tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2022-12-1-21-35tumors-942Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL REPORTSЭффективность неплатиновой монохимиотерапии в лечении платинорезистентных рецидивов рака яичников: мета‑анализEfficacy of non‑platinum chemotherapy in platinum‑resistant ovarian cancer: a meta‑analysisРумянцевА. А.RumyantsevA. A.

Алексей А. Румянцев, к. м. н., старший научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтического) № 4 отдела лекарственного лечения

Москва

Alexey A. Rumyantsev, MD, PhD, Senior Research Associate, Department of Chemotherapy № 4

Moscow

alexeymma@gmail.comТюляндинаА. С.TyulyandinaA. S.

Александра С. Тюляндина, д. м. н., заведующая отделением лекарственных методов лечения (химиотерапевтического) № 4 отдела лекарственного лечения; профессор кафедры онкологии института клинической медицины

Москва

Alexandra S. Tyulyandina, MD, PhD, DSc, Head of the Department, Department of Chemotherapy № 4; Professor, Department of Oncology, Institute of Clinical Medicine

Moscow

atjulandina@mail.ruИсраелянЭ. Р.IsraelyanE. R.

Эдгар Р. Исраелян, ординатор кафедры онкологии

Москва

Edgar R. Israelyan, Clinical Resident, Department of Oncology

Moscow

e.israelyan@yandex.ruПокатаевИ. А.PokataevI. A.

Илья А. Покатаев, д. м. н., руководитель службы химиотерапевтического лечения

Москва

Ilya A. Pokataev, MD, PhD, DSc, Head of the Medical Oncology Department

Moscow

pokia@mail.ruФедянинМ. Ю.FedyaninM. Yu.

Михаил Ю. Федянин, д. м. н., старший научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтического) № 2 отдела лекарственного лечения

Москва

Mikhail Yu. Fedyanin, MD, PhD, DSc, Senior Research Associate, Department of Chemotherapy № 2

Moscow

fedianinmu@mail.ruГлазковаЕ. В.GlazkovaE. V.

Елена В. Глазкова, к. м. н., врач-онколог онкологического отделения лекарственных методов лечения (химиотерапевтического) № 1 отдела лекарственного лечения

Москва

Elena V. Glazkova, MD, PhD, Medical Oncologist, Department of Chemotherapy № 1

Moscow

mdglazkova@gmail.comСергеевЮ. С.SergeevYu. S.

Юрий С. Сергеев, к. м. н., врач-онколог отделения хирургических методов лечения №16; доцент кафедры онкологии института клинической медицины

Москва

Yuri S. Sergeev, MD, PhD, Surgical Oncologist, Department of Cancer Surgery №16; Associate Professor of the Department of Oncology

Moscow

yurisergeevmd@mail.ruТюляндинС. А.TjulandinS. A.

Сергей А. Тюляндин, д. м. н., профессор, главный научный сотрудник отделения лекарственных методов лечения (химиотерапевтического) № 2 отдела лекарственного лечения

Москва

Sergey A. Tjulandin, MD, PhD, DSc, Professor, Chief Scientific Associate, Department of Chemotherapy № 2

Moscow

stjulandin@gmail.comФГБУ «НМИЦ онкологии им. Н. Н. Блохина» Минздрава РоссииРоссияN. N. Blokhin National Medical Research Center of OncologyRussian FederationФГБУ «НМИЦ онкологии им. Н. Н. Блохина» Минздрава России; ФГАОУ ВО Первый МГМУ им. И. М. Сеченова Минздрава России (Сеченовский Университет)РоссияN. N. Blokhin National Medical Research Center of Oncology; I. M. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationФГАО ВО «Российский национальный исследовательский медицинский университет им. Н. И. Пирогова» Минздрава РоссииРоссияPirogov Russian National Research Medical UniversityRussian FederationГБУЗ «Городская клиническая онкологическая больница № 1» Департамента здравоохранения города МосквыРоссияCity Clinical Oncological Hospital № 1Russian Federation2022080420221212135Copyright © Румянцев А.А., Тюляндина А.С., Исраелян Э.Р., Покатаев И.А., Федянин М.Ю., Глазкова Е.В., Сергеев Ю.С., Тюляндин С.А., 20222022Румянцев А.А., Тюляндина А.С., Исраелян Э.Р., Покатаев И.А., Федянин М.Ю., Глазкова Е.В., Сергеев Ю.С., Тюляндин С.А.Rumyantsev A.A., Tyulyandina A.S., Israelyan E.R., Pokataev I.A., Fedyanin M.Y., Glazkova E.V., Sergeev Y.S., Tjulandin S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/942Актуальность

Актуальность: Ключевую роль в лечении рецидивов РЯ играет правильное планирование стратегии лечения с последовательным назначением наиболее эффективных терапевтических опций. Неплатиновая химиотерапия может быть единственным вариантом лечения для пациенток с непереносимостью платины или платино-рефрактерным течением заболевания. Нами проведен мета-анализ, посвященный сравнению эффективности различных вариантов неплатиновой химиотерапии в лечении ранних рецидивов РЯ.

Материалы и методы

Материалы и методы: Был произведен поиск исследований в базе данных PubMed (с 01.01.2000 по 01.07.2019 гг.). Критерии отбора включали: 1) рецидивы эпителиального рака яичников, 2) бесплатиновый интервал ≤ 6 мес., 3) стандартная химиотерапия без включения таргетных, экспериментальных препаратов, высокодозной химиотерапии, 4) опубликованная частота объективного ответа и критерии оценки. Первичной конечной точкой анализа была частота объективного ответа (ЧОО). Статистический анализ данных был проведен методом мета-анализа (модель случайных эффектов) с использованием пропорций и бета-регрессионного анализа с помощью программного обеспечения R и RStudio (пакеты meta и betareg).

Результаты

Результаты: Проанализировано 7156 исследований, для дальнейшего анализа было отобрано 157 исследований, соответствующих критериям включения, из них эффективность платиновой и неплатиновой химиотерапии была оценена в 44 (n = 1055) и 113 (n = 5272) исследованиях соответственно, в данный анализ включены работы с неплатиновой химиотерапией. По результатам мета-анализа показатель ЧОО в группе монотерапии таксанами, этопозидом, доксорубицином/ПЛД, топотеканом и гемцитабином составил 27 % (95 % ДИ 0,21–0,34), 19 % (95 % ДИ 0,13–0,27), 15 % (95 % ДИ 0,11–0,19), 13 % (95 % ДИ 0,10–0,18) и 10 % (95 % ДИ 0,07–0,14), соответственно. Бета-регрессионный анализ, проведенный с учетом количества линий предшествующей терапии, метода оценки эффекта и других факторов продемонстрировал схожие результаты.

Выводы

Выводы: Монотерапия таксанами может быть наиболее эффективной неплатиновой химиотерапевтической опцией для пациентов, не являющихся кандидатами для назначения препаратов платины.

Background

Background: Recurrent ovarian cancer (OC) patients with platinum‑free interval (PFI) < 6 mo. are usually considered platinum‑resistant and treated with non‑platinum based chemotherapy. There is a lack of evidence to compare various non‑platinum therapeutic options in patients with platinum‑resistant ovarian cancer (PROC). We conducted meta‑analysis to assess efficacy of various therapeutic options in PROC patients. This article aimed to compare non‑platinum therapeutic regimens.

Methods

Methods: We queried the PubMed database for full‑text articles and abstracts on the treatment of PROC patients (01/01/2000–01/06/2019 timeframe). Inclusion criteria were: 1) epithelial ovarian cancer; 2) recurrent disease ≤ 6 mo. after platinum‑based chemotherapy; 3) standard therapy with platinum‑ or non‑platinum agents; 4) no targeted therapy, investigational agents or non‑platinum doublets; 5) reported response rate (RR) and assessment criteria. Proportion meta‑analysis (random‑effect model) and beta‑regression were conducted to assess efficacy of various options. Statistical analysis was dose with meta and betareg packages of R software.

Results

Results: We identified 7156 articles and screened them for title and abstract, 157 studies were left for further analysis. Efficacy of non‑platinum‑ and platinum‑based therapy was assessed in 113 (n = 5272) and 44 (n = 1055) trials respectively, only the latter were included in this analysis. In meta‑proportion random‑ effect model RR among patients treated with taxanes, etoposide, doxorubicin/PLD, topotecan and gemcitabine were 27 % (95 % CI 0.21–0.34), 19 % (95 % ДИ 0.13–0.27), 15 % (95 % CI 0.11–0.19), 13 % (95 % CI 0.10–0.18) and 10 % (95 % CI 0.07–0.14), respectively. Multiple beta‑regression model accounting for response assessment method, number of prior therapy lines and other factors confirmed the results.

Conclusions

Conclusions: Taxanes monotherapy may be the most effective therapeutic option for patients who are not candidates for platinum‑based chemotherapy.

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The authors declare that there are no conflicts of interest present.