目的 探討聚乙二醇化重組人粒細(xì)胞刺激因子（PEG-rhG-CSF）在宮頸癌同步放化療中預(yù)防中性粒細(xì)胞減少的療效及安全性。方法 按單中心單臂歷史對照研究，選取2019年6月—2021年1月32例符合入排條件，擬行同步放化療的宮頸癌患者組成試驗(yàn)組，同時(shí)搜集2017年1月—2019年6月行同步放化療且符合對照組治療方案的宮頸癌患者病歷資料，按1∶1傾向性評分匹配法組成對照組。試驗(yàn)組為前瞻性入組，患者第1次化療給藥結(jié)束24 h后sc聚乙二醇化重組人粒細(xì)胞刺激因子注射液，每次6 mg，每化療周期1次，共給藥2次。若使用PEG-rhG-CSF預(yù)防后，中性粒細(xì)胞計(jì)數(shù)（ANC）仍＜1.0×109·L^-1，可給予短效重組人粒細(xì)胞刺激因子注射液5 μg·kg^-1，sc給藥，直至ANC≥2.0×109·L^-1。對照組患者采用傾向性評分匹配既往同步放化療的宮頸癌患者，初始不給予PEG-rhG-CSF，當(dāng)患者出現(xiàn)ANC＜1.0×109·L^-1后sc給予重組人粒細(xì)胞刺激因子注射液，5 μg·kg^-1，持續(xù)使用，每日1次，直至ANC≥2.0×109·L^-1。記錄兩組患者3、4度中性粒細(xì)胞減少癥發(fā)生率及持續(xù)時(shí)間；粒細(xì)胞減少性發(fā)熱（FN）發(fā)生率；中性粒細(xì)胞減少導(dǎo)致化療延遲和放療中斷發(fā)生率；評價(jià)兩組不良反應(yīng)情況，包括乏力、骨關(guān)節(jié)痛、發(fā)熱、皮膚黏膜反應(yīng)、惡心及嘔吐等。結(jié)果 試驗(yàn)組與對照組各32例，兩組基線均衡。試驗(yàn)組中性粒細(xì)胞減少癥發(fā)生率59.4%，對照組為84.3%，試驗(yàn)組顯著低于對照組（P＜0.05）；3、4度中性粒細(xì)胞減少癥發(fā)生率試驗(yàn)組為31.3%（10/32），對照組為56.3%（18/32），試驗(yàn)組顯著低于對照組（P＜0.05）。3度中性粒細(xì)胞減少持續(xù)時(shí)間，試驗(yàn)組中位時(shí)間為0 d（0～29 d），顯著低于對照組2 d（0～38 d）；4度中性粒細(xì)胞減少持續(xù)時(shí)間，試驗(yàn)組中位時(shí)間為0 d（0～22 d），顯著低于對照組1 d（0～38 d）。兩組FN發(fā)生率比較無明顯差異，但試驗(yàn)組有降低趨勢。試驗(yàn)組放療中斷1例，對照組2例，兩組比較無顯著統(tǒng)計(jì)學(xué)差異（P＞0.05）；試驗(yàn)組延遲化療出現(xiàn)4例（12.5%），對照組出現(xiàn)12例（37.5%），兩組比較差異顯著（P＜0.05）。兩組不良反應(yīng)主要包括乏力、骨關(guān)節(jié)痛、發(fā)熱、皮膚黏膜反應(yīng)、惡心及嘔吐等，組間比較，差異不顯著（P＞0.05）。結(jié)論 宮頸癌同步放化療過程中預(yù)防性應(yīng)用PEG-rhG-CSF具有安全性、有效性，可以降低中性粒細(xì)胞減少癥發(fā)生率，減少FN和不良反應(yīng)，避免治療延遲。

Objective To explore effectiveness, safety and adverse reaction of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing radiochemotherapy-induced neutropenia of cervical cancer. Methods From June 2019 to January 2021, 32 cervical cancer patients who met the inclusion criteria and planned to receive concurrent chemoradiotherapy were selected as the experimental group. At the same time, medical records of cervical cancer patients who received concurrent chemoradiotherapy and met the treatment plan of the control group from January 2017 to June 2019 were collected, and the control group was constituted according to 1∶1 propensity score matching method. The experimental group was prospectively enrolled, and 24 h after the end of the first chemotherapy administration, the patients were injected with Polyethylene Glycol Recombinant Human Granulocyte Stimulating Factor Injection at a dose of 6 mg each time, once per chemotherapy cycle, and administered twice in total. If PEG-rhG-CSF is used for prevention, the neutrophil count (ANC) remains less than 1.0×109·L^-1, can be administered with short acting Recombinant Human Granulocyte Stimulating Factor Injection 5 μg·kg^-1, sc administered until ANC ≥ 2.0×109·L^-1. Patients in the control group were matched with cervical cancer patients who had previously undergone concurrent radiotherapy and chemotherapy using a propensity score, and initially did not receive PEG-rhG-CSF. When the patient showed ANC < 1.0×109·L^-1, administered with Recombinant Human Granulocyte Stimulating Factor Injection, 5 μg·kg^-1, continue to use once a day until ANC ≥ 2.0×109·L^-1. The incidence and duration of degree three and four neutropenia in two groups of patients, the incidence of granulocytopenic fever (FN), the incidence of delayed chemotherapy and interrupted radiotherapy due to neutropenia were recorded. The adverse reactions in both groups were evaluated, including fatigue, joint pain, fever, skin mucosal reactions, nausea, and vomiting. Results There were 32 cases in the experimental group and 32 cases in the control group, and the baseline of the two groups was balanced. The incidence of neutropenia was 59.4% in the experimental group and 84.3% in the control group, which was significantly lower than that in the control group (P < 0.05). The incidence of grade three neutropenia was 31.3% in the experimental group and 56.3% in the control group, which was significantly lower than that in the control group (P < 0.05). The median duration of grade three neutropenia in the experimental group was 0 d (0—29 d), which was significantly lower than 2 d (0—38 d) in the control group. The duration of grade four neutropenia in the experimental group was a median of 0 d (0— 22 d), which was significantly lower than 1 d (0—38 d) in the control group. There was no significant difference in the incidence of granulocytopenia fever (FN) between the two groups, but there was a trend to decrease in the experimental group. There was no significant difference between the two groups (P > 0.05). Delayed chemotherapy occurred in four cases (12.5%) in the experimental group and 12 cases (37.5%) in the control group, and there was a significant difference between the two groups (P < 0.05). The adverse reactions mainly included fatigue, arthralgia, fever, skin and mucosa reaction, nausea and vomiting, and there was no significant difference between the two groups (P > 0.05). Conclusion The prophylactic application of PEG-rhG-CSF in concurrent radiochemotherapy for cervical cancer was safe and effective, which can reduce the incidence of neutropenia, FN, adverse reactions and delayed chemotherapy cycles.

R969.4

中國臨床腫瘤學(xué)會(huì)-CSCO基金（Y-QL2019-0137）；內(nèi)蒙古自治區(qū)科技計(jì)劃項(xiàng)目（2019GG039/086、2021GG0167）；內(nèi)蒙古自然科學(xué)基金（2021MS08152/8154）；希思科-石藥腫瘤研究基金項(xiàng)目（Y-SY201901-0008）；希思科-2019年度齊魯腫瘤研究基金項(xiàng)目（Y-QL2019-0137）；三生TCP中青年科研基金（008）；北京醫(yī)學(xué)獎(jiǎng)勵(lì)基金項(xiàng)目（YXJL-2020-0785-0315）；內(nèi)蒙古自治區(qū)衛(wèi)生健康科技計(jì)劃項(xiàng)目（202202017）；三生TCP中青年科研基金（011）