Association between ABCG2 and SLCO1B1 polymorphisms and adverse drug reactions to regorafenib: a preliminary study .
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 theABCG2andSLCO1Bgenes are associated with adverse drug reactions to regorafenib.


METHODS
For these analyses, 37 Japanese cancer patients were treated with regorafenib, genotyped for polymorphisms inABCG2andSLCO1B, and evaluated for drug-related adverse drug reactions.


RESULTS
There was no association between theABCG2421C>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% amongSLCO1B1*1bcarriers and non-carriers, respectively. There were no significant associations between elevated ALT and bilirubin and theSLCO1B1*1ballele. However, there were significantly lower incidences of increased AST (8% vs. 42%) and anemia (16% vs. 50%) inSLCO1B1*1bcarriers than in non-carriers.


CONCLUSIONS
The absence ofSLCO1B1*1ballele 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. .
Akimitsu
A
Maeda
Hitoshi
H
Ando
Takashi
T
Ura
Azusa
A
Komori
Ayako
A
Hasegawa
Hiroya
H
Taniguchi
Shigenori
S
Kadowaki
Kei
K
Muro
Masahiro
M
Tajika
Makiko
M
Kobara
Masahide
M
Matsuzaki
Naoya
N
Hashimoto
Mieko
M
Maeda
Yasushi
Y
Kojima
Masahiro
M
Aoki
Eisaku
E
Kondo
Akiyoshi
A
Mizutani
Akio
A
Fujimura
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis / Q000235:genetics*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D027381:Liver-Specific Organic Anion Transporter 1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010597:Pharmacogenetics; D000071185:Pharmacogenomic Testing / Q000379:methods; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D010671:Phenylurea Compounds / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D012307:Risk Factors
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000970:Antineoplastic Agents; D027381:Liver-Specific Organic Anion Transporter 1; D009363:Neoplasm Proteins; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C503999:SLCO1B1 protein, human; C559147:regorafenib