Association of ABCB1 genotypes with paclitaxel-mediated peripheral neuropathy and neutropenia

Abstract

Here, we evaluated the relationships between ABCB1 (P-glycoprotein, MDR1) polymorphisms and paclitaxel (Taxol)-induced toxicity and pharmacokinetics. Twenty-six patients were assessable for pharmacogenetics and pharmacokinetics, 22 for neurotoxicity and 18 for myelotoxicity. Patients carrying two reference alleles for the ABCB1 3435C > T polymorphism trended toward a reduced risk to develop neuropathy as compared to patients carrying at least one variant allele (P = 0.09). Additionally, patients who were homozygous variant at the 2677 and 3435 loci had a significantly greater percent decrease in absolute neutrophil count at nadir (P = 0.02). Neither polymorphism correlated with paclitaxel pharmacokinetics. This pilot study suggests that paclitaxel-induced neuropathy and neutropenia might be linked to inherited variants of ABCB1 through a mechanism that is unrelated to altered plasma pharmacokinetics. © 2006 Elsevier Ltd. All rights reserved.