Vol 19, No 3 (2017)

Articles
BCD-100 - first russian PD-1 inhibitor
Tyulyandin S.A., Fedyanin M.Y., Semiglazova T.Y., Moiseenko V.M., Odintsova S.V., Alekseev B.Y., Ivanov R.A., Shustova M.S.
Abstract
Purpose. To evaluate pharmacokinetics, pharmacodynamics, safety, immunogenicity and efficacy of intravenous infusions of BCD-100 (JSC “BIOCAD”, Russia) in increasing doses. Patients (materials) and methods. Patients with advanced malignant tumors of various localizations without severe somatic pathology were consistently included in cohorts receiving the BCD-100 drug in monotherapy at different doses (0.3, 1.0, 3.0 and 10 mg/kg) every 2 weeks for at least 85 days. Safety, pharmacokinetics, pharmacodynamics, immunogenicity and efficacy of the therapy were assessed. Results. 15 patients were included in the study. The vast majority of adverse events were represented by deviations in the results of laboratory tests of 1-2 grade, there was only one confirmed case of dose-limiting toxicity (autoimmune thyroiditis of 2 grade). Pharmaco kinetic parameters were standard for drug based on monoclonal antibodies of class IgG1. The saturation of PD-1 receptors by BCD-100 was high (90-100%) at all dose levels. 1 partial response to antitumor therapy and 3 stabilization cases according to irRC criteria were registered. conclusion. BCD-100 demonstrated a favorable profile of safety and immunogenicity, expected pharmacokinetic parameters allowing the drug to be administered once every 2 or 3 weeks, high pharmacodynamic parameters and the presence of antitumor activity.
Journal of Modern Oncology. 2017;19(3):5-12
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Olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer
Khokhlova S.V.
Abstract
Ovarian cancer (OC) is the fifth most common cancer in women in developed countries. Despite advances in treatment of epithelial OC: improving techniques and increasing aggressive surgery, the appearance of new cytostatics, targeted drugs, - the overall survival (OS) rates are unsatisfactory (the overall 5-year survival is 38%) and there is still an urgent need in development of new therapeutic agents to improve the results of treatment women with this disease. Olaparib is the first poly (ADP-ribose) polymerase (PARP) inhibitor, which demonstrates the high efficacy of treatment patients with OC associated with mutations in the BRCA genes. And olaparib is approved as a maintenance monotherapy in the treatment of women with platinum sensitive recurrent BRCA-associated OC. This review deals with the information concerning the efficiency and toxicity of olaparib, showing practical guidance on the application. The article focuses on the toxic effects of the drug, which can occur during olaparib therapy, and shows the guidance on management of the disease. Nausea, vomiting, fatigue and anemia are the most commonly reported side effects of olaparib application in clinical studies. Side effects are usually recorded in mild to moderate degree and nondurable. Using proper application and timely monitoring for side effects one can control many toxic actions.
Journal of Modern Oncology. 2017;19(3):13-18
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Regorafenib: from clinical research to clinical practice
Fedyanin M.Y., Tryakin A.A.
Abstract
Regorafenib is a new multiple tyrosine kinase inhibitor with anti-cancer and anti-angiogenic activity which application has been recently approved by the Russian Federation in patients with colon cancer and gastrointestinal tumors. The approval of application of regorafenib for the treatment of patients with hepatocellular carcinoma is expected. This review discusses the main clinical studies of the drug: the steps of appointment, the prevention and the treatment of the complications using new tyrosine kinase inhibitor; the views of the Russian and foreign experts who should help chemotherapist in the clinical practice.
Journal of Modern Oncology. 2017;19(3):19-24
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Eribulin for the treatment of anthracyclineand taxane-resistant breast cancer: a big step forward towards problem solving
Artamonova E.V.
Abstract
The article shows the role and significance of eribulin in the treatment of anthracycline- and taxane-resistant breast cancer, describes the mechanism of action of eribulin and represents the results of a phase III randomized study of the efficacy of the drug in the treatment of breast cancer and soft tissue sarcomas. The article deals with the data of the real clinical practice and the studies of eribulin in different combinations.
Journal of Modern Oncology. 2017;19(3):25-34
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Diagnosis and treatment of malignant trophoblastic tumors: errors, dangers, complications (review of the literature)
Gasanbekova Z.A., Aliev S.A., Meshcheryakova L.A., Kozachenko V.P., Kuznetsov V.V.
Abstract
Early diagnosis of malignant trophoblastic tumors (MTT) and their possible complications is important for the timely and successful treatment of the disease while preserving young women's reproductive function. This article reflects the principles of diagnosis based on an integrated approach, as well as modern methods of treating MTT, primarily chemotherapy, regimens of which have been standardized to date. Unfortunately, having clear algorithms for diagnosis and treatment, we continue to face various kinds of errors, both at the stage of diagnostic search and at the stage of treatment of MTT. The most significant errors allowed by clinicians in the main sections on the way of diagnosis and management of patients are discussed within the framework of the article. The urgency of the problem is obvious, because at the cost of such errors are not only the loss of reproductive potential, but also the unjustified death of young women from a potentially curable disease.
Journal of Modern Oncology. 2017;19(3):35-41
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The experience with the application of first-line chemotherapy regimen with EDP-M (etoposide + doxorubicin + cisplatin + mitotane) in patients with advanced adrenocortical carcinoma in the Russian Federation
Kolomeytseva A.A., Yemelyanova G.S., Gorbunova V.A., Orel N.F., Perevodchikova N.I., Bokhyan V.Y., Fedenko A.A.
Abstract
A combination of etoposide, doxorubicin and cisplatin plus mitotane (EPD-M) is the most effective regimen in patients with advanced adrenocortical carcinoma (ACC). Because in the Russian Federation mitotane is not registered, there are no publications about the effectiveness of EPD-M in the Russian patients. In the chemotherapy department of the NMITS of oncology named N.N.Blokhin of the Ministry of Health we conducted a retrospective analysis of the efficacy and tolerability of the EDP-M regimen as a first-line treatment in advanced ACC. We enrolled 24 patients with histologically confirmed ACC. Evaluation of the treatment effectiveness and toxicity was possible in 23 patients. Six patients (26%; 95% CI 8-44%) achieved a partial response, disease control rate was observed in 14 patients (61%; 95% CI 41-81%). Median time to progression was 4.9 months. Three patients (12.5%) were performed a radical surgical resection of residual disease after 6 cycles of chemotherapy. Then patients continued mitotane monotherapy after surgical resection. Treatment was well tolerated, with grade III and IV toxicities consisting of neutropenia in 8 (33%) patients, anemia in 1 (4%) patient, asthenia in 3 (12.5%) patients. The central neurotoxicity associated with mitotane, was observed in 2 (8.3%) patients. The EDP-M regimen is a well-tolerated and active regimen in patients with advanced ACC.
Journal of Modern Oncology. 2017;19(3):42-45
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The predictive role of interim pet-ct in the treatment of hodgkin's lymphoma in children
Kulichkina N.S., Belyaeva E.S., Popa A.V., Valiev T.T., Odzharova A.A., Mentkevich G.L.
Abstract
Propose - to estimate a role of the interim PET-CT using 2 methods: visual (Deauville scale) and semiquantitative (calculation of the standard uptake value - SUV). Methods. The results of PET-CT of 40 children with the Hodgkin's lymphoma (HL) received treatment since June, 2012 to September, 2016 were analysed. 37 patients - with newly diagnosed HL, 2 - with a recurrence and 1 - with a refractory HL entered into this group. Patients received therapy under protocols of treatment of HL, proved in the Institute of Pediatric Oncology and Hematology N.N.Blokhin National Medical Reseach Center of Oncology, depending on the status and a stage of a disease. In addition to the traditional study techniques (TRT) - ultrasonic investigation (ultrasonography), a computer tomography with i.v. gain (KT), the magnetic resonance imaging (MRI), to all patients was three times executed by PET-CT at various stages of therapy: before treatment, during therapy and after completion of the program chemotherapy. All studies were executed in alone PET center in NMIC of N.N.Blochin. Results. The sensitivity and specificity of the intermediate PET-CT were 100% and 73% while the sensitivity of TMI at the intermediate stage of treatment was 50%, specificity of 79%. Assessment 3 points on Deauville scale (a visual method) at a stage of the intermediate PET-research demonstrates sensitivity of a tumor to the carried-out chemotherapy and does not demand strengthening of intensity of treatment, even on condition of existence of a residual tumor. Conclusion. At the choice of a method of assessment of results of PET preference should be given to a visual method with use of the Deauville five-point scale.
Journal of Modern Oncology. 2017;19(3):52-56
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Irreversible electroporation of locally advanced unresectable pancreatic cancer
Patyutko Y.I., Polyakov A.N., Kudashkin N.E., Podluzhnyi D.V., Chistyakova O.V.
Abstract
Aim: to improve the results of treatment of patients with locally advancesd pancreatic cancer. Matherials and methods. From February 2015 till June 2017 there was performed 6 irreversible electroporations of unresectable pancreatic cancers, one of which was combined with palliative gastropanreatoduodenectomy. The median tumor size was 41.7 mm (range from 22 to 65 mm). The median quantity of treated areas was 2.3 (1-5). Perioperative treatment was routinely used. Results. Two patients had complications. One died on the 21st day from the pancreonecrosis with parapancreatic abscesses. Autopsy showed there was no evidence of tumor cells in the site of electroporation performed. In the other case there were revealed several foci of destruction around the area of electroporation which required sanation under the endoscopic US-guidance. In different periods of observation (1-, 3-, 4 and 12 month) four patients were alive without sign of progression. One patient died in 13 month from progression. Conclusion: irreversible electroporation - is one of the effective local treatment methods for the patiemts with unresectable nonmetastatic pancreatic cancer. To increase treatment results it is recommended to combine electroporation with chemoor radiotherapy.
Journal of Modern Oncology. 2017;19(3):58-63
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Dynamics of circulating tumor cells during neoadjuvant chemotherapy in patients with locally-advanced breast cancer
Nenakhova Y.N., Lyadov V.K., Poddubnaya I.V.
Abstract
Abstract Relevance. Circulating tumor cells (CTC) are a biological marker of new generation, which provides additional information on the biological features and prognosis of the disease. The possibility of using CTC for early evaluation of the effectiveness of drug treatment of breast cancer (BC), including neoadjuvant chemotherapy, is an important but insufficiently studied issue. Goal - to study the dynamics of CTCs in the process of preoperative chemotherapy in patients with locally-advanced BC. Materials and methods. Between 2015 and 2016 59 women over the age of 18 with verified BC and signed informed consent were included in the study. Patients with stage II and III were included. CTCs were evaluated in the blood before the start of treatment, after 2 courses of chemotherapy and before surgical treatment. To detect CTCs we used the ISET (Isolation by Size of Tumor cells) technique, based on vacuum cell filtration through a membrane with a given pore size of 8 mcm. Results. In 22 (37%) women CTCs were detected before treatment, including 6 (10%) patients with CTCs found on every stage of treatment. Among 37 (63%) patients without baseline CTCs 19 (32%) developed them in the process of chemotherapy. Baseline CTCs correlated with tumor size more than 25 mm and stage III disease. Also a tendency to increased CTC prevalence in patients with poor pathological response to chemotherapy was revealed. Conclusions. CTCs represent a novel biomarker. Yet, methodology needs to be standardized and more structured studies are badly needed to reveal their true biological relevance.
Journal of Modern Oncology. 2017;19(3):64-68
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