Population Pharmacokinetic/Pharmacodynamic Modeling for the Time Course of Tumor Shrinkage by Motesanib in Thyroid Cancer Patients

To develop a population pharmacokinetic/pharmacodynamic model describing the relationship between motesanib exposure and tumor response in a phase 2 study of motesanib in patients with advanced differentiated thyroid cancer or medullary thyroid cancer.

Data from patients (n = 184) who received motesanib 125 mg once daily were used for population pharmacokinetic/pharmacodynamic modeling. Motesanib concentrations were fitted to a 2-compartment population pharmacokinetic model. Observed change in tumor size was the drug response measure for the pharmacodynamic model. Exposure measures in the pharmacokinetic/pharmacodynamic model included dose, plasma concentration profile, or steady-state area under the concentration versus time curve (AUC ss). A longitudinal exposure-tumor response model of drug effect on tumor growth dynamics was used.

Author(s): Jian‐Feng Lu, Laurent Claret, Liviawati Sutjandra, Mita Kuchimanchi, Rebeca Melara, Rene Bruno, Yi-Na Sun

Year: November 1, 2010