The role of thymidylate synthase in non-small cell lung cancer treated with pemetrexed continuation maintenance therapy

J Chemother. 2017 Apr;29(2):106-112. doi: 10.1080/1120009X.2016.1254940. Epub 2016 Nov 21.

Abstract

Pemetrexed continuation maintenance therapy has been proven to be beneficial for patients with advanced non-squamous non-small cell lung cancer (NSCLC). However, the eligibility criteria for maintenance treatment are too simple. This study sought to evaluate thymidylate synthase (TS) as a predicting biomarker for pemetrexed continuation maintenance treatment in NSCLC. Specimens were collected from 87 patients treated with pemetrexed continuation maintenance therapy before and after four-cycle induction chemotherapy. Real-time quantitative PCR was used to detect TS expression in tissues. The TS expression level was correlated with characteristic clinical data, radiographic response, progression-free time (PFS) and overall survival (OS). Low total TS expression (<8.47) was associated with improved PFS (median: 4.7 months vs. 3.5 months, p = 0.034) and improved OS (time from random assignment: 16.4 months vs. 11.7 months, p = 0.026; time from induction: 19.7 months vs. 14.8 months, p = 0.022). Our results indicate that in NSCLC patients treated with pemetrexed continuation maintenance therapy, low TS expression is associated with improved PFS and OS.

Keywords: Continuation maintenance treatment; Non-small cell lung cancer; Pemetrexed; Thymidylate synthase.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cetuximab / administration & dosage
  • Cisplatin / administration & dosage
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Irinotecan
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / secondary
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Pemetrexed / administration & dosage
  • Phenylurea Compounds / administration & dosage
  • Prognosis
  • Pyridines / administration & dosage
  • Retrospective Studies
  • Survival Rate
  • Thymidylate Synthase / metabolism*

Substances

  • Biomarkers, Tumor
  • Organoplatinum Compounds
  • Phenylurea Compounds
  • Pyridines
  • Pemetrexed
  • Oxaliplatin
  • regorafenib
  • Irinotecan
  • Thymidylate Synthase
  • Cetuximab
  • Cisplatin
  • Camptothecin