Does pharmacogenomics account for variability in control of acute chemotherapy-induced nausea and vomiting with 5-hydroxytryptamine type 3 receptor antagonists?

Abstract

Chemotherapy-induced nausea and vomiting is one of the most concerning adverse drug effects from cytotoxic chemotherapy. Despite appropriate use of antiemetic guidelines, 20-30 % of patients experience breakthrough nausea and vomiting secondary to chemotherapy. To assess the variability of 5-hydroxytryptamine type 3 receptor antagonist efficacy caused by genetic variation, a review of the available literature was conducted. From the literature, three sources of pharmacogenomic variability were identified: polymorphisms associated with 5-hydroxytryptamine type 3 receptor subunits, drug metabolism via cytochromes P450, and drug transport in the body. Testing for receptor subunit polymorphisms is not applicable to a clinical setting at this time; however, cytochrome P450 2D6 testing is FDA-approved and widely accessible. Cytochrome P450 2D6 ultrarapid metabolizers and poor metabolizers displayed altered antiemetic efficacy when compared with intermediate metabolizers and extensive metabolizers. We postulate that testing for cytochrome P450 2D6 phenotypes may be the most accessible way to provide individualized antiemetic therapy in the future.

Conflict of interest statement

Conflict of Interest

Morgan Trammel declares no conflict of interest.

Mary Roederer declares no conflict of interest.

Jai Patel declares no conflict of interest.

Howard McLeod declares no conflict of interest.

Figures

Fig. 1

An individualized antiemetic treatment algorithm using the cytochrome P450 (CYP) 2D6 genotype. An example of an enhanced drug treatment algorithm designed for individualized emetic prophylaxis for patients requiring 5-hydroxytryptamine type 3 receptor antagonists (5HT3-RAs). This algorithm suggests performing CYP2D6 genotyping on patients after their diagnosis and the decision to use chemotherapy agents that require 5HT3-RAs. The timing of the genotyping would differ on the basis of institutional ability to do in-house genotyping or the use of a clinical laboratory network. Variations on this algorithm could also include genotyping at diagnosis. ASCO American Society of Clinical Oncology, EM extensive metabolizer, ESMO European Society of Medical Oncology, IM intermediate metabolizer, MASCC Multinational Association of Supportive Care in Cancer, NCCN National Comprehensive Cancer Network, NK1-RA neurokinin 1 receptor antagonist, PM poor metabolizer, UM ultrarapid metabolizer,