tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2025-034tumors-1437Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL REPORTSРежим паклитаксел, ифосфамид, цисплатин (TIP) в индукционном лечении при несеминомных герминогенных опухолях неблагоприятного прогноза с замедленным снижением концентрации онкомаркеров: финальные результатыTIP regimen (paclitaxel, ifosfamide, cisplatin) in nonseminomatous germ cell tumors with poor-prognosis and unfavorable decline of serum tumor markers: final resultshttps://orcid.org/0000-0002-6666-549XИсраелянЭ. Р.IsraelyanE. R.

Исраелян Эдгар Рудикович

115478, Москва, Каширское шоссе, 23

Israelyan Edgar Rudikovich

23 Kashirskoe Shosse, Moscow 115478

e.israelyan@yandex.ruhttps://orcid.org/0000-0003-2245-214XТрякинА. А.TryakinA. A.

Трякин Алексей Александрович

115478, Москва, Каширское шоссе, 23

Tryakin Aleksei Aleksandrovich

23 Kashirskoe Shosse, Moscow 115478

https://orcid.org/0000-0003-4443-9974РумянцевА. А.RumyantsevA. A.

Румянцев Алексей Александрович

115478, Москва, Каширское шоссе, 23

Rumyantsev Aleksey Aleksandrovich

23 Kashirskoe Shosse, Moscow 115478

https://orcid.org/0000-0001-5615-7806ФедянинМ. Ю.FedyaninM. Yu.

Федянин Михаил Юрьевич 

115478, Москва, Каширское шоссе, 23; 108814, Москва, п. Коммунарка, ул. Сосенский стан, 8;105203, Москва, ул. Нижняя Первомайская, 70

Fedyanin Mikhail Yurevich

23 Kashirskoe Shosse, Moscow 115478; 8 Sosenskiy Stan St., Moscow 108814; 70, Nizhnyaya Pervomaiskaya St., Moscow 105203

https://orcid.org/0000-0003-4744-6141КононецП. В.KononetsP. V.

Кононец Павел Вячеславович

115478, Москва, Каширское шоссе, 23

Kononets Pavel Vyacheslavovich

23 Kashirskoe Shosse, Moscow 115478

https://orcid.org/0000-0002-0833-6452ГерасимовС. С.GerasimovS. S.

Герасимов Сергей Семенович 

115478, Москва, Каширское шоссе, 23

Gerasimov Sergei Semenovich

23 Kashirskoe Shosse, Moscow 115478

https://orcid.org/0000-0001-7748-9527МатвеевВ. Б.MatveevV. B.

Матвеев Всеволод Борисович

115478, Москва, Каширское шоссе, 23

Matveev Vsevolod Borisovich

23 Kashirskoe Shosse, Moscow 115478

https://orcid.org/0000-0001-7754-6624ВолковаМ. И.VolkovaM. I.

Волкова Мария Игоревна 

117152 Москва, Загородное шоссе, 18А;125993 Москва, ул. Баррикадная, 2/1, стр. 1

Volkova Maria Igorevna

18A Zagorodnoe Shosse, Moscow 117152;Build. 1, 2 / 1 Barrikadnaya St., Moscow 125993

https://orcid.org/0000-0003-0727-2976КлимовА. В.KlimovA. V.

Климов Алексей Вячеславович

115478, Москва, Каширское шоссе, 23

Klimov Alexey Vyacheslavovich

23 Kashirskoe Shosse, Moscow 115478

https://orcid.org/0000-0003-4538-8646СеменоваА. И.SemenovaA. I.

Семенова Анна Игоревна

197758 Санкт-Петербург, п. Песочный, ул. Ленинградская, 68

Semenova Anna Igorevna

68 Leningradskaya St., Pesochnyy, Saint Petersburg 197758

https://orcid.org/0000-0001-7912-8055ПайчадзеА. А.PaichadzeA. A.

Пайчадзе Анна Александровна 

125284, Москва, 2-й Боткинский проезд, д.3

Paichadze Anna Aleksandrovna

3 2nd Botkinskiy proezd, Moscow 125284

https://orcid.org/0000-0002-0635-9343ЦареваА. С.TsarevaA. S.

Царева Анастасия Сергеевна 

115478, Москва, Каширское шоссе, 23

Tsareva Anastasiya Sergeevna

23 Kashirskoe Shosse, Moscow 115478

https://orcid.org/0000-0002-9562-9113ЮнаевГ. С.YunaevG. S.

Юнаев Григорий Сергеевич 

115478, Москва, Каширское шоссе, 23

Yunaev Grigory Sergeevich

23 Kashirskoe Shosse, Moscow 115478

https://orcid.org/0000-0001-9807-2229ТюляндинС. А.TjulandinS. A.

Тюляндин Сергей Алексеевич

115478, Москва, Каширское шоссе, 23

Tjulandin Sergey Alekseevich

23 Kashirskoe Shosse, Moscow 115478

ФГБУ «Научный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииРоссияN. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaRussian FederationФГБУ «Научный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России; ГБУЗ «Московский многопрофильный клинический центр «Коммунарка» Департамента здравоохранения г. Москвы»; ФГБУ «Национальный медико-хирургический центр им. Н. И. Пирогова» Минздрава РоссииРоссияN. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; Moscow Multidisciplinary Clinical Center “Kommunarka», Moscow Healthcare Department; National Medical and Surgical Center named after N. I. PirogovRussian FederationОнкологический центр No 1 «Городской клинической больницы имени С. С. Юдина Департамента здравоохранения города Москвы»; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияOncology Center No. 1 of the City Clinical Hospital named after S. S. Yudin of the Moscow Department of Health; Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaRussian FederationФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Петрова» Минздрава РоссииРоссияN.N. Petrov National Medical Research Center of Oncology, Ministry of Health of RussiaRussian FederationФГБУ «Научный медицинский исследовательский центр радиологии» Минздрава РоссииРоссияNational Medical Research Radiological Center, Ministry of Health of RussiaRussian Federation202514022025151716Copyright © Исраелян Э.Р., Трякин А.А., Румянцев А.А., Федянин М.Ю., Кононец П.В., Герасимов С.С., Матвеев В.Б., Волкова М.И., Климов А.В., Семенова А.И., Пайчадзе А.А., Царева А.С., Юнаев Г.С., Тюляндин С.А., 20252025Исраелян Э.Р., Трякин А.А., Румянцев А.А., Федянин М.Ю., Кононец П.В., Герасимов С.С., Матвеев В.Б., Волкова М.И., Климов А.В., Семенова А.И., Пайчадзе А.А., Царева А.С., Юнаев Г.С., Тюляндин С.А.Israelyan E.R., Tryakin A.A., Rumyantsev A.A., Fedyanin M.Y., Kononets P.V., Gerasimov S.S., Matveev V.B., Volkova M.I., Klimov A.V., Semenova A.I., Paichadze A.A., Tsareva A.S., Yunaev G.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/1437Введение

Введение: Пациенты с герминогенными опухолями (ГО) и неблагоприятным прогнозом демонстрируют неудовлетворительные онкологические результаты, однолетняя выживаемость без прогрессирования (ВБП) составляет около 50 %. Мы предположили, что смена режима химиотерапии (ХТ) на TIP (паклитаксел, ифосфамид (месна), цисплатин) в случае замедленной скорости снижения онкомаркеров после 1 курса ВЕР (блеомицин, этопозид, цисплатин) сможет улучшить результаты лечения в данной подгруппе пациентов.

Материалы и методы

Материалы и методы: В многоцентровое проспективное нерандомизированное исследование II фазы включены пациенты с несеминомными ГО и неблагоприятным прогнозом по IGCCCG. Всем пациентам проведен 1 курс ХТ в режиме ВЕР. Пациентам с замедленным снижением концентрации опухолевых маркеров далее проведено 4 курса ХТ в режиме TIP (паклитаксел 120 мг / м2 в день 1, 2 + ифосфамид 1500 мг / м2 в дни 2–5 (+ месна) + цисплатин 25 мг / м2 в дни 2–5 + Г‑КСФ). При наличии остаточной опухоли размером более 1 см и технической возможности ее удаления выполнялось хирургическое лечение. Первичной конечной точкой явилась 1‑летняя ВБП.

Результаты исследования

Результаты исследования: С 2017 по 2023 годы в исследование включено 34 пациента. Набор в исследование досрочно прекращен в связи с крайне низкой вероятностью достижения первичной конечной точки. Однолетняя ВБП и общая выживаемость составили 57,1 % и 74,4 % соответственно. Благоприятная частота ответов, расцениваемая как полный ответ и маркер‑негативный неполный ответ, отмечена у 55,7 % пациентов. Прогрессирование заболевания зарегистрировано у 21 пациента, у 8 (37 %) из них первым сайтом прогрессирования явилась центральная нервная система. Хирургическое лечение выполнено 16 пациентам, жизнеспособная злокачественная резидуальная опухоль обнаружена у 4 больных. Проведение первого курса в «стабилизационном» режиме пациентам «сверхвысокого риска» не оказало влияния ни на ВБП (р = 0,28), ни на ОВ (р = 0,434). Профиль токсичности режима TIP оказался приемлемым.

Выводы

Выводы: Смена режима ВЕР на TIP для пациентов с несеминомными ГО и замедленным снижением скорости опухолевых маркеров не продемонстрировало своей эффективности. Необходимо изучение иных лекарственных подходов с целью улучшения результатов лечения.

Background

Background: Patients with germ cell tumors (GCTs) and poor-prognosis demonstrate unsatisfactory oncological outcomes, with a one-year progression-free survival (PFS) rate of approximately 50 %. We hypothesized that switching the chemotherapy regimen to TIP (paclitaxel, ifosfamide (mesna), cisplatin) in cases of unfavorable decline of serum tumor markers (STMs) after the first cycle of BEP (bleomycin, etoposide, cisplatin) could improve treatment outcomes in this subgroup of patients.

Materials and methods

Materials and methods: A multicenter, prospective, non-randomized phase II study included patients with nonseminomatous GCTs and poor-prognosis according to IGCCCG. All patients received the first cycle of chemotherapy in BEP regimen. Patients with an unfavorable decline of STMs subsequently received 4 cycles of TIP regimen (paclitaxel 120 mg / m² on days 1 and 2 + ifosfamide 1500 mg / m² on days 2–5 (+ mesna) + cisplatin 25 mg / m² on days 2–5 + G-CSF). In the presence of residual tumors larger than 1 cm and the technical feasibility of removal, surgical treatment was performed. The primary endpoint was one-year PFS.

Results

Results: From 2017 to 2023, 34 patients were included in the study. Enrollment was prematurely closed due to an extremely low likelihood of achieving the primary endpoint. One-year PFS and overall survival (OS) were 57.1 % and 74.4 %, respectively. The favorable response rate (complete response + partial response with normalization STM) was observed in 55,8 % of patients. Disease progression was observed in 21 patients, with the central nervous system being the first site of progression in 8 (37 %) of them. Surgical treatment was performed in 16 patients, with viable tumor obtained in 4 patients. Conducting the first cycle in a “stabilization» mode for ultra-high-risk patients did not affect PFS (p = 0.28) or OS (p = 0.434). The toxicity profile of the TIP regimen was acceptable.

Conclusion

Conclusion: Switching from BEP to TIP for patients with nonseminomatous GCTs and an unfavorable decline of STMs did not demonstrate efficacy. Further exploration of alternative therapeutic approaches is needed to improve treatment outcomes.

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