The pemetrexed-containing treatments in the non-small cell lung cancer is -/low thymidylate synthase expression better than +/high thymidylate synthase expression: a meta-analysis

BMC Cancer. 2014 Mar 19:14:205. doi: 10.1186/1471-2407-14-205.

Abstract

Background: The predictive value of thymidylate synthase (TS) for clinical sensitivity to pemetrexed-containing chemotherapy in patients with non-small cell lung cancer (NSCLC) remains controversial. This meta-analysis is performed to provide an assessment of whether expression variations of TS are associated with objective response in patients with NSCLC treated with pemetrexed-containing chemotherapy.

Methods: An electronic search was conducted using the databases MEDLINE, EMBASE and CNKI, from inception to June 10th, 2013. A systemic review of the studies on the association between TS expression in NSCLC and objective response of pemetrexed-containing regimen was performed. Pooled odds ratios (OR) for the response rate were calculated using the software Revman 5.0.

Results: There were a total of 526 patients in the eight studies that met our criteria for evaluation. +/high expression of TS was found in 269 patients (51.1%), and -/low expression for this gene was found in 257 (48.9%) patients. The objective response rate for pemetrexed-containing chemotherapy was significantly higher in patients with -/low expression TS expression (OR = 0.45; 95% CI, 0.29-0.70; p = 0.0004). Although patients with -/low expression of TS have a longer median overall survival time and progression free survival time than those with +/high expression of TS, the difference was not statistically significant.

Conclusions: -/low expression of TS was associated with higher objective response in NSCLC patients treated with pemetrexed-containing chemotherapy. TS may be a suitable marker of sensitivity to pemetrexed-based chemotherapy in patients with NSCLC.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use*
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Gene Expression Regulation, Neoplastic*
  • Glutamates / therapeutic use*
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / enzymology*
  • Pemetrexed
  • Thymidylate Synthase / biosynthesis*
  • Thymidylate Synthase / genetics*
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Glutamates
  • Pemetrexed
  • Guanine
  • Thymidylate Synthase