Saevets VV, Kuzmin NK, Shamanova AYu, Mukhin AA, Taratonov AV. Cost-effectiveness of using granulocyte colony-stimulating factor in the treatment of uterine body leiomyosarcomas. A retrospective analysis. Journal of Modern Oncology. 2024;26(3):335–340. DOI: 10.26442/18151434.2024.3.203011
Экономическая эффективность применения гранулоцитарного колониестимулирующего фактора при лечении лейомиосарком тела матки
Саевец В.В., Кузьмин Н.К., Шаманова А.Ю., Мухин А.А., Таратонов А.В. Экономическая эффективность применения гранулоцитарного колониестимулирующего фактора при лечении лейомиосарком тела матки. Современная Онкология. 2024;26(3):335–340. DOI: 10.26442/18151434.2024.3.203011
Saevets VV, Kuzmin NK, Shamanova AYu, Mukhin AA, Taratonov AV. Cost-effectiveness of using granulocyte colony-stimulating factor in the treatment of uterine body leiomyosarcomas. A retrospective analysis. Journal of Modern Oncology. 2024;26(3):335–340. DOI: 10.26442/18151434.2024.3.203011
Обоснование. При лечении пациенток с лейомиосаркомой тела матки главный подход к терапии – операция с последующей химиотерапией, которая является основой лечения. Жизнеугрожающим состоянием остается возникновение фебрильной нейтропении (ФН), поэтому применение гранулоцитарного колониестимулирующего фактора (Г-КСФ) после каждого цикла химиотерапии у данной категории больных остается неотъемлемой частью лечения. Цель. Оценить фармакоэкономическую эффективность применения Г-КСФ коротких и пролонгированных форм в условиях круглосуточного стационара (КСС). Материалы и методы. На базе ГАУЗ ЧОКЦОиЯМ проведен ретроспективный анализ экономических затрат за период с января 2018 по декабрь 2023 г. на проведенное лечение в условиях КСС 62 пациенток с диагнозом лейомиосаркомы матки IB–IVA-стадии согласно классификации Международной федерации гинекологии и акушерства (2009 г.) высокой степени злокачественности. Всем больным проведено хирургическое лечение в объеме экстирпации матки с придатками с последующей противоопухолевой лекарственной терапией с высоким риском развития ФН. При анализе экономических затрат сравнивались схемы лечения гемцитабин 900 мг/м2 1 и 8-й день + доцетаксел 100 мг/м2 + эмпэгфилграстим (код схемы sh1207.1) и гемцитабин 900 мг/м2 1 и 8-й день + доцетаксел 100 мг/м2 + филграстим (код схемы sh1070). Учитывали также затраты на проведение клинических анализов крови и пребывания в условиях КСС. Результаты. Пребывание в КСС составляло 9 койко-дней при схеме с применением Г-КСФ пролонгированного действия и 15 дней – при применении Г-КСФ короткого действия. При использовании схемы лечения с препаратом филграстим у 6 больных число койко-дней увеличено до 18 по причине стойкой нейтропении. Развития ФН не отмечено ни в одном случае. Расчеты складывались из стоимости койко-дня в КСС – 1660 руб., затрат учреждения на закупку Г-КСФ короткого и пролонгированного действия, без учета затрат на основную терапию. Затраты на лечение пациенток с применением Г-КСФ короткого действия и Г-КСФ пролонгированного действия сопоставимы. Заключение. Схема с применением Г-КСФ пролонгированного действия является эффективной, удобной в применении и экономически выгодной в рамках работы койки КСС.
Background. The main approach in the treatment of patients with uterine leiomyosarcoma is surgery followed by chemotherapy, which is the basis of treatment. Febrile neutropenia (FN) is a life-threatening condition, so the use of granulocyte colony-stimulating factor (G-CSF) after each cycle of chemotherapy in this category of patients remains an integral part. Aim. To evaluate the pharmacoeconomic efficacy of the use of short and long-acting G-CSF forms in a round-the-clock inpatient facility (RIF). Materials and methods. A retrospective analysis of economic expenditures was performed at the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine in the RIF setting for the period from January 2018 to December 2023 for the treatment of 62 patients with high-grade uterine leiomyosarcomas of stage IB–IVA according to the classification of the International Federation of Gynecology and Obstetrics (2009). All patients underwent surgical treatment, complete hysterectomy with appendages, followed by antitumor drug therapy with a high risk of FN. In the economic cost analysis, the treatment regimens gemcitabine 900 mg/m2 on day 1 and day 8 + docetaxel 100 mg/m2 + empegfilgrastim (regimen code sh1207.1) and gemcitabine 900 mg/m2 on day 1 and day 8 + docetaxel 100 mg/m2 + filgrastim (regimen code sh1070) were compared. The costs of clinical blood tests and staying in RIF were also considered. Results. The stay in the RIF was 9 bed days with a long-acting G-CSF regimen and 15 days with a short-acting G-CSF regimen. When using a treatment regimen with filgrastim in 6 patients, the number of bed days increased to 18 due to persistent neutropenia. No FN events were reported. The calculations consisted of the cost of a bed day in the RIF (1,660 rubles) and purchasing of short- and long-acting G-CSF, without the cost of the main therapy. The costs of treating patients with short-acting G-CSF were comparable to those with long-acting G-CSF. Conclusion. The regimen with long-acting G-CSF is effective, easy to use, and cost-effective in RIF settings.
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3. Mbatani N, Olawaiye AB, Prat J. Uterine sarcomas. Int J Gynaecol Obstet. 2018;143(Suppl. 2):51-8. DOI:10.1002/ijgo.12613
4. Giuntoli RL 2nd, Metzinger DS, DiMarco CS, et al. Retrospective review of 208 patients with leiomyosarcoma of the uterus: Prognostic indicators, surgical management, and adjuvant therapy. Gynecol Oncol. 2003;89(3):460-9. DOI:10.1016/s0090-8258(03)00137-9
5. Kostov S, Kornovski Y, Ivanova V, et al. New aspects of sarcomas of uterine corpus – A brief narrative review. Clin Pract. 2021;11(4):878-900. DOI:10.3390/clinpract11040103
6. Cui R, Wright J, Hou J. Uterine leiomyosarcoma: A review of recent advancesin molecular biology, clinical management and outcome. BJOG. 2017;124(7):1028-37.
DOI:10.1111/1471-0528.14579
7. Нечушкина В.М., Коломиец Л.А., Кравец О.А., и др. Практические рекомендации по лекарственному лечению рака тела матки и сарком матки. Практические рекомендации RUSSCO, часть 1. Злокачественные опухоли. 2023;13(3s2):263-79 [Nechushkina VM, Kolomiec LA, Kravec OA, et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu raka tela matki i sarkom matki. Prakticheskie rekomendacii RUSSCO, chast’ 1. Zlokachestvennye opukholi. 2023;13(3s2):263-79 (in Russian)].
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9. Hensley ML, Blessing JA, Degeest K, et al. Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: A Gynecologic Oncology Group phase II Study. Gynecol Oncol. 2008;109(3):323-8. DOI:10.1016/j.ygyno.2008.02.024
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12. Crawford J, Dale DC, Kuderer NM, et al. Risk and timing of neutropenic events in adult cancer patients receiving chemotherapy: the results of a prospective nationwide study of oncology practice. J Natl Compr Canc Netw. 2008;6(2):109-18. DOI:10.6004/jnccn.2008.0012
13. Rossi L, Tomao F, Lo Russo G, et al. Efficacy and safety analysis of once per cycle pegfilgrastim and daily lenograstim in patients with breast cancer receiving adjuvant myelosuppressive chemotherapy FEC 100: A pilot study. Ther Clin Risk Manag. 2013;9:457-62. DOI:10.2147/TCRM.S48387
14. Seebacher V, Reinthaller A, Koelbl H, et al. The impact of the duration of adjuvant chemotherapy on survival in patients with epithelial ovarian cancer – A retrospective study. PLoS One. 2017;12(1):e0169272. DOI:10.1371/journal.pone.0169272
15. Bonadonna G, Valagussa P, Moliterni A, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer – the results of 20 years of follow-up. N Engl J Med. 1995;332(14):901-6. PMID:7877646
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2006;106(10):2258-66. DOI:10.1002/cncr.21847
17. Jairam V, Lee V, Park HS, et al. Treatment-related complications of systemic therapy and radiotherapy. JAMA Oncol. 2019;5(7):1028-35. DOI:10.1001/jamaoncol.2019.0086
18. Handman E, Burgess AW. Stimulation by granulocyte-macrophage colony-stimulating factor of Leishmania tropica killing by macrophages. J Immunol. 1979;122(3):1134-7. PMID:312818
19. Сакаева Д.Д., Борисов К.Е., Булавина И.С., и др. Практические рекомендации по диагностике и лечению фебрильной нейтропении. Практические рекомендации RUSSCO, часть 2. Злокачественные опухоли. 2023;13(3s2):62-71 [Sakaeva DD, Borisov KE, Bulavina IS,et al. Prakticheskie rekomendatsii po diagnostike i lecheniiu febrilnoi neitropenii. Prakticheskie rekomendatsii RUSSCO, chast’ 2. Zlokachestvennie opukholi. 2023;13(3s2):62-71 (in Russian)]. DOI:10.18027/2224-5057-2023-13-3s2-2-62-71
20. Griffiths EA, Roy V, Alwan L, et al. NCCN Guidelines® insights: Hematopoietic growth factors, version 1.2022: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2022;20(5):436-42. DOI:10.6004/jnccn.2022.0026
21. Metcalf D. The colony stimulating factors. Discovery, development, and clinical applications. Cancer. 1990;65(10):2185-95. PMID:2189549
22. Crawford J, Glaspy JA, Stoller RG, et al. Final results of a placebo-controlled study of filgrastim in small-cell lung cancer: exploration of risk factors for febrile neutropenia. Support Cancer Ther. 2005;3(1):36-46. DOI:10.3816/SCT.2005.n.023
23. Clemons M, Fergusson D, Simos D, et al. A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer. Ann Oncol. 2020;31(7):951-7. DOI:10.1016/j.annonc.2020.04.005
24. Gabrilove JL, Jakubowski A, Fain K, et al. Phase I study of granulocyte colony-stimulating factor in patients with transitional cell carcinoma of the urothelium. J Clin Invest. 1988;82(4):1454-61. PMID:2459163
25. Weycker D, Barron R, Edelsberg J, et al. Risk and consequences of chemotherapy-induced neutropenic complications in patients receiving daily filgrastim: the importance of duration of prophylaxis. BMC Health Serv Res. 2014;14:189. DOI:10.1186/1472-6963-14-189
26. Schellekens H, Hennink WE, Brinks V. The immunogenicity of polyethylene glycol: Facts and fiction. Pharm Res. 2013;30(7):1729-34. DOI:10.1007/s11095-013-1067-7
27. Cornes P, Gascon P, Chan S, et al. Systematic review and meta-analysis of short- versus long-acting granulocyte colony-stimulating factors for reduction of chemotherapy-induced febrile neutropenia. Adv Ther. 2018;35(11):1816-29. DOI:10.1007/s12325-018-0798-6
28. Wang Y, Chen L, Liu F, et al. Efficacy and tolerability of granulocyte colony-stimulating factors in cancer patients after chemotherapy: A systematic review and Bayesian network meta-analysis. Sci Rep. 2019;9(1):15374. DOI:10.1038/s41598-019-51982-4
29. Методические рекомендации по способам оплаты медицинской помощи за счет средств обязательного медицинского страхования от 19.02.2024. Режим доступа: https://www.garant.ru/products/ipo/prime/doc/408486489/ Ссылка активна на 05.08.2024 [Metodicheskie rekomendatsii po sposobam oplaty meditsinskoi pomoshchi za schet sredstv obiazatel’nogo meditsinskogo strakhovaniia ot 19.02.2024. Available at: https://www.garant.ru/products/ipo/prime/doc/408486489/ Accessed: 05.08.2024 (in Russian)].
________________________________________________
1. Cancer Today. Available at: https://gco.iarc.fr/today/en/dataviz/bars?mode=cancer&group_populations=1&types=1. Accessed: 05.08.2024.
2. Zlokachestvennye novoobrazovaniia v Rossii v 2021 godu (zabolevaemost’ i smertnost’). Pod red. AD Kaprina, VV Starinskogo, GV Petrovoi. Moscow, 2022 (in Russian).
3. Mbatani N, Olawaiye AB, Prat J. Uterine sarcomas. Int J Gynaecol Obstet. 2018;143(Suppl. 2):51-8. DOI:10.1002/ijgo.12613
4. Giuntoli RL 2nd, Metzinger DS, DiMarco CS, et al. Retrospective review of 208 patients with leiomyosarcoma of the uterus: Prognostic indicators, surgical management, and adjuvant therapy. Gynecol Oncol. 2003;89(3):460-9. DOI:10.1016/s0090-8258(03)00137-9
5. Kostov S, Kornovski Y, Ivanova V, et al. New aspects of sarcomas of uterine corpus – A brief narrative review. Clin Pract. 2021;11(4):878-900. DOI:10.3390/clinpract11040103
6. Cui R, Wright J, Hou J. Uterine leiomyosarcoma: A review of recent advancesin molecular biology, clinical management and outcome. BJOG. 2017;124(7):1028-37.
DOI:10.1111/1471-0528.14579
7. Nechushkina VM, Kolomiec LA, Kravec OA, et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu raka tela matki i sarkom matki. Prakticheskie rekomendacii RUSSCO, chast’ 1. Zlokachestvennye opukholi. 2023;13(3s2):263-79 (in Russian). DOI:10.18027/2224-5057-2023-13-3s2-1-263-279
8. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines® Uterine Neoplasms Version 2.2024. March 6, 2024). Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed: 05.08.2024.
9. Hensley ML, Blessing JA, Degeest K, et al. Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: A Gynecologic Oncology Group phase II Study. Gynecol Oncol. 2008;109(3):323-8. DOI:10.1016/j.ygyno.2008.02.024
10. Hensley ML, Blessing JA, Mannel R, Rose PG. Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 2008;109(3):329-34. DOI:10.1016/j. ygyno.2008.03.010
11. Tanaka K, Joyama S, Chuman H, et al. Feasibility and efficacy of gemcitabine and docetaxel combination chemotherapy for bone and soft tissue sarcomas: multiinstitutional retrospective analysis of 134 patients. World J Surg Oncol. 2016;14(1):306. DOI:10.1186/s12957-016-1059-2
12. Crawford J, Dale DC, Kuderer NM, et al. Risk and timing of neutropenic events in adult cancer patients receiving chemotherapy: the results of a prospective nationwide study of oncology practice. J Natl Compr Canc Netw. 2008;6(2):109-18. DOI:10.6004/jnccn.2008.0012
13. Rossi L, Tomao F, Lo Russo G, et al. Efficacy and safety analysis of once per cycle pegfilgrastim and daily lenograstim in patients with breast cancer receiving adjuvant myelosuppressive chemotherapy FEC 100: A pilot study. Ther Clin Risk Manag. 2013;9:457-62. DOI:10.2147/TCRM.S48387
14. Seebacher V, Reinthaller A, Koelbl H, et al. The impact of the duration of adjuvant chemotherapy on survival in patients with epithelial ovarian cancer – A retrospective study. PLoS One. 2017;12(1):e0169272. DOI:10.1371/journal.pone.0169272
15. Bonadonna G, Valagussa P, Moliterni A, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer – the results of 20 years of follow-up. N Engl J Med. 1995;332(14):901-6. PMID:7877646
16. Kuderer NM, Dale DC, Crawford J, et al. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer.
2006;106(10):2258-66. DOI:10.1002/cncr.21847
17. Jairam V, Lee V, Park HS, et al. Treatment-related complications of systemic therapy and radiotherapy. JAMA Oncol. 2019;5(7):1028-35. DOI:10.1001/jamaoncol.2019.0086
18. Handman E, Burgess AW. Stimulation by granulocyte-macrophage colony-stimulating factor of Leishmania tropica killing by macrophages. J Immunol. 1979;122(3):1134-7. PMID:312818
19. Sakaeva DD, Borisov KE, Bulavina IS,et al. Prakticheskie rekomendatsii po diagnostike i lecheniiu febrilnoi neitropenii. Prakticheskie rekomendatsii RUSSCO, chast’ 2. Zlokachestvennie opukholi. 2023;13(3s2):62-71 (in Russian). DOI:10.18027/2224-5057-2023-13-3s2-2-62-71
20. Griffiths EA, Roy V, Alwan L, et al. NCCN Guidelines® insights: Hematopoietic growth factors, version 1.2022: featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2022;20(5):436-42. DOI:10.6004/jnccn.2022.0026
21. Metcalf D. The colony stimulating factors. Discovery, development, and clinical applications. Cancer. 1990;65(10):2185-95. PMID:2189549
22. Crawford J, Glaspy JA, Stoller RG, et al. Final results of a placebo-controlled study of filgrastim in small-cell lung cancer: exploration of risk factors for febrile neutropenia. Support Cancer Ther. 2005;3(1):36-46. DOI:10.3816/SCT.2005.n.023
23. Clemons M, Fergusson D, Simos D, et al. A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer. Ann Oncol. 2020;31(7):951-7. DOI:10.1016/j.annonc.2020.04.005
24. Gabrilove JL, Jakubowski A, Fain K, et al. Phase I study of granulocyte colony-stimulating factor in patients with transitional cell carcinoma of the urothelium. J Clin Invest. 1988;82(4):1454-61. PMID:2459163
25. Weycker D, Barron R, Edelsberg J, et al. Risk and consequences of chemotherapy-induced neutropenic complications in patients receiving daily filgrastim: the importance of duration of prophylaxis. BMC Health Serv Res. 2014;14:189. DOI:10.1186/1472-6963-14-189
26. Schellekens H, Hennink WE, Brinks V. The immunogenicity of polyethylene glycol: Facts and fiction. Pharm Res. 2013;30(7):1729-34. DOI:10.1007/s11095-013-1067-7
27. Cornes P, Gascon P, Chan S, et al. Systematic review and meta-analysis of short- versus long-acting granulocyte colony-stimulating factors for reduction of chemotherapy-induced febrile neutropenia. Adv Ther. 2018;35(11):1816-29. DOI:10.1007/s12325-018-0798-6
28. Wang Y, Chen L, Liu F, et al. Efficacy and tolerability of granulocyte colony-stimulating factors in cancer patients after chemotherapy: A systematic review and Bayesian network meta-analysis. Sci Rep. 2019;9(1):15374. DOI:10.1038/s41598-019-51982-4
29. Metodicheskie rekomendatsii po sposobam oplaty meditsinskoi pomoshchi za schet sredstv obiazatel’nogo meditsinskogo strakhovaniia ot 19.02.2024. Available at: https://www.garant.ru/products/ipo/prime/doc/408486489/ Accessed: 05.08.2024 (in Russian).
1ГАУЗ «Челябинский областной клинический центр онкологии и ядерной медицины», Челябинск, Россия; 2ФГБОУ ВО «Южно-Уральский государственный медицинский университет» Минздрава России, Челябинск, Россия
*lalili2013@mail.ru
________________________________________________
Valeriya V. Saevets*1,2, Nikita K. Kuzmin2, Anna Yu. Shamanova1,2, Arsentiy A. Mukhin1, Alexey V. Taratonov1
1Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine, Chelyabinsk, Russia; 2South Ural State Medical University, Chelyabinsk, Russia
*lalili2013@mail.ru