背景:推荐用于横纹肌肉瘤(RMS)和尤文肉瘤(ES)患者的化疗方案具有骨髓抑制性,可降低中性粒细胞绝对计数(ANC),并随后增加发热性中性粒细胞减少(FN)的风险。然而,只有少数研究关注粒细胞集落刺激因子(G-CSF)药物在RMS和ES的儿科和青少年患者中的疗效和安全性.我们的目的是研究mecapegfilgrastim的疗效和安全性,pegfilgrastim的生物仿制药,预防儿童和青少年RMS或ES患者的FN。
方法:在这个单臂中,单中心,前瞻性研究,患有RMS或ES的儿科和青少年患者被纳入接受VAC(长春新碱,环磷酰胺,放线菌素)方案或VDC(长春新碱,环磷酰胺,多柔比星)方案,为期3周,然后用美卡皮非格司亭(100μg/kg,最大6毫克)在完成化疗后24小时给予。主要终点是FN的发生率。次要终点包括4级中性粒细胞减少症的发生率,ANC的持续时间≤0.5×109/L,化疗延迟或减少的发生率,使用抗生素,和安全概况。
结果:总计,30人中的2人(6.7%,95%CI:0.82-22.07)患者在第一周期化疗后出现FN。八(26.7%,95%CI:12.28-45.89)患者在接受预防性mecapegfilgrastim后出现4级中性粒细胞减少症。8例患者发生ANC≤0.5×109/L,中位病程4.5天;6名患者在第7天达到其ANC水平的最低点,其中5名患者在第10天恢复。没有剂量减少,延迟,或报告停止化疗。21名(70.0%)患者在治疗期间接受了抗生素治疗。在0-5年和13-18年组没有患者经历FN,6-12年组2例患者发生FN。两个病人,6名患者,并且在0-5年内没有患者经历过4级中性粒细胞减少症,6-12年,和13-18岁组,分别。
结论:Mecapegfilgrastim在RMS或ES的儿科和青少年患者中显示出可接受的疗效和安全性。需要进一步的大样本量随机研究。
背景:该临床试验已在Chictr.org注册。cn(没有ChiCTR1900022249)。2019年3月31日注册。
BACKGROUND: The chemotherapy regimens recommended for both rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) patients are myelosuppressive and can reduce the absolute neutrophil count (ANC) and subsequently increase the risk of febrile neutropenia (FN). However, only a few studies have focused on the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) drugs in pediatric and adolescent patients with RMS and ES. Our objective was to investigate the efficacy and safety of mecapegfilgrastim, a biosimilar of pegfilgrastim, in prophylaxis of FN for pediatric and adolescent patients with RMS or ES.
METHODS: In this single-arm, single-center, prospective study, pediatric and adolescent patients with RMS or ES were enrolled to receive either VAC (vincristine, cyclophosphamide, dactinomycin) regimen or VDC (vincristine, cyclophosphamide, doxorubicin) regimen in a 3-week cycle, followed by treatment with mecapegfilgrastim (100 μg/kg, maximum 6 mg) given at 24 h after completing chemotherapy. The primary endpoint was the incidence rate of FN. Secondary endpoints included the incidence rate of grade 4 neutropenia, duration of ANC ≤ 0.5 × 109/L, incidence rate of chemotherapy delay or reduction, use of antibiotics, and safety profile.
RESULTS: In total, 2 of the 30 (6.7%, 95% CI: 0.82-22.07) patients experienced FN after the first cycle of chemotherapy. Eight (26.7%, 95% CI: 12.28-45.89) patients experienced grade 4 neutropenia after receiving prophylactic mecapegfilgrastim. Eight patients experienced ANC ≤ 0.5 × 109/L with a median duration of 4.5 days; among them, 6 patients reached the lowest point of their ANC level on day 7, and 5 of them recovered by day 10. No dose reductions, delays, or discontinuation of chemotherapy was reported. Twenty-one (70.0%) patients received antibiotics during the treatment period. No patient experienced FN in the 0-5 years and the 13-18 years groups, and 2 patients experienced FN in the 6-12 years group. Two patients, 6 patients, and no patient experienced grade 4 neutropenia in the 0-5 years, 6-12 years, and 13-18 years groups, respectively.
CONCLUSIONS: Mecapegfilgrastim showed acceptable efficacy and safety profile in pediatric and adolescent patients with RMS or ES. Further randomized studies with large sample size are warranted.
BACKGROUND: This clinical trial was registered at Chictr.org.cn (No.ChiCTR1900022249). Registered on March 31, 2019.