Abstract:
:This exploratory retrospective study examined the effects of polymorphisms in transporter genes related to irinotecan pharmacokinetics and those in genes related to irinotecan pharmacodynamics on the efficacy of first-line combination chemotherapy with irinotecan, 5-fluorouracil, and folinic acid (leucovorin) (FOLFIRI) in Japanese patients with advanced colorectal cancer. All patients harbored UDP-glucuronosyltransferase (UGT) 1A1*1/*1, *1/*6, or *1/*28 genotypes, which are associated with similar irinotecan pharmacokinetics and responses to FOLFIRI. Genetic polymorphisms were analyzed by direct sequencing. Overall response rate and median progression-free survival in a total of 61 patients were 43% and 7.5 months, respectively. The overall response rate was higher in patients with the CC genotype at -24 in ATP-binding cassette, subfamily C, and member 2 (ABCC2) than in the others (p = 0.0313). Median progression-free survival was the longest in patients with CC at -24 in ABCC2, followed by those with CT and TT (p = 0.00910). A clear gene-dose effect was seen between -24C>T and median progression-free survival. No other polymorphisms tested were related to the efficacy of FOLFIRI. We thus found that the -24C>T polymorphism in the ABCC2 gene was significantly associated with the efficacy of first-line FOLFIRI in Japanese patients with advanced colorectal cancer.
journal_name
Drug Metab Pharmacokinetjournal_title
Drug metabolism and pharmacokineticsauthors
Akiyama Y,Fujita K,Ishida H,Sunakawa Y,Yamashita K,Kawara K,Miwa K,Saji S,Sasaki Ydoi
10.2133/dmpk.dmpk-11-rg-128subject
Has Abstractpub_date
2012-01-01 00:00:00pages
325-35issue
3eissn
1347-4367issn
1880-0920pii
JST.JSTAGE/dmpk/DMPK-11-RG-128journal_volume
27pub_type
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