title: Phase I study of the tolerability and pharmacokinetics of palifermin in children undergoing allogeneic hematopoietic stem cell transplantation.
abstract: The maximum tolerated dose of palifermin, a keratinocyte growth factor, in children is not known, and its pharmacokinetics in this population has not been well studied. This is a phase I study of palifermin was designed to evaluate its tolerability at doses of 40, 60, and 90 μg/kg/day in children age 2-18 years of age, receiving a myeloablative preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT). In each cohort, palifermin was given for 3 consecutive days before the preparative regimen and for 3 days after the stem cell infusion. Twelve patients were enrolled. Palifermin 90 μg/kg/day was tolerated in 6 patients without dose-limiting toxicity. All patients had at least 1 adverse event, mostly National Cancer Institute grade 1 or 2 severity. Skin rash, grade 2 or lower, was the most common adverse event, seen in 67% of patients. Only 3 patients (25%) had mucositis. The area under the concentration-time curve increased proportionally to the dose, and approximately 97% of palifermin exposure occurred in the first 24 hours after administration. Palifermin clearance increased linearly with body weight, supporting dosing by body weight. The mean clearance was 1893 mL/hour/kg, and it did not change significantly between administration of the first and last doses (P = .80). The mean elimination half-life was 4.6 hours. Our data show that palifermin was tolerated at a dose of 90 μg/kg/day, and exhibits linear pharmacokinetics in children undergoing allogeneic HSCT.
authors.affiliation: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. ashok.srinivasan@stjude.org
authors.forename: Ashok
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kasow
authors.forename: Shane
authors.initials: S
authors.lastname: Cross
authors.forename: Melissa
authors.initials: M
authors.lastname: Parrish
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.forename: Deo K
authors.initials: DK
authors.lastname: Srivastava
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Cai
authors.forename: John C
authors.initials: JC
authors.lastname: Panetta
authors.forename: Wing
authors.initials: W
authors.lastname: Leung
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019337:Hematologic Neoplasms / Q000378:metabolism* / Q000601:surgery / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D011446:Prospective Studies; D014184:Transplantation, Homologous
chemical_list: D051523:Fibroblast Growth Factor 7