首页 | 本学科首页   官方微博 | 高级检索  
按 检索        


<Emphasis Type="Italic">UDP-glucuronosyltransferase 1A1*6</Emphasis> and <Emphasis Type="Italic">*28</Emphasis> polymorphisms as indicators of initial dose level of irinotecan to reduce risk of neutropenia in patients receiving FOLFIRI for colorectal cancer
Authors:Yoshinori Miyata  Tetsuo Touyama  Takaya Kusumi  Yoshitaka Morita  Nobuyuki Mizunuma  Fumihiro Taniguchi  Mitsuaki Manabe
Institution:1.Department of Medical Oncology,Saku Central Hospital Advanced Care Center,Saku,Japan;2.Department of Surgery,Nakagami Hospital,Okinawa,Japan;3.Department of Surgery,Keiyukai Sapporo Hospital,Sapporo,Japan;4.Department of Radiology,National Hospital Organization Kobe Medical Center,Kobe,Japan;5.Department of Gastroenterology,Cancer Institute Hospital of Japanese Foundation for Cancer Research,Tokyo,Japan;6.Hepato-Pancreatic Surgery Division,Japanese Red Cross Kyoto Daiichi Hospital,Kyoto,Japan;7.Yakult Honsha Co., Ltd.,Tokyo,Japan
Abstract:

Background

Irinotecan (CPT-11)-induced neutropenia is associated with UDP-glucuronosyltransferase (UGT) 1A1*6 and *28 polymorphisms. This prospective study investigated whether using these polymorphisms to adjust the initial dose of CPT-11 as part of FOLFIRI treatment in colorectal cancer patients might improve safety.

Methods

All data were collected by a physician. The relationship between UGT1A1 polymorphisms and first-cycle neutropenia, reasons for treatment discontinuation, and time-to-treatment failure were evaluated. Multivariate analysis was used to assess the risk of neutropenia.

Results

A total of 795 patients were divided into wild-type (*1/*1) (50.1 %), heterozygous (*28/*1, *6/*1) (41.1 %), and homozygous (*28/*28, *6/*6, *28/*6) (8.which are associated with a decrease in the8 %) groups, in which the median starting dose of CPT-11 was 143.0, 143.0, and 115.0 mg/m2, respectively. First-cycle grade ≥3 neutropenia occurred in 17.3, 25.4, and 28.6 % of these patients, respectively. Multivariate analysis revealed that the incidence of grade ≥3 neutropenia was significantly greater in the heterozygous and homozygous groups than in the wild-type group odds ratio (OR) 1.67; 95 % confidence interval (CI) 1.16–2.42; p = 0.0060, and OR 2.22; 95 % CI 1.22–4.02; p = 0.0088, respectively]. Age (OR 1.77; 95 % CI 1.24–2.53; p = 0.0017), coelomic fluid (OR 1.84; 95 % CI 1.05–3.25; p = 0.0343), and non-reduction in starting dose (OR 1.53; 95 % CI 1.08–2.18; p = 0.0176) were also identified as significant risk factors.

Conclusion

The risk of neutropenia was higher in the heterozygous and homozygous groups at initiation of CPT-11 treatment. This suggests that when a reduction in dose is required in patients harboring two variant alleles, the decrease should be approximately 20 %.
Keywords:
本文献已被 SpringerLink 等数据库收录！
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号