Severe Vincristine-induced Neuropathic Pain in a CYP3A5 Nonexpressor With Reduced CYP3A4/5 Activity: Case Study

Purpose: Peripheral neuropathy is a frequent vincristine-induced adverse effect. Vincristine is a substrate of P-glycoprotein and is metabolized by the cytochrome P-450 (CYP) 3A5 and 3A4 isoforms, with CYP3A5 contributing to 75% of the intrinsic clearance of vincristine. Alterations in the function of these proteins may lead to an increase in vincristine toxicity. CYP3A5 nonexpressor status has been associated with vincristine-induced peripheral neuropathy. The severity of neuropathy has been reported to be inversely correlated to vincristine metabolite concentrations. Recently, the presence of a mutation in the CEP72 gene, which encodes for a protein involved in microtubule formation, has also been associated with vincristine-induced peripheral neuropathy. However, a clear correlation between genetic polymorphisms and vincristine toxicity has not been established.

Methods: Here we report the case of a 21-year old patient in whom severe neuropathic pain developed after vincristine treatment.

Findings: The patient was a CYP3A5 nonexpressor and presented with reduced CYP3A4/5 functional activity, a likely reason for the occurrence of the adverse event, as genotyping showed that his status was wild type for the ABCB1 and CEP72 genes.

Implications: CYP phenotype and genotype may explain the occurrence of severe neuropathy in some patients treated with vincristine.