Reduced folate carrier (RFC) as a predictive marker for response to pemetrexed in advanced non-small cell lung cancer (NSCLC)

Invest New Drugs. 2014 Apr;32(2):377-81. doi: 10.1007/s10637-013-9992-1. Epub 2013 Aug 4.

Abstract

Introduction: 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.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Female
  • Glutamates / pharmacology
  • Glutamates / therapeutic use*
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • Guanine / therapeutic use
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Male
  • Middle Aged
  • Pemetrexed
  • Reduced Folate Carrier Protein / metabolism*
  • Thymidylate Synthase / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Glutamates
  • Reduced Folate Carrier Protein
  • Pemetrexed
  • Guanine
  • Thymidylate Synthase