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Improved Anti‐Emetic Efficacy of 5‐ HT 3 Receptor Antagonists in Cancer Patients with Genetic Polymorphisms of ABCB 1 ( MDR 1) Drug Transporter
Author(s) -
Zoto Teuta,
Kilickap Saadettin,
Yasar Umit,
Celik Ismail,
Bozkurt Atilla,
Babaoglu Melih Onder
Publication year - 2015
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12334
Subject(s) - ondansetron , nausea , vomiting , medicine , genotype , pharmacology , granisetron , chemotherapy induced nausea and vomiting , genotyping , palonosetron , gastroenterology , chemotherapy , pharmacogenetics , oncology , anesthesia , antiemetic , biology , gene , genetics
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 ABCB 1 ( MDR 1) gene affect anti‐emetic treatment with 5‐ HT 3 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 ABCB 13435 TT , 1236 TT or 2677 TT genotypes had a higher control rate of CINV than other genotype groups: (64.7% in 3435 TT versus 45.7% in 3435 CC + CT , p = 0.016; 65.1% in 1236 TT versus 46.4% in 1236 CC + CT , p = 0.027; 66.7% in 2677 TT versus 46.5% in other genotypes, p = 0.021). Subjects carrying homozygous variant alleles together ( TT ‐ TT ‐ TT ) showed a significantly higher protection from nausea and vomiting (67.7% in TT ‐ TT ‐ TT versus 47.1% in other genotypes, p = 0.032). After the logistic regression analysis with adjustment for other known covariates, the total control rate was significantly higher in the 3435 TT genotype group during the acute phase ( p = 0.021). No significant change was found between the total control rates among genotypes in the delayed phase. Each of three 3435 TT , C1236 TT , 2677 TT genotypes of ABCB 1 and their combination was associated with about 50% higher anti‐emetic response to 5‐ HT 3 receptor antagonists in the acute phase of chemotherapy in patients with cancer receiving moderately or highly emetogenic chemotherapy. ABCB 1 ( MDR 1 ) genotypes may contribute to predict the anti‐emetic efficacy of 5‐ HT 3 antagonists.