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Purpose of the study. An analysis of changes in the expression of the VEGF neoangiogenic factor in the tumor tissue of patients with squamous cell carcinoma of the oral mucosa receiving targeted therapy with cetuximab and chemotherapy.Patients and methods. We performed an immunohistochemical study of tumor samples obtained from 60 patients with squamous cell carcinoma of the oral mucosa T3-4N0-1M0. The main group comprised 30 patients who received therapy with cisplatin and fluoruracil plus cetuximab. The control group included 30 patients receiving standard chemotherapy without targeted therapy. Each group was divided into two subgroups with different treatment efficacy: patients sensitive to treatment (n = 17 in the group with cetuximab and n = 12 in the group without cetuximab) and resistant to treatment (n = 13 in the group with targeted therapy and n = 18 in the group with standard chemotherapy).Results. Quantification of the VEGF expression demonstrated minimal numbers of vessels stained positively for this marker in the field of view in patients of the main group sensitive to chemotherapy and cetuximab. The value was 5.3 times lower than initial values, and 4.3 times lower than in the subgroup of patients resistant to the treatment (the data were statistically significant, р = 0.0132 and р = 0.0455, respectively). In the control group, patients who were sensitive to the treatment showed 1.4 times lower values than initially (р = 0.921), and patients who were resistant to the treatment had 1.1 times lower values than initial values (р = 0.936). The data were not statistically significant.Conclusions. The study showed that the number of microvessels in patients resistant to chemotherapy and cetuximab was 4.3 times higher than in patients with effective targeted therapy (р = 0.0455). The differences in the control group were not statistically significant.

Purpose of the study. An analysis of parameters of the blood coagulation system in breast cancer patients after coronavirus disease.Materials and methods. 50 breast cancer patients were divided into groups: the main group included 30 patients after coronavirus disease, the control group 1–20 patients without confirmed COVID‑19, and control group 2–20 non-cancer women after corona‑ virus disease. All cancer patients received appropriate chemotherapy. The following parameters were studied: activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), prothrombin index (PTI), fibrinogen, soluble fibrin monomer complexes (SFMCs), thrombin time (TT), antithrombin III, D-dimer and plasminogen, fibrin degradation products. Blood tests were performed 4–6 weeks after the infection and two negative PCR test results for COVID‑19.Results. Patients of the main group demonstrated differences in INR values after treatment in the subgroups with asymptomatic disease (Me = 1.24) and with mild symptoms (Me = 0.97) U = 10; Z = 2.766; р = 0.0057, in subgroups with asymptomatic disease (Me = 1.24) and with moderate to severe symptoms (Me = 0.98) U = 26.5; Z = 2.199; р = 0.027, and in TT values in subgroups with asymptomatic disease (Me = 14.5) and with moderate to severe symptoms (Me = 16.5) U = 18.5; Z = –2.725; р = 0.0064. The comparison of the parameters in patients after COVID‑19 before (Me = 0.83) and after treatment (Me = 0.4) showed differences in the D-dimer values in patients with moderate to severe disease U = 6.5; Z = –2.2861; р = 0.022 towards their decrease after the therapy. Differences were found in APTT values between the main group (Me = 30.65) and control group 1 (Me = 27.85) U = 119; Z = 3.574; р = 0.00035, in antithrombin values between the main group (Me = 94) and control group 1 (Me = 106) U = 112; Z = 3.713; р = 0.00021, and in SFMCs values between the main group (Me = 17) and control group 1 (Me = 8) U = 180.5; Z = 2.356; р = 0.018.Conclusions. Determination of plasminogen levels can become an independent factor in detecting thrombotic risk in cancer patients who recovered from COVID‑19. Previous infection with COVID‑19 should be considered an additional risk factor for venous thromboembolic complications for cancer patients.

Introduction. Erythropoietin (EPO) application is a pathogenetic method for anemia correction in cancer patients.The purpose of study. Clinical evaluation of the efficacy and safety of Eralfon® (epoetin alpha) in treatment for anemia in patients with malignant solid tumors during medical anticancer therapy.Materials and methods. We analyzed the data on anemia treatment with Eralfon® in 184 patients with malignant solid tumors receiving various medical anticancer therapies. Eralfon® was injected subcutaneously 12 000 IU 3 times per week or 40 000 IU once a week. Clinical antianemic effect, the time to maximum antianemic effect, adverse events (AE) were analyzed.Results. Patients were stratified by the grade of anemia, stages of treatment, presence of bone metastases, bleeding, previous medical and radiation anticancer therapies, dosage of Eralfon®. The time to effect was shorter in patients under 65. There were no significant differences in efficacy depending on the dosing regimen of Eralfon®. Efficacy was lower in patients with advanced tumors, especially in bone metastases. A history of tumor bleeding, chemotherapy and/or radiation therapy prolonged the period of hemoglobin recovery to normal values. Arterial hypertension and venous thrombosis were the most common AE associated with Eralfon®. Eralfon® 12 000 IU 3 times per week caused less frequent complications, with no cases of ossealgia and myalgia.Conclusion. Eralfon® demonstrated clinical efficacy in treatment for anemia in patients with solid malignant tumors receiving medical anticancer therapy. Dosage of 12 000 IU 3 times per week provided better control of the antianemic effect and adverse events.

The development of a new area of antitumor drug therapy, immunotherapy using immune checkpoint inhibitors targeting PD-1/PD-L1, has significantly changed approaches to the treatment of advanced non-small cell lung cancer (NSCLC). Many clinical trials have demonstrated the clinical benefit as well as the long-term effect of these drugs. Currently, the problem of treatment of patients after disease progression against the background of the use of checkpoint inhibitors is relevant. Equally relevant is the issue of choosing the correct and most effective treatment tactics for NSCLC patients with oligoprogression, as well as with abscopal effect. This paper describes a clinical case of a patient with lung adenocarcinoma without driver mutations with PD-L1-positive status, who was treated with nivolumab after second-line chemotherapy for disease progression, and after oligoprogression of the disease into the brain was given stereotactic radiotherapy of metastatic lesion and continued therapy with nivolumab. Partial regression of metastases was achieved with a prolonged effect on the background of continued treatment with nivolumab for 24 months. Tolerability of therapy was satisfactory: no adverse events were observed. The patient retained the result for 1.5 years.

The development of a new direction in anticancer medical therapy – the use of immune checkpoint inhibitors targeting PD-1/ PD-L1 and CTLA-4 – has significantly changed the approach to tumor treatment in the last few years. The PD1 blocker nivolumab in major registered clinical trials improved overall survival, including in metastatic melanoma, with a favorable toxicity profile. However, its efficacy in patients with brain metastases from melanoma was poorly studied, since the inclusion criteria for most clinical trials do not envisage recruiting such patients. The immune-mediated toxicity of immune checkpoint inhibitors is currently well enough studied. However, cases of cutaneous toxicity are quite rare and present certain difficulties for differential diagnosis and treatment. This article presents two cases of effective nivolumab treatment in patients with generalized BRAFwt and BRAFmut cutaneous melanoma. The first case is of interest due to the presence of brain metastases in the patient. Nivolumab therapy helped achieving complete regression of intracranial metastases with the long-term effect. The second case, in addition to effective treatment, demonstrates a rare manifestation of skin toxicity – vitiligo on the face and upper extremities.

Background. Breast cancer is one of the most common malignancies and one of the leading causes of cancer deaths among women in the Russian Federation. The prognosis of the disease is largely determined by thebiological subtype of the tumor. Her2-positive breast cancer is characterized by an aggressive course and unfavorable prognosis. The use of pertuzumab, a recombinant humanized monoclonal antibody to the human epidermal growth factor receptor 2, significantly improved immediate and long-term treatment outcomes. The aim of the study was to evaluate treatment outcomes in patients with Her2-positive molecular subtype of breast cancer receiving chemotherapy combined with a dual anti-Her2 blockade, and to assess the intensityand incidence of side effects. Material and methods. Between 2015 and 2018, 37 patients with Her2-positive breast cancer received chemotherapy combined with a dual anti-HER2 blockade (docetaxel 75 mg/m2 i/v on day 1 + trastuzumab 6 mg/kg (loading dose 8 mg/kg) i/v on day 1 + pertuzumab 420 mg (loading dose 840 mg) i/v on day 1 once every 3 weeks). The mean age of the patients was 45.6 ± 11.6 years. Results. Neoadjuvant pertuzumab in combination with trastuzumab and docetaxel resulted in pathological complete response in 12 % of patients and pathological partial response in 36 % of patients. Among patients who received the above neoadjuvant therapy regimen, disease progression was observed in 4 % of patients. The most common side effects were weakness and fatigue (5.4 % of cases) and grade I–II leukopenia (5.4 %).Conclusion. The study demonstrated the efficacy of antitumor therapy with pertuzumab in combination with trastuzumab and docetaxel as well as the absence of severe side effects associated with this treatment regimen in patients with Her2-positive breast cancer.

Patients with brain metastases of HER2-positive breast cancer (BC) is a special group of patients who are difficult to treat and have a short life expectancy. The possibilities of whole brain radiotherapy, stereotactic radiosurgery and surgery in such patients are rather limited. Trastuzumab emtansine (T-DM1) showed potential activity in this subset of patients. T-DM1 is an antibody-chemical conjugate (ADC) that delivers directly to HER2-positive cancer cells, thereby limiting damage to healthy tissue. At this point, the efficacy of trastuzumab emtansine has been demonstrated in several randomized trials as a second and subsequent lines of therapy for advanced breast cancer with a favorable toxicity profile of the drug. This article describes a clinical case of a patient with luminal B HER-2 positive breast cancer who, underwent stereotactic radiosurgery and was treated with trastuzumab emtansine as a the second line of treatment for disease progression with metastatic brain lesions after trastuzumab/pertuzumab-containing therapy. Partial regression of metastases with long-term duration of the effect was achieved treatment with trastuzumab emtazine has been being continued for 24 months. Tolerability of therapy was good: thrombocytopenia 2 degree was the main among side effects. The effect has been persisted for 2 years and the patient continues the treatment. Discussion of the results of real clinical practice with well-known studies was carried out.

Introduction: Squamous cell carcinoma of the oral cavity is one of the most common head and neck cancers with an aggressive course and high mortality rates. The aim of the study was to determine the EGFR expression levels in tumor tissues in patients with squamous cell carcinoma of the tongue and oral mucosa depending on the efficacy of the therapy. Material and methods: The study included 60 patients with squamous cell carcinoma of the tongue and oral mucosa T3-4N0-1M0. The main group included 30 patients receiving chemotherapy (cisplatin/fluorouracil) in combination with targeted therapy with cetuximab. The control group included 30 patients receiving chemotherapy without cetuximab. Both groups were divided into two subgroups: sensitive and resistant. Results: In treatment-resistant patients of the main group with cetuximab, the average EGFR expression was twice lower than the initial levels (p = 0.0080) and 1.7 times higher than in treatment-resistant patients of the control group (p = 0.0157). In treatment-sensitive patients, the average EGFR expression was 19.8 times lower (p = 0.0020) than initial values and 14.9 times higher (p = 0.0067) than in treatment-sensitive controls. Conclusions: A natural decrease in the EGFR expression in tumor tissues due to the targeted therapy was revealed. However, some patients were resistant to cetuximab, which dictates the need to search for predictors of targeted therapy efficacy in patients with locally advanced squamous cell carcinoma of the tongue and oral mucosa.

Background. Metastatic breast cancer is still an incurable disease, and is currently regarded as a chronic process requiring longterm treatment with periodic therapy replacements. Hormonal therapy shows its therapeutic efficacy with less toxicity and a better quality of life for patients compared with chemotherapy and is one of the main treatment for patients with luminal subtypes of breast cancer.The purpose of the study was to assess the efficacy and toxicity of fulvestrant in treatment for metastatic breast cancer.Material and methods. The study included patients with metastatic breast cancer with positive hormonal status developing progression after adjuvant treatment or chemotherapy or hormonal therapy due to metastatic cancer, ECOG≤2, with normal liver, kidney and marrow function. Fulvestrant was administered intramuscularly 500 mg once a month with a loading dose 500 mg on day 14 of the first month. The effect was evaluated every 3 months.Results. We analyzed the efficacy and safety of fulvestrant in second-line and over treatment of 20 patients with metastatic breast cancer. Overall response was 65% (13 patients), including partial remission (PR) in 2 (10%) and stabilization in 11 (55%) patients. Progression was found in 7 (35%) patients. The median of relapse-free survival was 6 month. 1-year overall event-free survival was 45%. The median of overall survival was not reached due to the short observation period. 1-year overall survival was 70%. Adverse events in our group of patients included asthenia (80%), hot flushes (25%), headache and nausea (20%).Conclusions. The efficacy of fulvestrant in patients with metastatic breast cancer was high enough and did not depend on the previous treatment, with a favorable toxicity profile.

The authors analysed the efficacy and safety of Nab-paclitaxel (Nab-R) monotherapy in patients with metastatic breast cancer with visceral crisis (VC) in the second- and further-line chemotherapy. The objective response rate (ORR) was 35.3% (6 of 17 persons). The most frequent side effects were general weakness, nausea, symptoms of peripheral neuropathy. The degree of toxicity did not exceed 1–2 in 60% of cases. The median time to progression was 7.8 months. (95% CI 6–10.6). The median overall survival for patients with VC was 14.9 months. (95% CI 12.0–16.9). Efficacy and controlled toxicity of Nab-P allows its use in pre-treated patients, including ones with VC.

The data of the efficacy and safety regorafenib in the treatment of 7 patients with metastatic colorectal cancer (mCRC) refractory to treatment with cytostatics and monoclonal antibodies - blockers EGFR and VEGF were analyzed. The maximum anti-tumor effect in 1 patient had partial remission, in 6 - stabilization. The duration of progression-free period from start of treatment regorafenib ranged from 1.5 to 6 months. 3 patients continued antitumor therapy after progression, 3 - had the symptomatic therapy after progression, 1 - had stabilization within 4 months and continued therapy of regorafenib. Toxic effects of therapy were nausea, vomiting, diarrhea, complications of the skin, temperature reaction, increased blood pressure, dysphonia. The most clinically significant adverse events were changes in laboratory parameters in 3 patients (increase of ALT, AST and bilirubin), that resulted an interruption in the treatment and correction of the dose. The use of regorafenib in mCRC ensure adequate tumor control, and is characterized by mild toxicity that is relevant for pretreated patients resistant to other forms of anticancer therapy.