Vol 19, No 1 (2017)

Articles
Molecular characteristics of premalignant breast lesions
Vysotskaya I.V., Letyagin V.P., Pogodina E.M.
Abstract
The article is devoted to clinical and prognostic significance of the levels of markers, traditionally defined in breast cancer in the cohort of patients with benign breast diseases. The following parameters are analyzed: steroid hormone receptors, the proliferative activity of the micro-RNA, the expression of COX-2, E-cadherin gene amplification of c-erb-B2 and TP53. Identify the most important of them in various benign diseases and akzhe most typical changes that occur in diffuse dyshormonal dysplasia, fibroadenomas and atypical hyperplasia.
Journal of Modern Oncology. 2017;19(1):5-8
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Albumin-bound paclitaxel in the treatment of metastatic breast cancer
Artamonova E.V.
Abstract
Metastatic breast cancer (mBC) continues to be an incurable disease, but modern drug therapy, associated with the steady extension of the arsenal of active cytostatic drugs and the development of new treatment options, provides the long-term control of tumor growth, transforming into chronic pathology. Nab-paclitaxel (nanodispersed albumin-bound paclitaxel) is one of such options. This innovative dosage form provides the active transport of the drug through the vascular endothelium with the creation of the high concentration in the tumor tissue. Clinical trial of nab-paclitaxel compared with traditional taxanes (paclitaxel and docetaxel) have demonstrated high efficiency of a new drug both in the general population and in the selected subgroups of patients, including treated with anthracyclines, patients with invasive disease, damages of the visceral organs, younger patients and others. Nab-paclitaxel proved to act in patients treated with taxanes, the physician can use this drug one again and thus we have another line of therapy. Nab-paclitaxel can be effectively and safely combined with trastuzumab in patients with mBC associated with HER2+. In addition, the drug because of the unique formula does not cause hypersensitivity reactions and differs from traditional taxanes of the variant of application. No need for premedication with dexamethasone let us appoint the drug in patients with comorbid conditions: severe arterial hypertension, diabetes, gastric and duodenal ulcers and others. High safety of nab-paclitaxel was approved in elderly patients as well.
Journal of Modern Oncology. 2017;19(1):17-23
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Predictive factors of achievement pathological complete response at neoadjuvant chemotherapy of primary operable breast cancer
Pavlikova O.A., Kolyadina I.V., Komov D.V., Vishnevskaya Y.V., Poddubnaya I.V.
Abstract
Objective. To study the predictive factors of achievement pathological complete response (pCR) at neoadjuvant chemotherapy primary operable breast cancer. Materials and methods. Analyze of the rate of pCR after neoadjuvant systemic therapy in different clinical factors and biological characteristics was made for 164 patients (24-76 years; median - 47 years) treated in RCRC from 2004 to 2016. Results. Predictive factors for high rate of pCR after neoadjuvant systemic therapy in primary operable breast cancer were hormone negative status, HER2-overexpression, Ki-67≥20% and Grade 3 of tumors, p<0.05. Extremely low frequency of pCR was observed for HER2- negative luminal cancer (0% - for luminal A and 10.7% - for luminal B subtype); the highest rate of pCR was seen in HER2+ breast carcinomas (50% - non luminal; 38.1% - luminal) and in patients with triple-negative cancers (34.5%), p=0.003. The rate of pCR depends from type of neoadjuvant chemotherapy: the highest rate pCR (71.4%) was seen in serial combination anthracycline → taxanes and platinum regimes; 58.3% - in taxanes and platinum combination; 51.7% - in anthracycline and taxanes combination, p=0.001. Neoadjuvant chemotherapy with trastuzumab in HER2 + breast cancer reached the highest pCR (71.4%), p=0.001. Conclusions. The optimal assignments of neoadjuvant chemotherapy in primary operable breast cancer are the patients with HER2+ carcinomas (at adding trastuzumab) and triple negative breast cancer. Neoadjuvant chemotherapy in luminal HER2-negative breast cancer is associated with very low rate of pCR, which makes it inappropriate in this cohort of patients.
Journal of Modern Oncology. 2017;19(1):24-29
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The characteristics of determination of BRCA1 and BRCA2 mutations in serous ovarian cancer
Demidova I.A.
Abstract
Mutations of the BRCA1/BRCA2 genes occur in 15-20% cases of ovarian cancer (OC) and are associated with increased sensitivity to platinum drugs and new target drugs that inhibit proteins of poly(ADP-ribose) polymerase family. The discovery of new therapeutic options in the treatment of patients with OC associated with mutations of the BRCA1/BRCA2 genes is resulted in significant changes in national and international clinical guidelines and in the development of new approaches for identification of mutations in the Russian Federation. The first results of the project of Russian Society of Clinical Oncology aimed at improvement of molecular genetic testing in the Russian Federation and associated with enhancing the effectiveness of antitumor treatment (www.cancergenome.ru), have showed the relevance of new two-stage testing algorithm including next-generation sequencing in special groups of patients. 1385 patients with platinum-sensitive relapsed OC were examined. BRCA1 and BRCA2 mutations were found in 22% of patients. BRCA1 gene mutations were found in 93.5% of cases and in 6.5% of cases - BRCA2 mutations. Next-generation sequencing helped to identify another 47 mutations and to determine mutations frequency - 0.03-2.3%. Statistically significant mutations were determined in patients with classical signs of familial cancer and in patients under 50 years of age. Continuation of this project would fully describe the characteristics of group of patients with mutations of the BRCA1/BRCA2 genes as the candidates for new and highly efficient therapy.
Journal of Modern Oncology. 2017;19(1):30-33
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The role of bevacizumab in the treatment of patients with ovarian and cervical cancer
Khokhlova S.V.
Abstract
The development of cytostatic therapy in the treatment of ovarian and cervical cancer has resulted in a deadlocked situation. Thus, the basic aim of the investigations was to examine the biological basis of these diseases, last years. Angiogenesis is one of the main factors of the tumor microenvironment, associated with tumor growth and metastasis. In this regard, new drugs that work by inhibiting angiogenesis have started to appear. One of the first drugs studied in randomized phase III studies was bevacizumab. The application of bevacizumab demonstrated the significant increase both in progression free-survival and life expectancy in high-risk group of patients with ovarian cancer and in patients with recurrent and advanced cervical cancer.
Journal of Modern Oncology. 2017;19(1):34-41
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Pharmacoeconomic aspects of biosimilars
Tryakin A.A., Rudakova A.V., Fogt S.N., Vaganov A.S., Tolkacheva D.G.
Abstract
The tendency towards replacement of reference preparation for biosimilars can be observed around the world. Registrational studies, concerning biosimilars suggest the comparison of pharmacokinetics and pharmacodynamics of drugs, as well as their clinical efficacy, tolerability and immunogenicity in comparison with the original drugs. Biosimilars of monoclonal antibodies (bevacizumab, trastuzumab and rituximab) registered in Russia are widely used in oncology. The introduction of biosimilars to the pharmaceutical market has reduced costs (15-85%) on appropriate biological products and increased the availability of medicinal aid. Costs of rituximab have reduced by more than RUB 900 mln for the past 3 years of using biosimilar of rituximab in patients under 7 High-Cost Nosologies Federal Program. The first results of the treatment using such biosimilars as bevacizumab and trastuzumab in 2016, showed a significant increase in the availability of vital and highly effective drugs.
Journal of Modern Oncology. 2017;19(1):42-47
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Pharmacoeconomic characteristics of ixabepilone (Ixempra) monotherapy in patients with locally advanced and metastatic breast cancer resistant to treatment with anthracyclines, taxanes and capecitabin
Kolbin A.S., Mosikyan A.A., Kurilev A.A., Balykina Y.E., Proskurin M.A.
Abstract
This article represents data on economic evaluation of treatment with ixabepilone (Ixempra) as a single agent for patients with metastatic breast cancer with ineffective pretreatment with taxanes, anthracyclines and capecitabine. Two health technologies were evaluated: Ixabepilone as a single agent at the 1st day of a 21-day cycle of chemotherapy versus eribulin also as a single agent at the 1st and the 8th days of a 21-day cycle. Cost-effectiveness analysis is performed on the basis of published data and Markov modeling. As a result, ixabepilone as a single agent appeared to be economically reasonable as compared to eribulin as a single agent in case of ineffective pretreatment with taxanes, anthracyclines and capecitabine. Total expenditures for Ixabepilone strategy were 13.6% less than those for eribulin treatment. Furthermore, ixabepilone was found 16% more effective in terms of median progression-free survival, as compared to eribulin as a single agent. Sensitivity analysis has proved the results obtained in the main scenario. Price elasticity analysis revealed the equality of total expenditures on ixabepilone and eribulin treatment at a price of ixabepilone equal to 88 000 rubles per 45 mg vial and 30 298.87 rubles per 15 mg vial of ixabepilone.
Journal of Modern Oncology. 2017;19(1):48-53
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The comparative pharmacoeconomic analysis of tyrosine kinase inhibitor Iressa® (gefitinib) with TKI Giotrif® (afatinib) as first-line therapy for patients with advanced non-small cell lung cancer associated with mutations in the epidermal growth factor receptor
Ryazhenov V.V.
Abstract
This article deals with the pharmacoeconomic comparative analysis of different strategies of pharmacotherapy using low-molecular-weight tyrosine kinase inhibitors (afatinib and gefitinib) in patients with non-small cell lung cancer associated with mutation in the epidermal growth factor receptor (EGFR). We determined that gefitinib had clinical and economic benefits associated with the reducing financial costs and better cost effectiveness index.
Journal of Modern Oncology. 2017;19(1):54-57
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Anxiety and cognitive impairment in elderly patients with gastrointestinal cancers
Stilidi I.S., Kotyukova A.Y., Lyadov V.K.
Abstract
Introduction. Gastrointestinal cancer is a major healthcare problem in Russia, especially among elderly patients. Anxiety and cognitive disfunction are undersrudied in those patients. Aim. To evaluate in a pre-operative fashion the prevalence of anxiety and cognitive impairment in patients with different gastrointestinal tumors. Materials and methods. We performed a retrospective analysis of anxiety according to HADS scale and cognitive function by MoCA test in 297 patients operated between 2012-2015 for colon (54%), stomach (21%), liver (17%) and rectum (8%) tumors. Patients in the age 60-74 years constituted 35%, 75 years and older - 34% of the whole cohort. Results. We found a correlation between age and anxiety level as well as age and cognitive impairment, Spearman correlation 0.77 and 0.79, respectively. No differences according to tumor location or patient sex were shown. Anxiety didn't influence the length of hospital stay regardless presence of complications. Conclusion. An individualized oncopsychological assessment and tailored approach to treatment shall be developed in patients with gastrointestinal cancers according to anxiety and cognitive impairment.
Journal of Modern Oncology. 2017;19(1):61-63
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The choice of treatment method in patients with complicated gastrointestinal stromal tumors. Clinical observation and literature review
Nered S.N., Stilidi I.S., Shalenkov V.A., Arkhiri P.P., Perfilev I.B., Kalinin A.E., Bozhchenko Y.A., Glukhov E.V.
Abstract
Gastrointestinal stromal tumors (GISTs) can be complicated with gastrointestinal bleeding, ileus, gastrointestinal perforation at the site of tumor, spontaneous intraabdominal bleeding because of ruptured GIST and the formation of necrotic cavities in the tumor communicated with the lumens of hollow organs. Common practice in such cases is combined use of surgery with imatinib treatment. The article deals with the data of literature review concerning the incidence and clinical characteristics of complications in patients with different tumors. We showed the clinical study, where imatinib therapy was used as the first part of the treatment patients with luminal GIST of the stomach, complicated with gastric bleeding. Neoadjuvant therapy had significantly reduced tumor sizes; improved the condition of the patient and helped us to perform surgery.
Journal of Modern Oncology. 2017;19(1):64-68
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Posterior reversible encephalopathy syndrome in children with hematological and oncology diseases
Delyagin V.M., Serdyuk O.A., Balashov D.N., Skvortsova Y.V., Tereshchenko G.V.
Abstract
Subject. Posterior reversible encephalopathy syndrome (PRES) is often a complication in the treatment of hematological and malignancy diseases, in the post-transplant period in children. Objective. Describe the clinical, magnetic resonance imaging (MRI) and electroencephalography (EEG) changes in children with PRES. Materials and methods. We observed 7 patients with PRES aged 5-22 years (2 of them girls) with hematologic and malignancies diseases. Results. PRES developed because of hypertension in 6 patients, during immunosuppressive therapy (cyclosporine and methotrexate). 3 patients had generalized seizures. We observed in 1 child hyperkinesis of oral musculature, eye deviation, impaired consciousness. Development of hypertensive syndrome, altered mental status, visual disturbances were observed in 3 patients, 2 of them combined with a headache. Repeated signs of PRES were observed in 2 children, one of these as tonic-clonic seizures. According to the MRI changes were observed in patients of white matter of the brain predominantly parietal-occipital regions. EEG during debut PRES were recorded expressed diffuse changes in brain activity in the background recording marked disorganization brain activity slow waves and persistent hemispheric asymmetry. Local changes epileptic nature recorded in 1 child in the form of slow waves emphasis in the central parietal regions of the left with the inclusion of acute a-waves and single generalized paroxysm, the 2-nd - in the form of single epileptic complexes “sharp-slow wave” in the fronto-central department right, in the 3-rd - as a hotbed of epileptic activity in the fronto-temporal department left a sharp wave complexes and “sharp-slow wave”. These local changes in EEG corresponded described MRI picture of these children. PRES outcome was epilepsy in 2 patients, 3 children clinical-radiological symptoms were reversible. Underlying disease was fatal to 3 children. Conclusions. For the diagnosis of PRES and its outcome is paramount early clinical-radiological diagnosis with MRI registration, including the registration of EEG.
Journal of Modern Oncology. 2017;19(1):69-74
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The results of the treatment of patients with advanced hepatocellular carcinoma in Sverdlovsk region
Petkau V.V., Tarkhanov A.A., Kiselev E.A.
Abstract
The aim is to assess treatment outcomes of patients with advanced hepatocellular cancer (HCC) in daily clinical practice through the example of SHI Sverdlovsk Regional Oncology Dispensary. Materials and methods. The data of regional cancer registry, annual reports of SHI SROD and HCC patients’ medical records were retrospectively studied. 542 patients with stage III and stage IV primary liver cancer applied to outpatient department of SHI SROD in the period of 2011 to 2015. Morphological verification was received in 53 (9.8%) patients. These patients received antitumor treatment: surgery, transarterial chemoembolization (TACE), sorafenib therapy, chemotherapy and the combination of these methods. We examined median overall survival (OS) based on the stage of the process and on tactics. Results. The incidence of malignant neoplasms of the liver has increased in the Sverdlovsk Region over the past 5 years: from 5.58 to 7.6 cases per 100 000 population in men and from 4.93 to 5.1 - in women. Mortality rate has remained at the same level. We determined 82% of patients with stage III and IV HCC. Patients with intermediate-stage (stage B) HCC (n = 21) according to the Barcelona Clinical Liver Cancer staging system underwent surgery (10 patients) or TACE and doxorubicin (11 patients). Median OS was 20.7 and 13.3 months, respectively. Patients with advanced-stage (stage C) HCC (n=32) had undergone surgery before the start of sorafenib therapy (6 patients), TACE (8 patients), TACE plus sorafenib therapy (4 patients) and only sorafenib therapy (4 patients) or cytostatic systemic therapy (10 patients). Median OS was minimum (5.3 months) in the group of patients who had received only chemotherapy. Median OS was maximum (18 months) in sorafenib-treated patients and in patients who had undergone surgery. Conclusions. More than 80% of patients with stage III or IV HCC and with poor general condition usually apply to hospital and thus limiting the possibility of further antitumor treatment. The best approaches to the management of patients with advanced HCC are the combination of methods associated with local effect (surgical treatment and/or TACE) and systemic therapy using such drug as sorafenib.
Journal of Modern Oncology. 2017;19(1):75-79
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Own experience of treatment by epoetin-α (Eralfon®) of chemotherapy induced anemia
Bolshakova S.A., Bychkov Y.M., Kazarova M.V.
Abstract
Epoetin-α - is a medication, stimulating erythropoiesis. Is currently also used for the treatment of anemia induced by chemotherapy. Patients and methods. 124 patients with various solid tumors and a hemoglobin level <120 g/l received epoetin-α (Eralfon®) 10 000 ME or 12 000 ME three times a week. An evaluation of the increase in hemoglobin level was made, as well as an assessment of the pharmacoeconomic efficacy of various dosage forms. Results. It was noted that during chemotherapy with platinum, the hemoglobin level significantly increases with the use of an Eralfon® 12 000 ME. For patients weighing <70 kg, it is economically advantageous to use Eralfon® 10 000 ME, for patients ≥70 kg - Eralfon® 12 000 ME. The safety profile of both dosages is quite favorable.
Journal of Modern Oncology. 2017;19(1):80-84
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