Выбор терапии первой линии хронического миелолейкоза: моделирование клинико-экономических факторов

Шуваев В.А., Абдулкадыров К.М., Мартынкевич И.С., Фоминых М.С.

ФГБУ «Российский научно-исследовательский институт гематологии и трансфузиологии Федерального медико-биологического агентства», ул. 2-я Советская, д. 16, Санкт-Петербург, Российская Федерация, 191024

Для переписки: Василий Анатольевич Шуваев, канд. мед. наук, ул. 2-я Советская, д. 16, Санкт-Петербург, Российская Федерация, 191024; тел.: +7(921)636-54-72; e-mail: shuvaev77@mail.ru

Для цитирования: Шуваев В.А., Абдулкадыров К.М., Мартынкевич И.С., Фоминых М.С. Выбор терапии первой линии хронического миелолейкоза: моделирование клинико-экономических факторов. Клиническая онкогематология. 2015;8(1):78–83.


РЕФЕРАТ

Обоснование. Ингибиторы тирозинкиназ второго поколения (нилотиниб и дазатиниб) имеют преимущество перед иматинибом в частоте и скорости достижения цитогенетических и молекулярных ответов при лечении хронического миелолейкоза (ХМЛ). Вместе с тем они сопровождаются более выраженными побочными эффектами и имеют более высокую стоимость, чем иматиниб. Больные ХМЛ со стойким глубоким молекулярным ответом в настоящее время рассматриваются как кандидаты на включение в клинические исследования по ведению ремиссии без лечения. Постоянный рост затрат на диагностику и лечение ХМЛ вызывает необходимость проведения фармакоэкономического анализа с целью оптимизации расходов и экономической обоснованности внедрения новых высокоэффективных препаратов.

Цель. Фармакоэкономическое моделирование выбора стратегии лечения ХМЛ ингибиторами тирозинкиназ первого и второго поколений в первой линии терапии с проведением анализа чувствительности клинико-экономических факторов.

Методы. Фармакоэкономическое моделирование диагностики и лечения ХМЛ. Анализ «стоимость-полезность» применения ингибиторов тирозинкиназ первого и второго поколений в первой линии терапии. Анализ чувствительности моделей с определением наиболее значимых клинических и экономических факторов, влияющих на результаты лечения. Проведение симуляции с целью определить фармакоэкономическую целесообразность применения ингибиторов тирозинкиназ первого и второго поколений в первой линии терапии ХМЛ в масштабах страны.

Результаты. Анализ чувствительности фармакоэкономических моделей показал их устойчивость. Установлены пороговые значения стоимости лекарственных средств, частоты достижения полного молекулярного ответа, определяющих экономическую целесообразность выбора стратегии лечения ингибиторами тирозинкиназ первого и второго поколений.

Выводы. Разработанные фармакоэкономические модели могут быть использованы при усовершенствовании стандартов диагностики и лечения.


Ключевые слова: хронический миелолейкоз, ингибиторы тирозинкиназ, иматиниб, нилотиниб, дазатиниб, фармакоэкономика, стоимость-полезность.

Получено: 11 сентября 2014 г.

Принято в печать: 7 ноября 2014 г.

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Ингибиторы тирозинкиназ второго поколения и их токсичность у больных в хронической фазе хронического миелолейкоза

Лазорко Н.С.1,  Ломаиа Е.Г.1, РомановаЕ.Г.1,  Сбитякова Е.И.1, Мачюлайтене Е.Р. 2, Бутылин П.А. 1,3, Зарицкий А.Ю. 1,2

1 ФГБУ «Северо-западный федеральный медицинский исследовательский центр», ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341

2 ГОУВПО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова», ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022

3 Университет ИТМО, Институт трансляционной медицины, Кронверкский пр., д. 49, Санкт-Петербург, Российская Федерация, 197101

Для переписки: Елза Галактионовна Ломаиа, канд. мед. наук, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341; тел.: +7(812)702-37-65; e-mail: lomelza@gmail.com

Для цитирования: Лазорко Н.С., Ломаиа Е.Г., Романова Е.Г. и др. Ингибиторы тирозинкиназ второго поколения и их токсичность у больных в хронической фазе хронического миелолейкоза. Клиническая онкогематология. 2015;8(3):302–8.


РЕФЕРАТ

Обоснование и цели. В последнее время накоплен определенный опыт по применению новых ингибиторов тирозинкиназ у пациентов с хроническим миелолейкозом. В статье обобщены литературные данные по токсичности, полученные в международных клинических исследованиях. Цель исследования — изучить побочные эффекты ИТК 2-го поколения (ИТК2) в рутинной клинической практике и оценить их влияние на дальнейшую судьбу пациентов.

Методы. Анализу подвергнуты собственные данные, полученные в условиях рутинной клинической практики. В ретроспективное исследование включено 76 пациентов (36 мужчин и 40 женщин) старше 18 лет (медиана возраста 49 лет, диапазон 26–75 лет) с диагнозом хронического миелолейкоза. Нилотиниб получало 48 пациентов, дазатиниб — 28 в хронической фазе заболевания в качестве второй линии после отмены иматиниба мезилата. Степень токсичности определялась по критериям CTCAE 4.0.

Результаты. Гематологическая токсичность III–IV степени зарегистрирована у 36,8 % пациентов. Значимых различий в частоте осложнений в группах нилотиниба и дазатиниба не выявлено: 39,6 и 32,1 % соответственно. Негематологическая токсичность II–IV степени отмечалась у 35,4 % пациентов, получавших нилотиниб, и у 25 % — дазатиниб. Частота отдельных видов токсичности не превышала 15 %. Сочетание различных видов негематологической токсичности наблюдалось у 9,2 % пациентов. Летальных исходов из-за токсичности ИТК2 не зарегистрировано.

Заключение. Гематологическая и/или негематологическая токсичность, связанная с ИТК2, зарегистрирована более чем у 50 % больных. В большинстве случаев осложнения носили временный характер и купировались после перерывов в терапии ИТК2 или при снижении дозы препаратов. Осложнения при терапии ИТК2 не оказывали влияния на вероятность достижения полного цитогенетического ответа и его стабильность.


Ключевые слова: хронический миелолейкоз, ингибиторы тирозинкиназ, токсичность.

Получено: 29 января 2015 г.

Принято в печать: 1 июня 2015 г.

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Роль селективности ингибиторов тирозинкиназ в развитии побочных эффектов при терапии хронического миелолейкоза

А.А. Зейфман1,2, Е.Ю. Челышева3, А.Г. Туркина3, Г.Г. Чилов1,2

1 ФГБУ «Институт органической химии им. Н.Д. Зелинского РАН», Москва, Российская Федерация

2 ООО «Фьюжн Фарма», Москва, Российская Федерация

3 ФГБУ «Гематологический научный центр» МЗ РФ, Москва, Российская Федерация


РЕФЕРАТ

В обзоре рассмотрен вопрос о связи селективности ингибиторов Bcr-Abl-киназ со спектром нежелательных побочных эффектов у больных хроническим миелолейкозом при проведении терапии. Суммированы данные по структуре и естественным биохимическим функциям наиболее хорошо изученных побочных мишеней ингибиторов Bcr-Abl-киназ: BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, VEGFR1/2/3, а также оценена возможная связь их нецелевого ингибирования и нежелательных побочных эффектов ингибиторов тирозинкиназ.


Ключевые слова: хронический миелолейкоз, ингибиторы тирозинкиназ, селективность, иматиниб, нилотиниб, дазатиниб, понатиниб, PF-114, BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, VEGFR1/2/3.

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