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.