1. Association between ABCG2 and SLCO1B1 polymorphisms and adverse drug reactions to regorafenib: a preliminary study
- Author
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Makiko Kobara, Shigenori Kadowaki, Hitoshi Ando, Takashi Ura, Masahiro Aoki, Hiroya Taniguchi, Akimitsu Maeda, Mieko Maeda, Azusa Komori, Ayako Hasegawa, Naoya Hashimoto, Akiyoshi Mizutani, Eisaku Kondo, Masahide Matsuzaki, Masahiro Tajika, Kei Muro, Yasushi Kojima, and Akio Fujimura
- Subjects
Male ,Pharmacogenomic Variants ,Pyridines ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,Gene Frequency ,Japan ,Risk Factors ,ATP Binding Cassette Transporter, Subfamily G, Member 2 ,Pharmacology (medical) ,Prospective Studies ,media_common ,Aged, 80 and over ,Predictive marker ,biology ,Liver-Specific Organic Anion Transporter 1 ,Anemia ,Middle Aged ,Neoplasm Proteins ,Phenotype ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,Chemical and Drug Induced Liver Injury ,Adult ,Drug ,medicine.medical_specialty ,Bilirubin ,media_common.quotation_subject ,Antineoplastic Agents ,03 medical and health sciences ,Predictive Value of Tests ,Internal medicine ,Regorafenib ,medicine ,Humans ,Genetic Predisposition to Disease ,Increased total bilirubin ,Protein Kinase Inhibitors ,Aged ,Pharmacology ,Polymorphism, Genetic ,business.industry ,Phenylurea Compounds ,Cancer ,medicine.disease ,Pharmacogenomic Testing ,chemistry ,Pharmacogenetics ,biology.protein ,SLCO1B1 ,business - Abstract
OBJECTIVE Due to the occurrence of severe adverse drug reactions to regorafenib, a drug used in cancer therapy, the identification of a predictive marker(s) is needed to increase the therapeutic applicability of this compound. We therefore investigated whether polymorphisms in the ABCG2 and SLCO1B genes are associated with adverse drug reactions to regorafenib. METHODS For these analyses, 37 Japanese cancer patients were treated with regorafenib, genotyped for polymorphisms in ABCG2 and SLCO1B, and evaluated for drug-related adverse drug reactions. RESULTS There was no association between the ABCG2 421C>A variant and adverse drug reactions to regorafenib. After treatment, the incidences of increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as increased total bilirubin (grade ≥ 2) were 8%, 4%, and 12%, and 42%, 25%, and 25% among SLCO1B1*1b carriers and non-carriers, respectively. There were no significant associations between elevated ALT and bilirubin and the SLCO1B1*1b allele. However, there were significantly lower incidences of increased AST (8% vs. 42%) and anemia (16% vs. 50%) in SLCO1B1*1b carriers than in non-carriers. CONCLUSIONS The absence of SLCO1B1*1b allele appears to be associated with the development of adverse drug reactions to regorafenib; however, further studies involving larger test groups and other populations are needed to confirm these findings. .
- Published
- 2017
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