title: Reduced folate carrier (RFC) as a predictive marker for response to pemetrexed in advanced non-small cell lung cancer (NSCLC).
abstract: BACKGROUND
  RFC is the major transport system in mammalian cells for folate cofactors and antifolate therapeutics. The aim of this study was to assess the predictive value of RFC expression in patients receiving pemetrexed for advanced NSCLC.
  
  
  METHODS
  The study was carried out in a population of 48 patients with advanced NSCLC which have received pemetrexed monotherapy in second and third line. RFC expression was assessed using a two-step model of immunohistochemical staining in paraffin-embedded tissue samples.
  
  
  RESULTS
  RFC expression was detected in 16 (33 %) patients. In the global population, the median progression free survival (PFS) and the median overall survival (OS) were 3.3 and 6.5 months respectively. The subgroup of patients with expression of RFC had a tendency to better median PFS (4.5 vs 2.8 months; p = 0.926) and median OS (11.7 vs 4.8; p = 0.150). In patients with adenocarcinoma histology and RFC expression median OS after treatment with pemetrexed was 14.4 months versus 5.0 in those with adenocarcinoma but without RFC expression (p = 0.039).
  
  
  CONCLUSIONS
  These results suggest the possible relation between RFC expression and response to treatment with antifolates (pemetrexed) independently of the tumor histology. Further studies are required to confirm these results.
authors.affiliation: Department of Medical Oncology, Hospital Universitario Central de Asturias, Celestino Villamil s/n. 33006, Oviedo, Asturias, Spain, carlos.alvfer@gmail.com.
authors.forename: Carlos
authors.initials: C
authors.lastname: Alvarez-Fernandez
authors.forename: Quionia
authors.initials: Q
authors.lastname: Perez-Arnillas
authors.forename: Lucrecia
authors.initials: L
authors.lastname: Ruiz-Echeverria
authors.forename: David
authors.initials: D
authors.lastname: Rodriguez-Rubi
authors.forename: Luisa
authors.initials: L
authors.lastname: Sanchez-Lorenzo
authors.forename: Walter
authors.initials: W
authors.lastname: Li-Torres
authors.forename: Marta
authors.initials: M
authors.lastname: Izquierdo-Manuel
authors.forename: Jose P
authors.initials: JP
authors.lastname: Berros
authors.forename: Maria
authors.initials: M
authors.lastname: Luque-Cabal
authors.forename: Paula
authors.initials: P
authors.lastname: Jimenez-Fonseca
authors.forename: Noemi
authors.initials: N
authors.lastname: Villanueva-Palicio
authors.forename: Emilio
authors.initials: E
authors.lastname: Esteban-Gonzalez
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005971:Glutamates / Q000494:pharmacology / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D058978:Reduced Folate Carrier Protein / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005971:Glutamates; D058978:Reduced Folate Carrier Protein; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase
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