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The objective of the study is to compare the effectiveness of various systemic therapies in the 3rd and subsequent lines of therapy of metastatic colon cancer. Material and Methods. Retrospective multicenter study collected data from 2 clinics of the Russian Federation. We considered overall survival (OS) as the main criterion of effectiveness. Progression-free survival (PFS) was the additional criterion. We performed a single- and multifactorial analysis of the effect of various parameters on PFS. To evaluate the effectiveness of regorafenib and the reintroduction of previously effective drugs, we should prove the equivalence of reintroduction of the 3rd line chemotherapy (CT) and targeted therapy to regorafenib on the 6-month overall survival, provided that the equivalence boundaries would be between 0.8 and 1.25. To reach the 0.05 probability of type I error and the 80 % study power, 178 patients (89 in each group) should be included in the study. Results. The database identifed 215 patients with morphologically confrmed metastatic colon cancer who received two or more lines of antitumor drug therapy from 2010 to 2021. We selected 132 patients with the history of regorafenib therapy and 83 patients with the reintroduction of a previously used chemotherapy regimen as 3rd line treatment. The median OS in the reintroduction and regorafenib groups did not differ (HR, 1.01; 95 % CI, 0.7–1.45; p=0.920); 6-month OS were 74 and 70 %, respectively. Progression-free survival was signifcantly higher in the reintroduction group (HR, 1.94; 95 % CI, 1.3–2.7; p

Purpose of the study was to evaluate the safety and feasibility of preoperative chemotherapy in intrahepatic cholangiocarcinoma (IHCC).Patients and methods. A total of 171 liver resections for IHCC were performed between 2007 and 2021, of which 24 were preceded by preoperative therapy (14.0 %). Systemic therapy was conducted in 11 patients (45.8 %). Regional chemotherapy was provided to 13 patients (54.2 %). In two cases, regional chemotherapy was supplemented with systemic therapy.Results. A significant increase in the proportion of patients with clinical stage IIIb and higher was observed in the group of patients who had received preoperative therapy (83.3 % vs. 35.4 %, p < 0.0001). Complications of preoperative therapy occurred in 45.8 % of patients, with grade three and above complications identified in three patients (12.5 %). The incidence of postoperative complications (37.5 % vs. 42.9 %, p = 0.79), post‑resection liver failure (8.3 % vs. 13.6 %, p = 0.7) and postoperative mortality (4.2 % vs. 3.4 %, p = 0.68) in the preoperative therapy group were similar to those in the control group. The rate of radical resections was also identical, 83 % in both groups (p = 0.8). The relapses rates within the first six months after the surgery were similar: 25 % of patients in both groups (p = 0.62). The median OS reached 36 months in the main group and 32 months in the control one (p = 0.81).Conclusion. Since the main group predominantly included patients with more advanced stages of the disease and yet the treatment resulted in comparable immediate and long‑term outcomes, it can be concluded that preoperative therapy can be justified in patients with IHCC who have factors predisposing to poor prognosis. Randomized trials are necessary to determine the rationality, as well as the type and regimen of preoperative therapy to be used in patients with IHCC.

Introduction. Olaparib is the only PARP inhibitor approved in Russia for the maintenance therapy for BRCA-positive ovarian cancer after frontline chemotherapy. We conducted a real-world analysis of olaparib efficacy and safety for this indication.Aim. To assess the efficacy of PARP inhibitors in real-world clinical practice.Materials and methods. Patients with stage III-IV BRCA-mutated ovarian cancer who received olaparib maintenance therapy in expanded access program in 03.2019-12.2020 timeframe. Briefly, key inclusion criteria were: serous or endometrioid highgrade ovarian cancer; pathogenic BRCA1/2 mutation; primary or interval debulking; complete or partial response to frontline platinum-based therapy. Olaparib was administered as tablets (300 mg BID) up to 2-years, disease progression or unacceptable toxicity, whichever occurred first. The primary endpoint of the study was progression-free survival (PFS), overall survival (OS) and safety were key secondary endpoints. Statistical analysis was done with R and RStudio software.Results and discussion. 23 patients were enrolled. Median age was 49 years, all patients had high-grade serous adenocarcinoma histology. Complete debulking at primary or interval surgery was achieved in 30% of patients. With median follow-up time equal to 22 months, median PFS and OS were not reached. The 2-year PFS and OS were 65 and 84%, respectively. Grade 3-4 adverse events was detected in 7 (30.4%) patients.Conclusion. Our results supports high efficacy of olaparib in real clinical practice setting reported in the SOLO1 trial.

Endometrial cancer is the most common gynecologic malignancy in Russia. Surgery and/or chemoand radiotherapy remain standard clinical approach. This review describes multidisciplinary approach as the state of the art in the disease management. We notice the importance of molecular assessment for driving the clinic decision and newly emerging medical treatments, such as immunotherapy and antiangiogenic tyrosine kinase inhibitors and immunotherapy combinations.

Introduction. The discovery of immune checkpoints and immune checkpoint inhibitors (ICI) became a breakthrough in medical oncology. Currently a search for most effective and safe schemes of ICI therapy for different cancers is ongoing.Aim. To evaluate the efficacy and tolerability of a combination of nivolumab and ipilimumab in cancer patients in real-life clinical practice.Materials and methods. The study included 30 patients: 13 patients with melanoma, 10 patients with renal cell carcinoma (RCC) and 7 patients with colorectal cancer (CRC). All patients underwent 4 courses of combined immune therapy (melanoma - nivolumab 1 mg/kg + ipilimumab 3 mg/kg; RCC, CRC – nivolumab 3 mg/kg + ipilimumab 1 mg/kg once per 21 days). Nivolumab monotherapy was continued after the achievement of disease control. Objective tumor response was registered in cases of partial or complete tumor regression. Treatment response was determined using iRECIST criteria.Results. Treatment effect assessment was performed in 91 patients. Complete response (CR) was registered in 1 (5%) patient, partial response (PR) – in 3 (16%) patients, disease stabilization – in 8 (42%) patients, unconfirmed progression – in 7 (37%) patients. No cases of disease progression were registered. Thus, objective response rate was 21%; disease control was achieved in 63% of patients. The most significant immune-mediated adverse effects (imAEs) were gastric toxicity (20%), 1–2 grade fatigue (13%) and 2–3 grade hepatotoxicity (10%).Conclusions. Combined nivolumab and ipilimumab therapy in patients with melanoma, CRC and RCC is associated with a high rate of disease control with acceptable toxicity profile.

Introduction. Based on the subgroup analysis of the TRIBE study FOLFOXIRI with bevacizumab is the recommended option for patients (pts) with mBRAF metastatic colorectal cancer (mCRC) in the 1st line. However, subgroup analysis of other studies showed conflicting results. Therefore, we performed systemic review and meta-analysis to compare efficacy FOLFOXIRI and doublets with targeted therapy in pts with mBRAF mCRC in terms of progression free survival (PFS), objective response rate (ORR) and overall survival (OS).Methods. We performed a search of all prospective randomizes studies in PubMed, ASCO and ESMO congresses for all years before May, 2020, compared FOLFOXIRI plus bevacizumab or anti-EGFR antibodies and FOLFOX or FOLFIRI with targeted agents at the 1st line with information of the BRAF status. Primary outcome was hazard ratio (HR) for PFS and 95% confidence interval (CI); secondary – HR for OS and odds ratio (OD) for ORR. Fixed effects were used for analysis. Meta-analysis was conducted by Review Manager Ver. 5.3.Results. We identified 6 trials (CHARTA, STEAM, TRIBE, TRIBE2, VISNU, METHEP2), which included 158 pts with mBRAF (FOLFOXIRI – 82 (52%) and doublets – 76 (48%). According to results of the meta-analysis there was a tendency for higher ORR in pts with FOLFOXIRI (OR 2.07, 95% CI 0.61–7.06; p = 0.24; I2 = 27%, p for heterogeneity 0.26; 3 trials). However we didn’t find any significant improvement in PFS (HR 0.89, 95% CI 0.64–1.23; p = 0.48; I2 = 0%, p for heterogeneity 0.63; 5 trials) or OS (HR 0.9, 95% CI 0.37–1.19; p = 0.048; I2 = 71%, p for heterogeneity 0.06; 2 trials) in the group of triplet.Conclusions. FOLFOXIRI with targeted therapy did not show significant improvement in the PFS and OS in pts with mBRAF compared with FOLFOX or FOLFIRI with targeted antibodies. A prospective randomized trial is needed to determine the optimal chemotherapy regimen at the 1st line for pts with mBRAF mCRC.

The method of liquid biopsy allows detection of circulating tumor DNA (ctDNA) in patient blood, but the clinical significance of this approach in pancreatic cancer is still unclear. In this regard, we have carried out a meta-analysis of the studies dedicated to the predictive significance of ctDNA in pancreatic cancer. Materials and methods.We carried out the search for the articles and abstracts in PubMed, ASCO and ESMO databases published before February 2020, containing data about the connection between ctDNA and the prognosis of pancreatic cancer. The exclusion criteria were the studies including 10 or less participating patients, absence of the data about the relative risk of mortality and/or progression, and the 95% confidence interval. The meta-analysis was carried out by using the Review Manager software (RevMan), Version 5.3. Results.There were no significant systematic errors associated with the publications. The presence of ctDNA in patient blood showed poor overall survival of patients (odds ratio OR 2.21, 95% confidence interval CI 1.35-3.33,p=0.001) regardless of the prevalence of the disease. In case of the resectable process, the detection of ctDNA in patient blood both before and after surgery was a factor of worse progression-free survival (OR 2.32, 95% CI 1.543.5,p0.001 and OR 3.06, 95% CI 1.635.76,р=0.0005 and overall survival (OR2.01, 95% CI 1.123.63,р=0,02 and OR 3.39, 95% CI 2.125.44,р0.00001, respectively). Conclusions.The detection of ctDNA in the bloodstream in pancreatic cancer patients is a factor of poor prognosis in both localized and advanced cancer. It is very important to make further prospective studies to develop the optimal protocol for detecting ctDNA in patient bloodstream.

Epstein–Barr virus (EBV) associated gastric carcinoma is a special form of gastric adenocarcinoma that arises against the background of clonal growth of EBV-infected epithelial cells of the gastric mucosa. This subtype of tumors has unique genetic and epigenetic features that determine its characteristic phenotype. Determination of the molecular features of EBV-associated gastric cancer made it possible to identify potential targets for drug therapy of this subtype of tumors. The review presents modern data on the epidemiology and pathogenesis of EBVassociated gastric cancer, describes its unique pathomorphological and molecular features. Particular attention is paid to the prognostic role of EBV infection and drug therapy potentially applicable to the treatment of EBV-positive gastric cancer.

Purpose of the study was to provide medical oncologists and surgeons specializing in the treatment of pancreatic cancer patients with the most recent information on the importance and role of chemotherapy in the treatment of patients with resectable and borderline resectable pancreatic cancer.Material and Methods. Pubmed and COSMIC databases were used for literature search. Reports of the executive authorities in the field of Health Care of the Russian Federation, as well as worldwide data regarding morbidity and mortality of patients with pancreatic cancer were analyzed. The data of retrospective and prospective clinical trials were studied.Results. Based on the analysis of the most recent publications, the authors provided data on modern approaches to the treatment of operable pancreatic cancer.Conclusion. The data presented in the article summarize results of recent clinical trials. This will allow oncologists to choose the most correct and personalized tactics for the management of patients with resectable and borderline resectable pancreatic cancer.

Introduction. The randomized MPACT study showed that nab-paclitaxel plus gemcitabine results in statistically significantly longer life expectancy. The objective of this retrospective study is to obtain relevant data on the efficacy of this combination in real clinical practice in Russia. Materials and methods. The study included patients with morphologically proven locally advanced or metastatic pancreatic cancer, with a general condition assessed on the ECOG scale between 0-2, which received gemcitabine and nab-paclitaxel. Immediate and long-term treatment outcomes were evaluated. Results. 142 patients, who received treatment from 2009 to 2019 in 17 centers from 11 regions of Russia, were included in the study. Assessment of the objective effect was made in 134 patients. Objective effects were detected in 34 (25.4%) cases. The median time-to-progression was 6.1 months (95% confidence interval (CI) 4.8-7.4), the median length of life was 14.2 months (95% CI 10.6-17.9). An elevated CA19-9 level is the only independent adverse prognostic factor for progression-free survival (RR = 8.0, 95% CI 1.4 -43.8, p = 0.02) according to Cox multivariate regression analysis. The number of previously conducted chemotherapy lines (p = 0.34), ECOG status (p = 0.70), age over 70 years (p = 0.45), serious comorbidity (p = 0.97) did not have a statistically significant effect on progression-free survival. Findings. The gemcitabine and nab-paclitaxel combination has a relatively higher efficacy in advanced pancreatic cancer. The immediate and long-term results of its use in real clinical practice in Russia are consistent with data obtained in the Western countries.

Objective: to assess the frequency of liver resections in patients with metastatic colon cancer and isolated non-resectable liver metastases receiving FOLFOXIRI. Materials and methods. In this single-center non-randomized prospective study, we assessed the frequency of liver resections. According to the statistical hypothesis, the frequency of R0-resections in patients with metastatic colon cancer receiving FOLFOXIRI is between 11 % and 33 % (mean 20 %); to increase it up to 50 % in patients with isolated metastatic lesions in the liver, we had to recruit 20 patients (with β = 0.9 and a = 0.05). We enrolled 20 patients with potentially resectable metastases and 22 patients with non-resectable metastases. The primary endpoint was the frequency of R0 liver resections; secondary endpoints included objective response rate, progression-free survival, overall survival, and tolerability of therapy. Patients receiving targeted therapy (according to the tumor mutation status) were also included in the study.Results. Objective response was observed in 32 out of 42 patients (76 %) (in 17 out of 20 participants (85 %) with potentially resectable metastases), whereas progressive disease was registered in 2 patients (5 %). Radical resection of organs affected by metastasis was performed in 19 out of 42 patients (45 %): 15 out of 20 (75 %) in the group with potentially resectable metastases and 4 out of 22 (18 %) in the group with non-resectable metastasis (р

Objective: to analyze the frequency of metastasectomy in general population of patients with RAS wild-type metastatic colorectal cancer who received chemotherapy and anti-EGFR monoclonal antibodiesMaterials and methods. This prospective, non-randomized, multicenter study was designed to evaluate the frequency of resections of organs affected by metastasis. Our statistical hypothesis was that the addition of anti-EGFR antibodies should increase the frequency of metastasectomy from 5% to 15 %. Sample size calculations showed that to obtain a power of 80 % and an alpha level of 0.05 to detect the difference, we would need to recruit 50 patients. The primary endpoint was the frequency of resections of organs affected by metastasis, whereas the secondary endpoints included objective response rate, progression-free survival, and length of live. Tolerability of the therapy was analyzed separately.Results. Eighteen out of50 (36 %) patients achieved objective response; 32 (64 %) patents achieved stable disease and 18 (36 %) patients had disease progression. Radical resection of organs affected by metastasis was performed in 8 out of 50 patients (16 %): 1 individual had lung resection and 7 individuals had liver resection. Among participants with isolated liver lesions, the frequency of metastasectomy was 24 % (6 out of 25 patients). At a median follow-up of 14 months (between 1 and 34 months), median progression-free survival was 8 months (95 % confidence interval 6.2—9.8) and median length of life was 26 months (95 % confidence interval 19.7—32.2). The estimated 2-year overall survival was 83 % in patients who underwent metastasectomy vs. 51 % in those who had no metastasectomy.Conclusions. The addition of anti-EGFR monoclonal antibodies to standard combination chemotherapy (FOLFOX/FOLFIRI) increases the frequency of metastasectomy in patients with non-resectable metastatic colorectal cancer, which results in an increased length of life.

Objective: to identify factors associated with efficacy of an aflibercept-chemotherapy combination in patients with metastatic colon cancer.Materials and methods. This retrospective multicenter study was conducted in 20 clinics from 15 regions of the Russian Federation. The main efficacy outcome was progression-free survival (PFS). We performed univariate and multivariate analysis to assess the impact of various factors of PFS.Results. Two hundred and fifty-seven patients received aflibercept-containing chemotherapy; of them, 175 participants (68.1 %) received it as a second-line therapy. The objective response rate and median PFS were 18.7% and 5 months (95% confidence interval (CI) 4.2—5.8) respec -tively. The following factors were found to have a positive effect of PFS at multivariate analysis: grade I—II adverse events to aflibercept therapy (hazard ratio (HR) 0.58; 95 % CI 0.38—0.89; p = 0.01), therapy for concomitant diseases (HR 0.47; 95 % CI 0.29—0.76; p = 0.002), and ECOG performance status of 0 (HR 0.53; 95 % CI 0.34—0.81; p = 0.004). Patient with all 3 factors present had median PFS of 9 months, whereas patients without them demonstrated PFS of only 3 months (HR 1.9; 95 % CI 1.5—2.6; p

The process of angiogenesis is essential for the growth and spread of malignant tumours. Antiangiogenic therapy is deeply embedded in the standard treatment of disseminated ovarian cancer (OC). The numerous studies have demonstrated its efficacy in various stages of the therapy of this disease; bevacizumab is the best-investigated anti-angiogenic drug for OC. This article presents a review and analysis of the most significant studies of the efficacy of anti-angiogenic therapy in ovarian cancer, and describes various aspects of its use in this disease.

Objective: to evaluate the prognostic value of clinical and pathomorphological stages in patients with rectal cancer after preoperative chemoradiotherapy and to assess the effectiveness of adjuvant chemotherapy in these patients.Materials and methods. We conducted a retrospective analysis of the data from a prospectively maintained database for patients with rectal cancer. The study cohort included patients with stages I–III rectal cancer that underwent preoperative chemoradiotherapy followed by surgical treatment performed in the Department of Proctology and Clinical Pharmacology and Chemotherapy between 2004 and 2013. The relapse-free and overall survival rates were assessed to estimate treatment efficacy.Results. A total of 457 patients were eligible for the study; of them 98 patients (21.4 %) received adjuvant chemotherapy. The following independent factors were found to negatively affect relapse-free survival: perineural invasion (р

Objective: to determine the efficacy of 2 oxaliplatin-based chemotherapy regimens (FOLFOX and XELOX) for metastatic colorectal cancer (CRC) depending on the KRAS mutation status and primary tumor location. Materials and methods. We performed retrospective analysis of the data on patients with metastatic CRC taken from a prospective database. We included patients with known KRAS mutation status that received either FOLFOX or XELOX without targeted drugs. Progression-free survival (PFS) was used as a main criterion in estimating treatment efficacy. Results. The inclusion criteria were met by 157 patients. The FOLFOX regimen was more effective in patients with wild-type KRAS CRC: median PFS was 10 months versus 8 months in the XELOX group (hazard ratio (HR) = 0.7; 95 % confidence interval (CI) 0.4–1.2; р = 0.1). However, we observed no significant differences in median life expectancy between these groups: it was 37 and 38 months respectively (HR = 1.1; 95 % CI 0.6–2.1; p = 0.6). Similar trends were observed in patients bearing KRAS mutations: median PFS in the FOLFOX group was 9 months vs 5 months in the XELOX group (HR = 0.6; 95 % CI 0.3–1.2; р = 0.1; p value by Breslow – Day test = 0.04). No differences in median life expectancy between these groups were observed: 33 and 23 months respectively (HR = 0.8; 95 % CI 0.4–1.6; p = 0.5). Conclusion. We failed to find an association between the KRAS mutation status and response to a particular chemotherapy regimen. We found that patients with metastatic CRC receiving the FOLFOX regimen were more likely to achieve objective responses and demonstrated higher median PFS than patients on the XELOX regimen.

Background. Colorectal cancer (CRC) is the 4th most frequent cause of death among patients with malignant tumors worldwide. In 2012, approximately 1.3 million people were diagnosed with CRC, nearly 690 000 patients died.Objective: to assess the impact of various chemotherapeutic drugs and monoclonal antibodies penetration on the dynamics of CRC-associated mortality in patients with metastatic CRC in Russia.Materials and methods. We analyzed the mortality data for 2014 obtained from the National Cancer Register and the data from the Register of Chemotherapy Drugs (oxaliplatin, irinotecan, capecitabine) and Monoclonal Antibodies (bevacizumab, cetuximab, panitumumab) Procurement for cancer centers from 82 regions of Russia. We performed correlation and regression analysis to estimate the impact of various chemotherapeutic drugs and monoclonal antibodies penetration on the CRC-associated mortality, as well as the mortality from colon cancer and rectal cancer.Results. We observed a correlation between the mortality reduction in patients with metastatic CRC and penetration of irinotecan (k = –0.324, р = 0.003), capecitabine (k = –0.223, p = 0.04), bevacizumab (k = –0.229, p = 0.04), panitumumab (k = –0.232, p = 0.04), any anti-EGFR monoclonal antibody (k = –0.201, p = 0.07) and all monoclonal antibodies (k = –0.256, p = 0.02). Regression analysis demonstrated a decreased mortality rates in patients receiving irinotecan (β = –0.26, р = 0.02), anti-EGFR monoclonal antibodies (β = –0.19, р = 0.09) and oxaliplatin or irinotecan (β = –0.2, р = 0.06).Conclusion. Our results suggest a correlation between the administration of irinotecan and monoclonal antibodies and mortality reduction in patients with metastatic CRC.

Pancreatic cancer is characterized by its aggressive behaviour and high metastatic potential, and in most cases the disease is detected in inoperable stages. The main method of treatment of locally advanced and metastatic pancreatic cancer is chemotherapy. Until recently, gemcitabine monotherapy was considered the standard of chemotherapy; until the moment when more effective regimens of combination chemotherapy (FOLFIRINOX and the combination of nab-paclitaxel plus gemcitabine) were included in clinical practice. Application of these chemotherapy regimens is limited by their relatively high toxicity, which makes their use impossible in fragile patients and in patients with serious concomitant pathology. The article highlights criteria for choosing the best regimen of combination chemotherapy based on the assessment of patient’s condition, the possibility to manage side effects of chemotherapy, and the molecular and biological characteristics of the tumor.

Background. During the last years several trials emerged demonstrating high tumour heterogeneity, including those on colorectal cancer.Objective. These findings made us initiate a meta-analysis of trials dedicated to this question.Materials and methods. We searched PubMed database, ASCO and ESMO abstracts for publications presented until August 2016. Studies which compared concordance of KRAS, NRAS, BRAF and PIK3CA mutations between primary tumour and metastases of colorectal cancer and which included more than 10 patients were included in meta-analysis. Meta-analysis was performed using Review Manager (RevMan), version 5.3.Results. Statistically significant differences were observed in KRAS (5 %; RR 0.95; 95 % CI 0.92–0.98; р = 0.003), PIK3CA (7 %; RR 0.93; 95 % CI 0.86–0.99; р = 0.04) mutational status, but not BRAF and NRAS. We observed no significant publication-associated systematic errors. KRAS discordance was significantly higher between primary tumour and lymph node metastases – 13.2 % (р = 0.036).Conclusions. A possibility of KRAS discordance between primary tumour and colorectal cancer metastases was demonstrated. Considering a small number of patients with discordance it is necessary to distinguish a high-risk discordance group, which will require an additional mutational analysis of metastatic nodes tissue.

Objective: to evaluate tolerability and efficacy of maintenance treatment in the absence of progression after 16 weeks of first-line therapy in patients with unresectable metastatic colon cancer.Materials and methods. We have analyzed medical case histories of patients with metastatic colorectal cancer who underwent treatment in the department of clinical pharmacology and chemotherapy of N. N. Blokhin Russian Cancer Research Center from 2007 to 2015 years. Inclusion criteria were the following: 16–24 weeks of first-line chemotherapy with no signs of progression and the inability to perform metastasectomy. Progression-free survival was the main criterion for effectiveness in our study.Results. 160 (44.5 %) of 359 treated patients met the inclusion criteria. 102 (63.7 %) patients were followed up, while the other 58 (36.3 % – comparison group) patients underwent maintenance chemotherapy. Grade I–II toxic reactions and grade III complications associated with first-line chemotherapy were insignificantly more common in the group of patients left on maintenance chemotherapy: 72.4 % and 37.9 % versus 57.8 % and 24.5 % in the comparison group, p = 0.07 and p = 0.07 respectively. The frequency of grade I–II toxic reactions and grade III complications in the second-line treatment did not differ between treatment groups (p = 0.9 and p = 0.8). The median of progression-free survival in observation group and comparison group was 4, and 6 months (odds ratio (OR) 0.6; p = 0.009), and life expectancy – 23 and 31 months (OR 0.75; p = 0.1), respectively. Statistically significant differences between groups with respect to achieving the objective response and/or normalization of carcinoembryonic antigen level were revealed: median of progression-free survival was 13 (n = 26 of 57; 45.6 %) and 4 months (n = 31 of 57, 54.4 %), respectively (HR 0.38; p = 0.002), median of life expectancy – 34 months versus 26 months (OR 0.37; p = 0.3). Conclusions. Carrying out maintenance therapy is associated with increased incidence of grade III complications during the first-line treatment, but does not affect the tolerability of the second-line treatment. Supportive chemotherapy with fluoropyrimidines remains to be the most effective in patients with favorable prognostic factors such as normalization of carcinoembryonic antigen and/or achievement of the objective response on the background of first-line chemotherapy.

Metronomic chemotherapy implies the regular use of cytotoxic agents in doses much smaller than the maximum tolerable doses for a long time. Preclinical experiments show that this treatment option has a many-sided (antiangiogenic, immunostimulating, and direct cytotoxic) effect on tumor. Moreover, this approach has gained the widest acceptance in treating patients with metastatic breast cancer in clinical practice. By taking into account the high activity of angiogenesis in colon cancer progression, it is interesting to study the impact of metronomic chemotherapy regimens for this nosological entity as well. This literature review considers not only the history of metronomic chemotherapy, the mechanisms of action, and a range of drugs having an antitumor effect in the metronomic regimens, but also analyzes clinical trials of metronomic chemotherapy regimens in patients with metastatic colon cancer.

Despite the high initial susceptibility of ovarian cancer (OC) to chemotherapy, the vast majority of patients with Stages III–IV of the disease have its recurrences. Chemotherapy is a main treatment for recurrent OC. In Russia, the rate of platinum-resistant recurrences after first-line chemotherapy is more than 50 %, which may be due to the high extent of a tumor process at the moment of diagnosis, to the low rate of optimal cytoreductive interventions, and to non-optimal treatment. Many oncologists refuse to treat patients with recurrent platinum-resistant OC since the existing Russian and foreign guidelines point to the low efficiency of current chemotherapy for this type of recurrences. At the same time, whether chemotherapy should be used to treat platinum-resistant recurrences must be decided by taking into account a set of clinical factors that along with the duration of a platinum-free interval are also predictors for the efficiency of chemotherapy. These predictors should include mainly the histological pattern of a tumor; an immediate response to previous lines of chemotherapy; the number of previously used anticancer drugs; a patient’s general condition; and her existing factors that can influence the tolerability of chemotherapy. This paper describes a clinical case of a long-term survival in an OC patient who has developed a platinum-resistant recurrence just after first-line chemotherapy. Incomplete cross-resistance of the tumor to other drugs when a platinum-resistance recurrence develops, as well as its high susceptibility to the re-use of platinum-resistant derivatives possibly due to the artificial increase of a platinum-free interval should be identified among the factors that have influenced the prediction of treatment in this patient.

Despite large number of known risk factors of venous thromboembolism (VTE) in cancer patients existing prediction models do not allow definite identification of cancer patients that have indications for anticoagulant prevention. Besides, heparin and warfarin use for VTE prevention in cancer is accompanied by some problems. New oral anticoagulants (NOAC) are promising drugs for use in oncology practice; however their use is complicated by the lack of data on efficacy and safety in these patients, potential drug interactions and the possibility of unpredictable changes in effect during chemotherapy. Widespread use of NOAC for the prevention and treatment of tumor-associated VTE prior to phase III trials is not recommended. However, the criteria for selection of patients for whom the study of the efficacy and safety of NOAC is a priority can now be developed.

PARP-1 and PARP-2 enzymes are one of six known DNA damage repair systems - nitrogenous base excision repair. PARP inhibitor disrupts excision repair and under the conditions of the absence of another pathway of DNA damage repair (homologous recombination) can cause apoptosis in tumor cells. One of the most frequent causes of defects in homologous recombination is the loss of BRCA1 or BRCA2 function by means of inactivated mutations. It makes PARP-inhibitors the most effective in the treatment of tumors associated with BRCA germline and somatic mutations. This paper discusses the differences of PARP inhibitors (olaparib, niraparib, veliparib, rucaparib and talazoparib), the results of their clinical trials for female reproductive system cancers, toxicity of PARP inhibitors as monotherapy or in combination with cytotoxic drugs, as well as the registration of these products in Russia and in other countries.