Different relation between ERCC1 overexpression and treatment outcomes of two platinum agents in advanced biliary tract adenocarcinoma patients

Cancer Chemother Pharmacol. 2011 Oct;68(4):935-44. doi: 10.1007/s00280-011-1558-3. Epub 2011 Feb 5.

Abstract

Purpose: The aim of this study is to evaluate the effect of excision repair cross-complementation group 1 (ERCC1) expression on treatment outcomes in advanced biliary tract adenocarcinoma (ABTA) patients treated with platinum-based chemotherapy.

Methods: One hundred and six patients with histologically confirmed adenocarcinoma of biliary tract were enrolled at 5 institutions in South Korea between January 2002 and September 2008. Of 106 patients, 93 were assessed by immunohistochemistry from tissue specimens. Sixty-five patients were treated with cisplatin-based regimens and the other 28 treated with oxaliplatin-based ones.

Results: For total study population, no significant differences were noted in progression-free survival (PFS) and overall survival (OS) between ERCC1-negative and ERCC1-positive patients, respectively (4.2 vs. 2.9 months, p = 0.116; 7.0 vs. 7.8 months, p = 0.143). In patients treated with cisplatin-based regimens, median PFS and OS were significantly longer in ERCC1-negative group than in ERCC1-positive group, respectively (4.6 vs. 1.9 months, p = 0.014; 9.1 vs. 7.9 months, p = 0.017). Disease control rate (DCR) was better in patients with ERCC1 negative than in patients with ERCC1 positive (p = 0.048). On the other hand, in patients treated with oxaliplatin-containing regimens, median PFS and OS tended to be longer in ERCC1-positive group, but these did not reach statistical significances. Response rate was better in patients with ERCC1 positive (p = 0.005).

Conclusions: ERCC1 shows a significant prognostic value in ABTA patients treated with cisplatin. A survival benefit was observed in ERCC1-negative patients from cisplatin-containing chemotherapy but not from oxaliplatin-containing ones. The action mechanism of ERCC1 on cisplatin may be different from that on oxaliplatin.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / genetics
  • Biliary Tract Neoplasms / pathology
  • Cisplatin / administration & dosage
  • DNA-Binding Proteins / genetics*
  • Disease-Free Survival
  • Endonucleases / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Prognosis
  • Republic of Korea
  • Survival Rate
  • Treatment Outcome

Substances

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