MECHANISM OF DEVELOPMENT OF TAXAN-INDUCED NEUROPHYSIOLOGICAL CHANGES IN ONCOLOGICAL PATIENTS

Chemotherapy-induced peripheral neuropathy is a dose-limited side-effect of a number of chemotherapy drugs, including platinum, taxanes, alkaloid drugs, as well as new targeted drugs, including bortezamide and lenolidamide. In practice, prevention and treatment of chemotherapy-induced peripheral neuropathy is empirical and, in most cases, is performed on the second (moderate) stage of neuropathy. For prevention of peripheral neuropathy oncologists reduce doses of chemotherapy drugs or refuse taxanes at all, which in turn has a negative effect on the immediate effectiveness and long-term results of treatment. Taxanes are a class of anticancer agents that were first discovered in the 1960s as a result of a screen-ing program conducted by the United States National Cancer Institute. Extracts of various parts of several thousand plants from around the world were tested for antitumor activity. In 1962, botanist Arthur Barclay sent more than 200 species of plants to the National Cancer Institute's research laboratory. Among those collected materials were samples of the bark of a Pacific yew (Tax-us brevifolia), and it was found that they contained sub-stances that have a cytostatic effect. Further research was conducted at the Research Triangle Institute in North Carolina by the American biochemists Monroe Wall and Mansukh Wani, who first synthesised pure paclitaxel from bark of a Pacific yew (Taxus brevifolia). Subse-quently, for commercial purposes, production of paclitaxel was carried out from the needles of a more accessible and widespread European yew tree (Taxus baccata). At present, pathophysiological mechanism of taxanes-induced neuropathy is not fully known and understood. Suppression of tubulin depolarization and, as a consequence, microtubule dysfunction is currently the most commonly accepted explanation for taxanes neurotoxicity. Morphological study of peripheral nerves in patients , according to world literature, is lacking. Biopsy of the sural nerve followed by morphological study of changes in case of paclitaxel and docetaxel usage was performed in only a few patients. Moreover, the data of morphological studies is ambiguous and contradict the generally accepted theory of the pathogenesis of neuropathy. Taxanes are broad-spectrum chemotherapy drugs and are currently used as a first-line chemotherapy for breast, stomach, lung, head and neck, prostate, and gynaecologic malignancies. In breast cancer, taxanes are used as the first line of chemotherapy for early, locally advanced and metastatic forms. Taxan treatment is accompanied by a number of adverse reactions, including hypersensitivity reactions, suppression of bone marrow (neutropenia), gastrointesti-nal toxicity (nausea, vomiting, diarrhoea, mucositis), alopecia, neurotoxicity (peripheral neuropathy). This often requires a dose reduction up to the discontinuation of the drug, which in turn has a negative effect on the immediate effectiveness and long-term results of treat-ment. Neurotoxicity is the second most common compli-cation and manifests itself as peripheral sensory neuropathy, which usually begins with a tingling sensation and burning in the wrists and feet, with subsequent formation of a loss of sensitivity that can become irreversible. In order to prevent this adverse reaction in a timely and effective manner, it is necessary to know the causes that lead to the development of peripheral neuropathy and to understand what cellular structures and mechanisms are involved.