Risk factors for sorafenib-induced high-grade skin rash in Japanese patients with advanced renal cell carcinoma

• Published in: Anti-cancer drugs Vol. 24; no. 3; p. 310
• Main Authors: Tsuchiya, Norihiko, Narita, Shintaro, Inoue, Takamitsu, Hasunuma, Naoko, Numakura, Kazuyuki, Horikawa, Yohei, Satoh, Shigeru, Notoya, Takeshi, Fujishima, Naohito, Hatakeyama, Shingo, Ohyama, Chikara, Habuchi, Tomonori
• Format: Journal Article
• Language: English
• Published: England 01.03.2013
• Subjects: Aged; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Asian Continental Ancestry Group; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Cytochrome P-450 CYP3A - genetics; Dose-Response Relationship, Drug; Exanthema - chemically induced; Female; Glucuronosyltransferase - genetics; HLA-A24 Antigen - genetics; Humans; Kidney Neoplasms - drug therapy; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Male; Middle Aged; Multidrug Resistance-Associated Proteins - genetics; Niacinamide - administration & dosage; Niacinamide - adverse effects; Niacinamide - analogs & derivatives; Niacinamide - therapeutic use; Phenylurea Compounds - administration & dosage; Phenylurea Compounds - adverse effects; Phenylurea Compounds - therapeutic use; Retrospective Studies
• ISSN: 1473-5741
• DOI: 10.1097/CAD.0b013e32835c401c

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.