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- Title
Pharmacogenomic Assessment of Outcomes of Pemetrexed-Treated Patients with Adenocarcinoma of the Lung.
- Authors
Minkyu Jung; Chul Ho Lee; Hyung Soon Park; Ji Hyun Lee; Young Ae Kang; Se Kyu Kim; Joon Chang; Dae Joon Kim; Sun Young Rha; Joo Hang Kim; Byoung Chul Cho
- Abstract
Purpose: The main objective of this study was to evaluate the association between polymorphisms of the target genes of pemetrexed and clinical outcomes in non-small cell lung cancer (NSCLC) patients treated with pemetrexed. Materials and Methods: We assessed polymorphisms at 8 sites in 4 genes [thymidylate synthase (TS), dihydrofolate reductase (DHFR; 1610, 680, 317, intron 1), methylenetetrahydrofolate reductase (MTHFR; 677, 1298), glycinamide ribonucleotide formyl transferase (GARFT; 2255)] associated with pemetrexed metabolism using polymerase chain reaction, gene scanning, and restriction fragment length polymorphism analysis in 90 patients with adenocarcinoma of the lung. Results: Survival was significantly longer with pemetrexed in patients with TS 3RGCC/3RGCC or 3RGGC/3RGGC compared with the other groups (PFS; 5.2 months vs. 3.7 months, p=0.03: OS; 31.8 months vs. 18.5 months, p=0.001). Patients with DHFR 680CC experienced fatigue more frequently (50% vs. 8.6%, p=0.008). Polymorphisms of MTHFR and GARFT were not significantly associated with clinical outcomes of pemetrexed. Conclusion: The TS genotype was associated with survival and one DHFR polymorphism was associated with fatigue in NSCLC patients treated with pemetrexed. Further large prospective studies are required to identify other biomarkers that affect patients being treated with pemetrexed for adenocarcinoma of the lung.
- Subjects
LUNG cancer treatment; PHARMACOGENOMICS; HEALTH outcome assessment; ADENOCARCINOMA; GENETIC polymorphisms; POLYMERASE chain reaction
- Publication
Yonsei Medical Journal, 2013, Vol 54, Issue 4, p854
- ISSN
0513-5796
- Publication type
Article
- DOI
10.3349/ymj.2013.54.4.854