title: Risk factors for sorafenib-induced high-grade skin rash in Japanese patients with advanced renal cell carcinoma.
abstract: 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.
authors.affiliation: Departments of Urology, Akita University Graduatae School of Medicine, Akita 010-8543, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Shintaro
authors.initials: S
authors.lastname: Narita
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inoue
authors.forename: Naoko
authors.initials: N
authors.lastname: Hasunuma
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Numakura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satoh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Notoya
authors.forename: Naohito
authors.initials: N
authors.lastname: Fujishima
authors.forename: Shingo
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D044466:Asian People; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005076:Exanthema / Q000139:chemically induced*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics; D059871:HLA-A24 Antigen / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D000077157:Sorafenib; D000099148:UGT1A1 Enzyme
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D051544:Cytochrome P-450 CYP3A; D014453:Glucuronosyltransferase; D059871:HLA-A24 Antigen; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009536:Niacinamide; D010671:Phenylurea Compounds; D000077157:Sorafenib; D000099148:UGT1A1 Enzyme; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C510164:CYP3A5 protein, human