Multicenter phase II study of gemcitabine and oxaliplatin in advanced nasopharyngeal carcinoma--correlation with excision repair cross-complementing-1 polymorphisms

Ann Oncol. 2009 Nov;20(11):1854-9. doi: 10.1093/annonc/mdp065. Epub 2009 Jun 23.

Abstract

Background: Nasopharyngeal carcinoma (NPC) is a platinum-sensitive cancer and excision repair cross-complementing group 1 (ERCC1) polymorphisms have been shown to predict survival in several cancers following platinum therapy.

Patients and methods: This multicenter study evaluated the activity of oxaliplatin and prolonged infusion of gemcitabine ('GEMOX' regimen) in recurrent NPC. Baseline blood samples were genotyped for the presence of ERCC1-118 gene polymorphisms.

Results: Forty-two patients were recruited, of whom most (61%) had metastatic disease. Of the 40 patients evaluated for response, the respective overall response and disease control rates were 56.1% and 90.2%. At a median follow-up of 14.8 months, the respective median overall survival and time to progression were 19.6 months [95% confidence interval (CI) = 12.8-22 months] and 9 months (95% CI = 7.3-10 months). Grade 3-4 toxic effects were uncommon. The distribution of ERCC1-118 genotypes from 29 patients was C/C (n = 17, 40.5%), C/T (n = 10, 23.8%) and T/T (n = 2, 4.8%). No differences in survival or response rates were found between genotypes.

Conclusions: GEMOX is active in the treatment of recurrent NPC. Detection of single-nucleotide gene polymorphisms from genomic DNA in peripheral blood is feasible in NPC and further studies are warranted.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma / drug therapy
  • Carcinoma / genetics*
  • DNA-Binding Proteins / genetics*
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / genetics*
  • Endonucleases / genetics*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / genetics*
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Organoplatinum Compounds / therapeutic use
  • Polymorphism, Single Nucleotide

Substances

  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • Deoxycytidine
  • ERCC1 protein, human
  • Endonucleases

Supplementary concepts

  • gemcitabine-oxaliplatin regimen