No 7 (2018)

Currently, immunotherapy is the most promising method of treating malignant tumors. This review considers the main principles of its action: universality, inertiA., dualism, and the complexity of directed action. The original classification of immunotherapy methods according to the mechanism of their action is presented, which allows better understanding the features of individual methods of treatment. Methods for evaluating the effectiveness of immunotherapeutic agents and immuno-mediated adverse events are discussed in detail. Understanding and using the principles of immunotherapy discussed in the article will allow to optimize the use of immunooncological drugs and to maximally protect the patient from possible adverse events associated with their use.

High-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT с autoHSCT) is a modern standard for the treatment of primary refractory forms and the first relapses of Hodgkin’s lymphoma (HL). HDCT with autoHSCT is effective for 50-60% of patients with the first late chemosensitive relapse of HL. Chemoresistance is defined as a predictive factor for an unfavorable prognosis. Allogeneic hematopoietic stem cell transplantations (alloHSCT) can be performed in case of recurrence of HL after HDCT with autoHSCT with preserved chemosensitivity, and are preferable for young patients in prospective clinical trials. Among the monoclonal antibodies studied, the greatest therapeutic activity was detected for brentuximab vedotin. Brentuximab vedotin is registered for the treatment of patients with classic HL after failure (progression or early relapse) of HDCT with autoHSCT or patients who are not candidates for high-dose CT., if two or more HT lines fail, for consolidation after HDCT with autoHSCT in HL patients with a high risk for recurrence or progression. The high activity of PD-1/PD-L1 checkpoint inhibitors, activating antitumor immunity (nivolumab, pembolizumab) was noted for patients with recurrence of HL. Promising areas of therapy for HL are associated with further study of new targets of tumor cells and their signaling pathways.

Background. Every fourth patient with a newly diagnosed skin melanoma has metastatic or locally advanced inoperable stage of this tumor, which determines an unfavorable prognosis of the course of the disease. This article presents the experience of SPBSBHCI CCOD in the treatment of metastatic melanoma in adult patients with an evaluation of the effectiveness of nivolumab, the PD-1 inhibitor. Methods. Twelve patients with disseminated skin melanoma who received treatment at the St. Petersburg City Clinical Oncological Dispensary from 2002 to the present day were under observation. The time from the moment of diagnosing the IV stage of the disease to the initiation of nivolumab therapy ranged from 4 to 31 months. Results. By the present moment of time (May 2018) only 3 out of 12 patients (25%) have recorded progression of the process. At the stage of this analysis, the mean time without progression is 25.75±3.13 months (95% CI, 19.61-31.89), 10 out of 12 patients (83.33%) are alive. Now, the average overall survival rate is 28.27±2.49 months (95% CI, 23.30-33.03). A clinical example of female patient with metastatic melanomA., including brain lesions, treated with nivolumab is presented. The overall survival of the patient from the moment of diagnosing the 4th stage of the disease was 3.5 years, of which, 2.5 years with nivolumab therapy. At the momenT., the patient’s condition is stable clinically and according to the results of objective examination methods. Conclusion. The provided data confirm the high efficiency of the use of immune-oncological drugs, such as the PD-1 blocker nivolumab, in the treatment of metastatic melanoma. It is important to note that the use of nivolumab in addition to achieving an objective response allows to keep the effect achieved for a long time.

Background. In the vast majority of patients with suspected metastasis of breast cancer (BC), the luminal type of tumor - hormone sensitive (HR+) with no significant expression of the epidermal growth factor receptor (HER2-) is diagnosed at presentation. The sequential application of various variants of endocrine therapy provides a significant increase in the overall and disease-free survival in such patients, while maintaining a sufficiently high quality of life. Over time, however, the disease progresses due to the development of resistance to the treatment. The appearance of drugs with direct effect on the cell cycle regulators has given rise to a new stage in the treatment of patients with advanced HR+ HER2-BC. Ribociclib (Kisqaly, LEE001) is an oral, highly selective cyclin-dependent kinase inhibitor (CDK4/6), which stops the progression of the cell cycle at the G1/S phase. Description of the clinical case. Postmenopausal woman with BC was diagnosed with generalization of the process with the presence of bone metastases and visceral lesions 3 years after the end of adjuvant therapy with letrozole. In this clinical experience, we confirmed the rapid response to ribociclib therapy in combination with letrozole. A partial response was recorded after 3 months (tumor reduction by 31%) with further reduction of the tumor by 42% after 6 month of treatment. Clinically significant improvement in the quality of life and relief of pain in the bones was noted already at 8th week of therapy. The tolerability of therapy was satisfactory. Conclusion. Oral high selective CDK4/6 inhibitor ribociclib is an excellent therapeutic option for patients with hormone-dependent HER2-negative advanced breast cancer in real clinical practice.

Background. BRCA1-associated tumors demonstrate a unique sensitivity to platinum-based drugs, but the overall effectiveness of treatment remains limited. Despite the pronounced regression of the tumor, standard therapy with platinum-based drugs rarely leads to complete pathomorphological response. Objective: to evaluate the clinical efficacy, safety, frequency of complete pathomorphological responses of the new scheme of neoadjuvant therapy for patients with BRCA1-associated ovarian cancer (OC) using combination of mitomycin C and cisplatin. Methods. The study included 217 patients with OC who were treated during 2015-2017. Three oncological centers participated in the study. All patients with OC were subjected to polymerase chain reaction testing for mutations: BRCA1 c.5266dupC [5382insC], c.4034delA [4153delA], c.181T>G [C61G], c.68_69delAG [185delAG] prior to initiation of treatment. Of the 217 patients, 21 (10%) mutation carriers were identified; 12 (57%) patients received a combination of mitomycin C 10 mg/m2 and cisplatin 100 mg/m2 every 4 weeks in the neoadjuvant regimen. The results of a prospective study of the NACT of BRCAI-associated OC using combination of mitomycin C and cisplatin were compared to the retrospective data (n=62) of NACT of BRCA1-associated OC treated with standard neoadjuvant therapy. Results. All 12 OC patients demonstrated an objective clinical response to treatment. Complete cytoreductive surgery was achieved in all patients included in the study. The pathological evaluation of tissues removed during surgery established a complete pathomorphological response (pCR) in 2 (17%) of 12 cases. In addition, one patient had a complete pathomorphological r esponse in the ovaries and an almost complete response in the omentum. In general, 5 (42%) patients had a pronounced pathomorphological response (score 3, according to [12]). Conclusion. The combination of platinum doublets in combination with other drugs, whose activity is not limited to cells with BRCA1 deficiency, can be a promising chemotherapeutic approach. The use of platinum-taxane regimens, which are the current «gold» standard, apparently does not exceed other regimens in effectiveness for BRCA1 gene mutations carriers.

Background. Breast cancer (BC) is a serious medical and social problem for society. Treatment of metastatic breast cancer (MBC) involves the appointment of several lines of chemotherapy. Clinical recommendations contain a lot of options for choosing a treatment regimen. Existing limited resources, however, do not always allow using the most effective regimen for treatment of MBC. Objective. Evaluation of the effect of the oral vinorelbine (capsules) on the budget of the Russian Federation in comparison with the most frequently used and comparable in clinical effectiveness parenteral pharmacotherapy regimens for advanced MBC in patients previously treated with anthracyclines and taxanes. Methods. In order to select the optimal therapy for advanced BC, a cost analysis and «budget impact» analysis for oral vinorelbine were performed as compared with intravenous eribulin and ixabepilone. Results. The cost analysis and «budget impact» analysis have shown a positive economic effect from the use of oral vinorelbine as an alternative therapy for advanced BC. As a result of the «budget impact» analysis, suspected budget savings with the replacement of eribulin and ixabepilone on oral vinorelbine is 860,870.2 rubles per patient in a year in comparison with eribulin and 137,615.8 rubles for ixabepilone. Conclusion. The use of oral vinorelbine in the 2nd-3rd line therapy of advanced MBC is reasonable from the position of the healthcare economics.

Background. The use of a consistent approach to cytostatic therapy in the form of monotherapy as a first-line treatment for 20-25% of patients with metastatic colorectal cancer (mCRC) makes it possible to achieve a similar survival rate, as with polychemotherapy. The list of standard regimens of drug therapy for mCRC for various treatment lines includes monotherapy with fluoropyrimidines and cetuximab. The efficacy of cetuximab and panitumumab is indicated in patients with tumors that do not have KRas, NRas, and BRAF gene mutations. Currently, there is no evidence of the effectiveness of monotherapy with cetuximab as the first-line of therapy for patients selected by molecular factors. Methods. A prospective II phase study of monotherapy with cetuximab in patients with unresectable mCRC without KRas, NRas and BRAF gene mutations and without symptomatic manifestations of the tumor was conducted. After molecular analysis, the study included patients who had not previously received drug therapy for a advanced tumor and without mutation changes in any of the listed tumor genes. Patients received monotherapy with cetuximab in standard mode: loading dose of400 mg/m2, then - 250 mg/m2 once a week intravenously until progression or intolerable toxicity. The primary endpoint of the study was a 6-month progressionfree survival (PFS). For the independent validation of the results, retrospective data on the efficacy of standard monochemotherapy with fluoropyrimidines in a similar population of patients with wild type KRas, NRas and BRAF genes in tumor tissue were used. Results. Samples of tumor tissue of 73 patients were analyzed for mutations in the KRas, NRas and BRAF genes. In 33 of 73 tumors, no mutations were found in all 3 genes. Cetuximab therapy was initiated in 21 of 33 patients. Data for assessing the effect of treatment and survival were obtained for 19 patients. The median duration of cetuximab therapy was 3.9 months (95% CI, 2.18-5.69). Six months after the start of therapy, 11 (57.9%) of 19 patients had no progression of the disease. Median PFS was 6.4 months (95% CI, 4.31-8.39). In 2 of 19 patients partial regress of tumor foci was noted, complete responses to therapy were not noted. Control of the disease (partial regression or stabilization) was achieved in 68% of patients. The median overall survival was 14.9 months (95% CI, 13.1-16.7). Subgroup analysis showed no significant correlations of PFS or disease control with any of the clinical characteristics of patients. Compared with retrospective data on the efficacy of monotherapy with fluoropyrimidines as the first-line therapy in 19 patients with wild type KRas, NRas and BRAF genes in tumor tissue, PFS and overall survival of patients treated with cetuximab did not significantly differ in this study. Conclusion. This study showed the efficacy of monotherapy with cetuximab as the 1st-line therapy in patients with unresectable mCRR selected according to known molecular factors and not requiring urgent aggressive chemotherapy. Further research on the factors for the selection of patients with colorectal cancer to increase the effectiveness of therapy with epidermal growth factor receptor antibodies in patients of the selected subgroup is needed.

In modern health care, the problem of correction of motor-evacuation disorders of the digestive tracT., developing in the postoperative period, is extremely topical and relevant. Despite the possibility of developing enteroparesis after any surgical intervention, most often the latter results from an increase in the extent of the operation, multivisceral resections with multiple anastomoses, and extended variants of lymphadenectomy during oncosurgical interventions. It should be recognized that to date there is no universally recognized, adequate scheme for the prevention and treatment of postoperative paresis of the gastrointestinal tracT., and further in-depth studies with the development of action algorithms and clinical recommendations are required.

Background. Non-Hodgkin’s lymphomas (NHL) as oncopathology have long been known to oncologists. Good results have been achieved in the complicated course of NHL of the digestive tracT., but a lethal outcome is still often recorded because NHL of the digestive tract is diagnosed almost at the stage of development of complications. Description of the clinical case. A clinical case of NHL in a patient of 34 years is presented. Based on clinical, instrumental, laboratory, intraoperative and morphological datA., the diagnosis of «non-Hodgkin’s lymphoma of the cecum» was determined. Complications: hollow viscus perforation, diffuse fecal purulent peritonitis. Despite the presence of such a terrible, up to a fatal complication, as hollow viscus perforation with secondary diffuse fecal purulent peritonitis in the patienT., the life-saving medicinal treatment according to the R CHOP-21 scheme was carried out. After four courses of the 1st-line chemotherapy with complete regression of the tumor process, patient with the formed enteric fistula was hospitalized in the surgical thoracoabdominal unit where an combined-expanded right-sided hemicolectomy with extensive enterectomy with the formation of an end-to-side ileotransversostomy was performed. Currently, the patient is alive, and signs of recurrence and disease progression were not recorded during follow-up examination. Conclusion. The described clinical case proves that treatment of a complicated course of NHL of the digestive tract is not futile; complication is not a sign of neglect of the oncological process.