Association between ABCG2 and SLCO1B1 polymorphisms and adverse drug reactions to regorafenib: a preliminary study .

Abstract

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 <i>ABCG2</i> and <i>SLCO1B</i> genes are associated with adverse drug reactions to regorafenib. For these analyses, 37 Japanese cancer patients were treated with regorafenib, genotyped for polymorphisms in <i>ABCG2</i> and <i>SLCO1B</i>, and evaluated for drug-related adverse drug reactions. There was no association between the <i>ABCG2</i> 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 <i>SLCO1B1*1b</i> carriers and non-carriers, respectively. There were no significant associations between elevated ALT and bilirubin and the <i>SLCO1B1*1b</i> allele. However, there were significantly lower incidences of increased AST (8% vs. 42%) and anemia (16% vs. 50%) in <i>SLCO1B1*1b</i> carriers than in non-carriers. The absence of <i>SLCO1B1*1b</i> 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. .