Document Detail

Risk factors for sorafenib-induced high-grade skin rash in Japanese patients with advanced renal cell carcinoma.
MedLine Citation:
PMID:  23237922     Owner:  NLM     Status:  MEDLINE    
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.
Norihiko Tsuchiya; Shintaro Narita; Takamitsu Inoue; Naoko Hasunuma; Kazuyuki Numakura; Yohei Horikawa; Shigeru Satoh; Takeshi Notoya; Naohito Fujishima; Shingo Hatakeyama; Chikara Ohyama; Tomonori Habuchi
Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  24     ISSN:  1473-5741     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-25     Completed Date:  2013-07-22     Revised Date:  2014-03-28    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  310-4     Citation Subset:  IM    
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MeSH Terms
Antineoplastic Agents / adverse effects*,  therapeutic use
Asian Continental Ancestry Group
Carcinoma, Renal Cell / drug therapy*,  genetics,  pathology
Cytochrome P-450 CYP3A / genetics
Dose-Response Relationship, Drug
Exanthema / chemically induced*
Glucuronosyltransferase / genetics
HLA-A24 Antigen / genetics*
Kidney Neoplasms / drug therapy*,  genetics,  pathology
Middle Aged
Multidrug Resistance-Associated Proteins / genetics*
Niacinamide / administration & dosage,  adverse effects,  analogs & derivatives*,  therapeutic use
P-Glycoprotein / genetics
Phenylurea Compounds / administration & dosage,  adverse effects*,  therapeutic use
Retrospective Studies
Reg. No./Substance:
0/ABCB1 protein, human; 0/Antineoplastic Agents; 0/HLA-A24 Antigen; 0/Multidrug Resistance-Associated Proteins; 0/P-Glycoprotein; 0/Phenylurea Compounds; 0/multidrug resistance-associated protein 2; 0/sorafenib; 25X51I8RD4/Niacinamide; EC protein, human; EC P-450 CYP3A; EC 2.4.1.-/UGT1A1 enzyme; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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