培非格司亭预防横纹肌肉瘤或尤文肉瘤儿童和青少年发热性中性粒细胞减少症的前瞻性单臂试验研究。

Mecapegfilgrastim for prophylaxis of febrile neutropenia in children and adolescents with rhabdomyosarcoma or Ewing sarcoma: a prospective, single-arm, pilot study.

机构信息

Medical Oncology Department, Pediatric Oncology CenterNational Center for Children's HealthKey Laboratory of Pediatric Hematology Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, No. 56 Nanlishi Road, Beijing, 100045, China.

Hematology CenterNational Center for Children's HealthKey Laboratory of Pediatric Hematology Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, No. 56 Nanlishi Road, Beijing, 100045, China.

出版信息

BMC Cancer. 2024 Aug 15;24(1):1013. doi: 10.1186/s12885-024-12766-w.

DOI:10.1186/s12885-024-12766-w

PMID:39148050

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11325604/

Abstract

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 × 10/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 × 10/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.

CONCLUSION

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.

TRIAL REGISTRATION

This clinical trial was registered at Chictr.org.cn (No.ChiCTR1900022249). Registered on March 31, 2019.

摘要

背景

推荐用于横纹肌肉瘤（RMS）和尤因肉瘤（ES）患者的化疗方案具有骨髓抑制作用，可降低绝对中性粒细胞计数（ANC），从而增加发热性中性粒细胞减少症（FN）的风险。然而，只有少数研究关注了粒细胞集落刺激因子（G-CSF）药物在 RMS 和 ES 儿科和青少年患者中的疗效和安全性。我们的目的是研究美泊利珠单抗（pegfilgrastim 的生物类似物）在预防 RMS 或 ES 儿科和青少年患者 FN 中的疗效和安全性。

方法

在这项单臂、单中心、前瞻性研究中，招募了 RMS 或 ES 儿科和青少年患者，每 3 周接受 VAC（长春新碱、环磷酰胺、放线菌素 D）方案或 VDC（长春新碱、环磷酰胺、多柔比星）方案治疗，随后给予美泊利珠单抗（100μg/kg，最大 6mg）治疗，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≤0.5×10/L 的持续时间、化疗延迟或减少的发生率、抗生素的使用和安全性。

结果

在接受第一周期化疗后，30 例患者中有 2 例（6.7%，95%CI：0.82-22.07）发生 FN。接受预防性美泊利珠单抗治疗后，8 例（26.7%，95%CI：12.28-45.89）患者发生 4 级中性粒细胞减少症。8 例患者 ANC≤0.5×10/L，中位持续时间为 4.5 天；其中 6 例患者 ANC 水平的最低点出现在第 7 天，5 例患者在第 10 天恢复。没有报告化疗剂量减少、延迟或停止。21 例（70.0%）患者在治疗期间使用了抗生素。0-5 岁和 13-18 岁组各有 1 例患者发生 FN，6-12 岁组有 2 例患者发生 FN。0-5 岁、6-12 岁和 13-18 岁组的 4 级中性粒细胞减少症发生率分别为 2 例、6 例和无。