不同剂量rhG-CSF预防晚期非小细胞肺癌化疗后白细胞减少的临床研究

背景与目的：肿瘤化疗最常见的剂量限制性毒性是骨髓抑制，其中白细胞和中性粒细胞减少最为常见。骨髓抑制不但使化疗药物的剂量提高受到限制，而且影响了化疗的正常进行。基因重组人粒细胞集落刺激因子(recombinant human granulocyte colony-stimulating factor，rhG-CSF)不仅具有刺激粒细胞集落形成的能力，也有促进粒细胞生长、增殖和分化的能力，对化疗所致白细胞和中性粒细胞减少具有明显疗效。本研究观察晚期非小细胞肺癌(non-small cell lung cancer，NSCLC)患者接受化疗后预防性应用低、中、高3种不同剂量的rhG-CSF升白效果及不良反应，探讨该药合理的应用策略。方法：126例经病理证实为晚期NSCLC化疗的患者，按数字随机法分为A、B、C共3组。3组患者于化疗结束后24 h给予rhG-CSF。其中A组(低剂量)：rhG-CSF300 μg，皮下注射，每日1次，共1天；B组(中剂量)：rhG-CSF 300 μg，皮下注射，每日1次，共2天；C组(高剂量)：rhG-CSF 300 μg，皮下注射，每日1次，共3天。观察患者用药后出现的症状和体征以及rhG-CSF的不良反应。结果：化疗后预防性使用中、高剂量rhG-CSF可以使近60%的患者白细胞高于4.0×10⁹个/L；对于Ⅲ级白细胞减少的患者，低剂量组白细胞水平回升天数更长，高剂量组白细胞回升天数明显缩短，高剂量组和低剂量组之间差异有统计学意义(P<0.05)；从中性粒细胞的动态变化情况来看，化疗后加用高剂量rhG-CSF可以提高中性粒细胞的平均水平，能明显缩短化疗引起中性粒细胞低下的持续时间。126 例患者中感染发生率为4.76%，其中低剂量组为9.52%，中剂量组为4.76%。rhG-CSF引起的不良反应轻微，患者能耐受。结论：化疗后预防性使用不同剂量rhG-CSF 均可促进化疗患者白细胞和中性粒细胞的恢复，降低感染发生率。在相同化疗剂量下选用高剂量的rhG-CSF可使白细胞和中性粒细胞水平快速上升，安全可靠。

A clinical study of rhG-CSF of different dosages in preventing leukopenia after chemotherapy in patients with advanced non-small cell lung cancer

Background and purpose: Myelosuppression is the most common dose-limiting toxicity of tumor chemotherapy in which leukocytopenia and neutropenia are the most common conditions. Not only are uptitrations of the doses of chemotherapeutic drugs limited, but also normal process of the chemotherapy is affected. Filgrastim-Recombinant Human Granulocyte Colony-Stimulating Factor (rhG-CSF) has the activity of stimulating the formation of granulocyte colony and promoting the growth, proliferation and differentiation of granulocytes which can be significantly effective on leukocytopenia and neutropenia induced by chemotherapy. In this study, we observed the leukogenic effects, toxic and side effects of low, medium, and high doses of rhG-CSF used prophylactically after chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), to explore a rational application strategy for rhG-CSF.. Methods: One hundred and twenty six patients with pathologically proved advanced non-small cell lungcancer (NSCLC) under chemotherapy were digitally randomized to A, B and C groups. Filgrastim was given to patients of the three groups 24h after the end of chemotherapy. The dosages are: Group A (low dose): 300 μg of Filgrastim, s.c., qd × 1 day; Group B (medium dose): 300 μg of Filgrastim, s.c., qd × 2 days; Group C (high dose): 300 μg of Filgrastim, s.c., qd × 3 days. Then the signs and symptoms as well as toxic and side effects of Filgrastim after medication were observed. Results: Prophylactic usage of medium and high dosages of rhG-CSF could maintain WBC count at no less than 4.0×10⁹/L in nearly 60% of patients. In patients with Grade III leukopenia, more days were needed for recovery of white blood cell (WBC) count with the low dose, while significantly (P<0.05) less days were needed with the high dose. In view of the dynamic changes of neutrophil(ANC), additioning of the high dose of rhG-CSF after chemotherapy could increase the average level of ANC, notably shortening the duration of low ANC caused by chemotherapy. The incidence of infections was 4.76% for the 126 patients as a whole, 9.52% for the low dose group, and 4.76% for the middle dose group. The patients could tolerate the slight side effects incurred during treatment with Filgrastim. Conclusion: All of the three doses (low, medium, and high) of prophylactic administration of Filgrastim after chemotherapy can promote recoveries of WBCs and neutrophil granulocytes and reduce opportunities of infections. High doses of rhG-CSF can be faster and safer in increasing WBCs and neutrophil granulocytes.