Summary of best evidence for human granulocyte colony stimulating factor in cancer patients with febrile neutropenia_West China Medical Journal

Authors：

JIANG Yuan ¹ , YU Qin ² , LEI Lei ² , XUE Xiaojing ² , XIANG Miao ² ,  WANG Xiaoyan ²

1. Department of Respiratory and Critical Care Medicine, Mianyang Central Hospital, Mianyang, Sichuan 621000, P. R. China;
2. Department of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P. R. China;

Corresponding?author：

WANG Xiaoyan, Email: 273890354@qq.com

Keywords：

Cancer; febrile neutropenia; human granulocyte colony stimulating factor; evidence-based

DOI：

10.7507/1002-0179.202509296

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To evaluate the best available evidence regarding the prophylactic and therapeutic application of human granulocyte colony-stimulating factor (G-CSF) in cancer patients with febrile neutropenia (FN), aiming to inform standardized clinical practice. Methods The evidence on the use of G-CSF in cancer patients with FN was retrieved from both Chinese and English databases and websites by computer. The retrieval deadline was from January 2014 to December 2024. Two researchers independently conducted literature screening and quality evaluation, extracted and summarized evidence. Results A total of 15 articles were included, comprising 5 clinical practice guidelines, 6 expert consensus statements, and 4 systematic reviews. From these, 28 best evidence statements were synthesized, encompassing five key domains: FN risk stratification, prophylactic G-CSF administration, therapeutic G-CSF use, administration methodology, and patient education. Conclusions The overall quality of evidence for G-CSF in the prevention and treatment of FN is relatively good. The findings provide a robust, evidence-based foundation for standardizing the management of FN in this population, thereby more effectively controlling the risks associated with anti-tumor treatment

Citation： JIANG Yuan, YU Qin, LEI Lei, XUE Xiaojing, XIANG Miao, WANG Xiaoyan. Summary of best evidence for human granulocyte colony stimulating factor in cancer patients with febrile neutropenia. West China Medical Journal, 2026, 41(5): 792-798. doi: 10.7507/1002-0179.202509296 Copy

1.	Klastersky J, de Naurois J, Rolston K, et al. Management of febrile neutropaenia: ESMO clinical practice guidelines. Ann Oncol, 2016, 27(Suppl 5): v111-v118.
2.	Boccia R, Glaspy J, Crawford J, et al. Chemotherapy-induced neutropenia and febrile neutropenia in the US: a beast of burden that needs to be tamed. Oncologist, 2022, 27(8): 625-636.
3.	秦叔逵, 馬軍. 中國臨床腫瘤學會 (CSCO) 腫瘤放化療相關中性粒細胞減少癥規范化管理指南 (2021). 臨床腫瘤學雜志, 2021, 26(7): 638-648.
4.	中國抗癌協會腫瘤臨床化療專業委員會, 中國抗癌協會腫瘤支持治療專業委員會. 腫瘤化療導致的中性粒細胞減少診治中國專家共識 (2023 版). 中華腫瘤雜志, 2023, 45(7): 575-583.
5.	Tralongo AC, Antonuzzo A, Pronzato P, et al. Management of chemotherapy-induced neutropenia in patients with cancer: 2019 guidelines of the Italian medical oncology association (AIOM). Tumori, 2020, 106(4): 273-280.
6.	Leon Rapoport B, Garcia-Morillo M, Font C, et al. A prospective, real-world, multinational study of febrile neutropenia (FN) occurrence in oncology patients receiving chemotherapy with intermediate risk of FN: a MASCC neutropenia, infection, and myelosuppression study group initiative. Support Care Cancer, 2023, 31(12): 628.
7.	Carmona-Bayonas A, Jimenez-Fonseca P, de Castro EM, et al. SEOM clinical practice guideline: management and prevention of febrile neutropenia in adults with solid tumors (2018). Clin Transl Oncol, 2019, 21(1): 75-86.
8.	Aapro M, Boccia R, Leonard R, et al. Refining the role of pegfilgrastim (a long-acting G-CSF) for prevention of chemotherapy-induced febrile neutropenia: consensus guidance recommendations. Support Care Cancer, 2017, 25(11): 3295-3304.
9.	蔣媛, 王小艷, 雷蕾, 等. 免疫檢查點抑制劑誘導高血糖癌癥患者血糖管理的最佳證據總結. 中國癌癥防治雜志, 2024, 16(6):722-728.
10.	朱政, 胡雁, 邢唯杰, 等. 不同類型循證問題的構成. 護士進修雜志, 2017, 32(21): 1991-1994.
11.	韋當, 王聰堯, 肖曉娟, 等. 指南研究與評價(AGREE Ⅱ)工具實例解讀. 中國循證兒科雜志, 2013, 8(4): 316-319.
12.	朱政, 胡雁, 周英鳳, 等. 推動證據向臨床轉化(五)證據臨床轉化研究中的文獻質量評價. 護士進修雜志, 2020, 35(11): 996-1000.
13.	顧鶯, 張慧文, 周英鳳, 等. JBI 循證衛生保健中心關于不同類型研究的質量評價工具——系統評價的方法學質量評價. 護士進修雜志, 2018, 33(8): 701-703.
14.	王春青, 胡雁. JBI 證據預分級及證據推薦級別系統 (2014 版). 護士進修雜志, 2015, 30(11): 964-967.
15.	Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the Use of WBC growth factors: American Society of clinical oncology clinical practice guideline update. J Clin Oncol, 2015, 33(28):3199-3212.
16.	Krzyzanowska MK, Walker-Dilks C, Atzema C, et al. Approach to fever assessment in ambulatory cancer patients receiving chemotherapy: a clinical practice guideline. Curr Oncol, 2016, 23(4): 280-285.
17.	Griffiths EA, Roy V, Alwan L, et al. NCCN guidelines^? insights: hematopoietic growth factors, version 1. 2022. J Natl Compr Canc Netw, 2022, 20(5): 436-442.
18.	Adamo V, Antonuzzo L, Danova M, et al. Supportive therapies in the prevention of chemotherapy-induced febrile neutropenia and appropriate use of granulocyte colony-stimulating factors: a Delphi consensus statement. Support Care Cancer, 2022, 30(12):9877-9888.
19.	張英麗, 張師前. 婦科惡性腫瘤放化療期間應用聚乙二醇化重組人粒細胞集落刺激因子 (PEG-rhG-CSF) 的中國專家共識 (2023 年版). 腫瘤藥學, 2023, 13(1): 1-10.
20.	中國醫師協會放射腫瘤治療醫師分會, 中華醫學會放射腫瘤治療學分會, 中國抗癌協會腫瘤放射治療專業委員會. 同步放化療期間應用聚乙二醇化重組人粒細胞刺激因子中國專家共識 (2023 版). 中華腫瘤防治雜志, 2023, 30(6): 333-340.
21.	王丹波, 王建東, 孔為民, 等. 婦科惡性腫瘤放化療相關中性粒細胞減少癥規范管理中國專家共識 (2024 年版). 中國實用婦科與產科雜志, 2024, 40(6): 645-652.
22.	Mhaskar R, Clark OA, Lyman G, et al. Colony-stimulating factors for chemotherapy-induced febrile neutropenia. Cochrane Database Syst Rev, 2014, 2014(10): CD003039.
23.	Van Belle H, Hurvitz SA, Gilbar PJ, et al. Systematic review and meta-analysis of febrile neutropenia risk with TCH(P) in HER2-positive breast cancer. Breast Cancer Res Treat, 2021, 190(3):357-372.
24.	Tsuchihashi K, Ito M, Okumura Y, et al. Therapeutic use of granulocyte colony-stimulating factor (G-CSF) in patients with febrile neutropenia: a comprehensive systematic review for clinical practice guidelines for the use of G-CSF 2022 from the Japan society of clinical oncology. Int J Clin Oncol, 2024, 29(6): 700-705.
25.	Nozawa K, Ozaki Y, Yoshinami T, et al. Effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for invasive breast cancer: a systematic review and meta-analysis from clinical practice guidelines for the use of G-CSF 2022. Int J Clin Oncol, 2024, 29(8): 1074-1080.
26.	Krzyzanowska MK, Walker-Dilks C, Morris AM, et al. Approach to evaluation of fever in ambulatory cancer patients receiving chemotherapy: a systematic review. Cancer Treat Rev, 2016, 51:35-45.
27.	Clark OA, Lyman GH, Castro AA, et al. Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials. J Clin Oncol, 2005, 23(18):4198-4214.
28.	Estcourt LJ, Stanworth SJ, Hopewell S, et al. Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction. Cochrane Database Syst Rev, 2016, 4(4): CD005339.
29.	Wang L, Baser O, Kutikova L, et al. The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: a systematic review and meta-analysis of randomized controlled trials. Support Care Cancer, 2015, 23(11): 3131-3140.
30.	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): 702-716.
31.	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(10): 2475-2484.
32.	Ramsey SD, Bansal A, Sullivan SD, et al. Effects of a guideline-informed clinical decision support system intervention to improve colony-stimulating factor prescribing: a cluster randomized clinical trial. JAMA Netw Open, 2022, 5(10): e2238191.
33.	Hawkins A, Murphy A, McNamara M, et al. A survey of oncologists’ perceptions and opinions regarding the use of granulocyte colony-stimulating factors. J Cancer Educ, 2020, 35(1): 178-186.
34.	Ozaki Y, Yokoe T, Yoshinami T, et al. Optimal timing of prophylactic pegylated G-CSF after chemotherapy administration for patients with cancer: a systematic review and meta-analysis from clinical practice guidelines for the use of G-CSF 2022. IntJ Clin Oncol, 2024, 29(5): 551-558.
35.	Li X, Zheng H, Yu MC, et al. Is PEGylated G-CSF superior to G-CSF in patients with breast cancer receiving chemotherapy? A systematic review and meta-analysis. Support Care Cancer, 2020, 28(11): 5085-5097.
36.	Mahtani R, Crawford J, Flannery SM, et al. Prophylactic pegfilgrastim to prevent febrile neutropenia among patients receiving biweekly (Q2W) chemotherapy regimens: a systematic review of efficacy, effectiveness and safety. BMC Cancer, 2021, 21: 621.
37.	Kirshner JJ, Heckler CE, Janelsins MC, et al. Prevention of pegfilgrastim-induced bone pain: a phase III double-blind placebo-controlled randomized clinical trial of the university of rochester cancer center clinical community oncology program research base. J Clin Oncol, 2012, 30(16): 1974-1979.
38.	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): 1137-1143.
39.	Ba Y, Shi Y, Jiang W, et al. Current management of chemotherapy-induced neutropenia in adults: key points and new challenges. Cancer Biol Med, 2020, 17(4): 896-909.
40.	Finkel I, Sternschuss M, Wollner M, et al. Immune-related neutropenia following treatment with immune checkpoint inhibitors. J Immunother, 2020, 43(2): 67-74.
41.	Zhang B, Qi L, Wang X, et al. Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first-line treatment of advanced esophageal squamous cell carcinoma. Cancer Commun (Lond), 2020, 40(12): 711-720.
42.	Shiono A, Imai H, Wasamoto S, et al. Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. Cancer Med, 2023, 12(1): 73-83.
43.	Papadatos-Pastos D, Yuan W, Pal A, et al. Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumors. J Immunother Cancer, 2022, 10(6): e004495.
44.	Fuereder T, Minichsdorfer C, Mittlboeck M, et al. Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: a prospective phase I/II study. Oral Oncol, 2022, 124: 105634.
45.	Akamatsu H, Teraoka S, Hayashi H, et al. Pembrolizumab plus amrubicin in patients with relapsed SCLC: multi-institutional, single-arm phase 2 study. JTO Clin Res Rep, 2021, 2(7): 100184.

1. Klastersky J, de Naurois J, Rolston K, et al. Management of febrile neutropaenia: ESMO clinical practice guidelines. Ann Oncol, 2016, 27(Suppl 5): v111-v118.
2. Boccia R, Glaspy J, Crawford J, et al. Chemotherapy-induced neutropenia and febrile neutropenia in the US: a beast of burden that needs to be tamed. Oncologist, 2022, 27(8): 625-636.
3. 秦叔逵, 馬軍. 中國臨床腫瘤學會 (CSCO) 腫瘤放化療相關中性粒細胞減少癥規范化管理指南 (2021). 臨床腫瘤學雜志, 2021, 26(7): 638-648.
4. 中國抗癌協會腫瘤臨床化療專業委員會, 中國抗癌協會腫瘤支持治療專業委員會. 腫瘤化療導致的中性粒細胞減少診治中國專家共識 (2023 版). 中華腫瘤雜志, 2023, 45(7): 575-583.
5. Tralongo AC, Antonuzzo A, Pronzato P, et al. Management of chemotherapy-induced neutropenia in patients with cancer: 2019 guidelines of the Italian medical oncology association (AIOM). Tumori, 2020, 106(4): 273-280.
6. Leon Rapoport B, Garcia-Morillo M, Font C, et al. A prospective, real-world, multinational study of febrile neutropenia (FN) occurrence in oncology patients receiving chemotherapy with intermediate risk of FN: a MASCC neutropenia, infection, and myelosuppression study group initiative. Support Care Cancer, 2023, 31(12): 628.
7. Carmona-Bayonas A, Jimenez-Fonseca P, de Castro EM, et al. SEOM clinical practice guideline: management and prevention of febrile neutropenia in adults with solid tumors (2018). Clin Transl Oncol, 2019, 21(1): 75-86.
8. Aapro M, Boccia R, Leonard R, et al. Refining the role of pegfilgrastim (a long-acting G-CSF) for prevention of chemotherapy-induced febrile neutropenia: consensus guidance recommendations. Support Care Cancer, 2017, 25(11): 3295-3304.
9. 蔣媛, 王小艷, 雷蕾, 等. 免疫檢查點抑制劑誘導高血糖癌癥患者血糖管理的最佳證據總結. 中國癌癥防治雜志, 2024, 16(6):722-728.
10. 朱政, 胡雁, 邢唯杰, 等. 不同類型循證問題的構成. 護士進修雜志, 2017, 32(21): 1991-1994.
11. 韋當, 王聰堯, 肖曉娟, 等. 指南研究與評價(AGREE Ⅱ)工具實例解讀. 中國循證兒科雜志, 2013, 8(4): 316-319.
12. 朱政, 胡雁, 周英鳳, 等. 推動證據向臨床轉化(五)證據臨床轉化研究中的文獻質量評價. 護士進修雜志, 2020, 35(11): 996-1000.
13. 顧鶯, 張慧文, 周英鳳, 等. JBI 循證衛生保健中心關于不同類型研究的質量評價工具——系統評價的方法學質量評價. 護士進修雜志, 2018, 33(8): 701-703.
14. 王春青, 胡雁. JBI 證據預分級及證據推薦級別系統 (2014 版). 護士進修雜志, 2015, 30(11): 964-967.
15. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the Use of WBC growth factors: American Society of clinical oncology clinical practice guideline update. J Clin Oncol, 2015, 33(28):3199-3212.
16. Krzyzanowska MK, Walker-Dilks C, Atzema C, et al. Approach to fever assessment in ambulatory cancer patients receiving chemotherapy: a clinical practice guideline. Curr Oncol, 2016, 23(4): 280-285.
17. Griffiths EA, Roy V, Alwan L, et al. NCCN guidelines^? insights: hematopoietic growth factors, version 1. 2022. J Natl Compr Canc Netw, 2022, 20(5): 436-442.
18. Adamo V, Antonuzzo L, Danova M, et al. Supportive therapies in the prevention of chemotherapy-induced febrile neutropenia and appropriate use of granulocyte colony-stimulating factors: a Delphi consensus statement. Support Care Cancer, 2022, 30(12):9877-9888.
19. 張英麗, 張師前. 婦科惡性腫瘤放化療期間應用聚乙二醇化重組人粒細胞集落刺激因子 (PEG-rhG-CSF) 的中國專家共識 (2023 年版). 腫瘤藥學, 2023, 13(1): 1-10.
20. 中國醫師協會放射腫瘤治療醫師分會, 中華醫學會放射腫瘤治療學分會, 中國抗癌協會腫瘤放射治療專業委員會. 同步放化療期間應用聚乙二醇化重組人粒細胞刺激因子中國專家共識 (2023 版). 中華腫瘤防治雜志, 2023, 30(6): 333-340.
21. 王丹波, 王建東, 孔為民, 等. 婦科惡性腫瘤放化療相關中性粒細胞減少癥規范管理中國專家共識 (2024 年版). 中國實用婦科與產科雜志, 2024, 40(6): 645-652.
22. Mhaskar R, Clark OA, Lyman G, et al. Colony-stimulating factors for chemotherapy-induced febrile neutropenia. Cochrane Database Syst Rev, 2014, 2014(10): CD003039.
23. Van Belle H, Hurvitz SA, Gilbar PJ, et al. Systematic review and meta-analysis of febrile neutropenia risk with TCH(P) in HER2-positive breast cancer. Breast Cancer Res Treat, 2021, 190(3):357-372.
24. Tsuchihashi K, Ito M, Okumura Y, et al. Therapeutic use of granulocyte colony-stimulating factor (G-CSF) in patients with febrile neutropenia: a comprehensive systematic review for clinical practice guidelines for the use of G-CSF 2022 from the Japan society of clinical oncology. Int J Clin Oncol, 2024, 29(6): 700-705.
25. Nozawa K, Ozaki Y, Yoshinami T, et al. Effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for invasive breast cancer: a systematic review and meta-analysis from clinical practice guidelines for the use of G-CSF 2022. Int J Clin Oncol, 2024, 29(8): 1074-1080.
26. Krzyzanowska MK, Walker-Dilks C, Morris AM, et al. Approach to evaluation of fever in ambulatory cancer patients receiving chemotherapy: a systematic review. Cancer Treat Rev, 2016, 51:35-45.
27. Clark OA, Lyman GH, Castro AA, et al. Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials. J Clin Oncol, 2005, 23(18):4198-4214.
28. Estcourt LJ, Stanworth SJ, Hopewell S, et al. Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction. Cochrane Database Syst Rev, 2016, 4(4): CD005339.
29. Wang L, Baser O, Kutikova L, et al. The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: a systematic review and meta-analysis of randomized controlled trials. Support Care Cancer, 2015, 23(11): 3131-3140.
30. 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): 702-716.
31. 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(10): 2475-2484.
32. Ramsey SD, Bansal A, Sullivan SD, et al. Effects of a guideline-informed clinical decision support system intervention to improve colony-stimulating factor prescribing: a cluster randomized clinical trial. JAMA Netw Open, 2022, 5(10): e2238191.
33. Hawkins A, Murphy A, McNamara M, et al. A survey of oncologists’ perceptions and opinions regarding the use of granulocyte colony-stimulating factors. J Cancer Educ, 2020, 35(1): 178-186.
34. Ozaki Y, Yokoe T, Yoshinami T, et al. Optimal timing of prophylactic pegylated G-CSF after chemotherapy administration for patients with cancer: a systematic review and meta-analysis from clinical practice guidelines for the use of G-CSF 2022. IntJ Clin Oncol, 2024, 29(5): 551-558.
35. Li X, Zheng H, Yu MC, et al. Is PEGylated G-CSF superior to G-CSF in patients with breast cancer receiving chemotherapy? A systematic review and meta-analysis. Support Care Cancer, 2020, 28(11): 5085-5097.
36. Mahtani R, Crawford J, Flannery SM, et al. Prophylactic pegfilgrastim to prevent febrile neutropenia among patients receiving biweekly (Q2W) chemotherapy regimens: a systematic review of efficacy, effectiveness and safety. BMC Cancer, 2021, 21: 621.
37. Kirshner JJ, Heckler CE, Janelsins MC, et al. Prevention of pegfilgrastim-induced bone pain: a phase III double-blind placebo-controlled randomized clinical trial of the university of rochester cancer center clinical community oncology program research base. J Clin Oncol, 2012, 30(16): 1974-1979.
38. 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): 1137-1143.
39. Ba Y, Shi Y, Jiang W, et al. Current management of chemotherapy-induced neutropenia in adults: key points and new challenges. Cancer Biol Med, 2020, 17(4): 896-909.
40. Finkel I, Sternschuss M, Wollner M, et al. Immune-related neutropenia following treatment with immune checkpoint inhibitors. J Immunother, 2020, 43(2): 67-74.
41. Zhang B, Qi L, Wang X, et al. Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first-line treatment of advanced esophageal squamous cell carcinoma. Cancer Commun (Lond), 2020, 40(12): 711-720.
42. Shiono A, Imai H, Wasamoto S, et al. Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. Cancer Med, 2023, 12(1): 73-83.
43. Papadatos-Pastos D, Yuan W, Pal A, et al. Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumors. J Immunother Cancer, 2022, 10(6): e004495.
44. Fuereder T, Minichsdorfer C, Mittlboeck M, et al. Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: a prospective phase I/II study. Oral Oncol, 2022, 124: 105634.
45. Akamatsu H, Teraoka S, Hayashi H, et al. Pembrolizumab plus amrubicin in patients with relapsed SCLC: multi-institutional, single-arm phase 2 study. JTO Clin Res Rep, 2021, 2(7): 100184.

West China Medical Journal

Summary of best evidence for human granulocyte colony stimulating factor in cancer patients with febrile neutropenia

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