High RRM1 Expression Is Associated with Adverse Outcome in Patients with Cisplatin/Vinorelbine-treated Malignant Pleural Mesothelioma

Anticancer Res. 2015 Dec;35(12):6731-8.

Abstract

Background/aim: A possible predictive impact of ribonucleotide-reductase subunit-1 (RRM1) on vinorelbine efficacy in non-small cell lung cancer (NSCLC) has been previously reported. The present study aimed to further explore this finding in malignant pleural mesothelioma (MPM).

Materials and methods: Seventy-one patients with MPM receiving first-line chemotherapy with cisplatin-vinorelbine (CiV group, n=54) or carboplatin-pemetrexed (CaP group, n=17) were included. Formalin-fixed paraffin-embedded tumor specimens were analyzed by immunohistochemistry (IHC) for RRM1 expression using an H-score.

Results: In 66 patients eligible for IHC, the H-score was ≥upper quartile in 21 (RRM1-positive) and <upper quartile (RRM1-negative) in 45 cases. The long-term (2-year) survival rate for patients with RRM1-negative MPM in the CiV-treated group was significantly superior to that for patients with RRM1-positive MPM (47% versus 13%, p=0.002). No difference occurred in the CaP-treated group.

Conclusion: Our findings suggest a possible role of RRM1 in predicting efficacy of cisplatin-vinorelbine in MPM, supporting previous findings in NSCLC.

Keywords: Biomarkers; chemotherapy; malignant mesothelioma; vinorelbine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cisplatin / administration & dosage
  • Cohort Studies
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Male
  • Mesothelioma / drug therapy*
  • Mesothelioma / genetics
  • Mesothelioma / metabolism*
  • Mesothelioma, Malignant
  • Middle Aged
  • Pleural Neoplasms / drug therapy*
  • Pleural Neoplasms / genetics
  • Pleural Neoplasms / metabolism*
  • Ribonucleoside Diphosphate Reductase
  • Treatment Outcome
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives
  • Vinorelbine

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • Vinblastine
  • RRM1 protein, human
  • Ribonucleoside Diphosphate Reductase
  • Cisplatin
  • Vinorelbine