Title
|
|
|
|
Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed
| |
Author
|
|
|
|
| |
Abstract
|
|
|
|
Background: We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. Methods: Twenty-five patients treated with pemetrexed-based regimens were included. Genomic DNA was isolated prior to treatment. The variable number of tandem repeat (VNTR) polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3' untranslated region (UTR) polymorphisms were analyzed and correlated with overall response rate (ORR), progression-free survival (PFS), overall-survival (OS) and toxicity. Results: The genotype +6/+6 predicted a higher ORR among active/former smokers compared to +6/-6 genotype (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R genotype significantly correlated with a superior ORR in patients without EGFR activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%, 33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a trend towards a better PFS, although not significant, was found among subjects showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019). No significant correlation with the toxicity was observed. Conclusion: In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype. |
| |
Language
|
|
|
|
English
| |
Source (journal)
|
|
|
|
Journal of translational medicine. - London
| |
Publication
|
|
|
|
London
:
2014
| |
ISSN
|
|
|
|
1479-5876
| |
DOI
|
|
|
|
10.1186/1479-5876-12-98
| |
Volume/pages
|
|
|
|
12
(2014)
, 9 p.
| |
Article Reference
|
|
|
|
98
| |
ISI
|
|
|
|
000336928200001
| |
Medium
|
|
|
|
E-only publicatie
| |
Full text (Publisher's DOI)
|
|
|
|
| |
Full text (open access)
|
|
|
|
| |
|