Ondansetron serum concentration and polymorphisms of CYP2D6, ABCB1 and 5-HT3B receptor genes in the treatment of chemoterapy induced nausea and vomiting

Abstract

This study was aimed to understand differences of ondansetron serum concentration
in each antiemetic responses, polymorphisms of 5HT3B receptor, CYP2D6 and ABCB1
genes in Indonesian cancer patients treated with high emetogenic cytostatics. We recruited
cancer patients in Dr Sardjito Hospital treated with cisplatin (≥ 50 mg/m 2) as monotherapy
or combination therapy. Patients were treated with ondansetron 8 mg intravenously and
dexamethasone 8 mg intravenously and metoclopramide (10 mg orally) after cytostatic
administration until 5 days after chemotherapy. We cathegorized the nausea and vomiting
grade according to the National Cancer Institute Common Toxicity Criteria v.3. We also
determined some SNPs of ABCB1, 5HT3B and CYP2D6 genes using realtime PCR. We
recruited 191 cancer patients in this study with the average of ondansetron serum
concentration reached 33.48 ng/ml (SD: 18.54). According to the patients’ response to
the antiemetic, during the acute phase, 21.8% patients experienced acute nausea and
30.2% patients experienced acute vomiting. Only the haplotype of CTG-CTG of ABCB1
which have significant association with ondansetron serum concentration. EM patients of
CYP2D6 and patients with haplotype of delAG of 5HT3B had lower ondansetron serum
concentration. However, IM patients of CYP2D6 showed higher ondansetron serum
concentration and lower grade of nausea and vomiting. Variations of ABCB1, CYP2D6
and 5HT3B may be used as pharmacogenetic marker in predicting antiemetic response in
cancer patients receiving highly emetogenic cytostatic.