Response to first-line chemotherapy in patients with non-small cell lung cancer according to RRM1 expression

PLoS One. 2014 Mar 19;9(3):e92320. doi: 10.1371/journal.pone.0092320. eCollection 2014.

Abstract

Background: The response to cytotoxic chemotherapy varies greatly in patients with advanced non-small cell lung cancer (NSCLC), and molecular markers may be useful in determining a preferable therapeutic approach for individual patients. This retrospective study was performed to evaluate the predictive value of ribonucleotide reductase regulatory subunit M1 (RRM1) on the therapeutic efficacy of platinum-based chemotherapy in patients with NSCLC.

Methods: Patients with advanced NSCLC who received platinum doublet chemotherapy (n = 229) were included in this retrospective study, and their clinical outcomes were analyzed according to RRM1 expression.

Results: In patients receiving gemcitabine-based therapy, the disease control rate (DCR) and progression-free survival (PFS) of patients with RRM1-negative tumors were significantly higher than in patients with RRMI-positive tumors (P = 0.041 and P = 0.01, respectively), and multivariate analysis showed that RRM1 expression was an independent prognostic factor (P = 0.013). No similar differences were found in patients receiving docetaxel- or vinorelbine-based therapy. In RRM1-positive patients, the DCRs for docetaxel and vinorelbine were higher than for gemcitabine (P = 0.047 and P = 0.047, respectively), and docetaxel and vinorelbine showed a longer PFS than gemcitabine-based chemotherapy (P = 0.012 and P = 0.007). No similar differences were found among patients with RRM1-negative tumors.

Conclusions: Negative RRM1 expression in advanced NSCLC is associated with a higher response rate to gemcitabine-based chemotherapy. In patients with RRM1-positive tumors, docetaxel and vinorelbine showed a higher therapeutic efficacy than gemcitabine-based therapy. Additional prospective studies are needed to investigate the predictive meaning of RRM1 in the response to chemotherapy.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • Docetaxel
  • Female
  • Gemcitabine
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Ribonucleoside Diphosphate Reductase
  • Taxoids / therapeutic use
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Vinblastine / analogs & derivatives
  • Vinblastine / therapeutic use
  • Vinorelbine

Substances

  • Antineoplastic Agents
  • Taxoids
  • Tumor Suppressor Proteins
  • Deoxycytidine
  • Docetaxel
  • Vinblastine
  • RRM1 protein, human
  • Ribonucleoside Diphosphate Reductase
  • Vinorelbine
  • Gemcitabine

Grants and funding

These authors have no support or funding to report.