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Quantification of Radiation Injury on Neutropenia and the Link between Absolute Neutrophil Count Time Course and Overall Survival in Nonhuman Primates Treated with G-CSF.
Harrold, John; Gisleskog, Per Olsson; Delor, Isabelle; Jacqmin, Philippe; Perez-Ruixo, Juan Jose; Narayanan, Adimoolam; Doshi, Sameer; Chow, Andrew; Yang, Bing-Bing; Melhem, Murad.
Afiliación
  • Harrold J; Department of Clinical Pharmacology, Modeling and Simulation, Amgen Inc., Thousand Oaks, California, USA.
  • Gisleskog PO; Seattle Genetics, Bothell Washington, Massachusetts, USA.
  • Delor I; SGS Exprimo NV, Mechelen, Belgium.
  • Jacqmin P; POG Pharmacometrics, Hampshire, UK.
  • Perez-Ruixo JJ; SGS Exprimo NV, Mechelen, Belgium.
  • Narayanan A; SGS Exprimo NV, Mechelen, Belgium.
  • Doshi S; Department of Clinical Pharmacology, Modeling and Simulation, Amgen Inc., Thousand Oaks, California, USA.
  • Chow A; Janssen Research & Development, Valencia, Spain.
  • Yang BB; Department of Clinical Pharmacology, Modeling and Simulation, Amgen Inc., Thousand Oaks, California, USA.
  • Melhem M; Department of Clinical Pharmacology, Modeling and Simulation, Amgen Inc., Thousand Oaks, California, USA.
Pharm Res ; 37(6): 102, 2020 May 21.
Article en En | MEDLINE | ID: mdl-32440783
PURPOSE: To model absolute neutrophil count (ANC) suppression in response to acute radiation (AR) exposure and evaluate ANC time course as a predictor of overall survival (OS) in response to AR exposure with or without treatment with granulocyte colony-stimulating factor in nonhuman primates. METHODS: Source data were obtained from two pivotal studies conducted in rhesus macaques exposed to 750 cGy of whole body irradiation on day 0 that received either placebo, daily filgrastim, or pegfilgrastim (days 1 and 8 after irradiation). Animals were observed for 60 days with ANC measured every 1 to 2 days. The population model of ANC response to AR and the link between observed ANC time course and OS consisted of three submodels characterizing injury due to radiation, granulopoiesis, and a time-to-event model of OS. RESULTS: The ANC response model accurately described the effects of AR exposure on the duration of neutropenia. ANC was a valid surrogate for survival because it explained 76% (95% CI, 41%-97%) and 73.2% (95% CI, 38.7%-99.9%) of the treatment effect for filgrastim and pegfilgrastim, respectively. CONCLUSION: The current model linking radiation injury to neutropenia and ANC time course to OS can be used as a basis for translating these effects to humans.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Traumatismos Experimentales por Radiación / Filgrastim / Modelos Biológicos / Neutropenia / Neutrófilos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Pharm Res Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polietilenglicoles / Traumatismos Experimentales por Radiación / Filgrastim / Modelos Biológicos / Neutropenia / Neutrófilos Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Pharm Res Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos