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.

Figures

Fig 1

Association between risk of peripheral neuropathy and ABCB1 3435C>T genotype status in 22 patients. CC - ABCB1 3435-CC genotype; CT - ABCB1 3435-CT genotype; TT - ABCB1 3435- TT genotype. The P value was obtained from an exact two-tailed log rank test.

Fig 2

Association between ANC and ABCB1 2677G>T and 3435C>T genotype status in 18 patients. Non double variants - for both ABCB1 2677G>T and ABCB1 3435C>T alleles; Double variants - for both ABCB1 2677G>T and ABCB1 3435C>T alleles. The unadjusted P value was 0.0025.