Adaptive dosing approaches to the individualization of 13-cis-retinoic acid (isotretinoin) treatment for children with high-risk neuroblastoma.

ABSTRACT:

Purpose

To investigate the feasibility of adaptive dosing and the impact of pharmacogenetic variation on 13-cis-retinoic acid (13-cisRA) disposition in high-risk patients with neuroblastoma.

Experimental design

13-cisRA (160 mg/m(2) or 5.33 mg/kg/d) was administered to 103 patients ages 21 years or less and plasma concentrations of 13-cisRA and 4-oxo-13-cisRA quantitated on day 14 of treatment. Seventy-one patients were recruited to a dose adjustment group, targeting a 13-cisRA C(max) of 2 μmol/L, with dose increases of 25% to 50% implemented for patients with C(max) values less than 2 μmol/L. A population pharmacokinetic model was applied and polymorphisms in relevant cytochrome P450 genes analyzed.

Results

13-cisRA C(max) values ranged from 0.42 to 11.2 μmol/L, with

SUBMITTER: Veal GJ 

PROVIDER: S-EPMC3548903 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature