Sorafenib Population Pharmacokinetics and Skin Toxicities in Children and Adolescents with Refractory/Relapsed Leukemia or Solid Tumor Malignancies.

ABSTRACT:

Purpose

To determine the pharmacokinetics and skin toxicity profile of sorafenib in children with refractory/relapsed malignancies.

Patients and methods

Sorafenib was administered concurrently or sequentially with clofarabine and cytarabine to patients with leukemia or with bevacizumab and cyclophosphamide to patients with solid tumor malignancies. The population pharmacokinetics (PPK) of sorafenib and its metabolites and skin toxicities were evaluated.

Results

In PPK analysis, older age, bevacizumab and cyclophosphamide regimen, and higher creatinine were associated with decreased sorafenib apparent clearance (CL/f; P < 0.0001 for all), and concurrent clofarabine and cytarabine administration was associated with decreased sorafenib N-oxide CL/f (P = 7e-

SUBMITTER: Inaba H 

PROVIDER: S-EPMC6911639 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature