title: Semi-mechanistic model for neutropenia after high dose of chemotherapy in breast cancer patients.
abstract: OBJECTIVE
  To describe the absolute neutrophil counts (ANC) profile in breast cancer patients receiving high-dose of chemotherapy and peripheral blood stem-cells (PBSC) transplantation.
  
  
  METHODS
  Data from 41 subjects receiving cyclophosphamide, thiotepa and carboplatin were used to develop the ANC model consisting of a drug-sensitive progenitor cell compartment, linked to the peripheral blood compartment, through three transition compartments. PBSC were incorporated into the first transit compartment following a zero-order process, k(in), and the rebound effect was explained by a feedback mechanism. A 'kinetics of drug action' model was used to quantify the HDC effect on the progenitor cells according to a linear function, with a slope (alpha).
  
  
  RESULTS
  The typical of the ANC at baseline (Circ(0)), mean transit time (MTT), feedback parameter (gamma), k(in) and alpha were estimated to be 5,610 x 10(6)/L, 3.25 days, 0.145, 0.954 cell/kg/day and 2.50 h/U, respectively. rHuG-CSF shortens the MTT by 92% and increases the mitotic activity by 120%. Bootstrap analysis, visual predictive check and numerical predictive checks evidenced accurate prediction of the ANC nadir, time to ANC nadir and time to grade 4 neutropenia recovery.
  
  
  CONCLUSIONS
  The time course of neutropenia following high-dose of chemotherapy and PBSC transplantation was accurately predicted. Higher amount of CD34+ cells in the PBSC transplantation and earlier administration rHuG-CSF were associated with faster haematological recovery.
authors.affiliation: Pharmacy and Pharmaceutics Division, Department of Engineering, Miguel Hernandez University, San Juan de Alicante, Alicante, Spain.
authors.forename: Amelia
authors.initials: A
authors.lastname: Ramon-Lopez
authors.forename: Ricardo
authors.initials: R
authors.lastname: Nalda-Molina
authors.forename: Belen
authors.initials: B
authors.lastname: Valenzuela
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Perez-Ruixo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D009503:Neutropenia / Q000139:chemically induced*
chemical_list: D000970:Antineoplastic Agents