medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2022-16-22-112-118medsovet-7239Research ArticleПОДДЕРЖИВАЮЩАЯ ТЕРАПИЯSUPPORTIVE THERAPYКлинические и фармакоэкономические аспекты применения пролонгированных колониестимулирующих факторовClinical and pharmacoeconomic aspects of the use of prolonged colony-stimulating factorshttps://orcid.org/0000-0003-4443-9974РумянцевА. А.RumyantsevA. A.

Румянцев Алексей Александрович – кандидат медицинских наук, старший научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтическое) №4 отдела лекарственного лечения Научно-исследовательского института клинической онкологии имени Н.Н. Трапезникова.

115478, Москва, Каширское шоссе, д. 24

Alexey A. Rumyantsev - Cand. Sci. (Med.), Senior Researcher, Oncology Department (Chemotherapy) No. 4 of the Drug Therapy Department, Research Institute of Clinical Oncology named after N.N. Trapeznikov, Blokhin National Medical Research Center of Oncology.

24, Kashirskoye Shosse, Moscow, 115478

alexeymma@gmail.comНациональный медицинский исследовательский центр онкологии имени Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian Federation202206122022022112118Copyright © Румянцев А.А., 20222022Румянцев А.А.Rumyantsev A.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.med-sovet.pro/jour/article/view/7239

Фебрильная нейтропения - одно из частых осложнений системной противоопухолевой терапии, характеризующееся высокими показателями смертности пациентов, летальность особенно высока у пациентов с предсуществующей сердечно-сосудистой патологией, заболеваниями почек, а также при наличии анемии. Кроме того, развитие фебрильной нейтропении ассоциировано со снижением дозовой интенсивности химиотерапии, что также оказывает неблагоприятное влияние на отдаленные результаты лечения пациентов при ряде злокачественных опухолей. Это диктует необходимость широкого применения профилактических мер, направленных на минимизацию риска ФН у онкологических пациентов, получающих цитотоксическую химиотерапию. Результатами многочисленных исследований доказано, что профилактическое применение гранулоцитарных колониестимулирующих факторов позволяет значительно снизить длительность глубокой нейтропении, частоту возникновения ФН и - наиболее важно - связанной с ней смертности. Данная статья посвящена обзору современных подходов к применению гранулоцитарных колониестимулирующих факторов (Г-КСФ) в контексте сложившейся на территории Российской Федерации системы финансирования онкологической помощи - клинико-статистических групп (КСГ). Подробно рассмотрены различные аспекты применения препаратов этого класса для предотвращения фебрильной нейтропении в контексте ее первичной и вторичной профилактики; правила применения Г-КСФ, современные данные об эффективности и целесообразности использования при различных клинических сценариях. Рассмотрены преимущества современных длительно действующих лекарственных форм Г-КСФ и их место в современной клинической практике.

Febrile neutropenia is one of the frequent complications of systemic antitumor therapy, characterized by high rates of patient mortality, mortality is particularly high in patients with pre-existing cardiovascular disease, renal disease, as well as in the presence of anemia. In addition, the development of febrile neutropenia is associated with a decrease in the dose intensity of chemotherapy, which also has an adverse effect on the long-term results of treatment of patients with a number of malignant tumors. This dictates the need for widespread use of preventive measures aimed at minimizing the risk of FN in cancer patients receiving cytotoxic chemotherapy. Numerous studies have shown that prophylactic use of granulocyte colony-stimulating factors can significantly reduce the duration of profound neutropenia, the incidence of FN and - most importantly - related mortality. This article is devoted to a review of modern approaches to the use of granulocyte colony-stimulating factors (G-CSF) in the context of the current system of cancer care financing - clinical and statistical groups (CSGs) on the territory of the Russian Federation. Various aspects of the use of drugs of this class to prevent febrile neutropenia in the context of its primary and secondary prevention, the rules of G-CSF use, current data on the effectiveness and feasibility of use in different clinical scenarios are considered in detail. The advantages of modern long-acting dosage forms of G-CSF and their place in modern clinical practice are considered.

эмпэгфилграстимфилграстимГ-КСФколониестимулирующие факторыдозоинтенсивностьхимиотерапияskin melanomasurgical treatmentplastic defect replacementprogression-free survivaloverall survivalReferencesRanuhardy D. The Role of Febrile Neutropenia Guideline's Implementation on Mortality Rate in Dharmais Hospital-National Cancer Center. Indones J Cancer. 2019;12(3):71. https://doi.org/10.33371/ijoc.v12i3.612.Ranuhardy D. The Role of Febrile Neutropenia Guideline's Implementation on Mortality Rate in Dharmais Hospital-National Cancer Center. Indones J Cancer. 2019;12(3):71. https://doi.org/10.33371/ijoc.v12i3.612.Sereeaphinan C., Kanchanasuwan S., Julamanee J. Mortality-associated clinical risk factors in patients with febrile neutropenia: A retrospective study. IJID Reg. 2021;1:5-11. https://doi.org/10.1016/j.ijregi.2021.09.002.Sereeaphinan C., Kanchanasuwan S., Julamanee J. Mortality-associated clinical risk factors in patients with febrile neutropenia: A retrospective study. IJID Reg. 2021;1:5-11. https://doi.org/10.1016/j.ijregi.2021.09.002.Aagaard T., Reekie J., J0rgensen M., Roen A., Daugaard G., Specht L. et al. Mortality and admission to intensive care units after febrile neutropenia in patients with cancer. Cancer Med. 2020;9(9):3033-3042. https://doi.org/10.1002/cam4.2955.Aagaard T., Reekie J., J0rgensen M., Roen A., Daugaard G., Specht L. et al. Mortality and admission to intensive care units after febrile neutropenia in patients with cancer. Cancer Med. 2020;9(9):3033-3042. https://doi.org/10.1002/cam4.2955.Clark O.A.C., Lyman G.H., Castro A.A., Clark L.G.O., Djulbegovic B. ColonyStimulating Factors for Chemotherapy-Induced Febrile Neutropenia: A Meta-Analysis of Randomized Controlled Trials. J Clin Oncol. 2005;23(18):4198-4214. https://doi.org/10.1200/JCO.2005.05.645.Clark O.A.C., Lyman G.H., Castro A.A., Clark L.G.O., Djulbegovic B. ColonyStimulating Factors for Chemotherapy-Induced Febrile Neutropenia: A Meta-Analysis of Randomized Controlled Trials. J Clin Oncol. 2005;23(18):4198-4214. https://doi.org/10.1200/JCO.2005.05.645.Hussaini S., Gupta A., Anderson K.E., Ballreich J.M., Nicholas L.H., Alexander C. Biosimilar uptake of filgrastim and impact on spending in Medicare Part D from 2015 to 2019. J Clin Oncol. 2021;39(28 Suppl.):67-67. https://doi.org/10.1200/JCO.2020.39.28_suppl.67.Hussaini S., Gupta A., Anderson K.E., Ballreich J.M., Nicholas L.H., Alexander C. Biosimilar uptake of filgrastim and impact on spending in Medicare Part D from 2015 to 2019. J Clin Oncol. 2021;39(28 Suppl.):67-67. https://doi.org/10.1200/JCO.2020.39.28_suppl.67.Sternberg C.N., de Mulder P.H.M., Schornagel J.H., Theodore C., Fossa S.D., van Oosterom A.T. et al. Randomized Phase III Trial of High-Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European Organization for Research and Treatment of Cancer Protocol No. 30924. J Clin Oncol. 2001;19(10):2638-2646. https://doi.org/10.1200/JCO.2001.19.10.2638.Sternberg C.N., de Mulder P.H.M., Schornagel J.H., Theodore C., Fossa S.D., van Oosterom A.T. et al. Randomized Phase III Trial of High-Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European Organization for Research and Treatment of Cancer Protocol No. 30924. J Clin Oncol. 2001;19(10):2638-2646. https://doi.org/10.1200/JCO.2001.19.10.2638.Pfister C., Gravis G., Flechon A., Soulie M., Guy L., Laguerre B. et al. Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients with Muscle-invasive Bladder Cancer. Analysis of the GETUG/AFU V05 VESPER Trial Secondary Endpoints: Chemotherapy Toxicity and Pathological Responses. Eur Urol. 2021;79(2):214-221. https://doi.org/10.1016/j.eururo.2020.08.024.Pfister C., Gravis G., Flechon A., Soulie M., Guy L., Laguerre B. et al. Randomized Phase III Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin, or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients with Muscle-invasive Bladder Cancer. Analysis of the GETUG/AFU V05 VESPER Trial Secondary Endpoints: Chemotherapy Toxicity and Pathological Responses. Eur Urol. 2021;79(2):214-221. https://doi.org/10.1016/j.eururo.2020.08.024.Lewis I.J., Nooij M.A., Whelan J., Sydes M.R., Grimer R., Hogendoorn P.C.W. et al. Improvement in Histologic Response But Not Survival in Osteosarcoma Patients Treated With Intensified Chemotherapy: A Randomized Phase III Trial of the European Osteosarcoma Intergroup. JNCI J Natl Cancer Inst. 2007;99(2):112-128. https://doi.org/10.1093/jnci/djk015.Lewis I.J., Nooij M.A., Whelan J., Sydes M.R., Grimer R., Hogendoorn P.C.W. et al. Improvement in Histologic Response But Not Survival in Osteosarcoma Patients Treated With Intensified Chemotherapy: A Randomized Phase III Trial of the European Osteosarcoma Intergroup. JNCI J Natl Cancer Inst. 2007;99(2):112-128. https://doi.org/10.1093/jnci/djk015.Grier H.E., Krailo M.D., Tarbell N.J., Link M.P., Fryer C.J.H., Pritchard D.J. et al. Addition of Ifosfamide and Etoposide to Standard Chemotherapy for Ewing's Sarcoma and Primitive Neuroectodermal Tumor of Bone. N Engl J Med. 2003;348(8):694-701. https://doi.org/10.1056/NEJMoa020890.Grier H.E., Krailo M.D., Tarbell N.J., Link M.P., Fryer C.J.H., Pritchard D.J. et al. Addition of Ifosfamide and Etoposide to Standard Chemotherapy for Ewing's Sarcoma and Primitive Neuroectodermal Tumor of Bone. N Engl J Med. 2003;348(8):694-701. https://doi.org/10.1056/NEJMoa020890.Womer R.B., West D.C., Krailo M.D., Dickman P.S., Pawel B.R., Grier H.E. et al. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012;30(33):4148-4154. https://doi.org/10.1200/JCO.2011.41.5703.Womer R.B., West D.C., Krailo M.D., Dickman P.S., Pawel B.R., Grier H.E. et al. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012;30(33):4148-4154. https://doi.org/10.1200/JCO.2011.41.5703.Citron M.L., Berry D.A., Cirrincione C., Hudis C., Winer E.P., Gradishar W.J. et al. Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21(8):1431-1439. https://doi.org/10.1200/JCO.2003.09.081.Citron M.L., Berry D.A., Cirrincione C., Hudis C., Winer E.P., Gradishar W.J. et al. Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21(8):1431-1439. https://doi.org/10.1200/JCO.2003.09.081.Kosaka Y., Rai Y., Masuda N., Takano T., Saeki T., Nakamura S. et al. Phase III placebo-controlled, double-blind, randomized trial of pegfilgrastim to reduce the risk of febrile neutropenia in breast cancer patients receiving docetaxel/cyclophosphamide chemotherapy. Support Care Cancer. 2015;23(4):1137-1143. https://doi.org/10.1007/s00520-014-2597-1.Kosaka Y., Rai Y., Masuda N., Takano T., Saeki T., Nakamura S. et al. Phase III placebo-controlled, double-blind, randomized trial of pegfilgrastim to reduce the risk of febrile neutropenia in breast cancer patients receiving docetaxel/cyclophosphamide chemotherapy. Support Care Cancer. 2015;23(4):1137-1143. https://doi.org/10.1007/s00520-014-2597-1.Gilbar P., McPherson I., Sorour N., Sanmugarajah J. High incidence of febrile neutropenia following adjuvant breast chemotherapy with docetaxel, carboplatin and trastuzumab. Breast Cancer Manag. 2014;3(4):327-333. https://doi.org/10.2217/bmt.14.22.Gilbar P., McPherson I., Sorour N., Sanmugarajah J. High incidence of febrile neutropenia following adjuvant breast chemotherapy with docetaxel, carboplatin and trastuzumab. Breast Cancer Manag. 2014;3(4):327-333. https://doi.org/10.2217/bmt.14.22.Kondagunta G.V., Bacik J., Donadio A., Bajorin D., Marion S., Sheinfeld J. et al. Combination of Paclitaxel, Ifosfamide, and Cisplatin Is an Effective Second-Line Therapy for Patients With Relapsed Testicular Germ Cell Tumors. J Clin Oncol. 2005;23(27):6549-6555. https://doi.org/10.1200/JCO.2005.19.638.Kondagunta G.V., Bacik J., Donadio A., Bajorin D., Marion S., Sheinfeld J. et al. Combination of Paclitaxel, Ifosfamide, and Cisplatin Is an Effective Second-Line Therapy for Patients With Relapsed Testicular Germ Cell Tumors. J Clin Oncol. 2005;23(27):6549-6555. https://doi.org/10.1200/JCO.2005.19.638.Daugaard G., Skoneczna I., Aass N., De Wit R., De Santis M., Dumez H. et al. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974). Ann Oncol. 2011;22(5):1054-1061. https://doi.org/10.1093/annonc/mdq575.Daugaard G., Skoneczna I., Aass N., De Wit R., De Santis M., Dumez H. et al. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974). Ann Oncol. 2011;22(5):1054-1061. https://doi.org/10.1093/annonc/mdq575.Miller K.D., Loehrer P.J., Gonin R., Einhorn L.H. Salvage chemotherapy with vinblastine, ifosfamide, and cisplatin in recurrent seminoma. J Clin Oncol. 1997;15(4):1427-1431. https://doi.org/10.1200/JCO.1997.15.4.1427.Miller K.D., Loehrer P.J., Gonin R., Einhorn L.H. Salvage chemotherapy with vinblastine, ifosfamide, and cisplatin in recurrent seminoma. J Clin Oncol. 1997;15(4):1427-1431. https://doi.org/10.1200/JCO.1997.15.4.1427.de Wit R., Skoneczna I., Daugaard G., De Santis M., Garin A., Aass N. et al. Randomized Phase III Study Comparing Paclitaxel-Bleomycin, Etoposide, and Cisplatin (BEP) to Standard BEP in Intermediate-Prognosis Germ-Cell Cancer: Intergroup Study EORTC 30983. J Clin Oncol. 2012;30(8):792-799. https://doi.org/10.1200/JCO.2011.37.0171.de Wit R., Skoneczna I., Daugaard G., De Santis M., Garin A., Aass N. et al. Randomized Phase III Study Comparing Paclitaxel-Bleomycin, Etoposide, and Cisplatin (BEP) to Standard BEP in Intermediate-Prognosis Germ-Cell Cancer: Intergroup Study EORTC 30983. J Clin Oncol. 2012;30(8):792-799. https://doi.org/10.1200/JCO.2011.37.0171.Swisher E.M., Mutch D.G., Rader J.S., Elbendary A., Herzog T.J. Topotecan in Platinum- and Paclitaxel-Resistant Ovarian Cancer. Gynecol Oncol. 1997;66(3):480-486. https://doi.org/10.1006/gyno.1997.4787.Swisher E.M., Mutch D.G., Rader J.S., Elbendary A., Herzog T.J. Topotecan in Platinum- and Paclitaxel-Resistant Ovarian Cancer. Gynecol Oncol. 1997;66(3):480-486. https://doi.org/10.1006/gyno.1997.4787.von Pawel J., Schiller J.H., Shepherd F.A., Fields S.Z., Kleisbauer J.P., Chrysson N.G. et al. Topotecan Versus Cyclophosphamide, Doxorubicin, and Vincristine for the Treatment of Recurrent Small-Cell Lung Cancer. J Clin Oncol. 1999;17(2):658-658. https://doi.org/10.1200/JCO.1999.17.2.658.von Pawel J., Schiller J.H., Shepherd F.A., Fields S.Z., Kleisbauer J.P., Chrysson N.G. et al. Topotecan Versus Cyclophosphamide, Doxorubicin, and Vincristine for the Treatment of Recurrent Small-Cell Lung Cancer. J Clin Oncol. 1999;17(2):658-658. https://doi.org/10.1200/JCO.1999.17.2.658.Seddon B., Strauss S.J., Whelan J., Leahy M., Woll P.J., Cowie F. et al. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017;18(10):1397-1410. https://doi.org/10.1016/S1470-2045(17)30622-8.Seddon B., Strauss S.J., Whelan J., Leahy M., Woll P.J., Cowie F. et al. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017;18(10):1397-1410. https://doi.org/10.1016/S1470-2045(17)30622-8.Judson I., Verweij J., Gelderblom H., Hartmann J.T., Schoffski P., Blay J.-Y. et al. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15(4):415-423. https://doi.org/10.1016/S1470-2045(14)70063-4.Judson I., Verweij J., Gelderblom H., Hartmann J.T., Schoffski P., Blay J.-Y. et al. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15(4):415-423. https://doi.org/10.1016/S1470-2045(14)70063-4.Patel S.R., Vadhan-Raj S., Papadopolous N., Plager C., Burgess M.A., Hays C. et al. High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence. J Clin Oncol. 1997;15(6):2378-2384. https://doi.org/10.1200/JCO.1997.15.6.2378.Patel S.R., Vadhan-Raj S., Papadopolous N., Plager C., Burgess M.A., Hays C. et al. High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence. J Clin Oncol. 1997;15(6):2378-2384. https://doi.org/10.1200/JCO.1997.15.6.2378.McCabe M., Kirton L., Khan M., Fenwick N., Strauss S.J., Valverde C. et al. Phase III assessment of topotecan and cyclophosphamide and high-dose ifosfamide in rEECur: An international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES). J Clin Oncol. 2022;40(17 Suppl.):LBA2-LBA2. https://doi.org/10.1200/JCO.2022.40.17_suppl.LBA2.McCabe M., Kirton L., Khan M., Fenwick N., Strauss S.J., Valverde C. et al. Phase III assessment of topotecan and cyclophosphamide and high-dose ifosfamide in rEECur: An international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES). J Clin Oncol. 2022;40(17 Suppl.):LBA2-LBA2. https://doi.org/10.1200/JCO.2022.40.17_suppl.LBA2.Oudard S., Fizazi K., Sengel0v L., Daugaard G., Saad F., Hansen S. et al. Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial - FIRSTANA. J Clin Oncol. 2017;35(28):3189-3197. https://doi.org/10.1200/JCO.2016.72.1068.Oudard S., Fizazi K., Sengel0v L., Daugaard G., Saad F., Hansen S. et al. Cabazitaxel Versus Docetaxel As First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial - FIRSTANA. J Clin Oncol. 2017;35(28):3189-3197. https://doi.org/10.1200/JCO.2016.72.1068.Tannock I.F., Horti J., Oudard S., James N.D., Rosenthal M.A. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med. 2004;351(15):1502-1512. https://doi.org/10.1056/NEJMoa040720.Tannock I.F., Horti J., Oudard S., James N.D., Rosenthal M.A. Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med. 2004;351(15):1502-1512. https://doi.org/10.1056/NEJMoa040720.Sweeney C.J., Chen Y.-H., Carducci M., Liu G., Jarrard D.F., Eisenberger M. et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746. https://doi.org/10.1056/NEJMoa1503747.Sweeney C.J., Chen Y.-H., Carducci M., Liu G., Jarrard D.F., Eisenberger M. et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746. https://doi.org/10.1056/NEJMoa1503747.Borghaei H., Paz-Ares L., Horn L., Spigel D.R., Steins M., Ready N.E. et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373(17):1627-1639. https://doi.org/10.1056/NEJMoa1507643.Borghaei H., Paz-Ares L., Horn L., Spigel D.R., Steins M., Ready N.E. et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373(17):1627-1639. https://doi.org/10.1056/NEJMoa1507643.Hanna N., Shepherd F.A., Fossella F.V., Pereira J.R., De Marinis F., von Pawel J. et al. Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy. J Clin Oncol. 2004;22(9):1589-1597. https://doi.org/10.1200/JCO.2004.08.163.Hanna N., Shepherd F.A., Fossella F.V., Pereira J.R., De Marinis F., von Pawel J. et al. Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy. J Clin Oncol. 2004;22(9):1589-1597. https://doi.org/10.1200/JCO.2004.08.163.Rose P.G., Blessing J.A., Ball H.G., Hoffman J., Warshal D., DeGeest K. et al. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a gynecologic oncology group study. Gynecol Oncol. 2003;88(2):130-135. https://doi.org/10.1016/S0090-8258(02)00091-4.Rose P.G., Blessing J.A., Ball H.G., Hoffman J., Warshal D., DeGeest K. et al. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a gynecologic oncology group study. Gynecol Oncol. 2003;88(2):130-135. https://doi.org/10.1016/S0090-8258(02)00091-4.Iorio G.C., Spieler B.O., Ricardi U., Dal Pra A. The Impact of Pelvic Nodal Radiotherapy on Hematologic Toxicity: A Systematic Review with Focus on Leukopenia, Lymphopenia and Future Perspectives in Prostate Cancer Treatment. Crit Rev Oncol Hematol. 2021;168:103497. https://doi.org/10.1016/j.critrevonc.2021.103497.Iorio G.C., Spieler B.O., Ricardi U., Dal Pra A. The Impact of Pelvic Nodal Radiotherapy on Hematologic Toxicity: A Systematic Review with Focus on Leukopenia, Lymphopenia and Future Perspectives in Prostate Cancer Treatment. Crit Rev Oncol Hematol. 2021;168:103497. https://doi.org/10.1016/j.critrevonc.2021.103497.Bonadonna G., Brusamolino E., Valagussa P., Rossi A., Brugnatelli L., Brambilla C. et al. Combination Chemotherapy as an Adjuvant Treatment in Operable Breast Cancer. N Engl J Med. 1976;294(8):405-410. https://doi.org/10.1056/NEJM197602192940801.Bonadonna G., Brusamolino E., Valagussa P., Rossi A., Brugnatelli L., Brambilla C. et al. Combination Chemotherapy as an Adjuvant Treatment in Operable Breast Cancer. N Engl J Med. 1976;294(8):405-410. https://doi.org/10.1056/NEJM197602192940801.Bonadonna G., Valagussa P. Dose-Response Effect of Adjuvant Chemotherapy in Breast Cancer. N Engl J Med. 1981;304(1):10-15. https://doi.org/10.1056/NEJM198101013040103.Bonadonna G., Valagussa P. Dose-Response Effect of Adjuvant Chemotherapy in Breast Cancer. N Engl J Med. 1981;304(1):10-15. https://doi.org/10.1056/NEJM198101013040103.Loibl S., Skacel T., Nekljudova V., Luck HJ., Schwenkglenks M., Brodowicz T. et al. Evaluating the impact of Relative Total Dose Intensity (RTDI) on patients' short and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer- a pooled analysis. BMC Cancer. 2011;11(1):131. https://doi.org/10.1186/1471-2407-11-131.Loibl S., Skacel T., Nekljudova V., Luck HJ., Schwenkglenks M., Brodowicz T. et al. Evaluating the impact of Relative Total Dose Intensity (RTDI) on patients' short and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer- a pooled analysis. BMC Cancer. 2011;11(1):131. https://doi.org/10.1186/1471-2407-11-131.Denduluri N., Lyman G.H., Wang Y., Morrow P.K., Barron R., Patt D. et al. Chemotherapy Dose Intensity and Overall Survival Among Patients With Advanced Breast or Ovarian Cancer. Clin Breast Cancer. 2018;18(5):380-386. https://doi.org/10.1016/j.clbc.2018.02.003.Denduluri N., Lyman G.H., Wang Y., Morrow P.K., Barron R., Patt D. et al. Chemotherapy Dose Intensity and Overall Survival Among Patients With Advanced Breast or Ovarian Cancer. Clin Breast Cancer. 2018;18(5):380-386. https://doi.org/10.1016/j.clbc.2018.02.003.Fedyanin M., Tryakin A., Titov D., Zakharova T., Fainstein I., Figurin K. et al. Importance of maintenance of dose intensity (DI) during induction chemotherapy (iCT) for metastatic nonseminomatous germ cell tumors (NSGCT). J Clin Oncol. 2009;27(15 Suppl.):e16063-e16063. https://doi.org/10.1200/jco.2009.27.15_suppl.e16063.Fedyanin M., Tryakin A., Titov D., Zakharova T., Fainstein I., Figurin K. et al. Importance of maintenance of dose intensity (DI) during induction chemotherapy (iCT) for metastatic nonseminomatous germ cell tumors (NSGCT). J Clin Oncol. 2009;27(15 Suppl.):e16063-e16063. https://doi.org/10.1200/jco.2009.27.15_suppl.e16063.Crawford J., Denduluri N., Patt D., Jiao X., Morrow P.K., Garcia J. et al. Relative dose intensity of first-line chemotherapy and overall survival in patients with advanced non-small-cell lung cancer. Support Care Cancer. 2020;28(2):925-932. https://doi.org/10.1007/s00520-019-04875-1.Crawford J., Denduluri N., Patt D., Jiao X., Morrow P.K., Garcia J. et al. Relative dose intensity of first-line chemotherapy and overall survival in patients with advanced non-small-cell lung cancer. Support Care Cancer. 2020;28(2):925-932. https://doi.org/10.1007/s00520-019-04875-1.Lee J., Kim J.W., Ahn S., Kim H.W., Lee J., Kim Y.H. et al. Optimal dose reduction of FOLFIRINOX for preserving tumour response in advanced pancreatic cancer: Using cumulative relative dose intensity. Eur J Cancer. 2017;76:125-133. https://doi.org/10.1016/j.ejca.2017.02.010.Lee J., Kim J.W., Ahn S., Kim H.W., Lee J., Kim Y.H. et al. Optimal dose reduction of FOLFIRINOX for preserving tumour response in advanced pancreatic cancer: Using cumulative relative dose intensity. Eur J Cancer. 2017;76:125-133. https://doi.org/10.1016/j.ejca.2017.02.010.Kobayashi S., Ueno M., Omae K., Kuramochi H., Terao M., Mizuno N. et al. Influence of initial dose intensity on efficacy of FOLFIRINOX in patients with advanced pancreatic cancer. Oncotarget. 2019;10(19):1775-1784. https://doi.org/10.18632/oncotarget.26633.Kobayashi S., Ueno M., Omae K., Kuramochi H., Terao M., Mizuno N. et al. Influence of initial dose intensity on efficacy of FOLFIRINOX in patients with advanced pancreatic cancer. Oncotarget. 2019;10(19):1775-1784. https://doi.org/10.18632/oncotarget.26633.Gray R., Bradley R., Braybrooke J., Liu Z., Peto R., Davies L. et al. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet. 2019;393(10179):1440-1452. https://doi.org/10.1016/S0140-6736(18)33137-4.Gray R., Bradley R., Braybrooke J., Liu Z., Peto R., Davies L. et al. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet. 2019;393(10179):1440-1452. https://doi.org/10.1016/S0140-6736(18)33137-4.Ding Y., Ding K., Yang H., He X., Mo W., Ding X. Does dose-dense neoadjuvant chemotherapy have clinically significant prognostic value in breast cancer?: A meta-analysis of 3,724 patients. PLoS ONE. 2020;15(5):e0234058. https://doi.org/10.1371/journal.pone.0234058.Ding Y., Ding K., Yang H., He X., Mo W., Ding X. Does dose-dense neoadjuvant chemotherapy have clinically significant prognostic value in breast cancer?: A meta-analysis of 3,724 patients. PLoS ONE. 2020;15(5):e0234058. https://doi.org/10.1371/journal.pone.0234058.Cash T., Krailo M.D., Buxton A., Pawel B., Healey J.H., Binitie O. et al. Long-term outcomes in patients with localized Ewing sarcoma treated with interval-compressed chemotherapy: A long-term follow-up report from Children's Oncology Group study AEWS0031. J Clin Oncol. 2022;40(16 Suppl.):11505-11505. https://doi.org/10.1200/JCO.2022.40.16_suppl.11505.Cash T., Krailo M.D., Buxton A., Pawel B., Healey J.H., Binitie O. et al. Long-term outcomes in patients with localized Ewing sarcoma treated with interval-compressed chemotherapy: A long-term follow-up report from Children's Oncology Group study AEWS0031. J Clin Oncol. 2022;40(16 Suppl.):11505-11505. https://doi.org/10.1200/JCO.2022.40.16_suppl.11505.Zhou M., Thompson T.D., Lin H.-Y., Chen V.W., Karlitz J.J., Fontham E.T.H. et al. Impact of Relative Dose Intensity of FOLFOX Adjuvant Chemotherapy on Risk of Death Among Stage III Colon Cancer Patients. Clin Colorectal Cancer. 2022;21(2):e62-e75. https://doi.org/10.1016/j.clcc.2021.09.008.Zhou M., Thompson T.D., Lin H.-Y., Chen V.W., Karlitz J.J., Fontham E.T.H. et al. Impact of Relative Dose Intensity of FOLFOX Adjuvant Chemotherapy on Risk of Death Among Stage III Colon Cancer Patients. Clin Colorectal Cancer. 2022;21(2):e62-e75. https://doi.org/10.1016/j.clcc.2021.09.008.Lakkunarajah S., Breadner D.A., Zhang H., Yamanaka E., Warner A., Welch S. The Influence of Adjuvant Chemotherapy Dose Intensity on Five-Year Outcomes in Resected Colon Cancer: A Single Centre Retrospective Analysis. Curr Oncol. 2021;28(5):4031-4041. https://doi.org/10.3390/curroncol28050342.Lakkunarajah S., Breadner D.A., Zhang H., Yamanaka E., Warner A., Welch S. The Influence of Adjuvant Chemotherapy Dose Intensity on Five-Year Outcomes in Resected Colon Cancer: A Single Centre Retrospective Analysis. Curr Oncol. 2021;28(5):4031-4041. https://doi.org/10.3390/curroncol28050342.Lyman G.H., Dale D.C., Wolff D.A., Culakova E., Poniewierski M.S., Kuderer N.M. et al. Acute Myeloid Leukemia or Myelodysplastic Syndrome in Randomized Controlled Clinical Trials of Cancer Chemotherapy With Granulocyte Colony-Stimulating Factor: A Systematic Review. J Clin Oncol. 2010;28(17):2914-2924. https://doi.org/10.1200/JCO.2009.25.8723.Lyman G.H., Dale D.C., Wolff D.A., Culakova E., Poniewierski M.S., Kuderer N.M. et al. Acute Myeloid Leukemia or Myelodysplastic Syndrome in Randomized Controlled Clinical Trials of Cancer Chemotherapy With Granulocyte Colony-Stimulating Factor: A Systematic Review. J Clin Oncol. 2010;28(17):2914-2924. https://doi.org/10.1200/JCO.2009.25.8723.Nielson C.M., Bylsma L.C., Fryzek J.P., Saad H.A., Crawford J. Relative Dose Intensity of Chemotherapy and Survival in Patients with Advanced Stage Solid Tumor Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2021;26(9):e1609-e1618. https://doi.org/10.1002/onco.13822.Nielson C.M., Bylsma L.C., Fryzek J.P., Saad H.A., Crawford J. Relative Dose Intensity of Chemotherapy and Survival in Patients with Advanced Stage Solid Tumor Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2021;26(9):e1609-e1618. https://doi.org/10.1002/onco.13822.Dale D.C. The discovery, development and clinical applications of granulocyte colony- stimulating factor. Trans Am Clin Climatol Assoc. 1998;109:27-36. Available at: https://pubmed.ncbi.nlm.nih.gov/9601125.Dale D.C. The discovery, development and clinical applications of granulocyte colony- stimulating factor. Trans Am Clin Climatol Assoc. 1998;109:27-36. Available at: https://pubmed.ncbi.nlm.nih.gov/9601125.Сакаева Д.Д., Борисов К.Е., Булавина И.С., Когония Л.М., Курмуков И.А., Орлова Р.В. и др. Практические рекомендации по диагностике и лечению фебрильной нейтропении. Злокачественные опухоли. 2021;11(2):55-63. https://doi.org/10.18027/2224-5057-2021-11-3s2-39.Sakaeva D.D., Borisov K.E., Bulavina I.S., Kogonia L.M., Kurmukov I.A., Orlova R.V. et al. Practical recommendations for the diagnosis and treatment of febrile neutropenia. Malignant Tumours. 2021;11(2):55-63. (In Russ.) https://doi.org/10.18027/2224-5057-2021-11-3s2-39.Трякин А.А., Бесова Н.С., Волков Н.М., Гладков О.А., Карасева В.В., Сакаева Д.Д. и др. Практические рекомендации по общим принципам проведения противоопухолевой лекарственной терапии. Злокачественные опухоли. 2021;11(1):23-35. https://doi.org/10.18027/2224-5057-2021-11-3s2-01.Tryakin A.A., Besova N.S., Volkov N.M., Gladkov O.A., Karaseva V.V., Sakaeva D.D. et al. Practical recommendations on the general principles of antitumor drug therapy. Malignant Tumours. 2021;11(1):23-35. (In Russ.) https://doi.org/10.18027/2224-5057-2021-11-3s2-01.Clemons M., Fergusson D., Simos D., Mates M., Robinson A., Califaretti N. 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):951-957. https://doi.org/10.1016/j.annonc.2020.04.005.Clemons M., Fergusson D., Simos D., Mates M., Robinson A., Califaretti N. 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):951-957. https://doi.org/10.1016/j.annonc.2020.04.005.Wang Y., Chen L., Liu F., Zhao N., Xu L., Fu B. 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. https://doi.org/10.1038/s41598-019-51982-4.Wang Y., Chen L., Liu F., Zhao N., Xu L., Fu B. 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. https://doi.org/10.1038/s41598-019-51982-4.American Society of Clinical Oncology. Recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. J Clin Oncol. 1994;12(11):2471-2508. https://doi.org/10.1200/JCO.1994.12.11.2471.American Society of Clinical Oncology. Recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. J Clin Oncol. 1994;12(11):2471-2508. https://doi.org/10.1200/JCO.1994.12.11.2471.Truong J., Lee E.K., Trudeau M.E., Chan K.K.W. Interpreting febrile neutropenia rates from randomized, controlled trials for consideration of primary prophylaxis in the real world: a systematic review and meta-analysis. Ann Oncol. 2016;27(4):608-618. https://doi.org/10.1093/annonc/mdv619.Truong J., Lee E.K., Trudeau M.E., Chan K.K.W. Interpreting febrile neutropenia rates from randomized, controlled trials for consideration of primary prophylaxis in the real world: a systematic review and meta-analysis. Ann Oncol. 2016;27(4):608-618. https://doi.org/10.1093/annonc/mdv619.Scotte F., Simon H., Laplaige P., Antoine E.-C., Spasojevic C., Texier N. et al. Febrile neutropenia prophylaxis, G-CSF physician preferences: discretechoice experiment. BMJ Support Palliat Care. 2021:bmjspcare-2021-003082. https://doi.org/10.1136/bmjspcare-2021-003082.Scotte F., Simon H., Laplaige P., Antoine E.-C., Spasojevic C., Texier N. et al. Febrile neutropenia prophylaxis, G-CSF physician preferences: discretechoice experiment. BMJ Support Palliat Care. 2021:bmjspcare-2021-003082. https://doi.org/10.1136/bmjspcare-2021-003082.

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