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01-01-2015 | Original Article

Association of ABCG2 polymorphism with clinical efficacy of imatinib in patients with gastrointestinal stromal tumor

Authors: Dong-Hoe Koo, Min-Hee Ryu, Baek-Yeol Ryoo, Mo Youl Beck, Young-Soon Na, Jae-Gook Shin, Sang Seop Lee, Eun-Young Kim, Yoon-Koo Kang

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2015

Abstract

Purpose

Imatinib is a substrate of drug transporters and metabolizing enzymes, including members of the cytochrome P450 (CYP) system. Differences in imatinib pharmacokinetics among individuals might be influenced by genetic polymorphisms and be associated with variable clinical imatinib efficacy. This study sought to test how genetic polymorphisms can affect the clinical efficacy of imatinib and its blood levels in GIST patients.

Methods

A total of 209 GIST patients who had received imatinib 400 mg daily were genotyped for six single-nucleotide polymorphisms in three genes (CYP3A5 6986A>G; ABCB1 1236C>T, 2677G>A/T, and 3435C>T; and ABCG2 34G>A and 421C>A) via blood samples. Progression-free survival (PFS) and imatinib plasma trough levels were evaluated and compared according to genotypes.

Results

With a median follow-up of 39.6 months (range 16.7–97.5 months), the estimated 5-year PFS rate was 67.5 % (95 % CI 59.9–75.1). Among the CYP3A5, ABCB1, and ABCG2 genotypes, ABCG2 421C>A was associated with PFS. The 5-year PFS rate in patients with the AA variant of ABCG2 421C>A (92.3 %; 95 % CI 77.8–100.0) was significantly superior to that of patients with CC/CA genotypes (65.0 %; 95 % CI 56.9–73.1; p = 0.047). For the imatinib trough levels, there were no statistically significant differences when comparing polymorphisms among all genotypes, even after adjusting for clinical factors, including sex, age, body surface area, hemoglobin, albumin, and creatinine clearance.

Conclusions

The ABCG2 421C>A genetic variation could influence clinical efficacy in terms of PFS in patients with advanced GIST undergoing imatinib therapy.

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Title: Association of ABCG2 polymorphism with clinical efficacy of imatinib in patients with gastrointestinal stromal tumor
Authors: Dong-Hoe Koo
Min-Hee Ryu
Baek-Yeol Ryoo
Mo Youl Beck
Young-Soon Na
Jae-Gook Shin
Sang Seop Lee
Eun-Young Kim
Yoon-Koo Kang
Publication date: 01-01-2015
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2630-6

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