Improved Anti‐Emetic Efficacy of 5‐HT3 Receptor Antagonists in Cancer Patients with Genetic Polymorphisms of ABCB1 (MDR1) Drug Transporter. (6th November 2014)

• Record Type: Journal Article
• Authors: Zoto, Teuta; Kilickap, Saadettin; Yasar, Umit; Celik, Ismail; Bozkurt, Atilla; Babaoglu, Melih Onder
• Is Part Of: Basic & clinical pharmacology & toxicology. Volume 116:Number 4(2015:Apr.)
• Page Start: 354
• Page End: 360
• Publication Date: 2014-11-06
• Subjects: Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology -- Periodicals; Toxicology -- Periodicals; Pharmacology, Clinical -- Periodicals; Computer network resources; Electronic journals; 615.1
• DOI: 10.1111/bcpt.12334
• Languages: English
• ISSNs: 1742-7835

Abstract

<abstract abstract-type="main" id="bcpt12334-abs-0001"> <title>Abstract</title> <p>Chemotherapy‐induced nausea and vomiting (CINV) remains a major adverse effect decreasing quality of life in patients with cancer. Genetic variations among patients may be responsible for part of the lack of efficacy of anti‐emetic drugs. The aim of this study was to investigate how the genetic variants of the drug transporter <italic>ABCB1</italic> (<italic>MDR1)</italic> gene affect anti‐emetic treatment with 5‐HT<sub>3</sub> receptor antagonists. Patients (n = 239) receiving moderately or highly emetogenic chemotherapy and ondansetron or granisetron were included in the study. Anti‐emetic responses were recorded daily. The primary end‐point of the assessment was the total control rates of CINV in the acute and delayed phases after chemotherapy. Genotyping was performed by PCR‐RFLP. In the acute phase, patients with <italic>ABCB13435TT, 1236TT</italic> or <italic>2677TT</italic> genotypes had a higher control rate of CINV than other genotype groups: (64.7% in <italic>3435TT versus</italic> 45.7% in <italic>3435CC+CT, p</italic> = 0.016; 65.1% in <italic>1236TT versus</italic> 46.4% in <italic>1236CC+CT</italic>, <italic> p = </italic>0.027; 66.7% in <italic>2677TT versus</italic> 46.5% in other genotypes, <italic>p</italic> = 0.021). Subjects carrying homozygous variant alleles together (<italic>TT‐TT‐TT</italic>) showed a significantly higher protection from nausea and vomiting (67.7% in <italic>TT‐TT‐TT versus</italic> 47.1% in other genotypes, <italic>p</italic> = 0.032). After the logistic regression analysis with adjustment for other known covariates, the total control rate was significantly higher in the <italic>3435TT</italic> genotype group during the acute phase (<italic>p</italic> = 0.021). No significant change was found between the total control rates among genotypes in the delayed phase. Each of three <italic>3435TT, C1236TT, 2677TT</italic> genotypes of <italic>ABCB1</italic> and their combination was associated with about 50% higher anti‐emetic response to 5‐HT<sub>3</sub> receptor antagonists in the acute phase of chemotherapy in patients with cancer receiving moderately or highly emetogenic chemotherapy. <italic>ABCB1</italic> (<italic>MDR1</italic>) genotypes may contribute to predict the anti‐emetic efficacy of 5‐HT<sub>3</sub> antagonists.</p> </abstract>