Оптимизация химиотерапии раннего рака молочной железы: роль гранулоцитарного колониестимулирующего фактора

1. Каприн А.Д., Старинский В.В., Шахзадова А.О. Состояние онкологической помощи населению России в 2019 году. М., 2020. 
[Kaprin A.D., Starinskii V.V., Shakhzadova A.O. The state of cancer care for the population of Russia in 2019. Moscow, 2020 (in Russian).]
2. Peto R, Davies C, Godwin J et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 2012; 379: 432–44.
3. Available from: https://ascopost.com/issues/october-15-2013/dr-larry-norton-honored-at-2013-breast-cancer-symposium-... 
4. Mayordomo JI, López A, Viñolas N et al. Retrospective cost analysis of management of febrile neutropenia in cancer patients in Spain. Curr Med Res Opin 2009; 25 (10): 2533–42. DOI: 10.1185/03007990903209563 
5. 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 
6. 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. DOI: 10.1056/NEJM199504063321401
7. Bonadonna G, Moliterni A, Zambetti M et al. 30 years' follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ 2005; 330 (7485): 217. DOI: 10.1136/bmj.38314.622095.8F 
8. Lyman GH, Kuderer NM. Epidemiology of febrile neutropenia. Support Cancer Ther 2003; 1 (1): 23–35. DOI: 10.3816/SCT.2003.n.002 
9. De Miguel SC et al. Granulocyte colony-stimulating factors as prophylaxis against febrile neutropenia. Supportive Care in Cancer 2015; 23 (2): 547–59.
10. Aapro MS, Bohlius J, Cameron DA et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 2011; 47 (1): 8–32. DOI: 10.1016/j.ejca.2010.10.013
11. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). 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): 1440–52. DOI: 10.1016/S0140-6736(18)33137-4
12. Ding Y, Ding K, Yang H et al. 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. DOI: 10.1371/journal.pone.0234058
13. Bonilla L, Ben-Aharon I, Vidal L et al. Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst 2010; 102 (24): 1845–54. DOI: 10.1093/jnci/djq409 
14. Citron ML, Berry DA, Cirrincione C 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: 1431–9. 
15. Del Mastro L, De Placido S, Bruzzi P et al. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2×2 factorial, randomised phase 3 trial. Lancet 2015; 385: 1863–72.
16. Venturini M, Del Mastro L, Aitini E et al. Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial. J Natl Cancer Inst 2005; 97: 1724–33.
17. Foukakis T, von Minckwitz G, Bengtsson NO et al. Effect of tailored dose-dense chemotherapy vs standard 3-weekly adjuvant chemotherapy on recurrence-free survival among women with high-risk early breast cancer: a randomized clinical trial. JAMA 2016; 316: 1888–96.
18. Mobus V, Jackisch C, Luck HJ et al. Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial. Ann Oncol 2018; 29: 178–85.
19. Waks AG, Tolaney SM, Galar A et al. Pneumocystis jiroveci pneumonia (PCP) in patients receiving neoadjuvant and adjuvant anthracycline-based chemotherapy for breast cancer: incidence and risk factors. Breast Cancer Res Treat 2015; 154: 359–67.
20. Pathak R, Giri S, Aryal MR et al. Mortality, length of stay, and health care costs of febrile neutropenia-related hospitalizations among patients with breast cancer in the United States. Support Care Cancer 2015; 23 (3): 615–7.
21. Lyman GH. Impact of chemotherapy dose intensity on cancer patient outcomes. J Natl Compr Canc Netw 2009; 7 (1): 99–108.
22. Muss HB, Woolf S, Berry D et al. Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 2005; 293: 1073–81.
23. Lyman GH, Dale DC, Culakova E et al. The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol 2013; 24: 2475–84.
24. Klastersky J, de Naurois J, Rolston K et al. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Annals of Oncology 2016; 27 (Suppl. 5): v111–v118. DOI: 10.1093/annonc/mdw325
25. Smith TJ, Khatcheressian J, Lyman GH et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 24 (19): 3187–205. DOI: 10.1200/JCO.2006.06.4451 
26. 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 
27. 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. Annals of Oncology 2020; 31 (7): 951–7. DOI: 10.1016/j.annonc.2020.04.005
28. Green MD, Koelbl H, Baselga J et al. A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 2003; 14 (1): 29–35. DOI: 10.1093/annonc/mdg019
29. Holmes FA, O'Shaughnessy JA, Vukelja S et al. Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J Clin Oncol 2002; 20 (3): 727–31. DOI: 10.1200/JCO.2002.20.3.727 
30. Кононенко И.Б., Снеговой А.В., Гребенникова О.П. и др. Роль пролонгированных гранулоцитарных колониестимулирующих факторов в профилактике фебрильной нейтропении у пациентов, получающих двухнедельные режимы химиотерапии. ­Современная онкология. 2020; 22 (3): 133–41. 
[Kononenko I.B., Snegovoy A.V., Grebennikova O.P. et al. Reduction of febrile neutropenia by using long-acting granulocyte colony-stimulating factors in patients with solid tumors receiving every-2-week chemotherapy. Journal of Modern Oncology. 2020; 22 (3): 133–41 (in Rissian).]. DOI: 10.26442/18151434.2020.3.200279
31 Mitchell S, Li X, Woods M et al. Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: A systematic review. J Oncol Pharm Pract 2016; 22 (5): 702–16. DOI: 10.1177/1078155215625459
32. Kosaka Y, Rai Y, Masuda N 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): 1137–43. DOI: 10.1007/s00520-014-2597-1 
33. 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
34. Papakonstantinou A, Hedayati E, Hellström M et al. Neutropenic complications in the ­PANTHER phase III study of adjuvant tailored dose-dense chemotherapy in early breast cancer. Acta Oncologica 2020; 59 (1): 75–81. DOI: 10.1080/0284186X.2019.1670353
35. Криворотько П.В., Бурдаева О.Н., Нечаева М.Н. и др. Эффективность и безопасность препарата Экстимия® (эмпэгфилграстим) у пациентов с диагнозом «рак молочной железы», получающих миелосупрессивную химиотерапию: результаты двойного слепого сравнительного клинического исследования III фазы. Современная онкология. 2015; 17 (2): 45–52.
[Krivorotko P.V., Burdaeva O.N., Nechaeva M.N. et al. Efficacy and safety of Extimia® ­(empegfilgrastim): results of a double-blind controlled phase iii study in patients with diagnosis “breast cancer” receiving myelosuppressive chemotherapy. Journal of Modern ­Oncology. 2015; 17 (2): 45–52 (in Russian).]
36. Barcenas CH, Niu J, Zhang N et al. Risk of hospitalization according to chemotherapy regimen in early-stage breast cancer. J Clin Oncol 2014; 32 (19): 2010–7. DOI: 10.1200/JCO.2013.49.3676 
37. Zauderer M, Patil S, Hurria A. Feasibility and toxicity of dose-dense adjuvant chemotherapy in older women with breast cancer. Breast Cancer Res Treat 2009; 117 (1): 205–10. DOI: 10.1007/s10549-008-0116-0
38. Potosky LA, Malin JL, Kim B et al. Use of Colony-Stimulating Factors With Chemotherapy: Opportunities for Cost Savings and Improved Outcomes. JNCI 2011; 103 (12): 979–82.
39. Pietri E, Andreis D, Fabbri F et al. A phase II study of a dose-density regimen with fluorouracil, epirubicin, and cyclophosphamide on days 1 and 4 every 14 days with filgrastim support followed by weekly paclitaxel in women with primary breast cancer. The Oncologist 2015; 20 (3): 239–40. DOI: 10.1634/theoncologist.2014-0326
40. 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 
41. Schnipper LE, Smith TJ, Raghavan D et al. American Society of Clinical Oncology identifies five key opportunities to improve care and reduce costs: the top five list for oncology. J Clin Oncol 2012; 30 (14): 1715–24. DOI: 10.1200/JCO.2012.42.8375 

________________________________________________

1. Kaprin A.D., Starinskii V.V., Shakhzadova A.O. The state of cancer care for the population of Russia in 2019. Moscow, 2020 (in Russian).
2. Peto R, Davies C, Godwin J et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 2012; 379: 432–44.
3. Available from: https://ascopost.com/issues/october-15-2013/dr-larry-norton-honored-at-2013-breast-cancer-symposium-... 
4. Mayordomo JI, López A, Viñolas N et al. Retrospective cost analysis of management of febrile neutropenia in cancer patients in Spain. Curr Med Res Opin 2009; 25 (10): 2533–42. DOI: 10.1185/03007990903209563 
5. 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 
6. 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. DOI: 10.1056/NEJM199504063321401
7. Bonadonna G, Moliterni A, Zambetti M et al. 30 years' follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ 2005; 330 (7485): 217. DOI: 10.1136/bmj.38314.622095.8F 
8. Lyman GH, Kuderer NM. Epidemiology of febrile neutropenia. Support Cancer Ther 2003; 1 (1): 23–35. DOI: 10.3816/SCT.2003.n.002 
9. De Miguel SC et al. Granulocyte colony-stimulating factors as prophylaxis against febrile neutropenia. Supportive Care in Cancer 2015; 23 (2): 547–59.
10. Aapro MS, Bohlius J, Cameron DA et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 2011; 47 (1): 8–32. DOI: 10.1016/j.ejca.2010.10.013
11. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). 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): 1440–52. DOI: 10.1016/S0140-6736(18)33137-4
12. Ding Y, Ding K, Yang H et al. 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. DOI: 10.1371/journal.pone.0234058
13. Bonilla L, Ben-Aharon I, Vidal L et al. Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst 2010; 102 (24): 1845–54. DOI: 10.1093/jnci/djq409 
14. Citron ML, Berry DA, Cirrincione C 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: 1431–9. 
15. Del Mastro L, De Placido S, Bruzzi P et al. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2×2 factorial, randomised phase 3 trial. Lancet 2015; 385: 1863–72.
16. Venturini M, Del Mastro L, Aitini E et al. Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial. J Natl Cancer Inst 2005; 97: 1724–33.
17. Foukakis T, von Minckwitz G, Bengtsson NO et al. Effect of tailored dose-dense chemotherapy vs standard 3-weekly adjuvant chemotherapy on recurrence-free survival among women with high-risk early breast cancer: a randomized clinical trial. JAMA 2016; 316: 1888–96.
18. Mobus V, Jackisch C, Luck HJ et al. Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial. Ann Oncol 2018; 29: 178–85.
19. Waks AG, Tolaney SM, Galar A et al. Pneumocystis jiroveci pneumonia (PCP) in patients receiving neoadjuvant and adjuvant anthracycline-based chemotherapy for breast cancer: incidence and risk factors. Breast Cancer Res Treat 2015; 154: 359–67.
20. Pathak R, Giri S, Aryal MR et al. Mortality, length of stay, and health care costs of febrile neutropenia-related hospitalizations among patients with breast cancer in the United States. Support Care Cancer 2015; 23 (3): 615–7.
21. Lyman GH. Impact of chemotherapy dose intensity on cancer patient outcomes. J Natl Compr Canc Netw 2009; 7 (1): 99–108.
22. Muss HB, Woolf S, Berry D et al. Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 2005; 293: 1073–81.
23. Lyman GH, Dale DC, Culakova E et al. The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol 2013; 24: 2475–84.
24. Klastersky J, de Naurois J, Rolston K et al. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Annals of Oncology 2016; 27 (Suppl. 5): v111–v118. DOI: 10.1093/annonc/mdw325
25. Smith TJ, Khatcheressian J, Lyman GH et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 24 (19): 3187–205. DOI: 10.1200/JCO.2006.06.4451 
26. 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 
27. 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. Annals of Oncology 2020; 31 (7): 951–7. DOI: 10.1016/j.annonc.2020.04.005
28. Green MD, Koelbl H, Baselga J et al. A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 2003; 14 (1): 29–35. DOI: 10.1093/annonc/mdg019
29. Holmes FA, O'Shaughnessy JA, Vukelja S et al. Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J Clin Oncol 2002; 20 (3): 727–31. DOI: 10.1200/JCO.2002.20.3.727 
30. Kononenko I.B., Snegovoy A.V., Grebennikova O.P. et al. Reduction of febrile neutropenia by using long-acting granulocyte colony-stimulating factors in patients with solid tumors receiving every-2-week chemotherapy. Journal of Modern Oncology. 2020; 22 (3): 133–41 (in Rissian). DOI: 10.26442/18151434.2020.3.200279
31 Mitchell S, Li X, Woods M et al. Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: A systematic review. J Oncol Pharm Pract 2016; 22 (5): 702–16. DOI: 10.1177/1078155215625459
32. Kosaka Y, Rai Y, Masuda N 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): 1137–43. DOI: 10.1007/s00520-014-2597-1 
33. 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
34. Papakonstantinou A, Hedayati E, Hellström M et al. Neutropenic complications in the ­PANTHER phase III study of adjuvant tailored dose-dense chemotherapy in early breast cancer. Acta Oncologica 2020; 59 (1): 75–81. DOI: 10.1080/0284186X.2019.1670353
35. Krivorotko P.V., Burdaeva O.N., Nechaeva M.N. et al. Efficacy and safety of Extimia® ­(empegfilgrastim): results of a double-blind controlled phase iii study in patients with diagnosis “breast cancer” receiving myelosuppressive chemotherapy. Journal of Modern ­Oncology. 2015; 17 (2): 45–52 (in Russian).
36. Barcenas CH, Niu J, Zhang N et al. Risk of hospitalization according to chemotherapy regimen in early-stage breast cancer. J Clin Oncol 2014; 32 (19): 2010–7. DOI: 10.1200/JCO.2013.49.3676 
37. Zauderer M, Patil S, Hurria A. Feasibility and toxicity of dose-dense adjuvant chemotherapy in older women with breast cancer. Breast Cancer Res Treat 2009; 117 (1): 205–10. DOI: 10.1007/s10549-008-0116-0
38. Potosky LA, Malin JL, Kim B et al. Use of Colony-Stimulating Factors With Chemotherapy: Opportunities for Cost Savings and Improved Outcomes. JNCI 2011; 103 (12): 979–82.
39. Pietri E, Andreis D, Fabbri F et al. A phase II study of a dose-density regimen with fluorouracil, epirubicin, and cyclophosphamide on days 1 and 4 every 14 days with filgrastim support followed by weekly paclitaxel in women with primary breast cancer. The Oncologist 2015; 20 (3): 239–40. DOI: 10.1634/theoncologist.2014-0326
40. 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 
41. Schnipper LE, Smith TJ, Raghavan D et al. American Society of Clinical Oncology identifies five key opportunities to improve care and reduce costs: the top five list for oncology. J Clin Oncol 2012; 30 (14): 1715–24. DOI: 10.1200/JCO.2012.42.8375 

И.П. Ганьшина1, К.А. Иванова1, Е.В. Лубенникова*1, А.В. Архипов2, Л.Г. Жукова3

1 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России, Москва, Россия;
2 ФГАУ «Национальный медицинский исследовательский центр ”Лечебно-реабилитационный центр”» Минздрава России, Москва, Россия;
3 ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Россия
*lubennikova@yandex.ru

________________________________________________

Inna P. Ganshina1, Kristina A. Ivanova1, Elena V. Lubennikova*1, Alexandr V. Arkhipov2, Liudmila G. Zhukova3

1 Blokhin National Medical Research Center of Oncology, Moscow, Russia;
2 National Medical Research Center of Treatment and Rehabilitation, Moscow, Russia;
3 Loginov Moscow Clinical Scientific Center, Moscow, Russia
*lubennikova@yandex.ru