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Meditsinskiy sovet = Medical Council

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No 19 (2018)
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https://doi.org/10.21518/2079-701X-2018-19

News. Findings and events

Immunotherapy in oncology

12-16 707
Abstract

Immunotherapy has already become an important component of the standard treatment of patients with advanced cancer. Most treatment methods include monoclonal antibodies (mAbs) that block immune checkpoints, in particular, the programmed cell death 1 (PD-1) receptor and its ligand 1 (PD-L1) or are directed against T-lymphocyte-associated protein 4 (CTLA-4). The future prospects for immuno-oncology will be to determine whether these agents can be more effective if administered in a postoperative adjuvant or in a neoadjuvant regimen prior to surgical treatment. Vaccine therapy has shown promising results, and this therapy is especially attractive due to absence of pronounced toxicity.

Target therapy of tumors

17-21 817
Abstract

The process of angiogenesis is essential for the growth and spread of malignant tumours. Antiangiogenic therapy is deeply embedded in the standard treatment of disseminated ovarian cancer (OC). The numerous studies have demonstrated its efficacy in various stages of the therapy of this disease; bevacizumab is the best-investigated anti-angiogenic drug for OC. This article presents a review and analysis of the most significant studies of the efficacy of anti-angiogenic therapy in ovarian cancer, and describes various aspects of its use in this disease.

22-26 972
Abstract

The most effective first-and subsequent line drug regimens for metastatic colorectal cancer (mCRC) suggest the inclusion of targeted drugs (TD). The choice of TD for the second-line therapy takes into account not only the biological features of the tumor and the general condition of the patient, but also the option of the previous line therapy, its effectiveness and toxicity. Treatment with anti-EGFR antibodies (AT) did not significant improve overall survival (OS) in comparison with chemotherapy in the secondline regimens, in contrast to antiangiogenic drugs. Among this group of MAT, aflibercept provides the best results in a selected group of patients (the highly effective group) and a controlled toxicity profile.

28-30 1542
Abstract

Treatment of choice of metastatic hormone-dependent breast cancer regardless of age is hormone therapy (HT) even with visceral metastases. Now we have a new class of drugs called inhibitors of cyclin-dependent kinases 4/6, which significantly increase effectiveness of HT and prevent development of resistance to HT. In MONALEESA-7 inhibitor of cyclin-dependent kinases 4/6 ribociclib was studied in combination with ovarian suppression and hormone therapy in young patients with preserved ovarian function, and found no differences in the efficacy and safety of these drugs compared with menopausal patients. Our clinical experience strongly demonstrates the safety and efficacy of ribociclib in combination with HT and ovarian suppression in premenopausal patient with visceral metastases.

32-41 977
Abstract

Today, the researchers continue the search for the most optimal regimens of drug therapy for metastatic colorectal cancer (mCRC) which are supposed to increase progression-free survival (PFS) and overall survival (OS), improve patient quality of life. Due to significant progress in chemotherapy (CT) and surgical treatment of mCRC, and the multidisciplinary approach, the treatment algorithms have changed. The increase in life expectancy of patients is observed when all three of the most active chemotherapy drugs in this disease: oxaliplatin (Oxa), irinotecan (Iri), fluoropyrimidines are administered. The inclusion of the targeted drug cetuximab in modern mCRC treatment regimens led to a statistically significant increase in the objective response rate (ORR), median PFS and OS. The article presents the results of the most significant clinical studies of the eficacy of the antiEGFR drug cetuximab in combination with standard CT regimens for the first- and second-line treatment of mCRC, and describes a clinical case of the successful use of cetuximab in mCRC therapy.

Malignant tumor chemotherapy

42-49 636
Abstract

A study that enrolled 30 patients with advanced colorectal cancer, who had not previously received any specific drug treatment, was conducted to develop and study a three-component regimen with oral fluoropyrimidine tegafur (Ftorafur) in outpatient practice. The study evaluated the time to disease progression (TDP), the overall survival (OS) of patients, who received irinotecan + oxaliplatin + Ftorafur in the first-line therapy, as well as the effectiveness and safety of this regimen. 6 patients received a 3-week chemotherapy cycle (Fig. 1), 24 patients – a 2-week chemotherapy cycle (Fig. 2). The preliminary results of the study have been obtained. The median OS was not reached, the median TDP was 8.5 months. In Group I, there was partial regression of metastasis in 3/6 patients, and prolonged disease stabilization (≥ 6 months) in 3 patients. The therapeutic effect (partial remission + long-term stabilization ≥ 6 months) was observed in all patients. The duration of TDP was from 6 to 15 months. In group II, the effect was evaluated in 24 patients, who received at least 2 chemotherapy cycles. 14/24 patients had a partial response (PR), of which 4 (16.6%) patients were radically operated, 6 patients elicited disease stabilization. Thus, control over the disease was achieved in 83.33% of patients in Group II. Oxaliplatin combined with irinotecan and fluorafur was effective, had an acceptable toxicity profile, and therefore, can be used in debilitated patients with disseminated disease.

50-55 750
Abstract

Colorectal cancer (CRC) is a genetically heterogeneous disease, which prognosis and efficacy of treatment are determined by the localization of the primary tumour (left- and right-sided tumours). CRC ranks high in prevalence in the Russian Federation, a quarter of cases are diagnosed at stage IV. The choice of the most optimal therapy regimen is a topical issue for a modern oncologist, who has time-proven combinations of chemotherapy and modern targeted drugs in the arsenal. The aim of this article is to provide a pharmacoeconomic review, taking into account both clinical and economic parameters of one or another CRC pharmacotherapy regimen. As a result, it was found that the use of chemotherapeutic regimens in the first- and second-line therapies of patients with CRC is the most pharmacoeconomically justified as compared with the use of targeted therapy at the initial stage.

56-60 1085
Abstract

The article considers the place of nab-paclitaxel in the treatment of metastatic breast cancer. A number of studies have shown high efficacy and acceptable toxicity in comparison with traditional taxanes. The low frequency of hypersensitivity reactions allows the use of nab-paclitaxel in patients who had reactions with the introduction of traditional taxanes and in the presence of contraindications to corticosteroids premedication. The absence of cross-resistance makes possible to prescribe nabpaclitaxel in patients who had progression on treatment with paclitaxel and docetaxel. The cases of effective use of the drug from our own practice are presented.

62-66 846
Abstract

Despite significant advances in recent years, the drug therapy for breast cancer (BC) is still based on chemotherapy. The introduction of new effective cytostatic agents with a favorable toxicity profile is likely to remain an urgent objective for modern pharmacology in oncology. Ixabepilone, first in a new class of antineoplastic agents, the epothilones, has demonstrated high efficacy in the treatment of breast cancer both in its early stages and in patients, who have received 2 or more lines of chemotherapy. The article discusses the results of major studies, as well as the last meta-analysis of Ixabepilone studies in locally advanced and metastatic breast cancer. It presents the results of two large randomized studies of Ixabepilone in adjuvant regimens in patients with early breast cancer with an unfavourable prognosis.

68-72 666
Abstract

The article describes a clinical case of ALK-positive non-small cell lung cancer and its long-term treatment with a chemotherapy drug pemetrexed as first-line regimen followed by pemetrexed maintenance therapy.

Hormonotherapy

73-75 578
Abstract

In recent years, several studies have indicated that aromatase inhibitors (AIS) combined with a gonadotropin-releasing hormone agonist (GnRH agonist) are safe and effective in premenopausal patients with hormone receptor positive (HR+) breast cancer (BCA). The ABCSG-12 trial has shown a comparable DFS for 3-eyar adjuvant therapy with anastrazol-goserelin and tamoxifengoserelin. However a combined analysis of the data from SOFT and TEXT trials demonstrated that compared with tamoxifen plus ovarian suppression, adjuvant endocrine therapy with exemestane plus GnRH agonist (Triptorelin) in premenopausal patients with a significant improved DFS and an extended interval without distant recurrence. The differing results emerging from ABCSG-12 and the TEXT and SOFT trials misht be related to higher statistical power in the combined analysis.

76-84 1003
Abstract

Aromatase inhibitor (AI) combined with Gonadotropin-releasing hormone agonist (GnRH-a) have been recognized as an effective approach to adjuvant endocrinotherapy for breast cancer (BC) in premenopausal patients with adverse predictive factors. However, the risk of non-optimal suppression of the ovaries due to the mechanism of action of aromatase inhibitors has been proven. Recently published SOFT-EST studies showed that the blood estradiol (E2) level in 37% of patients was above the level that was permissible for the purpose of this group of drugs. And although today there is no enough scientific justification to interpret this result, the introduction of aromatase inhibitors in adjuvant therapy in young women requires the search for tactics to reduce the risk of mediated increase in estradiol against the background of such therapy. Alertness occurs when the E2 serum level exceeds the menopause limit by the time the aromatase inhibitors are prescribed. Objective of the study. Determine the tactics for minimizing the risk of increasing estradiol against the background of aromatase inhibitors in combination with GnRH-a in adjuvant therapy for breast cancer in premenopausal patients. Material and methods. 47 patients of ≤ 50 years old with GR + HER2- Stages I-III Breast Cancer and a regular menstrual cycle before the start of neo-/adjuvant chemotherapy were studied. E2 and FSH levels were assessed at the stage prior to chemotherapy and immediately prior to administering adjuvant endocrinotherapy. After the completion of chemotherapy, only 7 out of 47 women had the menstrual cycle - patients without clinical and biochemical suppression of ovarian function (SOF). 86% of cases had cytostatic amenorrhea (n = 40), of which 23 cases (58%) showed that this condition was not combined with the biochemical response of sex hormones, i.e. there was no biochemical SOF. Thus, the study group included 30 patients, who were supposed to be treated with aromatase inhibitors + GnRH analogues, and had no clinical or biochemical menopause by the time adjuvant endocrinotherapy was prescribed. In order to reduce the risk of mediated increase in estradiol, even with pharmaceutical “switching off” ovarian function, the patients were prescribed the GnRH analogue (Buserelin Depot) before starting aromatase inhibitors therapy. Results and conclusion. A progressive decrease in E2 level was determined after each subsequent administration of Buserelin Depot. The median values remained low only after the third injection. Following the chemotherapy, a decrease in estradiol was accompanied by a physiological increase in the FSH levels in 73% of women. The administration of Buserelin Depot led to a significant decrease in FSH median (p <0.01) in 90% of patients. Aromatase inhibitors and continuing GnRH-a were prescribed to 97% of patients. The results indicate that the achievement of ovarian function suppression prior to the administration of IA, can be considered as a reliable tactics for adjuvant endocrinotherapy in patients of reproductive age. The dynamic assessment of reproductive hormones (E2, FSH) is recognized useful when choosing or correcting therapy in such patients.

Oncourology

90-94 807
Abstract

Pazopanib is an oral multitargeted tyrozine kinase inhibitor that is used in advanced renal cancer in most countries of the world. Pazopanib inhibits tyrosine kinase receptors involved in tumor angiogenesis and proliferation, including VEGF, platelet-derived growth factor (PDGF) and stem cell growth factor receptor c-Kit, which leads to inhibiting angiogenesis, growth and proliferation of tumor cells. In clinical trials, pazopanib demonstrated improvement of progression-free survival (PFS) versus placebo in previously untreated patients and patients treated with cytokines, as well as the absence of worsening PFS versus sunitinib in the first-line therapy of clear cell RCC in the good- and intermediate prognosis groups. In addition, pazopanib demonstrated a better safety profile than sunitinib. The results of use of pazopanib in broad clinical practice are consistent with data from randomized trials that confirms the high efficacy combined with good tolerability of this drug even in patients who do not meet the generally accepted criteria for the inclusion in clinical trials.

96-100 1050
Abstract

Prostate cancer (PC) is the most pressing oncourological pathology due to a steady increase in morbidity and mortality from this pathology in the Russian Federation. The detection frequency of the common forms of the disease remains high. The combined chemo-hormonal therapy is the main method of treatment of metastatic prostate cancer. The refractoriness of the tumour to the ongoing castration therapy is an inevitable stage of the course of the disease in all patients receiving androgen deprivation therapy. However, castration therapy aimed at reducing endogenous testosterone in this cohort of patients should be continued. Eligard is one of the most studied drugs to conduct the drug castration therapy in patients with prostate cancer, which efficacy has been proven in numerous clinical studies in both continuous and intermittent mode using depot forms of various durations of action. The article presents a review of clinical studies that assessed the efficacy of Eligard therapy in different regimens and with the use of depot forms of various duration, which demonstrated equal effectiveness of such forms.

ONCOHEMATOLOGY

101-105 1008
Abstract

Progress in the treatment of Hodgkin lymphoma are among the most significant achievements of oncology of our age. Nevertheless, an early relapse or refractory course of the disease account for approximately 15–20% of cases. It was this category of patients, in which the target drug brentuximab vedotin was successfully used for the first time. This is an anti-CD30 (a cell surface antigen) humanized monoclonal antibody conjugated via a protease-cleavable linker to the cytostatic agent monomethyl auristatin E, the potent tubulin inhibitor. This article describes the characteristics of CD30 antigen and a new preparation, as well as clinical data confirming its efficacy, the results of major reviews and research on the use of brentuximab vedotin in mono and combination therapy regimens at the different stages of treatment for Hodgkin lymphoma.

Supportive care in oncology

106-112 766
Abstract

Oncourologic diseases are accompanied by a risk for subsequent venous thromboembolic complications, which are rated the most dangerous in terms of thrombogenic effect. The article presents a review of the clinical studies of efficacy and safety, and the experience in using of modern low-molecular-weight heparins in clinical practice - drugs of choice for the prevention of venous thromboembolic complications in cancer patients. Particular attention is paid to Bemiparin - a new second-generation low-molecular-weight heparin with a significant antithrombotic effect and improved pharmacological parameters that allow it to be successfully used in patients with impaired renal function in oncourological practice.

113-115 806
Abstract

Approaches to treating pain in cancer patients are individual in each case. However, there are general principals. Most often, physicians encounter difficulties when transfer patients from tramadol to more potent tertiary preparations of WHO Analgesic Ladder. The administration and titration of strong opioids to a dose that will ensure adequate pain control with minimal side effects is not an easy task. Here, the physician focuses on the pathogenesis of pain and takes into account the tolerability of drugs prescribed. Individual selection of adjuvants that can affect the cause of pain can reduce the rate of strong opioid dose escalation their side effects. However, what to do, if the use of effective adjuvants is limited? The article provides the discussion of these issues.

116-121 922
Abstract

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:64 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 of Group 1 (n=34) 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. Patients of Group 2 (n = 30) received 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). The quality of life of patients was assessed by Functional Living Index of emesis (FLIE). Results: During the first cycle of chemotherapy complete control of nausea and vomiting was achieved at 20 (58,8%) patients of Group 1 and at 4 (13.3%) %) patients of Group 2 (p<0.05). The average score on the Functional Living Index of emesis (FLIE) scale in Group 1 was 19.88, in Group 2-38.03 (p<0.05). Conclusion: Adequate regimen for prevention of nausea and vomiting is combination of NK1 receptor antagonist, 5-HT3 receptor antagonist and dexamethasone.

Original studies

122-125 684
Abstract

At the present time, a small group of patients with oligometastases (who have a solitary metastatic lesion in another organ along with the primary tumour of the lung) is differentiated among the patients with metastatic lung cancer. A total of 14 patients of the study citied in this article underwent a comprehensive treatment of oligometastatic non-small cell lung cancer (ONSCLC), which included systemic therapy and local influence on solitary metastasis. The median overall survival for this group was 20 months (16.0–32.6, CI 95%). The 1-year and 2-year overall survival rates accounted for 84.5 and 65.7%, respectively. The findings of the study demonstrate the possibilities of an aggressive approach to the treatment of patients with ONLDLC.

126-129 771
Abstract

Sarcoidosis is a systemic epithelioid cell granulomatous disease of unknown etiology, which prevalence has increased over the past three decades. The objective of this work was to analyse the register of patients with sarcoidosis, in which the patients from the Republic of Tatarstan were entered for the period from 1969 until now. Methods. A patient database was created and processed using the SPSS18 program with the calculation of frequencies, means, errors of the mean and confidence interval. The authors analysed the data at the time of detection of sarcoidosis. Results. A total of 2477 patients (69.9% of women) aged from 15 to 87 years old (44.04 ± 0.26 (12.9) years) were entered in the register. There were 28.7% under the age of 35, 51.6% were 36–55, and 19.8% were older than 55 years. Radiation stages were distributed as follows: 0 - 0.9%, I - 42.6%, II - 46.2%, III - 9.4% and IV - 0.8%. 13.1% of newly diagnosed patients had a Lofgren’s syndrome. Histological verification was carried out in 40.9% of cases. 31.4% of patients were affected by occupational or environmental factors that might negatively influence their health. The number of new cases of sarcoidosis in Tatarstan began to grow from 1995 (50 new cases) with a peak in 2016 (141 cases), which corresponds to the opinion of leading international experts on sarcoidosis, who reported an increase in the incidence rate over the last three decades. The proportion of verified patients in these years varied around 50%, reaching a maximum of 60.5% in 2012. Out of the total number of 1014 verified cases, 62.8% validated the diagnosis in oncological institutions, 25.2% in multidisciplinary institutions, 8.0% in phthisiological institutions, and 1 case at autopsy. Histological material (video-assisted thoracoscopy) was obtained in 75.1% of cases, and aspirate obtained during bronchoscopy was used in 24.9% of cases. Active monitoring was the most commonly used disease management (37.3%), vitamin E was used in 23.4%, vitamin E and pentoxifylline in 21.2%, systemic glucocorticosteroids were used in 14.9%, methotrexate was used in 1.7%, inhaled steroids in 1.3%, antibiotics in 0.2%, azathioprine in 0.1% and N-acetylcysteine was used in 1 patient. Conclusion. In Tatarstan, verified cases did not exceed half of cases against the background of increased detection of patients with sarcoidosis and the availability of skilled care. Patient management was consistent with modern international guidelines.

CLINICAL OBSERVATION

130-135 605
Abstract

Targeted therapy is the optimal treatment of patients with advanced EGFR-positive NSCLC. The first- and second-generation EGFR tyrosine kinase inhibitors provide a durable antitumor response in most patients during the year. Due to appearance of T790M secondary mutation of resistance at progression of the disease, the administration of osimertinib leads to full control of the tumour for another 10 months. However, this is not the only mechanism of acquired drug resistance. A repeated biopsy of the tumour followed by histological and molecular genetic research makes it possible to clarify the cause of resistance and personalize the further disease management.



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ISSN 2079-701X (Print)
ISSN 2658-5790 (Online)