Associations among regorafenib concentrations, severe adverse reactions, and ABCG2 and OATP1B1 polymorphisms.

Abstract

PURPOSE:

The ability of predicting severe adverse reactions caused by regorafenib is important. We evaluated regorafenib concentrations for adverse reaction risks and assessed the relevance of laboratory values and gene polymorphisms.

METHODS:

A total of 28 Japanese cancer patients who were treated with regorafenib were evaluated for the steady state of serum regorafenib concentrations and adverse reactions for 28 days. In addition, we determined the association of regorafenib concentrations with ABCG2 and OATP1B1 polymorphisms, which are regorafenib transporters.

RESULTS:

Regorafenib concentrations were significantly higher in the group with Grade 2 or higher total bilirubin elevation and thrombocytopenia compared with the group with grades 0 or 1 [3.45 (2.18-7.31) vs. 1.76 (0.26-2.77) µg/mL, P = 0.01 and 3.45 (2.12-7.31) vs. 1.76 (0.26-2.77) µg/mL, P = 0.02, respectively]. A strong association was noted between serum regorafenib concentrations and total bilirubin levels, but the physical and genetic factors predicting regorafenib pharmacokinetics could not be clarified.

CONCLUSIONS:

Regorafenib concentrations were associated with total bilirubin elevation and thrombocytopenia. Total serum bilirubin could be a useful marker when estimating regorafenib pharmacokinetics.

• Authors: Akimitsu Maeda, Kei Irie, Hitoshi Ando, Ayako Hasegawa, Hiroya Taniguchi, Shigenori Kadowaki, Kei Muro, Masahiro Tajika, Masahiro Aoki, Kazuhide Inaguma, Masaki Kajita, Akio Fujimura, Shoji Fukushima
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 83 Issue 1 Pg. 107-113 (01 2019) ISSN: 1432-0843 [Electronic] Germany
• PMID: 30368586 (Publication Type: Journal Article, Observational Study)

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• Liver-Specific Organic Anion Transporter 1
• Neoplasm Proteins
• Phenylurea Compounds
• Pyridines
• SLCO1B1 protein, human
• regorafenib

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2 (genetics)
• Adult
• Aged
• Aged, 80 and over
• Colonic Neoplasms (drug therapy, genetics, pathology)
• Female
• Follow-Up Studies
• Gastrointestinal Neoplasms (drug therapy, genetics, pathology)
• Gastrointestinal Stromal Tumors (drug therapy, genetics, pathology)
• Genotype
• Humans
• Liver-Specific Organic Anion Transporter 1 (genetics)
• Male
• Middle Aged
• Neoplasm Proteins (genetics)
• Phenylurea Compounds (adverse effects, blood)
• Polymorphism, Genetic
• Prognosis
• Prospective Studies
• Pyridines (adverse effects, blood)