Vol 21, No 1 (2019)

Articles
Efficacy and safety of eribulin in HER2-negative metastatic breast cancer: the results of long-term experience in real clinical practice in Russia
Gorbunova V.A., Kolyadina I.V., Kovalenko E.I., Manziuk L.V., Artamonova E.V., Zhukova L.G., Bolotina L.V., Semiglazova T.I., Manikhas A.G., Raevskaia N.A., Itkin I.M., Filonenko D.V., Zhilyaeva L.A., Gol'dberg V.E., Popova N.O., Ponomarenko D.M., Shikina V.E., Suslova I.R., Romanchuk O.V., Kozlov D.V., Rzaev A.S., Marfutov V.V., Andreiashkina I.I., Vladimirova L.I., Mitashok I.S., Tikhanovskaia N.M., Karabina E.V., Mukhametshina G.Z., Khasanova A.I., Safina S.Z., Shaidorov M.V., Morozov D.A., Prokof'eva E.P., Kramskaia L.V., Karandeeva T.V., Evstigneeva I.V., Ovchinnikova E.G., Klement'eva T.P., Khrupalo O.V., Tiuvinova E.V., Sherstnev V.M., Chernov I.S., Kolokolov D.D., Gaisina E.A., Levchenko N.V., Chubenko V.A., Povyshev A.I., Iudina I.V., Vorotilina L.V., Andreeva T.V., Tumanian G.S., Koziakov A.E., Gil'mutdinova L.A., Osipov M.A., Shatokhina A.S., Vazhenina A.A., Chichkanova A.S., Vladimirov V.I., Ivanov A.N., Belokhvostova A.S., Cherniakova E.M., Tul'china E.A., Maklashova S.A., Shkodenko O.N., Kostalanova I.V., Tarasova A.V., Kuz'mina E.S.
Abstract
Aim. The aim of the study is to examine the efficacy and safety of eribulin in HER2-negative metastatic breast cancer (BC) in Russian clinical practice. Materials and methods. The analysis included 459 patients with advanced BC from 44 federal and municipal medical clinics in Russia and received at least 2 courses of treatment with eribulin in accordance with the registered indications for drug. The average age of women was 56 years (between 29 and 81 years), 83% of patients had HER2-negative tumor subtype (49.9% - luminal BC and 33.1% - triple-negative BC) HER2-positive biological tumor subtype was registered in 17% of patients. Visceral metastases were diagnosed in 73% of patients and three-zone and multiple zone metastases were diagnosed in 41.6% of cases. The median number of prior lines of therapy in patients with disseminated disease was 2; anthracycline and taxane chemotherapy was applied in 94.3% of patients, and 38.1% of patients were recived CT plus capecitabine. Standard treatment regimen with eribulin was cotinuing (1.4 mg/m² as a 2-5-minute intravenous infusion administrated on days 1, 8 of a 21-day cycle) until disease progression, unacceptable toxic effects, or impossibility of the drug administration for any other reason. We estimated the efficacy and safety of treatment with eribulin in Russian patients with HER2-negative BC. Results. Objective response rate was achieved in 20.5% of cases, complete response rate was in 3.2%, partial - 17.3%, and the stable disease rate was marked in 52.7% of women, and in 19.7% of these cases was prolonged more than 6 months. The frequency of objective response was higher in luminal BC group compared with triple-negative BC: 23.5% vs 15.8%; tumor growth control 76.9% vs. 67.8%, respectively; p<0.05. Median progression-free survival was 4.83 months (5.17 months - luminal BC and 4.0 months - triple-negative BC). On application of eribulin in first-, second- and third-line treatment we achived maximum efficiency: the frequency of objective response rate was 24.2%, tumor growth control - 82.2%, median progression-free survival - 5.07 months; any data were achived on drug application in fourth-line and further lines of treatment: 15.4%, 58.6% and 4.27 months, respectively; p<0.05. We showed the group of women with "special response" to eribulin (72 cases, 19%) associated with the high efficacy of therapy, regardless of biological subtypes and metastases localization: objective response rate - 48.6%, long-term stable disease rate - 51.4%. The safety profile of eribulin was acceptable; the dose reduction to 1.1 mg/m² was required only in 14.2% of patients and after the reduction eribulin therapy was continued without moderate adverse events. Conclusions. Efficacy and safety of eribulin therapy in Russian patients completely confirm the results of earlier randomized studies. The combination of efficiency in tumors with different biological subtypes and a safety profile makes eribulin the therapeutic option of appling in patients with advanced anthracycline-and taxan-resistant BC.
Journal of Modern Oncology. 2019;21(1):12-23
views
Opportunities of the pharmacogenetic approach to personalized tamoxifen breast cancer therapy: case reports
Savelyeva M.I., Dudina I.A., Zaharenkova J.S., Ignatova A.K., Ryzhikova K.A., Sozaeva Z.A., Kudlay D.A., Perfileva O.M., Poddubnaya I.V.
Abstract
Tamoxifen is the selective modulator of estrogen receptors. Nowadays, it is widely used for treatment of premenopausal women with ER(+) breast cancer likewise for postmenopausal women with treatment contraindications to aromatase inhibitors. Tamoxifen is a prodrug which is metabolized by cytochrome P450 (CYP): CYP2D6, CYP3A4, CYP3A5, CYP2C9, CYP2C19 to active metabolites. There is high variability in the CYP genes therefore differences in tamoxifen metabolism, tamoxifen individual response and efficacy are observed among patients. This article presents two clinical case reports. Both patients have breast cancer luminal A subtype, similar prognosis and are administered tamoxifen but they have diverse clinical effects. Patients responded to the survey questionnaire, then samples of buccal epithelium were taken for genetic analysis of CYP2D6*4, CYP3A5*3, CYP3A4*17, CYP2C9*2,3, CYP2C19*2,3, ABCB1 gene mutations by use of real time PCR. In patient A samples were detected significant mutations in CYP2D6 (*1/*4), CYP3A5 (*3/*3) и CYP2С9 (*2/*3), but there were no mutations detected in patient B. It is interesting that patient B has had prominent tamoxifen adverse effects, such as flushes, ostealgia, faintness, after 1 month of tamoxifen therapy. Patient A has taken tamoxifen for 19 months without any adverse effects. Also there is a review in this article about clinical value of different CYP2D6, CYP3A5, CYP2C9 polymorphisms. Additionally, we make a suggestion about the role of polymorphisms in tamoxifen adverse effects and the way of solution for problems of tamoxifen resistance. We suppose that routine genetic study before tamoxifen administration would help to predict individual intolerance and increase the efficacy of treatment.
Journal of Modern Oncology. 2019;21(1):24-30
views
The potential use of oncolytic viruses in breast cancer: historical aspects and future prospects (literature review)
Morozov D.A., Kolyadina I.V., Poddubnaya I.V., Chumakov P.M., Ilinskaya G.V., Bokhian V.Y., Sopova M.I.
Abstract
Viral oncolysis, an approach to cancer therapy that emerged in the XX century and based on the natural ability of viruses to kill (lyse) cells in which it multiplies, has been developed in recent years by identifying viruses or their engineering variants with selective tumor replication. Over the past decades, a number of specific interactions of oncolytic viruses (both RNA and IDNA-containing) with malignant tumor cells have been described, individual candidate viruses and the types of tumors that they lase have been detected. The therapeutic efficacy of oncolytic viruses is achieved through a combination of selective destruction of tumor cells through a direct cytotoxic effect and activation of antitumor immunity; In addition, oncolytic viruses can affect abberant signaling pathways followed by blockade of tumor cell apoptosis, which gives the virus more time to complete its life cycle. A number of oncolytic viruses have shown promising therapeutic efficacy in preclinical studies in breast cancer; thus, the herpes simplex virus has a high selectivity for replication in tumor cells, which contributes to the death and the formation of infiltration of CD8+ and CD4+ T cells around tumor islands. The ability of reoviruses to enhance the expression of PD-L1 protein in cells was found, and the measles virus armed with the BNiP3 proapoptosis gene is more active in the cell lines of triple negative breast cancer. Improved viruses, from the point of view of the effectiveness and selectivity of effects on the tumor, as well as optimized combinations with other "standard" types of systemic therapy, are very promising, especially in patients with developed drug resistance.
Journal of Modern Oncology. 2019;21(1):31-35
views
Staging and identification of risk groups in pediatric germ cell ovarian tumors
Nechushkina I.V., Nechushkina V.M., Boychenko E.I., Susuleva N.A., Kazantsev A.P., Kerimov P.A., Nechushkin M.I., Rubansky M.A.
Abstract
Data on the staging and identification of the risk groups in pediatric germ cell ovarian tumors are presented in the review of the literature. Both staging and risk group identification are significantly different from accepted for adult patients.
Journal of Modern Oncology. 2019;21(1):36-39
views
Transthoracic biopsy under the control of computer tomography as a method for safe and effective morphological verification of the tumors of the chest cavity
Perepelevskiy A.N., Kiselev I.L., Nikulin A.I., Perepelevskaya Y.E., Frolova E.Y.
Abstract
Verification of volumetric peripheral neoplasms of the lung is quite a challenge for the modern minimally invasive methods of diagnosis. Aim. Application of transthoracic trepan biopsy of the thoracic cavity organs under the control of computed tomography to obtain morphological material with high accuracy and to make a correct diagnosis. Materials and methods. From January 2017 to December 2017 103 patients underwent a transthoracic biopsy of lung tumors and mediastinum under the control of computer tomography. Results. The effectiveness of the study was 96.2%. Complications in the form of post manipulation pneumothorax developed in 8.5% of cases. This technique is safe and effective and should be used in the daily diagnosis of tumors of the cavity chest.
Journal of Modern Oncology. 2019;21(1):40-44
views
HPV-associated lesions in the Russian Federation: assessment of the problem
Briko N.I., Lopukhov P.D., Kaprin A.D., Novikova E.G., Trushina O.I., Khaldin A.A., Isaeva D.R., Skvortsova A.I.
Abstract
Aim. To estimate the prevalence and trends of the long-term dynamics of morbidity and mortality associated with various manifestations of HPV infection in Russia in recent years. Materials and methods. We analyzed retrospective data with diagnostic codes related to cervical cancer, penile cancer, anal canal cancer, head and neck cancer (including the oral cavity, oropharynx, larynx and larynx), anogenital (venereal) warts from the official statistic of cancer register and STIs using incidence and mortality rates in Russia between January 2007 and December 2016 and retrospective data with diagnostic codes related to cancer of the vulva and cancer of the vagina between January 2011 and December 2016. Based on the available data on the involvement of HPV in the occurrence of pathological changes, the annual generalized indices for HPV-associated neoplasms were calculated. Results. The estimated number of HPV-associated lesions in the Russian Federation for 2007-2016 amounted to 5 761 170 cases, of which 224 630 - among men and 5 536 540 - among women. The estimated number of deaths from HPV-associated cancers was 109 510 cases, of which 32 080 - among men and 77 430 - among women. The estimated incidence of HPV-associated cancers neoplasms during this period increased by 10% among the male population and by 22% among the female population, reaching 8.0 cases per 100 000 male population in 2016 and 25.2 cases per 100 thousand female population. The death rate from HPV-associated cancers did not change significantly, and in 2016 it was 4.9 cases per 100 thousand male population and 10.2 cases per 100 thousand female population. Conclusion. There is an increase in morbidity and stabilization of mortality rates from HPV-associated cancers for both female and male populations, and a decrease in the incidence of anogenital (venereal) warts.
Journal of Modern Oncology. 2019;21(1):45-50
views
Molecular-biological marker Bcl-2 in colorectal cancer: the characteristics, the role of mechanisms regulating apoptosis, the effect on the prognosis (review of literature)
Darenskaia A.D., Dobrova N.V., Stepanova E.V.
Abstract
Background. Many studies concerning molecular-biological markers in colorectal cancer (CRC) were performed over the past decade. Вcl-2 protein (B-cell lymphoma 2) was one of the most studied molecular-biological markers and attracted the attention of different specialties as on studying carcinogenesis and the relationship with prognosis. Aim. To study in details the characteristics of Bcl-2; to study Bcl-2 role in the mechanisms regulating apoptosis; to show update data concerning the prognostic significance of this protein in CRC. Materials and methods. To write this literature review we have studied domestic and foreign publications from Russian and international systems of search (PubMed, eLibrary, etc.) over the past 2-30 years. Results. The evaluation of the expression of antiapoptopic protein Вcl-2 in tumor can give additional information about the course of malignant process independently of therapeutic effects, the biological behaviour of the tumor: the rapidity of growth, the ability of invasion and metastasis (i.e. the prognosis of a disease). Conclusion. The results concerning the impact of abnormal expression of apoptosis inhibitor Вcl-2 on the course and prognosis of CRC have been accumulated in the scientific literature, but there have been only several studies, analyzing the relationship between Вcl-2 and metastasis of CRC and factors influencing the invasive potential of tumor cells. Nowadays, there is no consensus about the prognostic significance of protein Вcl-2 in patients with CRC. In some studies, concerning CRC, have been shown the correlation between Bcl-2 overexpression in tumor cells and a favorable course of disease and good survival in patients. Other authors have been shown that tumors with Bcl-2 overexpression, by contrast, are more aggressive in comparison with tumors without Bcl-2 expression. There are a number of studies in which the prognostic significance of Bcl-2 protein is not proved. Many issues, concerning the correlation between this molecular-biological marker and clinico-morphological characteristics of tumor, might also need to be itemized. All shown in the article is a subject to further research.
Journal of Modern Oncology. 2019;21(1):52-58
views
Treatment of cancer-related thrombosis: from recommendations to real clinical practice
Somonova O.V., Elizarova A.L., Blindar V.N., Dobrovolskaya M.B., Nesterova Y.A., Borisenko N.N., Kornyushenko U.A., Davidova T.V.
Abstract
Aim. To highlight the modern treatment and secondary prevention of recurrent thrombotic complications in patients with cancer. Materials and methods. We studied 40 scientific sources published in the Russian and foreign press in the period of 1997 to 2018. Results. Oncology patients are at higher risk of thrombotic complications which can worse outcomes of antitumor treatment and occupy one of the leading places among causes of death. Low molecular weight heparins (LMWHs) are the drugs of first choice for the treatment of cancer-associated thrombosis. Taking into account the complexity of LMWH application, many patients stop receiving the recommended therapy and are switching to oral anticoagulants. For instance, according to the GARFIELD-AF prospective registry direct oral anticoagulants (DOACs) are used in 25% of cancer patients. The most promising drug in this group is rivaroxaban (Xarelto). Multiple studies are currently undergoing in the framework of CALLISTO Program, designed to study various issues of managing patients with cancer-associated thrombosis: primary and secondary prevention of thrombosis using rivaroxaban, to study quality of life and the treatment adherence. In the Mayo Clinic Thrombophilia database retrospective study was demonstrated comparable efficacy of rivaroxaban and LMWH and in the studies US claims analysis and US Humana database were noted the reduction of recurrences of thromboembolic complications on using rivaroxaban treatment in comparison with LMWH on the same frequency of severe bleeding. In subanalysis of the prospective XALIA study was showed a favorable profile of efficacy and safety of rivaroxaban therapy in cancer patients, so the results proved the results of real practice. Conclusion. In 2018 the results of submitted studies helped several international societies, such as International Society on Thrombosis and Hemostasis and The National Comprehensive Cancer Network, to recommend rivaroxaban as one of the treatment options for patients with cancer-associated thrombosis with low risk of bleeding and no drug-drug interactions with current systemic therapy. Rivaroxaban can be considered as an alternative to low molecular weight
Journal of Modern Oncology. 2019;21(1):60-65
views

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies