The MMP-9 expression determined the efficacy of postoperative adjuvant chemotherapy using oral fluoropyrimidines in stage II or III colorectal cancer

Cancer Chemother Pharmacol. 2006 May;57(5):577-83. doi: 10.1007/s00280-005-0081-9. Epub 2005 Aug 20.

Abstract

Background: The aim of this study was to determine any correlation between the efficacy of postoperative adjuvant chemotherapy using oral fluoropyrimidines and the matrix metalloproteinase 9 (MMP-9) expression in primary colorectal cancer tissues.

Patients and methods: The data on 307 patients with colorectal cancer at stage II or III, who underwent potentially curative resection with lymphadenectomy, were reviewed. Of these, 188 received postoperative administration of oral fluoropyrimidines such as UFT and 5'-DFUR (chemotherapy group), while the other 119 patients underwent surgery alone (surgery-alone group). Immunostaining for MMP-9 was performed using surgical specimens of all 307 primary tumors and 18 recurrent tumors.

Results: Overall, MMP-9 was positively expressed in the primary tumor in 44% of patients. Multivariate analysis revealed that the MMP-9 expression was a worse prognostic factor with a second highest hazard ratio for recurrence. The disease-free survival rate in the chemotherapy group was significantly higher than that in the surgery-alone group. However, no significant difference in disease-free survival rate between the two groups was found in patients with a tumor positive for MMP-9. There was a strong positive correlation of MMP-9 expression between the primary tumors and the recurrent liver or lung tumors.

Conclusions: The efficacy of postoperative adjuvant chemotherapy using oral fluoropyrimidines such as UFT and 5'-DFUR may not be as great for patients with a tumor positive for MMP-9 having a greater risk to postoperative recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / surgery
  • Disease-Free Survival
  • Female
  • Floxuridine / administration & dosage
  • Humans
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / secondary
  • Liver Neoplasms / therapy
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy
  • Lymph Node Excision
  • Lymphatic Metastasis / pathology
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Recurrence, Local / surgery
  • Neoplasm Staging
  • Postoperative Period
  • Retrospective Studies
  • Survival Rate
  • Tegafur / administration & dosage
  • Uracil / administration & dosage

Substances

  • Floxuridine
  • Tegafur
  • Uracil
  • Matrix Metalloproteinase 9
  • doxifluridine

Supplementary concepts

  • 1-UFT protocol