RS4673 and pon1 level in blood plasma - new prospects in prediction and early diagnostics of anthracycline-mediated cardiotoxicity.

The purpose of this study was to research the effectiveness of molecular genetic tests based on the determination of the rs4673 CYBA polymorphism (c.242C>T) and the level of paraoxonase 1 (PON1) in the blood plasma of patients with breast cancer (BC) for predicting and diagnosing anthracycline-mediated cardiotoxicity (AMC). The genotyping of rs4673 CYBA (c.242C>T) and the study of the PON1 level in the blood plasma of 280 patients of the Caucasian type with a histologically verified diagnosis of breast cancer, who received complex treatment on the basis of the National Medical Research Center of Oncology, were carried out. Based on the results of observation for at least 8 months, two groups were identified: group 1 (257 people) without diagnosed cardiovascular changes; group 2 (23 people) - patients with subacute and early chronic AMC. It was found that carriers of the rs4673 polymorphism increase the likelihood of developing AMC by 6.8 times (p = 0.001). In the blood plasma of both groups of patients, an increase in the level of PON1 was described after the fourth course compared to the initial level (group 1 - p = 0.036, group 2 - p = 0.048). The level of the studied enzyme was higher in the blood plasma of patients with diagnosed AMC compared with patients without cardiovascular complications (before chemotherapy - p = 0.001, after the fourth course - p = 0.023). The test based on the measurement of the concentration of PON1 in the blood plasma of patients after the fourth course of chemotherapy was distinguished by high quality metrics: sensitivity - 100%, specificity - 70.8%, area under the ROC-curve (AUC) - 0.825 with a threshold level of PON1 equal to 2, 9 ng/µL. The presence of the T/T genotype caused a high level of PON1 in the blood plasma after the fourth course of chemotherapy (p = 0.012). The results of our work are of undoubted practical importance, since they allow us to obtain data on the prognosis and diagnosis of a patient in a short time, which can later be verified using clinical and instrumental methods.

[Anti-EGFR monoclonal antibodies in locally advanced head and neck squamous cell cancer].

The article presents immediate results of neoadjuvant treatment of patients with locally advanced head and neck squamous cell cancer and an evaluation of the toxicity of cetuximab. Standard chemotherapy in combination with targeted therapy with cetuximab showed its high effectiveness and satisfactory tolerance.

[Experience with the use of palonosetron (onicit) in patients with solid tumors receiving cytostatic therapy].

Nausea and vomiting are among adverse effects of chemotherapy that significantly worsen quality of life of patients. 5-HT3 receptor antagonists have been used in recent decades to prevent and arrest these complications. Palonosetron is the most modern drug in this group. Palonosetron application during highly and moderately emetogenic chemotherapy showed its high effectiveness for nausea and vomiting prevention.

[The role of assessing UGT1A1 gene polymorphism in the prediction of irinotecan-induced toxicity in the course of chemotherapy for colorectal cancer].

There was performed a molecular genetic study of UGTlAl gene allelic variants polymorphism in patients with colorectal cancer who had had chemotherapy irinotecan-containing regimens FOLFIRI. Comparison of toxicity and the results of polymorphism of UGTlAl showed that dose-limiting hematologic and non-hematologic toxicities in patients with moderate and high risk of toxicity were higher (p = 0.050- 0.061) and the frequency of thrombocytopenia (p = 0.0257) and hyperbilirubinemia (p = 0.0439) were significantly higher compared to the low-risk group. Molecular genetic study of a complex examination of patients, which was planned to irinotecan should be performed to select the optimal dose and reduce the risk of toxicity of chemotherapy.