title: Influence of ABCB1 and ABCG2 polymorphisms on the antiemetic efficacy in patients with cancer receiving cisplatin-based chemotherapy: a TRIPLE pharmacogenomics study.
abstract: Resistance to antiemetic treatment with 5-hydroxytryptamine-3 receptor antagonist is an issue. This study evaluated the potential roles of ABCB1 and ABCG2 polymorphisms in antiemetic treatment resistance in patients with cancer previously enrolled in a randomized controlled trial. A total of 156 patients were evaluated for their responses to antiemetic therapy and then subdivided into granisetron or palonosetron groups. The genotypes were evaluated for their association with antiemetic efficacy in each treatment groups. Additional risk factors associated with complete response (CR) were examined using a multivariate regression analysis. No significant associations were identified for genetic polymorphisms in the palonosetron group. In the granisetron group, patients with ABCB1 2677TT and 3435TT genotypes had higher proportion of CR. In addition to ABCB1 polymorphisms, gender and cisplatin dose were associated with granisetron response by univariate analysis. Multivariate logistic regression analysis revealed that the ABCB1 3435C>T polymorphism and cisplatin dose were significant predictors of CR.
authors.affiliation: Department of Clinical Pharmacology &Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Tsuji
authors.affiliation: Department of Clinical Pharmacology &Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yokoi
authors.affiliation: Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Biostatistics, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Daimon
authors.affiliation: Department of Pharmacy, Osaka City General Hospital, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakao
authors.affiliation: Department of Pharmacy, Tokyo Medical University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ayuhara
authors.affiliation: Department of Pharmacy, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kogure
authors.affiliation: Department of Medical Oncology, Kouseiren Takaoka Hospital, Takaoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Department of Pharmacy, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Clinical Pharmacology &Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
authors.forename: K
authors.identifier: 0000-0001-8027-3508
authors.initials: K
authors.lastname: Hirai
authors.affiliation: Department of Clinical Pharmacology &Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hama
authors.affiliation: Department of Clinical Oncology, Osaka City General Hospital, Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nishio
authors.affiliation: Department of Clinical Pharmacology &Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Itoh
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D017829:Granisetron / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D000077924:Palonosetron; D000071185:Pharmacogenomic Testing; D020641:Polymorphism, Single Nucleotide; D011812:Quinuclidines / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000932:Antiemetics; D000970:Antineoplastic Agents; D002945:Cisplatin; D017829:Granisetron; D007546:Isoquinolines; D009363:Neoplasm Proteins; D000077924:Palonosetron; D011812:Quinuclidines; C513055:ABCB1 protein, human; C116614:ABCG2 protein, human