Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics.

ABSTRACT:

Purpose

We aim to identify genetic variation, in addition to the UGT1A1*28 polymorphism, that can explain the variability in irinotecan (CPT-11) pharmacokinetics and neutropenia in cancer patients.

Patients and methods

Pharmacokinetic, genetic, and clinical data were obtained from 85 advanced cancer patients treated with single-agent CPT-11 every 3 weeks at doses of 300 mg/m(2) (n = 20) and 350 mg/m(2) (n = 65). Forty-two common variants were genotyped in 12 candidate genes of the CPT-11 pathway using several methodologies. Univariate and multivariate models of absolute neutrophil count (ANC) nadir and pharmacokinetic parameters were evaluated.

Results

Almost 50% of the variation in ANC nadir is explained by UGT1A1*93, ABCC1 IVS11 -48C>T, SLCO1B1*1b, ANC baseline leve

SUBMITTER: Innocenti F 

PROVIDER: S-EPMC2690389 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature