Now the number of patients receiving immunotherapy with checkpoint inhibitors is growing. At the same time, clinicians increasingly encounter such a clinical phenomenon as pseudoprogression. Nowadays we have no radiological evidences of pseudoprogression. The every such case requires an individual decision.

Hepatocellular cancer (HCC) is a significant problem of modern Oncology. Until recently, sorafenib was the only drug in the treatment of locally advanced and metastatic HCC. Knowledge of the mechanisms of carcinogenesis and tumor escape from the immune response is the basis for immunotherapy in the treatment of malignant tumors and HCC, in particular. Сlinical trials have shown immunotherapy significantly improves the results of treatment of patients with locally advanced and metastatic HCC with controlled toxicity profile. Currently, nivolumab and pembrolizumab (сheckpoint inhibitors) have been registered as the second line of treatment after progression on sorafenib. Clinical trials are needed to identify optimal combinations of drugs and sequences of their use in different clinical situations.

Small-cell lung cancer (SCLC) is one of the most prognostically unfavorable malignant tumors for which an effective targeted inhibitor has not yet been found. Cytotoxic therapy for SCLC has not changed in the last thirty years. Immunotherapy is a fundamentally new method of treatment of malignant tumors, which has proven its effectiveness in various solid tumors. Fundamental prerequisites for the efficacy of immunotherapy in SCLC include a high level of mutational load and paraneoplastic syndromes typical for SCLC (Lambert - Eaton syndrome, etc.), leading to immunization against the tumor; factors that may adversely affect the efficacy of immunotherapy are low levels of PD-L1 expression, low content of T-lymphocytes infiltrating the tumor, and loss of histocompatibility of SCLC antigens by tumor cells. The first studies that studied the efficacy of CTLA-4 inhibitors in the first line of therapy of SCLC and PD-L1/PD-1 inhibitors during progression after the first line showed ambiguous results. However, the study to evaluate the efficacy of athezolizumab (antibody to PD-L1 receptor) in combination with chemotherapy in the first line of SCLC, where for the first time in 30 years in the studies of phase 3 at disseminated SCLC a significant increase in the total survival rate was shown. The study of immune control point inhibitors in SCLC, both localized and disseminated, continues, the prospects of immunotherapy in SCLC are already clearly defined, and further development and improvement in one of the most adverse forms of cancer is expected.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors. Currently, it is possible to carry out three consecutive lines of target therapy against metastatic GISTs: imatinib as first-line, sunitinib as second line and regorafenib as third line. The mutation status of the C-Kit gene is a predictor of GIST sensitivity to imatinib and sunitinib. Some patients have to stop the treatment due to sunitinib related toxicity. Regorafenib can be used as the second line therapy of metastatic GISTs in case of sunitinib intolerance.

Ceritinib is the second ALK tyrosine kinase inhibitor after crizotinib, registered in the Russian Federation for the treatment of ALKpositive patients with non-small cell lung cancer (NSCLC). Later alectinib was registered. Thus, we have the opportunity, firstly, to continue targeted therapy with second-generation drugs after progression on crizotinib, and secondly, the appointment of more active drugs in the first line provides the best results of treatment.

Breast Cancer is the most common type of cancer worldwide. Scientific advances and new ways of treating have significantly improved the prognosis of breast cancer in recent decades. The emergence of modern cyclin-dependent kinase (CDK) inhibitors has changed the treatment paradigm for metastatic hormone receptor (HR)-positive breast cancer. In the past four years, the CDK4/6 inhibitors, ribociclib, palbociclib and abemaciclib, received their first FDA approval for the treatment of Hormone Receptor (HR)- positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA, MONALEESA and the MONARCH randomized clinical trials, respectively. In the Russian standards for the treatment of metastatic HR positive and HER2-negative breast cancer are included two inhibitors of CDK4/6 – ribociclib, palbociclib. This review summarizes the background of clinical efficacy and potential toxicities seen with the use CDK4/6 inhibitors with endocrine treatment in pre- or postmenopausal women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer. Despite the similar toxicities, inhibitors of cyclin-dependent kinases differ in their severity and some types of adverse events. Most hematologic abnormalities seen with CDK4/6 inhibitors are not complicated and are adequately managed with standard supportive care and dose adjustments when indicated. This review focuses on the practical management of adverse events associated with CDK4/6 inhibitors.

Palbociclib is the first-in-class drug of CDK 4/6 inhibitors group. The use of palbociclib in combination with endocrinotherapy (ET) opens up new possibilities for the treatment of metastatic hormone receptor-positive (HRP+) HER2-negative (HER2-) breast cancer (mBC). Palbociclib has gained world attention and is included in all clinical guidelines, both international and domestic, as a new standard of first- and second-line therapy of HRP+ HER2- mBC. The article presents the updated results of PALOMA-2 and PALOMA-3 studies and the results of use of palbociclib in combination with ET in real clinical practice.

The article presents data on the efficacy of erlotinib in the treatment of NSCLC in the presence of EGFR gene mutation. Its advantages over chemotherapy in terms of survival, quality of life, and tolerability of treatment, both as monotherapy and in combination with cytostatics and other targeted drug – VEGF inhibitor – Bevacizumab, are shown. A clinical case of EGFR-positive NSCLC and its treatment with erlotinib was considered. Ways of overcoming resistance to treatment are studied. The use of erlotinib should be considered as one of the standard methods of first and subsequent therapy in patients with NSCLC in later stages with confirmed mutations of the EGFR gene.

Breast cancer steadily holds leading market positions in the malignancy morbidity and mortality pattern. The treatment of metastatic breast cancer remains an extremely topical issue, when its aim is not only to prolong the patient’s life, but also to preserve its quality. Due to advances in molecular diagnostics, it has become possible to use several new classes of drugs in recent times. CDK4/6 inhibitors that demonstrate high efficacy in the first-line therapy for luminal metastatic breast cancer is one of these groups. This review presents data from recent registration studies and a description of observations from our own clinical experience.

The authors analysed the efficacy and safety of Nab-paclitaxel (Nab-R) monotherapy in patients with metastatic breast cancer with visceral crisis (VC) in the second- and further-line chemotherapy. The objective response rate (ORR) was 35.3% (6 of 17 persons). The most frequent side effects were general weakness, nausea, symptoms of peripheral neuropathy. The degree of toxicity did not exceed 1–2 in 60% of cases. The median time to progression was 7.8 months. (95% CI 6–10.6). The median overall survival for patients with VC was 14.9 months. (95% CI 12.0–16.9). Efficacy and controlled toxicity of Nab-P allows its use in pre-treated patients, including ones with VC.

Breast cancer (BC) ranks first in the morbidity pattern among women in Russia. Adjuvant endocrinotherapy is an important step in the complex treatment of premenopausal patients with hormone-positive early breast cancer. The drug ovarian suppression with GnRH-agonists have supplanted surgical castration and radiation-based treatment of the ovaries in patients with hormone-positive early breast cancer. Today, several drugs authorised for the treatment of breast cancer are used in clinical practice: goserelin, buserelin and triptorelin. Buserelin-depo is an effective method for achieving ovarian suppression. The results obtained do not differ from similar indicators obtained in using imported LHRH analogues.

The urgency of the problem of treating patients with lung cancer is caused by a steady increase in the lung cancer incidence and lung cancer mortality rates in population. Most patients with NSCLC initially present with locally advanced or disseminated disease. Currently, simultaneous chemoradiation therapy (CRT) is the standard for the treatment of locally advanced NSCLC, which appears superior to the single chemotherapy or radiation therapy, while the overall survival (OS) rate remains not high enough. Therefore, the search for optimal combinations of chemotherapeutic drugs and radiation therapy (CRT), as well as fractionation regimens is a promising direction in the treatment of such patients. In this article, we will review the on-topic studies data that are currently available, future directions of the therapy and objectives.

Background: Several studies show that the combination chemotherapy with ramucirumab allows to improve the treatment results of advanced gastric cancer (GC). Irinotecan with fluoropyrimidines is own of the second line chemotherapy options for these patients. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of irinotecan and fluoropyrimidines with ramucirumab in metastatic GC.

Methods: Eligible patients had advanced morphologically verified GC and disease progression during or within 4 months following first-line therapy. They received FOLFIRI plus ramucirumab (8 mg/kg on day 1) or XELIRI in combination with ramucirumab (8 mg/kg on days 1 and 8). The primary end point was progression-free survival (PFS). Secondary end-points were disease control rate (DCR) and safety.

Results: Between September 2015 and April 2019, 39 patients (pts) were enrolled and 38 were evaluated for efficacy and toxicity. Median number of cycles was 9 (2-20). Seven patients achieved a partial response (PR) for an overall response rate of 17.9%. A total of 29 (74.4%) patients had stable disease (SD) for a DCR of 92.3%. With a median follow up 7,5 months, median PFS was 7.58 months (95% CI 6.6-8.5) and the median OS has not yet been reached. Median duration of PR response was 8,7 months (4,11-10,94+) and median duration of SD was 4,14 months (1,84-11,99+). The main treatment-related grade 3 or 4 adverse events were neutropenia (7/38; 18.4%), anemia (1/38; 2.6%) and diarrhea (2/38; 4.3%).The most frequent adverse events of special interest (AESIs) any grade were hypertension (16/38; 42.1%), bleeding/hemorrhage (10/38; 26.3%), proteinuria (6/38; 15.7%) and venous thromboembolic events (10/38; 26,3%). Gastrointestinal perforation developed in two patients (2/38; 5.3%). No treatment-related deaths occurred.

Conclusion: In our research ramucirumab with irinotecan and fluoropyrimidines demonstrate the high activity and a manageable safety profile in patients with pre-treated metastatic GC

In the open prospective non-randomized single-center study we recruited patients with advanced NSCLC harboring EGFR mutations. Initially there were two months of treatment by gefitinib 250 mg daily. Then, after a 2-week drug-free period, 3 cycles of paclitaxel 175 mg / m2 and carboplatin AUC5 were administrated at days 71-113. Thereafter, gefitinib was re-started on day 135 and continued until disease progression. The primary endpoint was progressive free survival (PFS) time. One-year PFS in all patients group included in the study at the time of the preliminary analysis was 79.8%, median PFS was 17 months (13.5–23, CI 95%). In the group of integrated chemotherapy one-year PFS was 89.3%, median PFS was 19 months (14–23.5, CI 95%).

The treatment efficacy and toxicity profile was evaluated in 33 patients with highly differentiated neuroendocrine tumors NEO (G1, G2), who received sunitinib therapy in various dose regimens. Stable disease was achieved in 24 patients (72.7%), partial effect in 1 patient (3%). The efficacy of treatment did not depend on the used dose regimen. The toxicity profile was consistent with international study data.

Gastric cancer (GC) is one of the most common types of malignant tumour worldwide and is ranked fifth in the cancer incidence pattern and third in the cancer mortality pattern. In the Russian Federation, 39.9% of patients are diagnosed with stage IV gastric cancer, 46.6% of patients die within the first year after diagnosis. The combinations of trastuzumab with platinum derivatives and fluoropyrimidines (trastuzumab + doublet) are regarded as the standard therapy against HER2 positive disseminated gastric cancer. We studied the efficacy and toxicity of the combination of trastuzumab with three-component (triple) chemotherapy regimens (docetaxel or irinotecan + platinum derivatives and fluoropyrimidines). In combination of trastuzumab with triplet chemotherapy, an objective response was achieved in 76.7% of cases, with doublet chemotherapy it was achieved in 60% (p = 0.228), of which complete tumour regression was observed in 10%, control of the disease was reported in 96.7% and 95.0 % (p = 1.0) patients, respectively. The median progression-free survival in patients, who received trastuzumab in combination with triplet chemotherapy, was 9.66 months, in combination with doublet chemotherapy was 11.07 months, the difference was not statistically significant (p = 0.800; OR = 0.908; 95% CI: 0.430–1.918). Median survival of patients is not achieved. The obtained results showed that adding a third cytostatic agent to the standard duplet chemotherapy in combination with trastuzumab does not lead to improvement in the treatment outcomes of first-line therapy in patients with HER2-positive disseminated gastric cancer.

Symptomatic central nervous system (CNS) metastases are diagnosed in 10–16% of patients with metastatic breast cancer (BC). Half of all these cases are HER2-positive. At present, there are no generally accepted algorithms regarding the combination and sequence of local and systemic treatment options for these patients. According to current guidelines, different local management options remain one of the main treatment methods of brain metastases control. When local treatment is limited, patients with HER2-positive BC with СNS metastases can receive anti-HER2 therapy in combination with chemo- or hormonal therapy (for luminal tumors) or as single option. Trastuzumab poorly penetrates the blood-brain barrier, but trastuzumab-based treatment schedules increase the life expectancy in patients with HER2-positive BC with CNS metastases mainly due to control of extracranial metastases. Lapatinib, by contrast, penetrates the blood-brain barrier well, and its combination with capecitabine achieves response in heavily pretreated patients, especially in those who have central nervous system metastases as the only site of disease progression.

The low efficacy of cytostatic therapy in mGC led to an active study of the role of molecular targets in the carcinogenesis of GC. Ramucirumab is the only neoangiogenesis inhibitor, which demonstrated its antitumor activity both as monotherapy and in combination with paclitaxel in patients with mGC. A clinical case demonstrated an example of a long-term (26+ months) response to paclitaxel therapy after it was combined with ramucirumab with an acceptable toxicity profile, which allowed a patient to participate in social activities and maintain quality of life.

The article describes the experience in effective use of the second-generation EGFR II blocker in palliative target therapy of EGFRnegative lung adenocarcinoma. The use of afatinib in the fifth-line palliative therapy of EGFR-negative lung adenocarcinoma allowed us to achieve a significant positive response to therapy in the lungs and improve the patient’s quality of life.

Cabazitaxel, an antineoplastic agent from the third generation taxan group, has demonstrated efficacy in the treatment of metastatic castration-resistant prostate cancer (mCRPC) refractory to docetaxel. This article is devoted to a critical analysis of studies on the use of cabazitaxel in this category of patients and key aspects of management of treatment-related toxicity. The authors also reviewed possible scenarios for the use of cabazitaxel in the sequential therapy of mCRPC, including androgen receptor signalling inhibitors and systemic radiotherapy.

Prostate cancer (PC) is one of the major health problems of the male population. The most difficult is the treatment of metastatic castration-resistant prostate cancer (mCRPC), which is the main cause of mortality from PC. In the course of treatment of PC, it inevitably becomes refractory to castration, characterized by the growth of PSA and clinical signs of progression. Octreotidedepo, a representative of the synthetic analogue of somatostatin of prolonged action, has a therapeutic effect in patients with CRPC with a positive total response in the form of a decrease or stabilization of the PSA level, the drug has a favorable safety profile and is easily tolerated by patients. The economic benefit of Octreotide-depo is estimated in the article. Cost-effectiveness analysis has shown its high clinical and economic efficiency. After the establishment of CRPC, first of all, the preparation Oсtreotide-depo will allow to postpone the start of chemotherapy with docetaxel or hormonal therapy of the 2nd line by 7–8 months and save up to 17% of funds in the first year of treatment.

Hodgkin’s lymphoma, being a highly malignant disease, has now acquired the property of a curative one. The article describes the basic principles of therapy of children with Hodgkin’s lymphoma, slow fixation of risk-adapted treatment positions. The possibility of complete cure of most patients appeared, which made this tumor a unique model for studying the remote consequences of cancer treatment. After the antitumor treatment of Hodgkin’s lymphoma, boys may suffer from testicular insufficiency (due to cytostatics), obstructive azoospermia (as a consequence of radiation therapy in the pelvic area), hypogonadism (secondary - after exposure of the pituitary gland to radiation, primary - after exposure of the pelvis due to the toxic effects of cytostatics). In order to reduce the gonadotoxicity of treatment, studies are being conducted to modify chemotherapy in the direction of lowering the doses of alkylating cytostatics, reducing the doses of radiation therapy without losing the effectiveness of treatment. Regardless of the cause of male infertility diagnosis includes the collection of reproductive history, external examination of the genitals, analysis of ejaculate, ultrasound examination of the scrotum, assessment of hormone levels (follicle stimulating hormone, total testosterone, serum testosterone, luteinizing hormone, prolactin, inhibin B, thyroid stimulating hormone).

Chronic pain syndrome (CPS) is an independent disease. Patients with disseminated malignant tumors may experience chronic pain even with successful anticancer therapy. For the control of CPS use the WHO analgesic ladder. Despite adequate pain relief, patients may experience breakthrough pain. Clinical guidelines suggest the use of opioids for the treatment of breakthrough pain. Dexketoprofen is a nonsteroidal anti-inflammatory drug (NSAIDs) of rapid action. The drug is highly effective for pain in the bones of various origins. Dexketoprofen can be used for incident predictable breakthrough pain.

Famous and familiar analgesics are being replaced by new drugs with improved properties. How to calculate their dose, in which category of patients to use, for what type of pain, with what dose to start therapy and with what adjuvants to combine? Many questions arise when a new opioid is being used. To answer these difficult questions, we decided to share our experience with the new analgesic tapentadol, describing real clinical cases from our practice.