Additive effects of drug transporter genetic polymorphisms on irinotecan pharmacokinetics/pharmacodynamics in Japanese cancer patients

来自 EBSCO

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作者：

K Sai，Y Saito，K Maekawa，SR Kim，N Kaniwa，T Nishimaki-Mogami，JI Sawada，K Shirao，T Hamaguchi，N Yamamoto

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摘要：

Purpose Effects of genetic polymorphisms/variations of ABCB1 , ABCC2 , ABCG2 and SLCO1B1 in addition to " UGT1A1 *28 or *6 " on irinotecan pharmacokinetics/pharmacodynamics in Japanese cancer patients were investigated. Methods Associations between transporter haplotypes/variations along with UGT1A1 *28 or *6 and SN-38 area under the time–concentration curve (AUC) or neutropenia were examined in irinotecan monotherapy (55 patients) and irinotecan–cisplatin-combination therapy (62 patients). Results Higher SN-38 AUC values were observed in ABCB1 2677G>T (A893S) ( *2 group) for both regimens. Associations of grade 3/4 neutropenia were observed with ABCC2 1774delG ( *1A ), ABCG2 421C>A (Q141K) and IVS12+49G>T ( # IIB ) and SLCO1B1 521T>C (V174A) ( *15 · 17 ) in the irinotecan monotherapy, while they were evident only in homozygotes of ABCB1 *2 , ABCG2 # IIB , SLCO1B1*15 · 17 in the cisplatin-combination therapy. With combinations of haplotypes/variations of two or more genes, neutropenia incidence increased, but their prediction power for grade 3/4 neutropenia is still unsatisfactory. Conclusions Certain transporter genotypes additively increased irinotecan-induced neutropenia, but their clinical importance should be further elucidated.

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关键词：

Irinotecan Transporter Genetic polymorphism Haplotype

DOI：

10.1007/s00280-009-1138-y

被引量：

315

年份：

2010