Clinical observation of prophylactic use of pegylated recombinant human granulocyte stimulating factor in breast cancer patients with postoperative radiotherapy

doi:10.3760/cma.j.issn.1673-422X.2020.03.003

Abstract

Abstract:

Objective To investigate the efficacy and adverse effects of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia in patients undergoing sequential adjuvant radiotherapy after postoperative chemotherapy for breast cancer. Methods A total of 43 female patients with breast cancer from January 2017 to January 2019 in Shandong Cancer Hospital and Institute were analyzed prospectively. Twenty-one patients in the experimental group were given 6 mg of PEG-rhG-CSF subcutaneously 1-3 days before radiotherapy. In the control group, 22 patients were enrolled without PEG-rhG-CSF utilization. The lowest absolute neutrophil count (ANC), the number of days of radiotherapy interruption due to neutropenia, the number of recombinant human granulocyte colony-stimulating factor (rhG-CSF) used during radiotherapy and the occurrence of drug-induced skeletal muscle pain in the two groups were statistically analyzed. Results No neutropenia fever was observed in the two groups during radiotherapy. In the experimental group, there was no case of grade Ⅲ neutropenia; while in the control group, there were 3 cases of grade Ⅲ neutropenia. The median value of the lowest ANC in the experimental group was 1.56×10 ⁹/L, higher than that in the control group (1.37×10 ⁹/L), with a statistically significant difference (Z=-2.261, P=0.023). The median number of rhG-CSF used in the experimental group was 1, which was smaller than 2 in the control group, and the difference was statistically significant (Z=-2.498, P=0.012). The median numbers of days of radiotherapy interruption due to neutropenia were 0 and 3 in the experimental group and the control group, with a statistically significant difference (Z=-3.117, P=0.001). One case (4.8%) of drug-induced skeletal muscle pain was found in the experimental group and 5 cases (22.7%) in the control group, with no statistically significant difference (χ ²=1.586, P=0.208). Conclusion PEG-rhG-CSF can effectively prevent neutropenia caused by radiotherapy after postoperative chemotherapy for patients with breast cancer, and can reduce the interruption of radiotherapy and the use of rhG-CSF during radiotherapy, which is helpful to the smooth process of radiotherapy.

Key words: Breast neoplasms, Radiotherapy, Neutropenia, Granulocyte colony-stimulating factor, Pegylation

Du Yanfang, Fan Yanling, Hu Bing, Sun Lei, Liu Yuanjian, Li Baosheng, Huang Wei. Clinical observation of prophylactic use of pegylated recombinant human granulocyte stimulating factor in breast cancer patients with postoperative radiotherapy[J]. Journal of International Oncology, 2020, 47(3): 141-145.

Figures/Tables 2

References 22

[1]	韩小伟 . 北京地区一项单中心乳腺癌主要流行病学指标演变趋势的研究(2000-2015)[D]. 北京: 中国人民解放军军事医学科学院, 2017. DOI: CNKI:CDMD:2.1017.230495.
[2]	Bray F, Ferlay J, Soerjomataram I , et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018,68(6):394-424. DOI: 10.3322/caac.21492. doi: 10.3322/caac.v68.6
[3]	范奎, 代良敏, 伍振峰 , 等. 放化疗所致骨髓抑制的研究进展[J]. 中华中医药杂志, 2017,32(1):210-214.
[4]	林万龙, 陈瑶, 杨剑辉 . 重组人粒细胞刺激因子用于乳腺癌化疗后辅助治疗专项点评[J]. 中国现代应用药学, 2018,35(6):900-904. DOI: 10.13748/j.cnki.issn1007-7693.2018.06.025.
[5]	Pawloski PA, Larsen M, Thoresen A , et al. Pegfilgrastim use and bone pain: a cohort study of community-based cancer patients[J]. J Oncol Pharm Pract, 2016,22(3):423-429. DOI: 10.1177/1078155215585188. doi: 10.1177/1078155215585188
[6]	张永娜, 贺宝霞, 张振鑫 , 等. 长、短效粒细胞刺激因子预防和治疗肺部恶性肿瘤化疗所致骨髓抑制的成本-效果分析[J]. 中国药房, 2019,30(13):1826-1830. DOI: 10.6039/j.issn.1001-0408.2019.13.20.
[7]	吴凤鹏, 王惠, 李娜 , 等. 聚乙二醇化重组人粒细胞刺激因子对同步放化疗所致Ⅳ度粒缺患者挽救性治疗的临床观察[J]. 中华肿瘤杂志, 2014,36(9):708-712. DOI: 10.3760/cma.j.issn.0253-3766.2014.09.015.
[8]	Vanitha S, Goswami U, Chaubey N , et al. Functional characterization of recombinant human granulocyte colony stimulating factor (hGMCSF) immobilized onto silica nanoparticles[J]. Biotechnol Lett, 2016,38(2):243-249. DOI: 10.1007/s10529-015-1984-0. doi: 10.1007/s10529-015-1984-0
[9]	汪蕊, 郭园园, 李玉梅 , 等. PEG-rhG-CSF对恶性肿瘤患者化疗间期生活质量的影响[J]. 重庆医学, 2018,47(22):2921-2923, 2927. DOI: 10.3969/j.issn.1671-8348.2018.22.010.
[10]	石远凯, 许建萍, 吴昌平 , 等. 聚乙二醇化重组人粒细胞刺激因子预防化疗后中性粒细胞减少症的多中心上市后临床研究[J]. 中国肿瘤临床, 2017,44(14):679-684. DOI: 10.3969/j.issn.1000-8179.2017.14.291.
[11]	Pfeil AM, Allcott K, Pettengell R , et al. Efficacy, effectiveness and safety of long-acting granulocyte colony-stimulating factors for prophylaxis of chemotherapy-induced neutropenia in patients with cancer: a systematic review[J]. Support Care Cancer, 2015,23(2):525-545. DOI: 10.1007/s00520-014-2457-z. doi: 10.1007/s00520-014-2457-z
[12]	Xu X, Yang J, Liu Y , et al. The induction of prolonged myelopoietic effects in monkeys by GW003, a recombinant human granulocyte colony-stimulating factor genetically fused to recombinant human albumin[J]. J Pharm Sci, 2015,104(2):760-767. DOI: 10.1002/jps.24121. doi: 10.1002/jps.24121
[13]	Pettengell R, Bias P, Mueller U , et al. Clinical safety of tbo-filgrastim, a short-acting human granulocyte colony-stimulating factor[J]. Support Care Cancer, 2016,24(6):2677-2684. DOI: 10.1007/s00520-015-3057-2. doi: 10.1007/s00520-015-3057-2
[14]	Hacioğlu S, Sari I, Doğu MH , et al. The effect of gradual increment in rhG-CSF dose on stem cell yields in patient with multiple myeloma mobilized with intermediate dose cyclophosphamide plus rhG-CSF[J]. Transfus Apher Sci, 2014,50(1):71-74. DOI: 10.1016/j.transci.2013.11.003. doi: 10.1016/j.transci.2013.11.003
[15]	朱大年 . 生理学. 第9版[M]. 北京: 人民卫生出版社, 2009: 50.
[16]	李丛, 张欣, 吴府容 , 等. 食管癌术后放疗骨照射剂量与骨髓抑制相关性[J]. 肿瘤预防与治疗, 2019,32(1):25-29. DOI: 10.3969/j.issn.1674-0904.2019.01.004.
[17]	Brito M, Esteves S, André R , et al. Comparison of effectiveness of biosimilar filgrastim (Nivestim ^TM), reference Amgen filgrastim and pegfilgrastim in febrile neutropenia primary prevention in breast cancer patients treated with neo(adjuvant) TAC: a non-interventional cohort study [J]. Support Care Cancer, 2016,24(2):597-603. DOI: 10.1007/s00520-015-2818-2. doi: 10.1007/s00520-015-2818-2
[18]	Singh VK, Kulkarni S, Fatanmi OO , et al. Radioprotective efficacy of gamma-tocotrienol in nonhuman primates[J]. Radiat Res, 2016,185(3):285-298. DOI: 10.1667/RR14127.1. doi: 10.1667/RR14127.1
[19]	刘青, 关嵩, 曹峰 , 等. PEG-rhG-CSF对同步放化疗中性粒细胞缺乏挽救性治疗临床分析[J]. 中华肿瘤防治杂志, 2017,24(7):481-485. DOI: 10.16073/j.cnki.cjcpt.2017.07.010.
[20]	马一鸣, 张明川, 张新慧 , 等. 宫颈癌同步放化疗预防应用PEG-rhG-CSF的临床价值[J]. 武汉大学学报(医学版), 2020,41(1):44-47. DOI: 10.14188/j.1671-8852.2018.1185.
[21]	杨晟, 何小慧, 刘鹏 , 等. 聚乙二醇化重组人粒细胞集落刺激因子预防化疗后中性粒细胞减少的有效性分析[J]. 中国肿瘤临床, 2015,42(12):626-631. DOI: 10.3969/j.issn.1000-8179.20150577. doi: doi:10.3969/j.issn. 1000- 8179.20150577
[22]	Lambertini M, Del Mastro L, Bellodi A , et al. The five "Ws" for bone pain due to the administration of granulocyte-colony stimulating factors (G-CSFs)[J]. Crit Rev Oncol Hematol, 2014,89(1):112-128. DOI: 10.1016/j.critrevonc.2013.08.006. doi: 10.1016/j.critrevonc.2013.08.006

临床特征	观察组 (n=21)	对照组 (n=22)	χ²值	P值
年龄(岁)
<50	11	11	0.024	0.876
≥50	10	11
KPS评分
80~90	12	11	0.220	0.639
>90	9	11
术后分期
Ⅱ期	7	6	0.187	0.665
Ⅲ期	14	16
初始ANC
<3×10⁹/L	12	12	0.029	0.864
≥3×10⁹/L	9	10

指标	观察组 (n=21)	对照组 (n=22)	Z值	P值
ANC最低值(×10⁹/L)	1.56(1.19~4.03)	1.37(0.82~3.06)	-2.261	0.023
rhG-CSF使用支数(支)	1(0~3)	2(0~14)	-2.498	0.012
放疗中断天数(d)	0(0~2)	3(0~4)	-3.117	0.001