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

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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.

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Sissung, T. M., Mross, K., Steinberg, S. M., Behringer, D., Figg, W. D., Sparreboom, A., & Mielke, S. (2006). Association of ABCB1 genotypes with paclitaxel-mediated peripheral neuropathy and neutropenia. European Journal of Cancer, 42(17), 2893–2896. https://doi.org/10.1016/j.ejca.2006.06.017

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