Antiestrogennaya terapiya pri rake molochnoy zhelezy. Naskol'ko bezopasny ingibitory aromatazy?

Abstract


Около 75% больных раком молочной железы (РМЖ) имеют положительные рецепторы к эстрогену и/или прогестерону на клетках опухоли. Взаимодействие этих рецепторов с эстрогеном стимулирует пролиферацию и выживание клеток рака.блокада яичников не обеспечивает полной остановки образования этих гормонов, и требуется дополнительное воздействие, чтобы прервать стимуляцию опухоли. Эффективной последующей антиэстрогенной стратегией явилась блокада рецепторов этих гормонов. С этой целью были синтезированы селективные модуляторы рецепторов к эстрогенам (SERM) тамоксифен и торимефен. Назначение тамоксифена в течение пяти лет у пациенток с рецептор-позитивными опухолями в менопаузе позволило сократить частоту рецидивов и возникновения рака контралатеральной молочной железы на 50%, уменьшить смертность на 28%. В течение 10 лет тамоксифен оставался "золотым стандартом" адъювантной эндокринной терапии РМЖ в постменопаузе. В то же время применение препаратов этой группы оказывается эффективным лишь у 50–55% больных с рецептор-положительными опухолями.Применение тамоксифена, особенно с адъювантной целью, когда препарат назначается длительно, сопровождается неоптимальной переносимостью. В крупных исследованиях было показано, что более 60% больных отмечали те или иные побочные реакции, связанные с приемом препарата. В 23–40% случаев это приводило к его отмене.В последние годы все более широко применяются селективные ингибиторы ароматазы третьего поколения – анастрозол (Аримидекс) и летрозол (Фемара), а также стероидный инактиватор экземестан (Аромазин). Отличительной особенностью данных препаратов является высокая активность (снижение уровня эстрогенов на 96–98%), избирательность действия, удобство применения. Клинические исследования показали, что их эффективность при неоадъювантной терапии местно-распространенного, метастатического РМЖ как минимум не уступает активности тамоксифена.Ингибиторы ароматазы 3-го поколения обладают высокоизбирательным действием, приводящим к блокаде превращения андрогенов в эстрогены. Препараты широко используются в терапии рецептор-позитивного РМЖ как при лечении его распространенных форм, так и в качестве адъювантной и неоадъювантной терапии. Они удобны в применении (пероральная форма, необходимость приема 1 раз в сутки), не требуют коррекции дозы при наличии почечной или печеночной недостаточности. Их использование сопровождается меньшей частотой тяжелых и приводящих к отмене препарата осложнений, чем при применении тамоксифена.

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V V Ptushkin

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