) patients. And one patient reported grade 1 epistaxis during the study. There was no case of gastrointestinal perforation, fistula development, ulceration, arterial or venous thromboembolism. During this study seven serious adverse events were documented in 5 (6.5 %) patients of 77. The reason for treatment discontinuation in 5 (11.1 %) of 45 cases was adverse event. No death, classified as related to any component of therapy, was reported in this study. Conclusion. This national (Russian) prospective multicentre non-interventional study conducted in patients with mCRC in daily practice suggests that aflibercept plus FOLFIRI has a manageable safety profile in line with VELOUR phase III study.

Metastatic damage to the brain is a frequent manifestation in tumors of various localizations, including breast cancer. Until recently, systemic therapy of metastatic brain damage was of limited use; however, with the advent of targeted drugs that are better understood in terms of the specific molecular targets and biological characteristics of metastases, it is now possible to improve treatment results. In an analysis of the results of studies on the problem of metastasis of breast cancer in the brain, a comparison of the use of various targeted drugs in the treatment of metastatic HER2 + breast cancer is presented. The results of a comparison of the degrees of effectiveness of targeted drugs, both in monotherapy and in combination with chemotherapy, were obtained and analyzed.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of rare epithelial tumors that arise from cells with a neuroendocrine phenotype. NENs are found in the gastrointestinal tract and pancreas – 60 % of all localities. The incidence of gastric NENs is about 9 % of all neuroendocrine tumors of the gastrointestinal tract and 0.3 % of all stomach tumors. Stomach neuroendocrine tumors (NETs) are classified into three clinico-pathological types, based on etiology, pathogenesis and morphology. There are also separate neuroendocrine cancers: small- and large-cell. The prognosis and approach to treatment of various types of gastric NENs differs significantly. Modern methods of instrumental diagnostics, immunohistochemical methods of morphological research, along with light microscopy, do not always allow us to accurately assess the malignant potential of a tumor and individualize the treatment process. One of the promising directions in the study of NETs is to determine the molecular mechanism underlying their development, in particular the role of microRNAs. This direction can open a new vector of understanding the pathogenesis, determining the prognosis of the disease, as well as finding new application points for the drug treatment of NETs. MicroRNAs are a class of short non-coding RNA molecules (18–25 nucleotides). MicroRNAs can be involved in the regulation of all major cellular processes, including proliferation and differentiation, metabolism, signaling pathways, and apoptosis. A study of microRNA expression in tissues revealed tumor-specific microRNAs. In contrast to a number of other malignant tumors, microRNA expression in patients diagnosed with NENs is poorly understood. MicroRNA-222 and microRNA-202 are among the few microRNAs that have been demonstrated in the NETs of the stomach.

Lung cancer still holds the leading position in terms of morbidity and mortality, both among men and women. The five-year survival rate for lung cancer is one of the lowest among cancers and varies from 5% to 15% for different countries. The study of new directions in the treatment of this nosology is an extremely urgent problem at the present time. The most common histological variant is non-small cell lung cancer. The presence of driver mutations (EGFR, ALK, ROS1) makes it possible to use targeted therapy in these patients. However, in the absence of driver mutations, the treatment of disseminated non-small cell lung cancer is still based on chemotherapy, which has a low efficiency, making up only about 30% in the first line of treatment. A promising approach to the treatment of this group of patients is the use of immunotherapy, in particular anti-PD-1 and anti-PD-L1 checkpoint-inhibitors. In large randomized international clinical trials, pembrolizumab and atezolizumab were shown to be effective in the first line of treatment, and nivolumab in the second line of treatment. Moreover, according to meta-analyses on the effectiveness and safety of immunotherapy, PD-L1 inhibitors (atezolizumab, avelumab, and durvalumab) have a lower toxicity profile compared to PD-1 inhibitors (pembrolizumab and nivolumab). This article presents a clinical observation of effective treatment of a patient with disseminated non-squamous non-small cell lung cancer with a combination of atezolizumab with bevacizumab and chemotherapy. The partial effect of treatment achieved in this patient is maintained for 3 years without the unacceptable toxicity.

Advanced well differentiated neuroendocrine tumors (NET) have poor sensitivity to chemotherapy. Approaches to the second and subsequent lines of treatment have not been developed to date Aranosa is a derivative of nitrosourea. it is close to streptozotocin in terms of its chemical structure, but it has a more favorable toxicity profile. Aranoza is actively studied in well differentiated NET. The drug was effective in the fourth line of treatment of the patient with NET and liver metastases.

Background. The diagnostics of neuroendocrine tumors (NET) is complex due to many factors such as the heterogeneity of the tumors themselves, different localization of the tumor process, and the presence of severe hormonal syndromes. A special place in the diagnostic search is given to the study of biochemical markers which are conditionally divided into universal and specific ones.Materials and methods. Chromogranin A (CGA) is a universal marker that in most cases identifies tumors of a neuroendocrine nature and is characterized by the best combination of diagnostic sensitivity and specificity. Pancreatic polypeptide (PP) and neuron-specific enolase (NSE) are determined in addition to CGA in pancreatic tumors and in low-grade forms of neuroendocrine cancer. Specific markers, serum serotonin and its metabolite in daily urine 5-hydroxyindolacetic acid (5-GIUC), are the generally recognized specific markers for diagnosing of carcinoid syndrome. Other specific markers such as gastrin, insulin, glucagon, and others, are associated with certain hyperfunctional syndromes and are being investigated to confirm their presence. The article presents generalized recommendations for the use of biochemical markers, taking into account the existing clinical signs, syndromes, and types of NETs. To monitor the course of the tumor process and evaluate the effectiveness of treatment in patients with an established diagnosis of NET, it is recommended to determine the biochemical markers with increased basal levels. At the same time, there is a need to standardize the survey timing. For more accurate monitoring and interpretation of data, serial marker studies should be performed with the same test systems used in the same specialized laboratory.

The treatment efficacy and toxicity profile was evaluated in 33 patients with highly differentiated neuroendocrine tumors NEO (G1, G2), who received sunitinib therapy in various dose regimens. Stable disease was achieved in 24 patients (72.7%), partial effect in 1 patient (3%). The efficacy of treatment did not depend on the used dose regimen. The toxicity profile was consistent with international study data.

Gastric cancer (GC) is one of the most common types of malignant tumour worldwide and is ranked fifth in the cancer incidence pattern and third in the cancer mortality pattern. In the Russian Federation, 39.9% of patients are diagnosed with stage IV gastric cancer, 46.6% of patients die within the first year after diagnosis. The combinations of trastuzumab with platinum derivatives and fluoropyrimidines (trastuzumab + doublet) are regarded as the standard therapy against HER2 positive disseminated gastric cancer. We studied the efficacy and toxicity of the combination of trastuzumab with three-component (triple) chemotherapy regimens (docetaxel or irinotecan + platinum derivatives and fluoropyrimidines). In combination of trastuzumab with triplet chemotherapy, an objective response was achieved in 76.7% of cases, with doublet chemotherapy it was achieved in 60% (p = 0.228), of which complete tumour regression was observed in 10%, control of the disease was reported in 96.7% and 95.0 % (p = 1.0) patients, respectively. The median progression-free survival in patients, who received trastuzumab in combination with triplet chemotherapy, was 9.66 months, in combination with doublet chemotherapy was 11.07 months, the difference was not statistically significant (p = 0.800; OR = 0.908; 95% CI: 0.430–1.918). Median survival of patients is not achieved. The obtained results showed that adding a third cytostatic agent to the standard duplet chemotherapy in combination with trastuzumab does not lead to improvement in the treatment outcomes of first-line therapy in patients with HER2-positive disseminated gastric cancer.

Small cell cancer of the prostate is extremely rare. No sound on the research recommendations for the treatment of patients with small cell cancer of the prostate. The article gives its own observation of the patient’s small cell cancer of the prostate. A discussion of possible methods to treat such patients using own results and literature data.

Anaplastic lymphoma kinase (ALK) translocation is a rare genetic disorder that underlies lung cancer development. As a rule, these are young people, people with no or little smoking experience in whom the diagnosis is made at a late stage of the disease, when there are distant metastases; the liver and brain are often affected.The right choice of treatment policy in patients with ALK-positive non-small cell lung cancer can significantly improve survival rates. And molecularly targeted therapy with ALK inhibitors is effective even in these cases.Crizotinib (Xalkori). is the first ALK inhibitor that has been proven its antitumor activity. However, despite the initial pronounced antitumor effect, most patients develop drug resistance after 1–2 years of administration to krizotinib. In this case, the prescription of the second-generation drugs alectinib (Alecensa) and ceritinib (Zykadia) allows half of the patients to achieve a long objective response. Nevertheless today, alectinib in first-line demonstrates the best long-term results: the median progression-free survival is more than 34 months, 4-year overall survival rate is 64.5%. The drug has been shown a high activity in patients with brain metastases. Alektinib therapy not only has an advantage in terms of survival over Crizotinib, but also has an acceptable safety profile. This opens up new perspectives in the treatment of ALK-positive patients.