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症临床疗效观察

A Randomized Controlled Clinical Study of Pegylated Recombinant Human Granulocyte Colony-stimulating Factor in Chemotherapy-induced Neutropenia

目的：比较聚乙二醇化重组人粒细胞集落刺激因子（PEG—rhG—CSF）和重组人粒细胞集落刺激因子（rhG—CSF）预防化疗后中性粒细胞减少症的有效性和安全性。方法：采用随机自身交叉对照，选择初治恶性肿瘤患者接受2个周期相同方案的化疗，其中试验周期给予PEG—rhG—CSF100μg／kg皮下注射一次，对照周期每日一次皮下注射rhG—CSF5μg／kg，直至外周血中性粒细胞绝对值（ANC）在低谷后连续两次检查≥5．0×10^9／L。结果：入组78例患者，在76个试验周期和74个对照周期中，ANC〈1．5×10^9／L的发生率分别为30-26％和21．16％，持续时间分别为2．34d和2．31d；ANC〈0．5×10^9／L的发生率分别为3．8％和3．0％；抗生素使用率分别为11．59％和9．60％（P均〈0．05）。试验药和对照药的不良反应均为骨骼肌肉疼痛、乏力、发热、头晕等，发生率与严重程度相似。结论：PEG—rhG—CSF一次给药的疗效和不良反应与rhG—CSF多次给药相似。

Objective： To compare the efficacy and safety of a single subcutaneous injection of PEG-rhG-CSF and daily rhG-CSF in chemotherapy-induced neutropenia. Methods： In the present randomized, open-label, match, and cross-over study, 78 patients with previously untreated non-small cell lung cancer, breast cancer, and non-Hodgkin＇s lymphoma With normal bone marrow function were enrolled. The patients were randomized into AB and BA groups. Each patient received two cycles of chemotherapy with identical regimens. In the study cycle, they received a single subcutaneous injection of 100μg/kg PEG-rhG-CSF on day 3; and in the control cycle, daily subcutaneous infections of 5 μg/kg/d rhG-CSF began on day 3 and continued either for 14 days or until the absolute neutrophil count （ANC） 〉 5.0 × 10^9/L twice post nadir, whichever occurred first. The efficacy and safety parameters were monitored. Results： The incidence ofANC 〈 1.5 ×10^9/L in 76 evaluable study cycles and 74 evaluable control cycles were 30.00% and 21.00%, with durations of 2.34 days and 2.31 days, respectively. Additionally, those with grade 4 neutropenia were 3.80% and 3.00%, respectively, in the trial and control cycles. The differences above were not statistically significant. None of the patients experienced febrile neutropenia after receiving PEG-rhG-CSF and rhG-CSF. Compared with that of rhG-CSF, the ANC profile of PEG-rhG-CSF exhibited limited ＂over- shoot＂ of neutrophils after the nadir. Subgroup analysis according to disease type yielded similar results. The safety profiles of PEG-rhG-CSF and rhG-CSF were similar. Musculoskeletal pain or arthralgias occurred in 16.5% of the cases during the study cycles and 26.00% in the control cycles （ P = 0.963 ）, which were mostly mild or moderate. Other adverse effects, such as fever, fatigue, dizziness, gastrointestinal effects and injection-site pain, were transient and easily manageable. Conclusion： A single subcutaneous injection of 100 μg/kg PEG-rhG-CSF provides neutrophil support and a safety profile comparable to daily subcutaneous injections of 5 μg/kg/d rhG-CSF in Chinese patients receiving a variety of myelosuppressive chemotherapy regimens.