Vol 20, No 3 (2018)

Articles
The first experience of immunotherapy application of ipilimumab in combination with chemotherapy of small-cell lung cancer in the Russian population. Analysis of the combined data of two centers, participating in the multicenter randomized phase III study СА 184-156
Kuzminov A.E., Gorbunova V.A., Poddubskaya E.V., Bagrova S.G., Baranova M.P., Laktionov K.K.
Abstract
Introduction. Patients with advanced small cell lung cancer (SCLC) have an extremely poor prognosis on the background of standard chemotherapy combination of etoposide and platinum-based drugs. In a randomized, double-blind of СА184-156 phase III study, the efficacy and safety of ipilimumab (immune checkpoint inhibitor) or placebo in combination with etoposide and platinum drugs were evaluated as the first-line therapy of disseminated SCLC. The article deals with the results of treatment of patients with advanced SCLC, who participated in the international multicenter phase III study CA184-156 in two Russian Research Centers: the Department of chemotherapy (33 patients) and the Department of diagnostic (23 patients) N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. Materials and methods. Randomization of patients was carried out in a ratio of 1:1 in the group of therapy: etoposide + platinum drug (carboplatin or cisplatin) + ipilimumab and etoposide + platinum drug + placebo. Ipilimumab/placebo was administered at a dose of 10 mg/kg every 3 weeks in parallel with the third and fourth cycles of chemotherapy, further two administrations of ipilimumaba/placebo were performed at intervals of 3 weeks. Further, in the absence of progression, the maintenance therapy with ipilimumab/placebo was performed every 12 weeks. The main endpoints of the study were the assessment of progression-free survival (PFS) and overall survival (OS). Results. In the study CA184-156, the median PFS was 4.6 months in the chemotherapy group with ipilimumab (95% CI 4.5-5.0) and 4.4 months in the chemotherapy group with placebo (95% CI 4.4-4.6). There were no statistically significant differences. The analysis of 56 patients in the subgroup in our centers showed similar findings of median PFS: 4.4 and 4.3 months, respectivelyIn the study CA184-156, the median OS was 11 months in the chemotherapy group with ipilimumab (95% CI 10.5-11.3) and 10.9 months in the chemotherapy group with placebo (95% CI 10-11.5). There were no statistically significant differences. The analysis of 56 patients in the subgroup in our centers showed the following results: median OS was 9.7 months (95% CI 7.8-14) and 10.7 months (95% CI 6.5-20.1), respectively. The multifactorial analysis confirmed the significant effect of such factors as: ECOG 1/2 performance status and age on PFS, and ECOG 1/2 performance status and scheme of chemotherapy (etoposide + cisplatin/etoposide + carboplatin) on OS. Unexpected adverse events in the group of chemotherapy with ipilimumab were not noted. Conclusion. The addition of ipilimumab to chemotherapy did not contribute to an increase either in PFS or in OS in comparison with chemotherapy alone for advanced SCLC patients. Unexpected adverse events in the group of chemotherapy with ipilimumab were not noted. The study of the efficacy of ipilimumab in patients with disseminated SCLC in combination with PD1 inhibitors (nivolumab) is ongoing. The results obtained in the analysis of the data in the subgroups of patients, who participated in the study on the basis of the Department of chemotherapy (33 patients) and Department of diagnostic (23 patients) of N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation corresponded to the data received in the entire multicenter study CA184-156.
Journal of Modern Oncology. 2018;20(3):5-9
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The evolution of views on the possibilities of drug therapy in overcoming acquired resistance not associated with Т790М mutation to anti-EGFR drugs in non-small cell lung cancer
Karabina E.V., Lubchenko L.N., Garunov A.N.
Abstract
Understanding the mechanisms of acquired resistance to tyrosine kinase inhibitors is important for clinicians from the perspective of the possibility of forming more effective options for the second and subsequent treatment of non-small cell lung cancer. The prospects of treatment strategies for patients with non-small cell lung cancer featuring the acquired resistance to tyrosine kinase inhibitors, not associated with the Т790М mutation, are quite vast from a scientific point of view, but in routine clinical practice they are not yet available in full. This article describes the current understanding of the mechanisms of acquired resistance to tyrosine kinase inhibitors not associated with the mutation of T790M, the evolution of views concerning the treatment of non-small cell lung cancer, progressing in the course of the treatment by this group of drugs. The possibilities of effective use of targeted therapy and various combinations of antitumor agents in such cases are also considered. Taking into account the diversity of unresolved issues and directions of further scientific research, we should not forget about the available research results and the ability to use the described options in routine clinical practice in a proper way.
Journal of Modern Oncology. 2018;20(3):10-18
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Olaparib in the maintenance treatment of platinum-sensitive relapse of BRCA mutant ovarian cancer in routine clinical practice: first results of observational study in Russian patients
Artamonova E.V., Kovalenko E.I., Snegovoy A.V., Aksarin A.A., Anciferova T.A., Belonogov A.V., Bilan E.V., Bilenko S.N., Varvus I.M., Gorkovenko E.A., Enikeev R.F., Ermolaeva A.M., Kramskaya L.V., Kononenko I.B., Pechenyy A.P., Safina S.Z., Chupriyanova T.V., Chuhua G.G., Shemyakina A.I., Shikina E.V.
Abstract
Background and aims. There is no data on olaparib efficacy and safety in Russian routine clinical practice. Methods. We analysed the 30 consecutive patients who received maintenance olaparib treatment for platinum-sensitive relapse (PSR) of ovarian or fallopian tube cancer in Russian Cancer Centers. Patients were prescribed olaparib capsules 400 mg twice daily. Radiographic assessments were done every 8 weeks. Patient characteristics. Age median 55 (range 39-68); 26 (86,6%) patients had gBRCA1, 2 (6,6%) patients had sBRCA1, 2 (6,6%) patients had gBRCA2. Number of relapse: median 1 (range 1-10), number of lines of chemotherapy: median 2 (range 2-11). Last regimen of chemotherapy: taxane + platinum (± bevacizumab) 90% (27/30), platinum monotherapy 10% (3/30). Best response to the last chemotherapy complete response 43,3% (13/30), partial response 36,7% (11/30), stable disease 20% (6/30). Results. Median follow-up in 13 CR patients was 12 mos. 1 CR patient progressed after 9 mos of maintenance olaparib. Median follow-up in 11 PR patients was 7 mos. 3 PR patients achieved CR on olaparib. 1 PR patient progressed after 6 mos of olaparib maintenance. Median follow-up in SD patients was 12 mos. 1 SD patient achieved PR on olaparib, there were no progressions. 10 (30%) patients had adverse events (AEs). 1 patient had grade 3 AE and 2 patients had AEs leading to dose reduction. There were no grade 4 AEs. Conclusions. Olaparib is safe and effective maintenance treatment of PSR ovarian cancer in routine clinical settings.
Journal of Modern Oncology. 2018;20(3):19-25
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The role of capecitabine and eribulin in the treatment of metastatic HER2-negative metastatic breast cancer
Kolyadina I.V., Poddubnaya I.V.
Abstract
The review analyzed the role of capecitabine and eribulin in the treatment of HER2-negative metastatic breast cancer in patients pretreated with anthracyclines and taxanes. The mechanism of the antitumor action of capecitabine and eribulin, the efficacy in various biological subtypes of breast cancer and safety of treatment is described. The results of a comparative analysis of the efficacy and safety of eribulin monotherapy compared with capecitabine therapy as a second-line treatment for advanced HER2-negative breast cancer are presented.
Journal of Modern Oncology. 2018;20(3):26-29
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Diagnosis and treatment of metastatic melanoma of unknown primary
Krylovetskaya M.A., Komarov I.G., Karseladze D.A.
Abstract
Melanoma is a malignant tumor that originates in melanocytes. Melanoma is characterized by rapid and early development of metastatic disease. Most often, metastases develop in regional lymph nodes. Metastases of melanoma can be the first signs of advanced process and the only manifestation of the disease. Patients with metastatic melanoma of unknown primary site represent approximately 1 to 8% of all cases of melanoma and up to 12.6% of all cases of metastatic melanoma of unknown primary site. The understanding of clinical course of metastatic melanoma of unknown primary is necessary to determine disease prognosis. This article shows the analysis of issues devoted to the description of the clinical manifestations of the disease and the characteristics of the clinical course, depending on the localization of the tumor.
Journal of Modern Oncology. 2018;20(3):30-34
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Catamnesis of pediatric thoracic and abdominal cancer survivours
Mikhailova S.N., Zaeva G.E., Gavrilenko T.F., Sinyagina Y.V., Kazantsev A.P.
Abstract
Background. Malignancies of thoracic and abdominal localization are the second in pediatric oncopathology, after hemoblastoses. A progress in treatment of this heterogeneous tumors had been achieved by surgery approaches, chemotherapy, supportive care and irradiation role definition in multimodal therapy. Inspite of high survival rate, health condition of pediatric thoracic and abdominal cancer survivours in 5 years and more time in our country are unknown. Aim. To analyze health condition of pediatric thoracic and abdominal cancer survivours and kids, who were born in survivours families. Materials and methods. 324 patients, survived from thoracic and abdominal malignancies were enrolled the study from 1979 to 2015. Patients were subdided into 2 groups: 1st - 126 (38.9%) patients, treated from 1979 to 1996 and 2nd - 198 (61.1%) patients - from 1997 to 2015. Such approach aligned with historical treatment modification - upward 1996 modern anticancer treatment protocols are using and indications for irradiation are limited. Results. By improving therapy of nephroblastoma, decreased number of skeletal disorders from 11.5% in 1st group to 3.9% in 2nd, but increased concomitant renal complications from 5.3% to 21.5% and endocrinopathy from 2.4% to 6.7% in 1st and 2nd groups respectively. In hepar tumours survivours, chronic gastroduodenitis and pancreatoduodenopathy were registrated in 25% and 16% in 1st and 2nd groups respectively. In neuroblastoma survivours, locomotor system pathology (including osteoporosis) was found in 12.1%. Second malignant tumours in period from 8 months to 25 years after end of treatment were in 0,9%, benign - 1,6% of pediatric thoracic and abdominal cancer survivours. Kids, who were born in survivours families, had health condition as their equals in age without oncological family anamnesis. Conclusions. Catamnesis of pediatric thoracic and abdominal cancer survivours can predict possible complications, develop individual rehabilitation and personalized follow up programs. Besides, afterhistory data can help in development of complex treatment approaches for this heterogenous tumours.
Journal of Modern Oncology. 2018;20(3):35-42
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Vliyanie na prognoz estrogenovykh retseptorov a v opukholevykh kletkakh u patsientov, radikal'no operirovannykh po povodu nemelkokletochnogo raka legkogo
Novikov D.V., Polotskiy B.E., Bogush T.A., Davidov M.M., Ahmedov B.B., Rotobelskaya L.E.
Abstract
Aim. Evaluation of prognostic role of estrogen receptors a (ERa) expression level at patients with non-small cell lung cancer (NSLC) after surgical treatment. Methods and materials. 115 clinical cases of patients who underwent treatment in N.N.Blokhin Russian Cancer Research Center fr om 2009 to 2016 were studied. There were 95 males and 20 females. All patients had NSLC confirmed by histological analysis and followed-up for long term results. Results. There was no statistical evidence that the level of estrogen a expression in tumor cells has an impact on relapse free survival among men with both adenocarcinoma and squamous cell carcinoma of the lung. Similar results were obtained for women group. Also, no correlations between overall survival and the level of estrogen a expression were noticed among men and women. Thus ERa can’t be used as a predictor marker for patients with NSLC. Conclusion. The level of ERa expression in tumor cells among male patients does not influence on disease prognosis regardless stage of the disease and tumor morphology and can’t be used as a prognostic factor. The impact of the ERa expression level in tumor cells among female patients on disease prognosis is questionable.
Journal of Modern Oncology. 2018;20(3):43-50
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Clinical prognostic factors of bilateral synchronous renal cancer
Komarov M.I., Matveev V.B., Volkova M.I., Komarov I.G., Ridin V.A.
Abstract
The aim of the study is to assess the positive and negative prognostic factors of survival in patients with bilateral synchronous renal cancer (BRC). Materials and methods. The study was conducted on the basis of N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. Cohort of patients with the synchronous BRC consisted of 160 patients between 1996 and 2014. All patients after finishing treatment were observed on an ambulatory basis during the period from 11 months to 12 years (median follow-up 81.05±46.7 months). We studied factors affecting 5-year survival rate, both positive and negative. Statistical analysis of the obtained results carried out using generally accepted statistical methods such as SPSS 23.0 - block of programs for Windows. Results. In case of synchronous BRC in 2/3 (65%) of patients the first kidney was operated on using organ-preserving surgery, in 1/4 of patients (n=21, 26.2%) both kidneys were operated on using organ-preserving surgery. In case of synchronous renal cancer the best results of survival, but without statistical significance (p=0.112) had patients with bilateral renal cancer who operated on using organ-preserving surgery. The 10-year overall survival in this group of patients was 90.5% in comparison with 62.5% - when nephrectomy was performed on the first stage and 76.4% in patients who had nephrectomy performed because of the renal cancer in the second kidney. Conclusions. The main factors affecting the 5-year survival rate of patients with synchronous BRC were: smoking, primary tumor size, age and type of surgery.
Journal of Modern Oncology. 2018;20(3):51-54
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Differential diagnosis of lung cancer and tuberculosis: review
Belova O.S., Komarov I.G.
Abstract
The neglect of lung cancer and the unsatisfactory results of its treatment depend to a large extent on untimely diagnosis in the early stages of the disease. The reason for this is the absence of pathognomonic clinical signs and a specific radiographic picture of early lung cancer, which has to be differentiated from other respiratory diseases, including those occurring with infiltrative changes. According to statistical data, hyperdiagnosis of infiltrative pulmonary tuberculosis in patients with oncological diseases of the respiratory system was from 14 to 39%, which leads to long-term monitoring of patients with lung cancer in phthisiological institutions with anti-tuberculosis therapy, which causes delays in the treatment of patients with lung cancer. The pronounced visual similarity of various pathological processes of the lungs, the mixed incidence and immunodeficiency combined with subjective factors, such as gaps in the training of doctors, omissions in the survey method and the lack of continuity, can collectively be the cause of differential diagnostic errors. This article describes the similarities and differences between these diseases, the main causes of erroneous diagnosis, as well as the prospects for the development of modern diagnostic methods.
Journal of Modern Oncology. 2018;20(3):56-61
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