title: Pharmacogenomic assessment of outcomes of pemetrexed-treated patients with adenocarcinoma of the lung.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
authors.forename: Minkyu
authors.initials: M
authors.lastname: Jung
authors.forename: Chul Ho
authors.initials: CH
authors.lastname: Lee
authors.forename: Hyung Soon
authors.initials: HS
authors.lastname: Park
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Kang
authors.forename: Se Kyu
authors.initials: SK
authors.lastname: Kim
authors.forename: Joon
authors.initials: J
authors.lastname: Chang
authors.forename: Dae Joon
authors.initials: DJ
authors.lastname: Kim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Joo Hang
authors.initials: JH
authors.lastname: Kim
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D005971:Glutamates / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D000068437:Pemetrexed; D010597:Pharmacogenetics; D051026:Phosphoribosylglycinamide Formyltransferase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; D051026:Phosphoribosylglycinamide Formyltransferase
keywords: Polymorphism; lung neoplasms; pemetrexed