Vol 17, No 3 (2015)

Articles
Pamyati Gianni Bonadonna
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Abstract
В начале сентября мировое онкологическое сообщество потеряло одного из своих выдающихся деятелей - профессора Gianni Bonadonna. Профессор Gianni Bonadonna известен своими революционными работами в области рака молочной железы и лимфомы Ходжкина, на основании которых он был назван «отцом итальянской онкологии».
Journal of Modern Oncology. 2015;17(3):5
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Press-release Combination treatment with Vargatef® and docetaxel contributes to statistically significant tumor reduction in patients with progressive adenocarcinoma of the lung in comparison with docetaxel in monotherapy
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Abstract
Терапия препаратом Варгатеф® (нинтеданиб*) в комбинации с доцетакселом способствует значительному уменьшению и замедлению роста опухоли у пациентов с аденокарциномой легкого после 1-й линии химиотерапии по сравнению с монотерапией доцетакселом. У пациентов с прогрессирующей аденокарциномой, получавших комбинированную терапию препаратами Варгатеф® и доцетаксел, в течение 6 мес лечения наблюдалось более выраженное замедление роста опухоли - на 10% медленнее по сравнению с группой, получавшей плацебо в комбинации с доцетакселом. Выраженное преимущество комбинированной терапии препаратами Варгатеф® и доцетаксел было показано у прогностически наиболее неблагоприятной группы пациентов с прогрессирующей аденокарциномой легкого
Journal of Modern Oncology. 2015;17(3):6-7
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Rasprostranennost' melanomy
Demidov L.V.
Abstract
Заболеваемость меланомой растет более высокими темпами по сравнению с любыми другими новообразованиями.
Journal of Modern Oncology. 2015;17(3):8-9
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Molekulyarnaya biologiya i osnovnye geneticheskie narusheniya pri melanome
Demidova I.A.
Abstract
Сообщение посвящено генетическим нарушениям, возникающим и диагностируемым при меланоме.
Journal of Modern Oncology. 2015;17(3):9-10
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Sovremennyy podkhod k lecheniyu nerezektabel'noy i metastaticheskoy melanomy. Rol' ingibitorov BRAF i MEK
Stroyakovskiy D.L.
Abstract
Были рассмотрены подходы к лечению метастатической меланомы и определено место ингибиторов BRAF и MEK.
Journal of Modern Oncology. 2015;17(3):10-13
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Rol' klinicheskikh rekomendatsiy v vybore taktiki lecheniya patsientov s melanomoy kozhi
Kharkevich G.Y.
Abstract
В своем выступлении автор привела важные составляющие последних европейских и российских рекомендаций по лечению меланомы кожи.
Journal of Modern Oncology. 2015;17(3):13-15
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Osobennosti profilya toksichnosti ingibitorov BRAF i MEK
Protsenko S.A.
Abstract
Автор подробно остановилась на различных проявлениях токсичности ингибиторов BRAF (BRAFi) и MЕK (MЕKi).
Journal of Modern Oncology. 2015;17(3):15-17
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Osobennosti korrektsii naibolee chastykh nezhelatel'nykh yavleniy na fone primeneniya ingibitorov BRAF i MEK
Samoylenko I.V.
Abstract
Выступление было посвящено интерактивному разбору клинических случаев.
Journal of Modern Oncology. 2015;17(3):17-18
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Primenenie kombinatsii ingibitorov BRAF i MEK u patsientov s BRAF+ metastaticheskoy melanomoy
Vakhabova Y.V.
Abstract
Выступление было посвящено разбору клинических случаев. В ФГБУ РОНЦ им. Н.Н.Блохина было проведено клиническое исследование МЕК116513 по применению комбинации ингибиторов BRAF - BRAFi (дабрафениб, Тафинлар) и MEK - MEKi (траметиниб, Мекинист). В исследование были включены 13 пациентов.
Journal of Modern Oncology. 2015;17(3):18-20
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Atsellbiya® - opyt primeneniya pervogo bioanaloga rituksimaba v rutinnoy praktike klinitsista
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Abstract
Краткий обзор результатов регистрационного исследования препарата Ацеллбия® - российского биоаналога ритуксимаба
Journal of Modern Oncology. 2015;17(3):21-29
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Diagnosis and treatment of diffuse large B cell lymphoma in children and adults (review of literature)
Levashov A.S., Valiev T.T., Kovrigina A.M., Popa A.V., Mentkevich G.L.
Abstract
Diffuse large B-cell lymphoma (DLBCL) includes heterogeneous disease variants according to clinical, morphological, immunological, cytogenetic and molecular-biological features. Several different pediatric and adult protocols are presented in this article (AIEOP NHL92, B-NHL-BFM90, POG APO - IDM/HiDAC, B-NHL-BFM95, FAB/LMB96, BNHL03, FAB/LMB96 + rituximab, B-NHL2004m + rituximab, R-CHOP, DA-EPOCH-R, RB-CHOP, RBV-CHOP). There were revealed some factors of unfavorable outcome of disease in adult patients with DLBCL, that allow to improve risk group stratification and reduce chemotherapy intensiveness in some patients but require additional study in pediatric patients at the present time. Particular attention is paid to study of sensitiveness to target therapy (anti-CD20 monoclonal antibodies).
Journal of Modern Oncology. 2015;17(3):30-41
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Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial
Soria J., Felip E., Cobo M., Lu S., Syrigos K., Lee K.H., Göker E., Georgoulias V., Li W., Isla D., Guclu S.Z., Morabito A., Min Y.J., Ardizzoni A., Gadgeel S.M., Wang B., Chand V.K., Goss G.D.
Abstract
Background. There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. Methods. We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov, NCT01523587. Findings. 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6.7 months (IQR 3.1-10.2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib [median 2.4 months (95% CI 1.9-2.9) vs 1.9 months (1.9-2.2); hazard ratio (HR) 0.82 (95% CI 0.68-1.00), p=0.0427]. At the time of the primary analysis of overall survival [median follow-up 18.4 months (IQR 13.8-22.4)], overall survival was significantly greater in the afatinib group than in the erloinib group [median 7.9 months (95% CI 7.2-8.7] vs 6.8 months (5.9-7.8); HR 0.81 (95% CI 0.69-0.95), p=0.0077], as were progression-free survival [median 2.6 months (95% CI 2.0-2.9) vs 1.9 months (1.9-2.1); HR 0.81 (95% CI 0.69-0.96), p=0.0103] and disease control [201 (51%) of 398 patients vs 157 (40%) of 397; p=0.0020]. The proportion of patients with an objective response did not differ significantly between groups [22 (6%) vs 11 (3%); p=0.0551]. Tumour shrinkage occurred in 103 (26%) of 398 patients versus 90 (23%) of 397 patients. Adverse event profiles were similar in each group: 224 (57%) of 392 patients in the afatinib group versus 227 (57%) of 395 in the erlotinib group had grade 3 or higher adverse events. We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib [39 (10%) vs 9 (2%)], of grade 3 stomatitis with afatinib [16 (4%) vs none], and of grade 3 rash or acne with erlotinib [23 (6%) vs 41 (10%)]. Interpretation. The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung.
Journal of Modern Oncology. 2015;17(3):42-52
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The results of Epidemiological HER2 screening program in patients with breast cancer in 2014
Poddubnaya I.V., Frank G.A., Yagudina R.I., Koroleva N.I., Zavalishina L.E.
Abstract
Since 2006 the epidemiological HER2 screening program in patients with breast cancer was started in all federal regions of Russia. The main aims of this program were implementation HER2 diagnostic in routine practice and improvement diagnostic on regional level. The data received in frame of execution of this program is important additional information that used for analysis of annually published journal "State of Oncology Aid Rendered to Population of Russia". This article presents results of HER2 screening epidemiological program in 2014 and provides comparative data analysis since 2012 to 2014 years.
Journal of Modern Oncology. 2015;17(3):53-60
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Multimodal approach to the treatment of hepatocellular carcinoma
Skipenko O.G., Chekunov D.A., Shatverian G.A., Bagmet N.N., Sekacheva M.I., Polyakov R.S., Bedzhanyan A.L., Abdullaev A.G., Moysyuk Y.G.
Abstract
Background. Hepatocellular carcinoma (HCC) is a malignancy of the liver associated with poor prognosis. The understanding of the prevalence of liver damage and functional status of the liver can complicate therapy in these patients and often requires non-standard treatment approach. In this context, the study of the results of radical liver resection, locoregional and systemic therapy for HCC remains of current interest. Materials and methods. We analyzed the experience in the treatment of HCC in 70 patients, who were treated between 1991 and 2015. We studied the main demographic characteristics, local prevalence and liver status at the beginning of therapy, the application of therapeutic methods, intraoperative data, postmanipulation complications, overall and recurrence-free survival. The paper presents the following treatment options: liver resection (n=27), transarterial chemoembolization - TACE (n=16), radiofrequency ablation - RFA (n=3) and systemic therapy (n=4), TACE + transplantation (n=6), TACE + resection (n=3), TACE + sorafenib (n=3), resection + sorafenib (n=1), resection + RFA + sorafenib (n=2), transarterial embolization + resection (n=1), resection + RFA (n=1), TACE + resection + sorafenib (n=1), RFA + TACE (n=1), transarterial embolization + sorafenib (n=1). Results. Median overall survival (OS) was 33 months in the liver resection group, 5-year survival rate was 49%, and median recurrence-free survival (RFS) was 9 month, 1-year RFS rate - 40%. Median survival of patients who underwent TACE in mono-regimen (n=16) was 9 months; 1-year survival rate was 44%, the disease relapse after radical treatment, included resection and RFA (n=40) was noted in 25 (59.5%) patients. Median RFS was 9 months in this group. OS was significantly lower in group of patients with relapse of HCC in comparison with the group without recurrences (p=0.004). Conclusions. Although we see recent advances of interventional and drug therapy in patients with HCC, surgical treatment remains a priority. Liver resection allows radically remove malignant lesion and achieve the most satisfactory results, nowadays. The combined approach is a promising direction and the studying of the efficacy of combined treatment protocols and the development of new options will help us to improve the prognosis of treatment of HCC severe categories patients.
Journal of Modern Oncology. 2015;17(3):61-69
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Hereditary ovarian cancer
Demidova I.A.
Abstract
Epithelial carcinoma or ovarian cancer (OC) is the fifth most common cause of cancer mortality in women, and hereditary/familial OC occurs in 15-20% of all cases. Approximately 1/2 of these cases are developed due to germline mutations in the BRCA1/BRCA2 genes. OC associated with BRCA1/BRCA2 mutations are highly sensitive to platinum based chemotherapy regimens and to chemotherapy with the inclusion of targeted drugs. BRCA1 and BRCA2 mutations are multivarious, but they lead to one result: the synthesis of defective protein which is unable to participate in homologous recombination or damaged DNA reparation. There is an interesting fact that the large variety of mutations can be found in different ethnic populations. The Slavic Russian population is characterized by a "founder effect" in BRCA1 gene, especially in case of hereditary breast cancer. However, OC has its special characteristics as in the distribution of frequency BRCA1 mutations and occasional BRCA2 mutations, and in the incidence rate of somatic mutations in the same genes. This phenomenon requires special approach in case of choice of population, material for mutations testing and in choosing the most appropriate research methodology.
Journal of Modern Oncology. 2015;17(3):70-75
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Clinical and prognostic significance of matrix metalloproteinase-7 and vascular endothelium growth factor in patients with ovarian cancer
Knyazev R.I., Poddubnaya I.V., Bokin I.I., Barinov V.V.
Abstract
Matrix metalloproteinase-7 (MMP-7) is able to cleave almost all the elements of the extracellular matrix. It is believed that due to its ability to degrade the basal membrane, it is involved in the processes of invasion, metastasis and neoangiogenesis. Vascular endothelium growth factor (VEGF) has demonstrated its role in tumor progression. Subjects and methods. The study included 65 patients with tumors of the ovary, 44 cancer was diagnosed. Using enzyme-linked immunosorbent assay we determined the content of MMP-7 and VEGF in the serum and tumor tissue in patients with tumors of the ovary. Results. Serum levels of MMP-7 and VEGF are positively correlated with the prevalence of ovarian cancer (OC). In the tissue of adenocarcinoma of the ovary are determined higher levels of MMP-7 and VEGF than in tissue of benign tumors. In the tumor tissue of OC registered positive correlation between VEGF and MMP-7 (r=0.6); p=0.0001. The period of observation did not exceed 2 years from the start of treatment, median follow-up time was 14 months. Only the size of residual tumor after cytoreductive surgery is significantly associated with long-term results. Communication levels of MMP-7 with long-term results of treatment of OC patients is not established. Two-year disease-free survival in patients with baseline serum VEGF value of more than 440 PG/ml was 24%, less than 440 PG/ml - 55%. Conclusions. The levels of MMP-7 and VEGF in tumor tissue and serum in patients with OC increase with the prevalence and aggressiveness of tumor process. Elevated levels of VEGF can be considered as a factor of poor prognosis in patients with OC.
Journal of Modern Oncology. 2015;17(3):76-80
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Choice of anti-angiogenic agents in second-line treatment in patients with metastatic colon cancer: bevacizumab, aflibercept, ramucirumab (a literature review)
Fedyanin M.I.
Abstract
Over the last decade, the possibility of the drug therapy for patients with metastatic colon cancer (mCC) has increased due to the targeted drugs, because most of those drugs have had antiangiogenic activity (bevacizumab, aflibercept, ramucirumab, regorafenib). The combination of chemotherapy and bevacizumab, especially in the patients with mutations in the EGFR signaling pathway, is one of the standard therapy variant in first-line treatment of such patients. However, sooner or later, most patients will develop progression, and no one can say what kind of drugs will be added in 2nd-line treatment in this case. The subject of this review is the difficulty of choosing the sequence of therapy in patients with mCC using antiangiogenic drugs in first-line therapy.
Journal of Modern Oncology. 2015;17(3):81-87
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Adenosquamous carcinoma of the colon: case report
Nefedova N.A., Kharlova O.A., Malkov P.G., Kharlov N.S., Danilova N.V.
Abstract
Adenosquamous carcinoma of the colon is an extremely rare histological type of cancer (0.1% of all malignant neoplasms of the colon), and is characterized by a worse prognosis compared with adenocarcinoma. Here, we report a case of an adenosquamous carcinoma in a 67-year-old female, T3N0M1 (IV) stage.
Journal of Modern Oncology. 2015;17(3):88-90
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Experience of use of everolimus and long-acting somatostatin analogues combination in highly differentiated (G1-G2) neuroendocrine tumors
Markovich A.A., Kuzminov A.E., Orel N.F., Odintsova A.S., Emelyanova G.S., Gorbunova V.A.
Abstract
Everolimus is the targeted drug approved for the treatment of neuroendocrine tumors (NET). Efficacy of everolimus in combination with octreotide-depo has been shown in Radiant-2 randomized trial in patients with well-differentiated NET in different locations. Everolimus as monotherapy versus placebo was studied in patients with pancreatic NET in the framework of Radiant-3 randomized trial, where the statistically significant advantage of everolimus was proved. The article presents the experience of targeted therapy in 33 patients with highly-differentiated NET in different locations, and some aspects of everolimus use are analyzed. Efficacy, toxicity and long-term results of therapy are evaluated. Everolimus has demonstrated its efficacy in the unfavorable group of patients, most of whom were heavily pretreated with multiple courses of chemo - and biotherapy. Tumor growth control was 79%. Toxic complications were adequately managed by dose reduction of the drug without compromising its effectiveness. Moreover, clinically significant toxicity appeared an efficacy predictor as complicated cases showed twofold increase in median disease-free survival. Preliminary data suggest that therapy with everolimus is preferable at the first stages of treatment of NET.
Journal of Modern Oncology. 2015;17(3):92-95
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Latent herpes virus infection in the carcinogenesis of bladder cancer
Loran O.B., Sinyakova L.A., Gundorova L.V., Kosov V.A., Kosova I.V., Kolbasov D.N., Kononkov I.V.
Abstract
This article discusses the basic mechanisms of latency some of the herpes viruses and the role of persistence of these viruses in oncogenesis. A statistically significant increase of the level of viral antibodies in patients with recurrent, locally advanced bladder cancer with high potential of malignancy; the statistically significant correlations between the presence of viral DNA cytomegalovirus and Epstein-Barr virus in the tumor and the level of antibodies, the stage of the process and recurrent nature of the tumor were found. The presence of viral DNA in the tumor was determined in 30% of cases.
Journal of Modern Oncology. 2015;17(3):96-99
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Efficacy of cisplatin-based combinations in chemoradiation therapy of cervical cancer
Bazaeva I.Y., Gorbounova V.A., Kravets O.A., Khokhlova S.V., Romanova E.A.
Abstract
Introduction. High incidence of stage III-IV cervical cancer and high recurrence rate after treatment causes scientific research of alternative approach in patient’s treatment. Objective - improvement results of treatment patients with locally advanced cervical cancer (LACC). Materials and methods. 101 patients with T2b-3bN0-1M0-1 cervical cancer (M1 - paraaortic lymph nodes metastases by radiologic exam) received concurrent chemoradiation therapy followed by adjuvant chemotherapy (CT). External-beam conformal radiation therapy (EBRT) on pelvic and regional lymph nodes 50 Gy (25 fractions) with weekly chemotherapy: arm A - cisplatin 20 mg/m2 + paclitaxel 30 mg/m2, arm В - cisplatin 20 mg/m2 + irinotecan 20 mg/m2, arm C - cisplatin 40 mg/m2. Brachytherapy 30 Gy (4 fractions) following ERBT. In arm A and В after chemoradiation therapy patient received 2 cycles of adjuvant CT: paclitaxel 175 mg/m2 + cisplatin 75 mg/m2 every 3 weeks or irinotecan 65 mg/m2 on day 1 and 8 + cisplatin 75 mg/m2 on day 1 every 3 weeks. Results. All regimens shows high efficacy: objective responses in arm A obtained 96,9%, in arm В - 100%, in arm C - 100%. Median overall survival (OS) and progression free survival (PFS) in all arms not obtained. PFS at 1 year was significantly improved in arm A and В versus arm C: IIIb stage (arm A vs arm C, p=0,036; arm В vs arm C, p=0,005), pelvic lymph node metastases (arm В vs arm C, p=0,013), low-differentiation tumors (arm В vs arm C, p=0,013). 1-year OS did not shows improvement. Toxicity of all three regimens was tolerable. Conclusions. Our regimens showed high efficacy and tolerable toxicity. Significantly improvement in 1-year recurrence rate in poor-prognostic group of patients obtained encouraging results. Pending of medians OS and PFS allows to make the final conclusion about the benefits of combination chemoradiation therapy with adjuvant chemotherapy in LACC.
Journal of Modern Oncology. 2015;17(3):100-104
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Current understanding of the role of insulin-like and vascular endothelial growth factors in development, prognosis and targeted therapy in patients with ovarian cancer
Knyazev R.I., Poddubnaya I.V., Barinov V.V., Bokin I.I.
Abstract
The system of the insulin-like growth factors (IGF) through its mitogenic and antiapoptotic effects plays an important role in carcinogenesis. IGF with interaction with own receptor activates Ras - and Akt-signaling pathways that lead to enhanced cell proliferation and reduction of apoptosis. Via stimulation of proangiogenic factors, such as vascular endothelial growth factor (VEGF), IGF also mediates processes of neoangiogenesis that are necessary for the development, progression and metastasis of malignant tumors. Recent data show a linkage between IGF, VEGF and ovarian cancer. New drugs of targeted therapy for patients with ovarian adenocarcinoma, that inhibit the components of IGF and VEGF families, are under experimental and clinical trials. This review presents the results of investigations of IGF′ and VEGF′ role in the development, prognosis and treatment of patients with ovarian cancer.
Journal of Modern Oncology. 2015;17(3):105-108
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The treatment of patients with metastatic brain tumors Draft clinical guidelines
Golanov A.V., Bekiashev A.K., Dolgushin M.B., Kobiakov G.L., Naskhletashvili D.R., Smolin A.V., Nazarenko A.V., Medvedev S.V., Ilialov S.R., Vetlova E.R., Banov S.M.
Journal of Modern Oncology. 2015;17(3):109-117
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