Abstract
Methotrexate (MTX) is a widely used anti-tumor drug, folic acid antagonists. The effectiveness of high doses (more than 1 g/m2) of MTX in a monotherapy or in a combination with other chemotherapeutic drugs has been proven in a treatment of a large spectrum of oncological diseases in children such as osteosarcoma, tumors of the central nervous system, lymphomas, acute lymphoblastic leukemia. The use of high doses of MTX is often fraughted with development of life-threatening complications such as MTX-induced acute kidney injury, neurotoxicity, myelosuppression. Currently developed recommendations for therapeutic monitoring and supportive care, including hyper-hydration, urine alkalization and leucovorin therapy, allow to reduce toxicity of MTX, but in some patients it is not always possible to prevent the development of complications. Cohort studies in order to identify risk factors for toxicity after high doses of MTX in children with different forms of cancer are limited, as well as comparing various types of supportive care regimens, including, infusion therapy. Studying of development mechanisms of MTX toxicity depending on background conditions will allow to improve existing recommendations and develop new and most effective standards of supportive therapy with respect to the individual specifics of patients.
Highlights
Метотрексат (МТХ) — широко используемый противоопухолевый препарат из группы антиметаболитов, антагонистов фолиевой кислоты
The effectiveness of high doses of MTX in a monotherapy or in a combination with other chemotherapeutic drugs has been proven in a treatment of a large spectrum of oncological diseases in children such as osteosarcoma, tumors of the central nervous system, lymphomas, acute lymphoblastic leukemia
The use of high doses of MTX is often fraughted with development of life-threatening complications such as MTX-induced acute kidney injury, neurotoxicity, myelosuppression
Summary
Следует подчеркнуть малочисленность когортных исследований по выявлению факторов риска развития токсичности при использовании высоких доз МТХ у детей с различными нозологическими формами онкологических заболеваний, а также сравнению различных режимов сопроводительной, в том числе инфузионной, терапии. Анамнез тяжелой нефротоксичности после использования ВДMTX повышает риск развития ОПН при повторных курсах, тем не менее в случаях ее преодоления и восстановления функциональной активности почек последующая терапия может проводиться без ограничений [7, 10]. Учитывая высокий уровень аденозина в ЦНС, исследователи оценивали влияние одночасовой инфузии аминофиллина в дозе 2,5 мг/кг при развитии нейротоксичности 3–4-й степени в течение 24 часов после введения МТХ у детей, при этом они опирались на его способность вытеснять аденозин из центральных рецепторов. Декстрометорфан, являясь слабым антагонистом рецепторов N-метилD-аспартата, может ослаблять нейротоксическое действие гомоцистеина [11]
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