Semi-Mechanistic Model for Neutropenia after High Dose of Chemotherapy in Breast Cancer Patients

Abstract

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.

Romiplostim Dose Response in Patients With Immune Thrombocytopenia

“…Two patients in the 10-µg/kg cohort and 1 patient in the 0.2-µg/kg and in the 0.4-µg/kg cohorts received a single dose of romiplostim. Predose platelet counts were obtained on days -8 and -2 and on days 1, 3,5,8,10,12,15,17,19,22,24,26,29,32,36,43,50, and 64 postdose. Different patients were enrolled in parts A and B.…”

“…Patients subsequently received 2 doses of 30, 100, 300, or 500 µg of romiplostim. Platelet counts were obtained at baseline on days -8 and -2 and on days 1, 3, 5, 8, 10,12,15,17,19,22,24,26,29,32,36,43,50,64, and 78 after romiplostim administration.…”

A simultaneous analysis of the time-course of leukocytes and neutrophils following docetaxel administration using a semi-mechanistic myelosuppression model

“…Proposed alterations of the model structure include a log-linear drug effect model instead of a linear or Emax model [10], an addition of an effect delay compartment to account for the distribution of drug from the plasma to the bone marrow [10] and an addition of a neutrophil pool to describe an early increase of neutrophil count after dosage [20]. The model has further been extended to describe the combined drug effect following combination therapy of anticancer drugs [13,17,18,[21][22][23][24], to incorporate the effect of administrated exogenous G-CSF [22,25,26] and to capture the time-course of neutrophils following peripheral blood stem-cell transplantation [26]. Additionally covariates [6,9,10,20,[27][28][29][30] and inter-occasion variability [16] have been explored using the model.…”

Pharmacokinetic–pharmacodynamic modelling of neutrophil response to G‐CSF in healthy subjects and patients with chemotherapy‐induced neutropenia

“…The ANC dynamics component of the model was represented by a catenary chain of four compartments to mimic the production and maturation of neutrophils in the bone marrow . The receptors were tracked through the production, maturation and turnover of neutrophils, which were represented by stem cells ( R SM ), cells undergoing mitosis ( R MT ) and the two precursor states in the bone marrow ( R PM 1 and R PM 2 ).…”