Early neutrophil-to-lymphocyte ratio reduction as a surrogate marker of prognosis in never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as first-line therapy

J Cancer Res Clin Oncol. 2012 Dec;138(12):2009-16. doi: 10.1007/s00432-012-1281-4. Epub 2012 Jul 7.

Abstract

Purpose: An inflammatory-immunological marker, neutrophil-to-lymphocyte ratio (NLR), was evaluated as a surrogate indicator for prognosis of advanced lung adenocarcinoma patients.

Methods: The subjects of this study were 199 never smokers with advanced lung adenocarcinoma, who were enrolled in a prospective randomized phase III study (First-SIGNAL) comparing gefitinib with gemcitabine plus cisplatin as first-line therapy. The values of NLR were assessed at two time points: at baseline (pretreatment) and on day 1 of the second cycle (posttreatment).

Results: A higher posttreatment NLR was associated with a worse tumor response (median posttreatment NLR, 1.56 for partial response, 1.64 for stable disease, and 2.70 for progressive disease; P < 0.001). The risk of progression was higher when the posttreatment NLR was higher [hazard ratio (HR) = 1.23, 95 % confidence interval (CI) 1.15-1.31; P < 0.001]. A high posttreatment NLR was associated with an increased risk of death (HR = 1.13, 95 % CI 1.06-1.21; P < 0.001). These associations did not differ according to treatment arms. When total patients were divided into four groups according to the cutoff points of pre- and posttreatment NLRs, those with a high pretreatment NLR that declined substantially after treatment showed improved survival compared with those with a high pretreatment NLR that remained high even after treatment (median overall survival, 22.0 and 15.8 months, respectively; P < 0.001).

Conclusions: A high posttreatment NLR is associated with poor prognosis. An early reduction in the NLR after effective treatment may indicate survival improvement in the patients with poor prognosis.

Trial registration: ClinicalTrials.gov NCT00455936.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Early Detection of Cancer / methods
  • Female
  • Follow-Up Studies
  • Gefitinib
  • Gemcitabine
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy*
  • Lymphocytes / pathology*
  • Male
  • Middle Aged
  • Neutrophils / pathology*
  • Prognosis
  • Prospective Studies
  • Quinazolines / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Quinazolines
  • Deoxycytidine
  • Cisplatin
  • Gefitinib
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT00455936