聚乙二醇化重组人粒细胞集落刺激因子初级与次级预防化疗后中性粒细胞减少的有效性和安全性临床研究

Efficacy and safety of PEG-rhG-CSF therapy in the primary and secondary prevention of chemotherapy-induced neutropenia

目的:评价聚乙二醇化重组人粒细胞集落刺激因子(pegylated recombinant human granulocyte colony-stimulating factor,PEG-rhG-CSF)初级与次级预防化疗后中性粒细胞减少的有效性和安全性.方法:本研究为单中心、开放、单臂临床研究,分析2016年5月至2018年12月北京大学肿瘤医院217例受试者.非髓性恶性肿瘤患者于化疗结束后24~48 h皮下注射PEG-rhG-CSF,体质量≥45 kg者给予6 mg/次,<45 kg者给予3 mg/次,每个化疗周期注射1次.结果:217例患者共完成774个化疗周期,患者包括18例妇科肿瘤(3例子宫内膜癌、15例卵巢癌),50例乳腺癌,30例骨肿瘤和119例淋巴瘤,146例接受初级预防,71例接受次级预防.中性粒细胞减少性发热(febrile neutropenia,FN)发生率为5.7%,初级预防组发生率为4.9%,次级预防发生率为7.2%.Logistic单因素与多因素分析显示,PEG-rhG-CSF持续治疗周期越长,FN发生率越低.初级与次级预防的FN发生率均在治疗第2个周期显著低于第1个周期.初级预防为第1个周期11.6%vs.第2个周期4.4%,(P=0.039);次级预防为第1个周期16.9%vs.第2个周期5.6%,(P=0.034).Ⅳ度中性粒细胞减少发生率为10.3%(80/774),其中初级预防组为6.7%(34/510),次级预防组为17.4%(46/264),差异具有统计学意义(P<0.001).Ⅳ度中性粒细胞减少发生率均在治疗第2个周期显著低于第1个周期.初级预防为第1个周期17.1%vs.第2周期5.3%,(P=0.004);次级预防为第1个周期46.5%vs.第2个周期11.3%,(P<0.001).药物相关不良反应主要为骨痛,患者Ⅰ/Ⅱ度骨痛发生率为3.7%(8/217),Ⅲ/Ⅳ度骨痛发生率为1.8%(4/217).结论:PEG-rhG-CSF预防性应用于非髓性恶性肿瘤,可有效降低FN发生率.初级预防比次级预防显著降低整个化疗周期Ⅳ度中性粒细胞减少的发生.

Objective:To evaluate the efficacy and safety of PEG-rhG-CSF therapy in the primary and secondary prevention of chemo-therapy-induced neutropenia.Methods:This single-center,one-arm,and open-label clinical study involved 217 patients with non-my-eloid malignant tumors.These patients included 18 gynecologic oncology(3 endometrial and 15 ovarian cancer),50 breast cancer,30 bone tumor,and 119 lymphoma patients who underwent a total of 774 cycles of chemotherapy,comprising 146 primary and 71 sec-ondary prevention patients.The patients≥45 kg and those<45 kg received a single subcutaneous injection of 6 mg and 3 mg PEG-rhG-CSF,respectively,24-48 h after the chemotherapy was completed.All patients received only one dose of PEG-rhG-CSF admin-istration per chemotherapy cycle.Results:The overall incidence of febrile neutropenia(FN)was found to be 5.7%,with rates of 4.9%and 7.2%in the primary and secondary prevention groups,respectively.Univariate and multivariate Logistic regression analyses re-vealed that the longer PEG-rhG-CSF was sustained in the treatment cycle,the lower the incidence of FN was.The incidence of FN was significantly lower in the second cycle of the treatment than in the first in both the primary and secondary prevention groups(cycle 1 vs.cycle 2:11.6%vs.4.4%,respectively,P=0.039,in the primary group;16.9%vs.5.6%,respectively,P=0.034,in the secondary group).The overall incidence of gradeⅣneutropenia was 10.3%(80/774),with rates of 6.7%(34/510)and 17.4%(46/264)in the primary and secondary prevention groups,respectively(P<0.001).The incidence of gradeⅣneutropenia was significantly lower in the second cy-cle of the treatment than in the first(cycle 1 vs.cycle 2:17.1%vs.5.3%,respectively,P=0.004,in the primary group;46.5%vs.11.3%,respectively,P<0.001,in the secondary group).The treatment-induced toxicity mainly involved bone pain,with 3.7%(8/217)and 1.8%(4/217)incidence rates for grade 1-2 and 3-4 bone pain,respectively.Conclusions:PEG-rhG-CSF administration can effectively reduce the incidence of FN(5.7%)when prophylactically applied to patients with non-myeloid malignant tumors.Primary prevention can significantly reduce the risk of grade IV neutropenia in all chemotherapy cycles relative to the secondary prevention.