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Over the last few decades there was a little progress in the treatment of small cell lung cancer (SCLC). But now the approaches are changing with immune checkpoint inhibitors coming into clinical practice. Using a combination of immunotherapy with the standard chemotherapy in the first line of extensive stage small cell lung cancer (ES-SCLC) results in significant overall survival improvement, for the first time the median survival in these patients exceeded one year. Here we present a clinical case of ES-SCLC patient treated with durvalumab, a monoclonal antibody against PD-L1, in combination with etoposide and carboplatin in the CASPIAN clinical trial. In the CASPIAN trial more than 20% of patients treated with durvalumab stay alive more than two years. In the presented case we also reported durable control of the disease, the patient continued to receive durvalumab of more than two years with acceptable tolerability.

The purpose of the study was a comparative assessment of long-term toxic effects of cytotoxic drugs (anthracycline antibiotics, topoisomerase activity inhibitors, platinum and taxane complex compounds) on male reproductive function. Material and methods. 2.5-month-old male Wistar rats were used in the experiment. The following cytotoxic drugs were administered to animals in the maximum tolerated dose: Vepesid (etoposide, Teva, Israel), Irinotecan (Campto, Rhone-Poulens, Great Britain), Carboplatin (kemokarb, Dabur India Ltd., India), Paclitaxel (mitotax, Dr. Reddy`s, India), Platidiam (Lachema, Czech Republic), Pharmorubicin (Farmitalia, Carlo Erba). The reproductive status was assessed 90 and 180 days after administration of cytotoxic drugs. The fertilizing ability, productivity of spermatogenesis and the viability of a fertilized egg were evaluated. To determine the sensitivity of different types of spermatogonia to the drugs, we studied the dynamics of the number of their cell populations 2, 5, 10, 15, 30, 90 and 180 days after starting the experiment. Results. In long-term follow-up following administration of farmorubicin and paclitaxel to male rats, a complete (pharmacorubicin) or partial (paclitaxel) decrease in the fertilizing ability due to oligospermia was detected. The decrease in spermatogenesis productivity was reversible. In rats treated with topoisomerase activity inhibitors, the fertilizing ability was preserved, however spermatogenic failure was also seen, as judged by the total sperm number. In the long term after the administration of platinum complexes, no decline in the reproductive function was observed, and the spermatogenesis productivity corresponded to the control values. The severity of toxic effects on gonads was determined by the sensitivity of different types of spermatogonia to the action of drugs. Pharmorubicin and paclitaxel exerted a pronounced toxic effect on stem spermatogonial cells. Paclitaxel and carboplatin induced dominant lethal mutations in spermatogonia, but the likelihood of gametes bearing genetic damage incompatible with life decreased over time.

Цель работы. Оценка противоопухолевой активности нового препарата дэкоглиц на животных с опухолевым штаммом саркома 45 в сравнении с препаратом дэкоцин, из которого он получен, а также с 5-фторурацилом и этопозидом, и выявление их влияния на синтез НК. Материалы и методы. Изучение выполнено на 48 беспородных крысах с перевиваемой опухолью С-45, которым вводили препараты на 4-й день после перевивки опухоли 10-кратно. Оценку результатов проводили по стандартным критериям: торможение роста опухоли (ТРО), масса тела и селезенки животных. Достоверными считали различия при р, Purpose of work. Assessment of the antitumor activity of the new drug Decoglitz in animals with the tumor strain Sarcoma 45 in comparison with the drug dekocin, from which it was obtained, as well as with 5-fluorouracil and etoposide, and the identification of their effect on the synthesis of nucleic acids (NA). Materials and methods. The study was carried out on 48 outbred rats with a C-45 transplantable tumor, which were injected 10 times on the 4th day after tumor transplantation. The results were evaluated according to standard criteria: tumor growth inhibition (TPI), body weight and spleen of animals. Differences at p, Евразийский онкологический журнал, Выпуск 4 2021, Pages 358-366

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.

Background: Therapeutic efficiency in treatment of acute myeloid leukemia (AML) ranges from 20 to 45%. One of the causes of the latter is a drug resistance acquired by leukemic cells under the influence of treatment with antitumor medicines. More important cause is a development of the primary resistance of myeloid leukemic cells to induction of cellular death associated with elemental microenvironment within the bone marrow. Studying primary resistance is very important, and first of all, to prevent development of drug resistance of leukemic cells and, correspondingly, to increase the efficiency of medicamental therapy. Aim: To study the mechanisms of primary resistance of AML cells to induction of cellular death. Materials and methods: Human AML cells of THP-1 line and mononuclear cells of the bone marrow were used in the study of patients with diagnosed AML. Multicellular aggregates were formed during cell cultivating on the 1.5% agarose. To cut off intercellular adhesion, the cells were cultivated in the medium with methylcellulose (0.9%). The viability of the cells was assessed by reduction of Alamar Blue indicator. Results: Within multicellular aggregates, about 75±5% of THP-1 cells were resistant to the activity of recombinant protein izTRAIL, 70±5% – to etoposide, and 40±7% – to sorafenib. Cutting off intercellular contacts decreased the resistance to them. Within multicellular aggregates of primary mononuclear cells, 45±5% of cells were resistant to sorafenib, 57±4% – to etoposide, and all cells were resistant to izTRAIL. Cutting off intracellular adhesion reduced the resistance to sorafenib and etoposide but not to izTRAIL. Conclusion: In multicellular aggregates, AML cells of THP-1 line and mononuclear cells of the bone marrow showed increased resistance to activity of recombinant protein izTRAIL, etoposide, and sorafenib. Diminishing intracellular adhesion in the medium including methylcellulose decreases cellular resistance to cytotoxic agents.

The aim of the investigation was to obtain a tumor cell clone of gastrointestinal stromal tumors (GISTs) possessing resistance to chemotherapeutic agents of different mode of action, and to assess its sensitivity to various groups of chemotherapeutic agents. Materials and methods. GIST cell line T-1 was used to obtain a clone of chemoresistant GIST cells. The viability assessment of tumor cells was carried out by using i-CELLigence RTCA cell analyzer (ACEA Biosciences, USA). The sensitivity of GIST T-1-29R cell clone to type II topoisomerase inhibitors (doxorubicin and etoposide); chemotherapeutic agents affecting the dynamic state of the spindle microtubules (vinblastine and paclitaxel); hydroxyurea; cisplatin; targeted drug imatinib were evaluated by using the MTT-based assay. Expression of apoptosis, the markers of DNA damage and chemoresistance was examined by immunoblotting. Results. A clone of GIST T-1 tumor cell line with the signs of chemoresistance (T-1-29R) was obtained after 8-month of cultivation of GIST tumor cells in the presence of the gradually increasing doses of paclitaxel. T-1-29R cells were found to possess resistance to paclitaxel, and cross-resistance to doxorubicin and etoposide, as well. Sensitivity of T-1-29R cells to other chemotherapeutic agents, including imatinib, did not change. Some multiple drug resistance proteins, e.g. MDR-1, were revealed to have an increased expression level in T-1-29R tumor cells when compared to parent T-1 cells. Conclusion. A clone of GIST T-1-29R cell line possesses phenotypical features of multiple drug resistance, that makes its perspective use for the assessment of GIST chemosensitivity, and for screening of new compounds for their cytotoxic and antitumor activities in vitro and in vivo, as well.