Патогенетические аспекты введения соединений с предполагаемым противоопухолевым действием в метрономном режиме (обзор)

Abstract

Chemotherapy is the main treatment method for malignant neoplasms. Classical administration regimens for chemotherapeutic agents are accompanied by strong side effects. Thus, there is a need for a rational mode of administration that can increase the effectiveness of chemotherapy and reduce its side effects. Development of new antitumour drugs must involve testing their pharmacological activity at various administration regimens. At the stage of preclinical studies of new compounds with an alleged antitumour effect, determining an optimal dosage regimen is an urgent task for interdisciplinary research. This article analyses literature on the possible use and effectiveness of metronomic administration of antitumour drugs in clinical practice and in preclinical studies depending on the pathogenetic mechanism of their action. According to recent research, metronomic administration of antitumour and antimetastatic drugs is, undoubtedly, a rational way to solve the problem of severe side effects and poor drug tolerability in cancer patients. The greatest antitumour effectiveness in the metronomic regimen is achieved at combined administration of compounds with different mechanisms of action. In preclinical studies of new antitumour agents, it is important to adhere to the basic principles of developing a metronomic administration regimen: 1) at the testing stage, it is advisable to perform screening administration of low doses of new compounds along with a therapy with a known antitumour drug; 2) the minimum dose of the new compound can be calculated using its maximum tolerated dose (initial approximate series of administration in the amount of 1/10 of the maximum tolerated dose).