The aim of this study was to evaluate the clinical factors, drug-related genetic polymorphisms, and human leukocyte antigen (HLA) types to determine the association with sorafenib-induced high-grade skin rash (HGSR) in Japanese patients with advanced renal cell carcinoma (RCC).
A total of 55 patients with advanced RCC treated with sorafenib were analyzed retrospectively. Of these, 33 patients were subjected to HLA typing and polymorphism analyses of CYP3A5, ABCB1, ABCC2, and UGT1A1, which are involved in the metabolism and membrane transport of sorafenib. Grade 3 or higher SR developed in 12 (22%), and a higher incidence was observed in female patients than in male patients (40 vs. 15%, P=0.046). The initial dose, initial dose per body weight, and initial dose per body surface area in patients with HGSR were significantly higher than those in patients without HGSR. Patients with the ABCC2 -24CC genotype were at a significantly higher risk of SR than those with the CT genotype (35 vs. 0%, P=0.032). HLA-A*24 was significantly associated with the occurrence of HGSR (P=0.049). Our finding suggested that women, higher initial dose per body weight or body surface area, the ABCC2 -24CC genotype, and HLA-A*24 are associated with the risk of sorafenib-induced HGSR in Japanese RCC patients.
Written by:
Tsuchiya N, Narita S, Inoue T, Hasunuma N, Numakura K, Horikawa Y, Satoh S, Notoya T, Fujishima N, Hatakeyama S, Ohyama C, Habuchi T. Are you the author?
Departments of Urology, Akita University Graduatae School of Medicine, Akita 010-8543, Japan.
Reference: Anticancer Drugs. 2013 Mar;24(3):310-4.
doi: 10.1097/CAD.0b013e32835c401c
PubMed Abstract
PMID: 23237922
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