Том 30, № 11 (2023)

Endocrine therapy for 5–10 years is the standard treatment for women with ER-positive breast cancer (BC). However, the side effects of endocrine therapy with tamoxifen (TAM) reduce the quality of life of BC patients and adversely affect treatment compliance. Currently, the problem of hyperplastic processes and endometrial cancer against the background of long-term use of TAM is especially relevant, because the incidence of endometrial pathology is associated with the duration of TAM use. pharmacogenetics is an important factor predisposing to the occurrence of adverse drug reactions (ADR), incl. endometrial hyperplasia, when taking TAM. Differences in the genes encoding the enzymes CYP2D6, CYP2C9 and CYP2C19, namely, CYP2D6*4, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, as well as the polymorphic marker of the ABCB1 gene (C3435T), encoding the glycoprotein transport protein – P, may be the main predisposition factor to the occurrence of side effects when taking TAM, which in turn leads to a decrease in patient adherence to therapy. However, at the moment, algorithms for monitoring such patients have not been developed, and risk factors that increase the likelihood of ADRs when taking TAM have not been fully identified. An integrated approach to assessing ADRs to TAM, taking into account pharmacogenetic testing data, and resulting predictive models that include both genetic and non-genetic determinants of response may further improve the prediction of individual response to TAM.

Venous thromboembolism (VTE) is a common but preventable cause of death in women after surgery for gynecological cancer. the use of unfractionated heparins or low molecular weight heparins for a month is the standard of thromboprophylaxis after major abdominal and pelvic surgery for malignant neoplasms. Direct oral anticoagulants (DOACs) are approved for the treatment of VTE in the general population. This regimen has significant advantages over other types of anticoagulant regimens, in particular the oral administration without the need for laboratory monitoring. The review presents the benefits of using DOACs based on updated information from completed and ongoing clinical trials.

Adjuvant chemotherapy (ACT) for breast cancer (BC) has been successfully used as part of complex treatment for several decades. The concept of BC as a systemic disease has made it possible to develop optimal treatment algorithms, including both local methods of disease control, such as surgery and radiation therapy, and systemic drug treatment. The effectiveness of adjuvant systemic therapy in increasing overall and relapse-free survival is not in doubt, however, the optimal timing of initiation of chemotherapy after radical surgical treatment has not been reliably determined to date. Many factors, such as age, comorbidity, type of surgery, and patient compliance with treatment, can delay chemotherapy. We analyzed the largest studies in this area to gain insight into what may cause delays in adjuvant treatment and the long-term consequences of such delays for the patient.

Background. Information on choosing the optimal treatment regimen for renal cell carcinoma (RCC) associated with chronic kidney disease (CKD) is limited. It seems relevant to study the actual practice of providing oncological care to patients suffering from RCC against the background CKD.

Objective. Evaluation of the effectiveness and safety of therapy for renal cell carcinoma (RCC) against the background of CKD with a combination of pembrolizumab and axitinib.

Methods. A retrospective study with the participation of 194 patients with RCC against the background of CKD who received treatment at the Pletnev City Clinical Hospital in 2020–2022 was carried out. Patients were divided into groups according to the IMDC prognostic model and renal function status. The control group consisted of similar patients with conditionally preserved renal filtration function. The effectiveness of therapy was assessed by median progression-free survival (PFS) and overall survival (OS).

Results. The probability of complete or partial response, as well as OS with a favorable and intermediate prognosis in patients with concomitant CKD were comparable with the control group (P>0.05). The negative impact of CKD can be seen only with an unfavorable prognosis, where the probability of progression was higher than in the control group (21.4 and 7.7%, respectively; P<0.05). Side effects requiring discontinuation of therapy were observed in 5.9–8.8% of patients without significant differences between groups (P>0.05).

Conclusion. In CKD (stage II–III), RCC therapy, including pembrolizumab and axitinib, demonstrated comparable efficacy and safety compared to patients with conditionally preserved renal function.

Objective. Evaluation of the effectiveness and safety of the empegfilgrastim (Extimia^®, BIOCAD) for various modes of mobilization of hematopoietic stem cells (HSCs) in patients with lymphoproliferative diseases (LPDs).

Methods. The study included 32 patients with LPDs who were treated at the National Medical Research Center for Hematology from October 2022 to April 2023. Mobilization of hematopoietic stem cells using empegfilgrastim at a dose of 7.5 mg in a “stable state of hematopoiesis” was carried out in 16 patients; and another 16 patients, drug was administered one day after polychemotherapy (PCT). A complete blood count and the blood CD34⁺ cell concentration at a “stable state of hematopoiesis” were estimated on the 4th and 5th days, and after the previous PCT – on the 8th and 9th days after the administration of empegfilgrastim. Leukapheresis was started if the CD34⁺ cell concentration exceeded 10 cells/μl, and the number of leukocytes in the blood was >5×10⁹/l. HSC mobilization was considered effective when the CD34⁺ cell count was ≥2 million × 10⁶/kg body weight. To analyze the obtained data, standard methods of descriptive statistics and frequency analysis were used.

Results. Mobilization of HSCs was effective in 20 (62.5%) of 32 patients. There were no statistically significant differences depending on the mode of HSC mobilization (P=0.76). Such factors as age, bone marrow damage, stage of the disease, presence of bulky disease, number of previous courses of chemotherapy, antitumor response status, radiation therapy, grade 3–4 anemia did not correlate with unsuccessful mobilization of HSCs. Mobilization of HSCs was more often effective in patients with Hodgkin lymphoma than in non-Hodgkin lymphomas: 55 and 25%, respectively (P=0.15).

Conclusion. The use of empegfilgrastim in a single fixed dose of 7.5 mg led to effective mobilization of HSCs in 62.5% of patients with LPDs.

Objective. Evaluation of the effects of GSTT1 and GSTM1 deletion polymorphisms on the risk of relapse in patients with hormone-positive breast cancer (BC) treated with tamoxifen.

Methods. The study examined blood samples from 102 women diagnosed with stage IIA–III BC, aged from 23 to 79 (average age – 48±13) years, who received adjuvant hormonal therapy (HT). Identification of deletion (null) genotypes of GSTM1 and GSTT1 was carried out using multiplex polymerase chain reaction followed by analysis of melting curves of the reaction products.

Results. A statistically significant association between the double GSTT1-GSTM1 deletions carriage and a reduced risk of developing BC relapse was revealed. According to estimates, in such patients the probability of relapse was 4.5 times lower compared with carriers of the “functional” GSTT1 and GSTM1 genotypes simultaneously (OR=0.219, 95% CI: 0.033–1.444, χ²=4.377; P=0.037). At the same time, the presence of a “null” GSTT1 variant reduced the relative risk (RR) of developing BC relapse by 1.9 times (RR=0.513, 95% CI: 0.211–1.246, χ²=2.909) compared with carriage of functionally active forms of GSTT1 (0/+, +/+). In this case, we can only talk about an emerging trend, because there was no statistically significant difference in values (P=0.089). According to estimates, the RR for the development of BC recurrence in the group of patients with a functionally inactive form of GSTM1 (0/0) was 1.2 times lower (RR=0.856, 95% CI: 0.541–1.356, χ²=0.442; P=0.507), however the resulting difference was not statistically significant.

Conclusion. A study of deletion polymorphisms of glutathione-S-transferase genes in women with BC revealed a significant association of the combination of “null” genotypes GSTM1 and GSTT1 with a reduced risk of disease relapse. Thus, carriage of these genotypes, leading to the absence of the corresponding glutathione-S-transferases, can be considered as a favorable predictive factor when conducting adjuvant HT with tamoxifen in patients with luminal BC type.

Background. Despite the development of new, more effective drug combinations, the increase in life expectancy of patients with disseminated gastric cancer (dGC) does not exceed 3.5 months. In this regard, new ways to improve long-term treatment results are being sought. One of these direction is conversion treatment – a combination of drug therapy with a surgical method in case of achieving stable control of the disease against the background of effective chemotherapy and the possibility of complete removal of all tumor foci (R0).

Objective. Evaluation of the long-term results of conversion therapy of patients with dGC and identification of predictive factors for overall survival. Goals: 1) assessment of progression-free survival; 2) assessment of overall survival with conversion treatment; 4) determination of prognostic factors for overall survival; 5) determination of the optimal timing of surgical treatment; 6) evaluation of event-free and postoperative survival.

Methods. The analysis included 55 operated patients with morphologically confirmed dGC aged from 21 to 77 years (median 50.5 years), male/female – 33/22, ECOG status 0–1 in 94.5% of patients. According to the histological structure, the signet ring cell variant (49.1%) and the diffuse subtype according to the Lauren classification (54.6%) predominated. Initially, ascites was detected in 23.64% of patients, metastases in the peritoneum – in 61.8%, in retroperitoneal lymph nodes – in 20%, in peripheral lymph nodes – in 10.9%, in the liver – in 18.18%, in the ovaries – in 12.73% of women. Localization of metastases in 1 anatomical area (zone) was noted in 22 (40%), in 2 areas - in 26 (47.3%), in 3 or more – in 7 (12.7%) patients. All patients received one line of chemotherapy (CT) for 18 weeks, in the FOLFIRINOX regimen – 19 (34.5%) patients, in the FLOT/mDCF regimen - 22 (40%), platinum-fluoropyrimidine doublets (XELOX, mFOLFOX6) – 14 (25.5%). R0 surgery was performed in 53 (96.3%) patients, R1-R2 – in 2. The median overall survival (mOS) was 29.33 months, 1-year survival – 85.5%, 3-year – 25.5%, 5-year – 9.1%. Median progression-free survival (mPFS) was 18.5 months, median event-free survival – 9.8 months, and median postoperative OS – 20.47 months. A significant increase in OS was obtained with an follow-up period interval from the date of completion of chemotherapy to the date of surgery of more than 3.4 months. The independent factors for a favorable prognosis of OS in a multivariate analysis were: 1) non-signet ring cell morphological variant; 2) absence of lymphovascular invasion; 3) FOLFIRINOX mode.

Conclusion. Conversion therapy for dGC is a promising area that can provide long-term survival for some patients.

Breast cancer (BC) is the most common tumor in women. Human epidermal growth factor receptor type 2 (HER2) – positive tumors account for approximately 25–30% of all breast cancer subtypes and are correlated with a poor prognosis. Trastuzumab, a monoclonal antibody, has been used for many years to inhibit HER2 activity. The introduction of this drug into clinical practice has made a real revolution in the world of treatment of HER2-positive breast cancer. However, today there are cases of primary resistance to anti-HER2 therapy. In this regard, identifying mechanisms of resistance and exploring new therapeutic agents may lead to the development of more effective blockade of HER family receptor signaling. Over the past few years, many mechanisms of resistance have been studied, and attempts to introduce new therapeutic drugs to treat patients with resistance to trastuzumab-containing therapy are regularly made, but adequate effectiveness has not been achieved to date. In this regard, the purpose of this article was to review the mechanisms of resistance to anti-HER2 therapy and ways to overcome it, as well as demonstrate clinical experience in managing a patient with a similar condition.

The range of anticancer drugs for the treatment of non-small cell lung cancer has changed significantly in recent years due to the advent of immunotherapy and targeted drugs targeting driver mutations. Today it has become possible to prescribe more effective and less toxic treatment to patients than chemotherapy. This review focuses on the ceritinib, 2nd generation ALK inhibitor. Data from clinical studies confirming the effectiveness of the drug and the feasibility of its use both in pre-treated patients and in patients with newly diagnosed metastatic ALK-positive non-small cell lung cancer are presented.

Prostate cancer (PC) is one of the most common malignant neoplasms both in the world and in Russia. This disease is one of the leading causes of cancer mortality in the male population. Currently, the pathogenesis of PC has been studied in detail, which makes successful radical treatment possible in most cases, but on average, 10–20% of patients gradually develop castration-resistant (CRPC) and metastatic (mPC) prostate cancer. The mechanisms that contribute to the development of prostate cancer in the absence of androgen stimulation are currently being actively studied. A personalized approach in oncology makes it possible to timely identify specific mutations and correctly select the most effective therapy. This article attempts to summarize the current evidence on one such treatment approach, the use of PARP inhibitors. Drugs in this group are most effective against cancer with BRCA1/2 gene mutations and are also successfully used in ovarian, breast and pancreatic cancer. The presented clinical case of patient R., 67 years old with adenocarcinoma (Gleason 7), in whom BRCA2 mutations were identified based on the results of a genetic study, illustrates the successful use of olaparib in mCRPC. The use of personalized tests has made it possible to formulate clear indications for the use of PARP inhibitors in the treatment of mCRPC. Research in new areas of use of PARP inhibitors is currently relevant.