Abstract

PurposeNeutropenia is a common complication from chemotherapy, limiting optimal dosing and treatment. Lipegfilgrastim is a long-acting granulocyte colony-stimulating factor developed for the management of chemotherapy-induced neutropenia. The objectives of this phase 1, multinational, open-label, single-arm study were to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a single body weight-adjusted dose of lipegfilgrastim and to evaluate the efficacy, safety, and tolerability of the drug in children with Ewing family of tumors or rhabdomyosarcoma treated with myelosuppressive chemotherapy.MethodsEnrolled patients received lipegfilgrastim (100 µg/kg) 24 h after the last chemotherapy treatment in week 1. Patients were stratified into three age groups: 2 to <6, 6 to <12, and 12 to <18 years. Blood samples for PK analyses were obtained at baseline and at 3, 8, 24, 30, 48, 72, 96, 144, and 240 h postdose for the two oldest groups and up to 144 h in the youngest group.ResultsTwenty-one patients were enrolled and received lipegfilgrastim, seven in each age group. Lipegfilgrastim exposure levels were comparable across age groups, with concentrations maintained over a prolonged period after a single injection. Differences in PD were mainly associated with chemotherapy type. Most investigator-reported adverse events were attributed to chemotherapy and not to lipegfilgrastim. Severe adverse events were noted in 57% of patients; febrile neutropenia, leukopenia, neutropenia, and thrombocytopenia were more frequent among the oldest patients.ConclusionsResults support the use of a body weight-adjusted dose to achieve equivalent initial peak exposure levels of lipegfilgrastim in children of various ages.

Highlights

  • Dose-intensive chemotherapy provides substantial clinical benefit for pediatric patients with nonmetastatic sarcomas, as shown by studies indicating that the intensity of chemotherapy is correlated with improved outcomes [1]

  • The objectives of this study were to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a single body weight-adjusted dose (100 μg/kg) of lipegfilgrastim administered as a subcutaneous injection and to evaluate the efficacy, safety, and tolerability of the drug in children with Ewing family of tumors or rhabdomyosarcoma treated with myelosuppressive chemotherapy

  • Twenty-three pediatric patients with Ewing family of tumors or rhabdomyosarcoma scheduled to receive chemotherapy were screened for eligibility; 21 patients at 11 study centers in five countries (Czech Republic, Hungary, Poland, Russia, and Ukraine) met all inclusion criteria and were enrolled

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Summary

Introduction

Dose-intensive chemotherapy provides substantial clinical benefit for pediatric patients with nonmetastatic sarcomas, as shown by studies indicating that the intensity of chemotherapy is correlated with improved outcomes [1]. Granulocyte colony-stimulating factor (G-CSF) is routinely administered to adults and children to counter dose-limiting effects of chemotherapy. Pegfilgrastim (Neulasta, Amgen Inc., USA), a human recombinant G-CSF conjugated at the N terminus to a single 20-kDa polyethylene glycol (PEG) molecule, is administered to adults as a single injection after each cycle of cytotoxic chemotherapy but has not been approved for children [6]. Prospective, randomized studies have shown that the efficacy and safety of pegfilgrastim are similar to those of filgrastim among pediatric patients with sarcoma, without evidence for differences in the pharmacologic properties between adults and children [7–10]

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