КЛИНИЧЕСКОЕ ИЗУЧЕНИЕ РАДИОФАРМАЦЕВТИЧЕСКОГО ЛЕКАРСТВЕННОГО ПРЕПАРАТА «НАНОТЕХ, 99mTс» ДЛЯ ВЫЯВЛЕНИЯ СТОРОЖЕВЫХ ЛИМФАТИЧЕСКИХ УЗЛОВ У ПАЦИЕНТОК С РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ

Abstract

Purpose: To evaluate the diagnostic efficacy and safety of the use of the radiopharmaceutical drug “Nanotech, 99mTc” in the detection of sentinel lymph nodes (SLN) in malignant breast cancer by indirect radionuclide lymphography and intraoperative radiometry. Material and methods: The results of clinical studies of the drug «Nanotech, 99mTc», conducted in two research centers: N.N.Petrov National Medical Research Center of Oncology (128 patients) and N.N. Blokhin National Medical Research Center of Oncology (20 patients), were analyzed in 148 patients with breast cancer, aimed at sectoral breast resection, radical or subcutaneous mastectomy. The patients included in the clinical trials met all the requirements of the inclusion/non-inclusion criteria assessed at the screening stage. Radiopharmaceutical drug “Nanotech, 99mTc” was injected into the affected mammary gland at 4 mutually perpendicular points intradermally periareolar. The administered activity was 20.0–40.0 MBq for each injection site, the volume of administered drug «Nanotech, 99mTc» was 0.1–0.3 ml for each injection site. The total single administered dose was 80–160 MBq in a volume of 0.4– 1.2 ml. 1–2 hours after administration of the drug, 4–24 hours before surgery, the patients underwent planar polypositional scintigraphy in three standard projections with a marker mark applied to the patient’s skin surface corresponding to the projection of each SLN. The procedure of intraoperative radiometry was performed using a specialized portable gamma detector in the operating room during the main surgical intervention. The main efficiency parameter was the frequency of identification of SLN during intraoperative radiometry, safety indicators were considered adverse events. When evaluating the results, all adverse events that occurred during the study were considered, and their relationship with the drug under study was also evaluated. For statistical analysis, the patients were divided into the following populations: FAS – all patients who received a dose of the finished drug; ITT population – all patients who received a dose of the finished drug and who underwent intraoperative radiometry; PP population – all patients who completed the study in accordance with the protocol. The main efficiency analysis was carried out in the ITT population. The safety analysis was carried out in the FAS population. Results: The frequency of detection of SLN during intraoperative radiometry in 148 patients, in the main efficacy population (ITT), was 142/148 (95.95 %) with a one-sided 95 % confidence interval of 92.24 %, while the width of the lower part of the confidence interval was 3.71 %. Based on the analysis of primary efficacy, a conclusion was made about diagnostic efficacy, since the boundary of the one-sided 95 % confidence interval for the frequency of detection of SLN during intraoperative radiometry exceeds 84 %, while the width of the lower part of the 95 % one-sided interval does not exceed 5 %. When analyzing secondary endpoints in the ITT population, the frequency of detection of hyperfixation foci during diagnostic lymphoscintigraphy was 97.30 % with a one-sided 95 % confidence interval of 93.97 %, while the width of the lower part of the confidence interval was 3.33 %. The results of the analysis of primary and secondary endpoints of diagnostic effectiveness in the PP population were similar to those obtained in the main population of the effectiveness assessment (ITT). The analysis of diagnostic effectiveness, carried out depending on the method of statistical analysis of the primary variable of effectiveness, led to consistent conclusions. No adverse events were registered during the study. The assessment of safety and tolerability based on the results of statistical assessments of vital signs and the condition of the skin at the injection site showed a high degree of safety and tolerability of drug “Nanotech, 99mTc”. Conclusions: This study obtained data confirming the diagnostic efficacy and high degree of safety and tolerability of radiopharmaceutical drug “Nanotech, 99mTc”, which justifies the possibility of its medical use and registration.