40 ; 29 Sibirskiy Trakt St., Kazan' 420029, Republic of Tatarstan; 2 Altai Regional Oncology Dispensary; 77 Nikitina St., Barnaul 656049, Russia; 3 N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; 24 Kashirskoe Shosse, Moscow 115478, Russia; 4 Primorsky Regional Oncology Center; 59/63 Russkaya St., Vladivostok 690105, Russia; 5

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.

Anemic syndrome (АС) is a frequent complication of cancer that gives poor results of treatment and reduces quality of live of patients. The literature review is devoted to the role of the peptide hormone hepcidin 25 (HP25), which regulates systemic and local iron homeostasis, in the development of anemia. The main biological function of HP25 is to reduce the level of iron in the bloodstream, which realizes a decrease of the mobilization of iron from the depot and a decrease of absorption of iron in the intestine. Modern approaches to the diagnosis and treatment of anemic disease in oncological practise necessarily include an assessment of the level of HP25. It was shown that HP25 is involved in the pathogenesis of anemia in malignant neoplasms. Oncological diseases are often accompanied by high levels of pro-inflammatory cytokines, in particular interleukin-6 (IL-6), which causes an increase in the production of HP25. Under the influence of IL-6, HP25 blocks ferroportins and iron release by macrophages, which leads to the development of functional iron deficiency and iron deficiency erythropoiesis, thus, with prolonged exposure to pro-inflammatory cytokines, anemia of chronic disease develops. The treatment of АС associated with malignant neoplasms is a complex procedure. Therapeutic effect on HP25 and IL-6 is a promising prospect for the correction of anemia in cancer patients. New strategies in the pathogenetic therapy of patients with anemia are associated with the use of antihepcidin drugs that reduce the level of HP25 in the blood. However, some studies have shown that an increase in the iron content in the bloodstream increases its accessibility to the tumor and promotes its growth; therefore, further, more in-depth study of the problem of correcting АС in cancer patients is necessary

Neutropenia is a common hematological complication of chemotherapy (СT). The number of studies showed that the underperformance of the treatment program due to the development of this type of hematological toxicity could lead to the decrease in therapy efficacy and to the increase in cancer mortality. Infections that occur as a result of prolonged neutropenia are extremely dangerous. The most severe manifestation of grade 4 neutropenia is febrile neutropenia (FN), which can lead to death from severe infections. Such patients should be immediately hospitalized and should receive empirical therapy with broad-spectrum antibiotics. The costs, associated with the hospitalization, due to FN increase total cost of cancer patients treatment. The application of recombinant forms of the natural protein granulocyte colony-stimulating factor (G-CSF) in clinical practice has solved the number of important problems on that front. The clinical studies and common use show that primary and secondary prevention using recombinant G-CSF reduces the risk of FN development and improves the results of the treatment of malignancies. The review provides actual data concerning pharmacological properties, clinical efficacy and reasonable use of G-CSF with prolonged action to prevent FN in patients with solid tumors during 2-week CT cycles. Special attention is paid to CH regimens with the inclusion of 5-fluorouracil, oxaliplatin, irinotecan in the treatment of colorectal cancer (CRC). The use of neoadjuvant treatment in such patients allows to achieve resectability of the tumor and to perform radical surgery. The maintenance of drugs dose intensity throughout the cycle of CT plays an important role in achieving the treatment success. Therefore, the prevention of CT-induced severe neutropenia and FN is especially important in patients who are the candidates for surgical treatment. The results of some studies confirm the necessity of using G-CSF with prolonged action during 2-week CT cycles in patients with CRC.