title: A pharmacokinetic study of lipegfilgrastim in children with Ewing family of tumors or rhabdomyosarcoma.
abstract: OBJECTIVE
  Neutropenia 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.
  
  
  METHODS
  Enrolled 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.
  
  
  RESULTS
  Twenty-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.
  
  
  CONCLUSIONS
  Results support the use of a body weight-adjusted dose to achieve equivalent initial peak exposure levels of lipegfilgrastim in children of various ages.
authors.affiliation: Pediatric Oncology and Hematology, City Clinical Hospital #31, 3 Dinamo Pr., St. Petersburg, Russian Federation, 197110. deton.hospital31@inbox.ru.
authors.forename: Margarita B
authors.initials: MB
authors.lastname: Belogurova
authors.affiliation: Department of Surgery, West Ukrainian Specialized Children's Medical Center, Lviv, Ukraine.
authors.forename: Zoryana P
authors.initials: ZP
authors.lastname: Kizyma
authors.affiliation: Unit of Solid Tumors, 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Garami
authors.affiliation: Unit of Solid Tumors, 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Mónika
authors.initials: M
authors.lastname: Csóka
authors.affiliation: Nuventra, Inc, Durham, NC, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lamson
authors.affiliation: Teva ratiopharm, Merckle GmbH, Ulm, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Buchner
authors.affiliation: Teva ratiopharm, Merckle GmbH, Ulm, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bias
authors.affiliation: Teva ratiopharm, Merckle GmbH, Ulm, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lammerich
mesh_terms: D000293:Adolescent; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012208:Rhabdomyosarcoma / Q000188:drug therapy*; D012512:Sarcoma, Ewing / Q000188:drug therapy*
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim
keywords: Chemotherapy; G-CSF; Neutropenia; Pediatric; Pharmacodynamics; Phase 1